A Phase 2a, Randomized, Observer-Blind, Placebo Controlled, Dose-Confirmation Study to Evaluate the Safety, Reactogenicity, and Immunogenicity of mRNA-1273 SARS-COV-2 Vaccine in Adults Aged 18 Years and Older
Phase: PHASE2
Conditions: SARS-CoV-2
Sponsor: ModernaTX, Inc.

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CLINICAL STUDY PROTOCOL
A PHASE 2a, RANDOMIZED, OBSERVER-BLIND,
PLACEBO-CONTROLLED, DOSE-CONFIRMATION STUDY TO 
EVALUATE THE SAFETY, REACTOGENICITY, AND
IMMUNOGENICITY OF MRNA-1273 SARS-COV-2 VACCINE IN 
ADULTS AGED 18 YEARS AND OLDER
IND NUMBER: 19745
PROTOCOL NUMBER: mRNA-1273-P201
Sponsor:
ModernaTX, Inc.
200 Technology Square
Cambridge, MA 02139
Sponsor Contact: 
ModernaTX, Inc.
200 Technology Square
Cambridge, MA 02139
Telephone:
e-mail:
Amendment Number:
6 
Date of Amendment 6:
28 Apr 2021
Date of Amendment 5:
19 Feb 2021
Date of Amendment 4:
15 Jan 2021
Date of Amendment 3:
02 Sep 2020
Date of Amendment 2:
01 Jul 2020
Date of Amendment 1:
18 May 2020
Date of Original Protocol:
22 Apr 2020
CONFIDENTIAL
The concepts and information contained in this document or generated during the study are 
considered proprietary and may not be disclosed in whole or in part without the expressed, 
written consent of ModernaTX, Inc. 
The study will be conducted according to E6(R2) Good Clinical Practice: International 
Council for Harmonisation (E6(R2) Good Clinical Practice: Integrated Addendum to ICH 
E6(R1).
Confidential
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NCT #NCT04405076

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Protocol mRNA-1273-P201 Amendment 6 
mRNA-1273
Signature Page
PROTOCOL TITLE:
A Phase 2a, Randomized, Observer-Blind,
Placebo-Controlled, Dose-Confirmation Study to 
Evaluate the Safety, Reactogenicity, and 
Immunogenicity of mRNA-1273 SARS-CoV-2 Vaccine 
in Adults Aged 18 Years and Older 
PROTOCOL NUMBER: 
AMENDMENT NUMBER: 
AMENDMENT 6 DATE:
mRNA-1273-P201 
6 
28 Apr 2021
See esignature & date signed on last of the document
ModernaTX, Inc.
Date

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Protocol mRNA-1273-P201 Amendment 6 
mRNA-1273
Investigator Protocol Agreement Page
I agree to conduct the study as outlined in the protocol entitled “A Phase 2a, Randomized, 
Observer-Blind, Placebo-Controlled, Dose-Confirmation Study to Evaluate the Safety, 
Reactogenicity, and Immunogenicity of mRNA-1273 SARS-CoV-2 Vaccine in Adults Aged
18 Years and Older” in accordance with the guidelines and all applicable government regulations 
including US Title 21 of the Code of Federal Regulations Part 54. I have read and understand all 
sections of the protocol. 
Signature of Investigator
Date
Printed Name of Investigator

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Protocol mRNA-1273-P201 Amendment 6 
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Protocol Amendment Summary of Changes
DOCUMENT HISTORY
Document
Date
Amendment 6
28 Apr 2021
Amendment 5
19 Feb 2021
Amendment 4
15 Jan 2021
Amendment 3
02 Sep 2020
Amendment 2
01 Jul 2020
Amendment 1
18 May 2020
Original Protocol
22 Apr 2020
Amendment 6, 22 Apr 2021: Current Amendment 
Main Rationale for the Amendment:
This protocol amendment will add an analysis at the end of Part A. An analysis of safety and 
immunogenicity data will be performed after all participants have completed Part A of the study. 
All data collected in Part A of the study will be cleaned (ie, data that are as clean as possible) and 
locked and a report may be generated as needed.
The summary of changes table provided here describes the major changes made in Amendment 6 
relative to Amendment 5, including the sections modified and the corresponding rationales. The 
synopsis of Amendment 6 has been modified to correspond to changes in the body of the 
protocol.
Summary of Major Changes in Protocol Amendment 6:
Section # and Name
Description of Change
Brief Rationale
Synopsis and Section 4.7.6 (End of 
Study Analysis)
End of Part A clarified
To clarify that an analysis will be 
performed at the conclusion of Part A
Synopsis and Section 4.7.2 (Analysis 
at End of Blinded part A Only)
Added an analysis of 
safety and
immunogenicity at the 
end of Part A
To clarify that an analysis of safety and 
immunogenicity will be performed on all
participants upon completion of Part A of 
the study.

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Protocol mRNA-1273-P201 Amendment 6 
mRNA-1273
IRB and Regulatory Authority Approval
A copy of this amended protocol will be sent to the institutional review board (IRB) and regulatory 
authority.
The changes described in this amended protocol require IRB approval prior to implementation. In 
addition, if the changes herein affect the informed consent, sites are required to update and submit 
a revised informed consent for approval that incorporates the changes described in this amended 
protocol.

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Table of Contents
Signature Page.................................................................................................................................. 2
Investigator Protocol Agreement Page............................................................................................. 3
Protocol Amendment Summary of Changes .................................................................................... 4
IRB and Regulatory Authority Approval................................................................................. 5
List of Tables................................................................................................................................. 11
List of Figures ............................................................................................................................... 11
Protocol Synopsis...........................................................................................................................12
List of Abbreviations.......................................................................................................................26
1
INTRODUCTION .................................................................................................................29
1.1
Background ..................................................................................................................29
1.2
Nonclinical Studies in Development of mRNA-1273..................................................31
1.3
Clinical Studies 
.........................................31
2
STUDY OBJECTIVES..........................................................................................................34
2.1
Primary Objectives (Part A, Blinded) ..........................................................................34
2.1.1
Primary Safety Objective................................................................................34
2.1.2
Primary Immunogenicity Objective................................................................. 34
2.2
Secondary Objective (Part A, Blinded)........................................................................34
2.3
Exploratory Objectives (Part A, Blinded) ....................................................................34
2.4
Primary Objectives (Part B, Open Label) ....................................................................35
2.4.1
Primary Safety Objective................................................................................35
2.4.2
Primary Immunogenicity Objective................................................................. 35
2.5
Secondary Objective (Part B, Open Label).................................................................. 35
2.6
Exploratory Objectives (Part B, Open Label) ..............................................................35
2.7
Primary Objectives (Part C, Open Label) ....................................................................36
2.7.1
Primary Safety Objective................................................................................36
2.7.2
Primary Immunogenicity Objective................................................................. 36
2.8
Secondary Immunogenicity Objective (Part C, Open Label).......................................36
2.9
Exploratory Objectives (Part C, Open Label) ..............................................................36
3
INVESTIGATIONAL PLAN................................................................................................. 37
3.1
General Study Design................................................................................................... 37

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3.1.1
Part A, the Blinded Phase............................................................................... 37
3.1.2
Part B, Open-Label Interventional Phase....................................................... 41
3.1.3
Part C, Open-Label Interventional Phase of mRNA-1273.351 and mRNA-
1273/mRNA-1273.351 Mixture Booster Vaccines........................................ 43
3.1.4
Rationale for Dose Selection.......................................................................... 44
3.1.5
Rationale for Study Design............................................................................ 45
3.1.6
Inclusion Criteria............................................................................................ 46
3.1.6.1
Inclusion criterion specific for Parts A and B .............................. 47
3.1.6.2
Inclusion criterion specific for Part C .......................................... 48
3.1.7
Exclusion Criteria .......................................................................................... 49
3.1.7.1
Exclusion Criteria (Part A and Part B)......................................... 49
3.1.7.2
Exclusion Criteria (Part C)........................................................... 51
3.1.8
Screen Failures (Part A: Blinded Phase Only) ............................................... 53
3.1.9
Participant Restrictions During the Study...................................................... 53
3.1.9.1
General and Dietary ..................................................................... 53
3.2
Withdrawal of Participants From the Study or Study Dosing..................................... 53
3.2.1
Participant Withdrawal From the Study......................................................... 53
3.2.2
Handling Withdrawal From the Study ........................................................... 54
3.2.3
Lost to Follow-up........................................................................................... 54
3.2.4
Replacements (Part A, Blinded Phase Only).................................................. 54
3.2.5
Participant Withdrawal From Study Dosing.................................................. 54
3.3
Study Dosing Groups .................................................................................................. 55
3.3.1
Method of Assigning Participants to Dosing Groups (Part A and Part C) ..... 55
3.3.2
Investigational Product Administration.......................................................... 57
3.3.2.1
Pause Rules.................................................................................. 58
3.3.2.2
Contraindications to Subsequent Injection................................... 59
3.3.3
Identity of Investigational Product................................................................. 60
3.3.4
Management of Investigational Product ........................................................ 61
3.3.4.1
Delivery and Receipt.................................................................... 61
3.3.4.2
Packaging and Labeling............................................................... 61
3.3.4.3
Storage ......................................................................................... 62
3.3.4.4
Investigational Product Accountability ........................................ 62
3.3.4.5
Handling and Disposal................................................................. 63
3.3.5
Blinding.......................................................................................................... 63
3.3.6
Breaking the Blind......................................................................................... 64
3.3.7
Dosing Compliance........................................................................................ 64
3.3.8
Prior and Concomitant Medications............................................................... 65

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3.3.8.1
Prior Medications and Therapies ................................................. 65
3.3.8.2
Concomitant Medications and Therapies..................................... 65
3.4
Study Procedures......................................................................................................... 66
3.4.1
Assessment for SARS-CoV-2 Infection......................................................... 67
3.4.2
Use of Electronic Diaries ............................................................................... 68
3.4.3
Safety Telephone Calls................................................................................... 70
3.4.4
Safety Laboratory Assessments...................................................................... 71
3.4.5
Immunogenicity Assessments........................................................................ 71
3.4.6
Blood Sampling Volumes .............................................................................. 72
3.4.7
Safety Assessments ........................................................................................ 73
3.4.8
Safety Definitions........................................................................................... 74
3.4.8.1
Adverse Event.............................................................................. 74
3.4.8.2
Medically Attended Adverse Event.............................................. 75
3.4.8.3
Serious Adverse Event ................................................................. 75
3.4.8.4
Solicited Adverse Reactions......................................................... 76
3.4.8.5
Pregnancy..................................................................................... 80
3.4.8.6
Definition and Reporting of Adverse Events Consistent with
Anaphylaxis ................................................................................. 81
3.4.8.7
Eliciting and Documenting Adverse Events ................................ 82
3.4.8.8
Reporting Adverse Events............................................................ 82
3.4.8.9
Assessment of Severity ................................................................ 83
3.4.8.10
Assessment of Causality .............................................................. 84
3.4.8.11
Follow-up of Adverse Events....................................................... 84
3.4.9
Vital Sign Measurements ............................................................................... 84
3.4.10
Physical Examinations ................................................................................... 85
4
STATISTICALANALYSIS PLAN....................................................................................... 86
4.1
Blinding and Responsibility for Analyses................................................................... 86
4.2
Hypothesis Testing...................................................................................................... 87
4.3
Analysis Endpoints...................................................................................................... 87
4.3.1
Part A, Blinded............................................................................................... 87
4.3.1.1
Primary Endpoints........................................................................ 87
4.3.1.2
Secondary Endpoints.................................................................... 87
4.3.1.3
Exploratory Endpoints ................................................................. 88
4.3.2
Part B, Open Label......................................................................................... 88
4.3.2.1
Primary Endpoints (Part B, Open Label)..................................... 88
4.3.2.2
Secondary Endpoints (Part B, Open Label)................................. 89

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4.3.2.3
Exploratory Endpoints (Part B, Open Label)................................89
4.3.3
Part C, Open Label ..........................................................................................90
4.3.3.1
Primary Endpoints (Part C, Open Label)......................................90
4.3.3.2
Secondary Immunogenicity Endpoint...........................................90
4.3.3.3
Exploratory Endpoints (Part C, Open Label)................................91
4.4
Analysis Populations ....................................................................................................91
4.4.1
Randomized Set ..............................................................................................91
4.4.2
Solicited Safety Set .........................................................................................91
4.4.3
Safety Set ........................................................................................................91
4.4.4
Full Analysis Set .............................................................................................92
4.4.5
Per-Protocol Set ..............................................................................................92
4.5
Sample Size Determination..........................................................................................92
4.6
Statistical Methods.......................................................................................................93
4.6.1
Summary of Baseline Characteristics and Demographics................................93
4.6.2
Safety Analyses................................................................................................94
4.6.3
Immunogenicity Analyses................................................................................95
4.6.4
Exploratory Analyses ......................................................................................96
4.7
Study Analyses.............................................................................................................97
4.7.1
Primary Study Analysis for Blinded Part A Only............................................97
4.7.2
Analysis at End of Blinded Part A Only..........................................................97
4.7.3
Interim Study Analysis for Open-Label Part B Only......................................97
4.7.4
Interim Study Analysis for Open-Label Part C Only......................................97
4.7.5
Additional Study Analyses..............................................................................97
4.7.6
End of Study Analysis .....................................................................................98
4.8
Data Quality Assurance................................................................................................98
5
INVESTIGATOR OBLIGATIONS.......................................................................................99
5.1
Confidentiality..............................................................................................................99
5.2
Institutional Review .....................................................................................................99
5.3
Participant Consent ......................................................................................................99
5.4
Study Reporting Requirements ..................................................................................100
5.5
Financial Disclosure and Obligations.........................................................................100
5.6
Investigator Documentation .......................................................................................101
5.7
Study Conduct............................................................................................................101
5.8
Data Collection...........................................................................................................102
5.8.1
Case Report Forms and Source Documents..................................................102

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5.9
Adherence to Protocol................................................................................................102
5.10 Reporting Adverse Events..........................................................................................102
5.11 Investigator’s Final Report.........................................................................................102
5.12 Records Retention.......................................................................................................103
5.13 Publications ................................................................................................................103
6
STUDY MANAGEMENT .................................................................................................. 104
6.1
Monitoring..................................................................................................................104
6.1.1
Safety Monitoring Committee.......................................................................104
6.1.2
Monitoring of the Study................................................................................104
6.1.3
Inspection of Records....................................................................................105
6.2
Management of Protocol Amendments and Deviations.............................................105
6.2.1
Modification of the Protocol..........................................................................105
6.2.2
Protocol Deviations.......................................................................................105
6.3
Study Termination......................................................................................................105
6.4
Clinical Study Reports ...............................................................................................106
7
APPENDICES .....................................................................................................................107
7.1
Appendix 1: Schedule of Events................................................................................107
7.2
Appendix 2: Toxicity Grading Scale Tables ..............................................................118
7.3
Appendix 3: Protocol Amendment History................................................................123
7.3.1
Amendment 5, 19 Feb 2021 ..........................................................................123
7.3.2
Amendment 4, 15 Jan 2021...........................................................................129
7.3.3
Amendment 3, 02 Sep 2020..........................................................................132
7.3.4
Amendment 2, 01 Jul 2020...........................................................................133
7.3.5
Amendment 1, 18 May 2020.........................................................................134
8
REFERENCE LIST.............................................................................................................138

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List of Tables
Table 1:
Dose Group Assignment (Part A).......................................................................... 56
Table 2:
Dose Group Assignment (Part C).......................................................................... 56
Table 3:
Pause Rule Criteria, Events, and Thresholds ........................................................ 58
Table 4: 
Maximum Blood Sampling Volumes per Participant by Visit (Part A, Blinded) . 73
Table 5: 
Maximum Blood Sampling Volumes per Participant by Visit (Part B and Part C
Open-label)............................................................................................................ 73
Table 6:
Solicited Adverse Reactions and Grades............................................................... 78
Table 7: 
95% Confidence Interval for One Participant with AE and the Lowest Detectable
Incidence Rate at 95% Probability in Selected Sample Size................................. 93
Table 8: 
Analysis Strategy for Safety Parameters ............................................................... 95
Table 9: 
Schedule of Events (Part A, Blinded Phase only) ............................................... 108
Table 10:
Part B: Participant Decision Clinic Visit..............................................................111
Table 11: 
Part B: Open-label Schedule of Events: ONLY for Participants Receiving 2 Doses
of mRNA-1273 28 Days Apart.............................................................................112
Table 12: 
Part B and Part C: Open-label Schedule of Events (Participants Receiving a
Booster Dose)9.....................................................................................................................................................115
Table 13:
Tables for Clinical Abnormalities.........................................................................118
Table 14:
Tables for Laboratory Abnormalities................................................................... 121
List of Figures
Figure 1: 
Study Flow Schema (Part A, Blinded Phase)........................................................ 38
Figure 2:
Sentinel and Expansion Cohort Schema (Part A, Blinded Phase)......................... 39
Figure 3:
Part B, Open-Label Schema.................................................................................. 41
Figure 4: 
Part C, Open-Label Schema for Boosting with mRNA-1273.351 and mRNA-
1273/mRNA-1273.351 Mixture ............................................................................ 43

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Protocol Synopsis
Protocol Number:    mRNA-1273-P201
Title:
A Phase 2a, Randomized, Observer-Blind, Placebo-Controlled, Dose- 
Confirmation Study to Evaluate the Safety, Reactogenicity, and 
Immunogenicity of mRNA-1273 SARS-CoV-2 Vaccine in Adults Aged 
18 Years and Older 
Study Phase: 
2 
Study Sites:
Approximately 10 study sites in the United States or its territories.
Objectives:
PART A (BLINDED)
Primary:
•
To evaluate the safety and reactogenicity of 2 dose levels of 
mRNA-1273 vaccine, each administered in 2 doses 28 days 
apart
•
To evaluate the immunogenicity of 2 dose levels of
mRNA-1273 vaccine, each administered in 2 doses 28 days 
apart, as assessed by the level of specific binding antibody 
(bAb)
Secondary:
•
To evaluate the immunogenicity of 2 dose levels of
mRNA-1273 vaccine, each administered in 2 doses 28 days 
apart, as assessed by the titer of neutralizing antibody (nAb) 
Exploratory:

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PART B (OPEN LABEL)
Primary:
•
To evaluate the safety and reactogenicity of 50 µg of
mRNA-1273 vaccine administered as a single booster dose or 
100 µg of mRNA-1273 administered as 2 doses 28 days apart
•
To evaluate the immunogenicity of 50 µg of mRNA-1273 
vaccine administered as a single booster dose or 100 µg of 
mRNA-1273 administered as 2 doses 28 days apart, as 
assessed by the level of specific bAb
Secondary:
•
To evaluate the immunogenicity of 50 µg of mRNA-1273 
vaccine administered as a single booster dose or 100 µg of 
mRNA-1273 administered as 2 doses 28 days apart, as 
assessed by the titer of nAb
Exploratory:
PART C (OPEN LABEL)
Primary:
•
To evaluate the safety and reactogenicity of 2 dose levels 
(20 and 50 µg) of mRNA-1273.351 or one dose level of a 
mixture of 25 µg mRNA-1273 and 25 µg mRNA-1273.351 
(mRNA-1273/mRNA-1273.351 mixture) (50 µg total) vaccine 
administered as a single booster dose after completing a 
two-dose vaccination schedule of mRNA-1273 at least 6 
months earlier
•
To evaluate the immunogenicity of 2 dose levels (20 and 
50 µg) of mRNA-1273.351 or one dose level of 
mRNA-1273/mRNA-1273.351 mixture (50 µg total) vaccine 
administered as a single booster dose after completing a 
two-dose vaccination schedule of mRNA-1273 at least 6 

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months earlier, as assessed by the level of specific nAb 
directed against the S2P antigen derived from B.1.351 variant
Secondary:
•
To evaluate the immunogenicity of 2 dose levels (20 and 
50 µg) of mRNA-1273.351 or one dose level of 
mRNA-1273/mRNA-1273.351 mixture (50 µg total) vaccine 
administered as a single booster dose after completing a 
two-dose vaccination schedule of mRNA-1273 at least
6 months earlier, as assessed by the level of specific bAb 
directed against the S2P antigen derived from B.1.351 variant
Exploratory:

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Study Design and 
Methodology:
This is a three-part Phase 2a study: Part A, Part B, and Part C. 
Participants in Part A, the Blinded Phase of this study, are blinded to 
their treatment assignment. Part B, the Open-Label Interventional 
Phase of this study, is designed to offer participants who received 
placebo in Part A of this study the option to receive 2 injections of 
open-label mRNA-1273. Participants who received 1 or 2 doses of
50 µg or 100 µg mRNA-1273 in Part A will be offered a single booster 
dose of mRNA-1273 (50 µg) in Part B. Part C will be a proof-of- 
concept rollover study of approximately 60 participants, who are 
currently enrolled in Moderna’s Phase 3 mRNA-1273-P301 COVE 
study, have already been unblinded, and have previously received 2 
doses of mRNA-1273 at least 6 months earlier. Upon enrollment into 
Part C of this study, they will receive a single IM injection of
mRNA-1273.351 (20 µg or 50 µg) or mRNA-1273/mRNA-1273.351
mixture (50 µg total) at least 6 months after receiving the second 
vaccination in the mRNA-1273-P301 COVE study. At enrollment into 
this study, their participation in mRNA-1273-P301 COVE study will 
be terminated.
Part A, the Blinded Phase:
The Blinded Phase of this study is randomized, observer-blind, and 
placebo-controlled, with adult participants at least 18 years of age. 
Two dose levels (50 µg and 100 µg) will be evaluated in this study, 
based in part on initial safety data from the Phase 1 Division of 
Microbiology and Infectious Diseases (DMID) study of mRNA-1273. 
The study will include 2 age cohorts: Cohort 1 with 300 participants 
(≥ 18 to < 55 years old) and Cohort 2 with 300 participants (≥ 55 years 
old). Approximately 600 participants will receive either mRNA-1273 
vaccine or saline placebo control according to a 1:1:1 randomization 
ratio; ie, within each age cohort, 100 participants will receive 
mRNA-1273 50 µg, 100 participants will receive mRNA-1273 100 µg, 
and 100 participants will receive saline placebo.
The study will be initiated with a parallel enrollment of all 
300 participants in Cohort 1 (≥18 to < 55 years old) and a sentinel 
group of 50 participants in Cohort 2 (≥55 years old) receiving study 
treatment. Before initiating study treatment of the remaining 
participants in Cohort 2, safety data through Day 7 from the sentinel 
group of Cohort 2 and all available data from Cohort 1 will be reviewed 
by the Safety Monitoring Committee (SMC). 
If no safety concerns are found, expansion enrollment (N=250) of 
Cohort 2 will proceed. 
Part A of the study comprises up to 10 scheduled study site visits: 
Screening, Day 1, Day 8, Day 15, Day 29 (Month 1), Day 36, Day 43,

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Day 57 (Month 2), Day 209 (Month 7), and Day 394 (Month 13) or 
initiation of Part B, whichever is earlier. There are also scheduled 
participant contacts approximately every 2 weeks after Day 57 to 
collect medically attended adverse events (MAAEs), adverse events 
(AEs) leading to withdrawal, serious adverse events (SAEs), 
concomitant medications associated with these events, receipt of
non-study vaccinations, exposure to someone with known COVID-19 
or SARS-CoV-2 infection, and participant experience of COVID-19 
symptoms. Every 4 weeks from Day 71 through Day 183 and from 
Day 223 through Day 363, each participant will complete a 
questionnaire in an electronic diary (eDiary) that will be reviewed by 
study site personnel. Safety telephone calls will occur every 4 weeks 
from Day 85 through Day 197 and from Day 237 through Day 377. 
The study duration for Part A will be approximately 14 months for each 
participant: a screening period of up to 1 month and a study period of 
13 months that includes the first dose of vaccine on Day 1 and the 
second dose on Day 29. The participant’s final visit will be on Day 394 
(Month 13), 12 months after the second dose of vaccine on Day 29 
(Month 1), or initiation of Part B, whichever is earlier. 
To test for the presence of SARS-CoV-2, nasopharyngeal swab samples 
will be collected at Day 1, Day 29, and Day 57. During the course of 
the study, participants meeting pre-specified disease criteria that 
suggest possible SARS-CoV-2 infection will be asked to contact the 
study site to arrange for a prompt, thorough, and careful assessment. 
Each participant will receive 2 injections of mRNA-1273 or placebo 
by 0.5 mL intramuscular (IM) injection on Day 1 and Day 29. Vaccine 
accountability, dose preparation, and vaccine administration will be 
performed by unblinded pharmacy personnel who will not participate 
in any other aspects of the study during Part A, the Blinded Phase. The 
remainder of the study staff, all participants, and Sponsor personnel (or 
its designees) will remain blinded to dosing assignment. 
All participants will be followed for safety and reactogenicity and 
provide pre- and post-injection blood specimens for immunogenicity 
through 12 months after the last dose of investigational product. 
The end of Part A is defined as the earlier of Visit 9, the completion of 
the last participant’s last visit, or initiation of Part B. Participants are 
considered to have completed Part A of the study if they complete the 
final visit on Day 394 (Month 13) or initiated Part B of the study.
At each dosing visit, participants will be instructed (Day 1) or reminded 
(Day 29) how to document and report solicited adverse reactions (ARs) 
within a provided eDiary. Solicited ARs will be assessed for 7 days (the 
day of injection and the following 6 days) after each injection and

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unsolicited AEs will be assessed for 28 days after each injection; SAEs 
and MAAEs will be assessed throughout the study. 
Participants will have blood sampled at scheduled study site visits 
during the study for safety and immunogenicity assessments or other 
medical concerns according to the investigator’s judgment. In addition, 
participants may have blood sampled at unscheduled visits for acute 
respiratory symptoms. 
Part B, the Open-Label Interventional Phase:
Part B, the Open-Label Interventional Phase of the study, is prompted 
by the authorization of a COVID-19 vaccine under Emergency Use 
Authorization (EUA). Transitioning the study to Part B permits all 
ongoing study participants to be informed of the availability and 
eligibility criteria of any COVID-19 vaccine made available under an 
Emergency Use Authorization (EUA) and the option to offer all 
ongoing study participants an opportunity to schedule a Participant 
Decision Visit to know their original treatment assignment (placebo vs. 
mRNA-1273 [50 µg or 100 µg] vaccine). 
Part B, the Open-Label Interventional Phase of the study, also provides 
the opportunity for study participants who previously received placebo 
to actively request to receive 2 doses of mRNA-1273 (100 µg) vaccine. 
In addition, all participants who previously received 1 or 2 doses (50 µg 
or 100 µg) of the mRNA-1273 vaccine will be able to receive a single 
50 µg booster dose of mRNA-1273. All study participants will receive 
a Notification Letter summarizing the basis for a COVID-19 vaccine 
to receive an EUA and will be asked to schedule a Participant Decision 
Clinic Visit. 
At the Participant Decision Clinic Visit, all participants will:
•
Be given the option to be unblinded as to their original group 
assignment (placebo vs. mRNA-1273 vaccine [50 µg or 
100 µg]), 
•
Be counselled about the importance of continuing other public 
health measures to limit the spread of disease including social 
distancing, wearing a mask, and hand-washing, 
•
Sign a revised ICF, and
•
Provide a nasopharyngeal (NP) swab for RT-PCR for 
SARS-CoV-2 and a blood sample for serology and 
immunogenicity.

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NOTE: After the Participant Decision Clinic Visit, all participants will 
proceed to the open label, Part B of the study, and will follow the Part B 
Schedule of Events as follows: 
•
Participants received placebo in Part A and consent to 
unblinding and to receiving 2 doses of mRNA-1273 in
Part B: These participants will proceed to Part B.
•
Participants received 1 dose of mRNA-1273 in Part A 
(regardless of the initial dose level received) and consent to 
unblinding
and
to
receiving 
booster 
injection 
of 
mRNA-1273 in Part B: These participants will proceed to Part 
B.
•
Participants received 2 doses of mRNA-1273 in Part A and 
consent to unblinding and to receiving booster injection of 
mRNA-1273 dose in Part B: These participants will proceed 
to Part B (note that these participants will receive 3 injections 
of mRNA-1273 during the course of the study). 
•
Participants received 2 doses of mRNA-1273 in Part A and 
consent to unblinding, but decline receiving another booster 
injection of mRNA-1273 in Part B: These participants will 
proceed to Part B.
•
Participants decline breaking of blind: These participants 
will proceed to Part B.
PART C, the Open-Label Interventional Phase of mRNA-1273.351 
and mRNA-1273/mRNA-1273.351 mixture booster vaccines: 
Part C, the Open-Label Interventional Phase of the study of 
mRNA-1273.351 and mRNA-1273/mRNA-1273.351 mixture booster 
vaccines, is prompted by the need to pro-actively prepare for 
vaccination strategies that induce a broader protection, including 
variants such as B.1.351. This proof-of-concept study design will 
evaluate the safety and immunogenicity of two dose levels of mRNA- 
1273.351 (20 µg and 50 µg), and mRNA-1273/mRNA-1273.351
mixture (50 µg total), given as a single IM injection booster. Upon 
meeting eligibility criteria, approximately 60 participants from 
Moderna’s Phase 3 mRNA-1273-P301 COVE study will be enrolled 
into this Part C to receive a single IM injection of mRNA-1273.351 (20 
µg or 50 µg) or a single IM injection of mRNA-1273/mRNA-1273.351 
mixture (50µg). An additional booster dose may be added 
approximately 56 days after the first boost at OL-D1. This additional 
booster dose will be triggered following review of immunogenicity 
data up to OL-D15 of the initial mRNA-1273.351 (20 µg and 50 µg) 
and mRNA-1273/mRNA-1273.351 mixture injections. 

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Study 
Population:
Safety 
Assessments:
Participants (males and females 18 years of age or older at time of 
consent) will be included in the study if they are in good health 
according to the assessment of the investigator and can comply with 
study procedures. Negative pregnancy tests will be required at 
Screening and before vaccine administration for female participants of 
childbearing potential. The full lists of inclusion and exclusion criteria 
are provided in the body of the protocol. 
Safety assessments will include monitoring and recording of the 
following for each participant: 
•
Solicited local and systemic ARs that occur during the 7 days 
following each injection (ie, the day of injection and 
6 subsequent days); solicited ARs will be recorded daily using 
eDiaries. (Part A, Blinded Phase, Part B, Open Label, and
Part C, Open Label).
•
Unsolicited AEs observed or reported during the 28 days 
following each
injection
(ie,
the
day of
injection
and 
27 subsequent days); unsolicited AEs are AEs that are not 
included in the protocol-defined solicited ARs. (Part A, Blinded 
Phase, Part B, Open Label, and Part C, Open Label).
•
AEs leading to discontinuation from dosing and/or study 
participation from Day 1 through Day 394 (Part A) and
OL-Month 6 or 7 (Part B and Part C) or withdrawal from the 
study.
•
MAAEs from Day 1 through Day 394 (Part A) and OL-Month 
6 or 7 (Part B and Part C) or withdrawal from the study. 
•
SAEs from Day 1 through Day 394 (Part A) and OL-Month 
6 or 7 (Part B and Part C) or withdrawal from the study. 
•
Results of safety laboratory tests (Part A).
•
Vital sign measurements (Part A, Part B, and Part C).
•
Physical examination findings (Part A, Part B, and Part C).
•
Assessments for SARS-CoV-2 infection from Day 1 through 
study completion (Part A, Part B, and Part C). 

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Immunogenicity 
Assessments:
Investigational
Product, Dosage, 
and Route of 
Administration:
Immunogenicity assessments will include the following in Part A and 
Part B:
•
Serum bAb level against SARS-CoV-2 as measured by 
enzyme-linked immunosorbent assay (ELISA) specific to the 
SARS-CoV-2 spike protein 
•
Serum nAb titer against SARS-CoV-2 as measured by 
pseudovirus and/or live virus neutralization assays 
In Part C, serum samples for immunogenicity assessment will be 
analyzed for:
•
Serum nAb against SARS-CoV-2 as measured by 
pseudovirus (and/or live virus) using the B.1.351 and the 
D614G variant sequences of SARS-CoV-2 S protein 
(and/or variant strains) 
•
Serum bAb against SARS-CoV-2 as measured by ELISA 
against the B.1.351 and the D614G variant sequences of 
SARS-CoV-2 S protein 
mRNA-1273 vaccine, dosed in Part A and Part B, is a lipid nanoparticle 
(LNP) dispersion of an mRNA encoding the prefusion stabilized S 
protein of SARS-CoV-2 formulated in LNPs composed of 4 lipids 
(1 proprietary and 3 commercially available). The mRNA-1273 
vaccine is provided as a sterile liquid for injection, white to off white 
dispersion in appearance, at a concentration of 0.5 mg/mL in 20 mM 
Tris buffer containing 87 mg/mL sucrose and 10.7 mM sodium acetate 
at pH 7.5. 
The mRNA-1273 vaccine dosed in Part C is provided at a concentration 
of 0.2 mg/mL in 20 mM Tris buffer containing 87 mg/mL sucrose and
4.3 mM sodium acetate at pH 7.5.
mRNA-1273.351 vaccine, dosed in Part C, is a LNP dispersion, with 
an mRNA encoding the prefusion stabilized S protein of SARS-CoV-2 
variant B1.351. The mRNA is formulated in LNPs composed of 4 lipids 
(1 proprietary and 3 commercially available). The mRNA-1273.351 
vaccine in Part C is in 20 mM Tris buffer containing 10.7 mM of 
sodium acetate at pH 7.5 and provided at a concentration of 0.5 mg/mL. 
mRNA-1273 and mRNA-1273.351 vaccines will be mixed at the 
clinical site to enable dosing of the mRNA-1273/mRNA-1273.351 
(50 µg total) arm. 
The placebo is 0.9% sodium chloride (normal saline) injection, United 
States Pharmacopeia (USP).
Investigational product will be administered as an IM injection into the 
deltoid muscle on a 2-dose injection schedule on Day 1 and Day 29 in 
Part A and on Open Label (OL) Days 1 and 29 in Part B 

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(for participants receiving 2 doses of mRNA-1273), with a 28-day 
interval between doses. Participants receiving a single booster dose of 
mRNA-1273 in Part B will receive their dose on OL-D1. Each injection 
will have a volume of 0.5 mL and contain mRNA-1273 50 µg, 
mRNA-1273 100 µg, or saline placebo. Upon consent to roll over, 
participants in Part C will receive a single booster dose of 
mRNA-1273.351 (20 µg or 50 µg) or mRNA-1273/mRNA-1273.351
mixture (50 µg total). Preferably, the vaccine should be administered 
into the nondominant arm. 
Unblinded pharmacy personnel, who will not participate in any other 
aspect of the study during Part A, the Blinded Phase, will perform 
vaccine accountability, dose preparation, and vaccine administration. 
In Part B, study site personnel who were blinded during the Blinded 
Phase, will be unblinded at the Participant Decision Visit.
Part B and C of the study will be open label.
Sample Size:
There is no hypothesis testing in this study. The number of proposed 
participants is considered sufficient to provide a descriptive summary
of the safety and immunogenicity of different dose levels of 
mRNA-1273.
In the blinded Part A, approximately 600 participants will be randomly 
assigned in a 1:1:1 ratio to mRNA-1273 50 µg, mRNA-1273 100 µg, 
or placebo. A total of 400 participants will receive mRNA-1273, 200 
participants in each dose level, or 100 participants in each age cohort 
and dose level. A sample size of 400 has at least a 95% probability to 
observe at least 1 participant with an AE at a true 0.75% AE rate. 
Participants who received any injection in Part A will have the 
opportunity to enter Part B provided that they meet the eligibility 
criteria.
In the open-label Part C, approximately 60 participants from 
Moderna’s Phase 3 mRNA-1273-P301 COVE study will be enrolled 
and will be assigned to receive a single IM injection of mRNA- 
1273.351 (20 µg or 50 µg) or mRNA-1273/mRNA-1273.351 mixture 
(50 µg total). The enrollment and vaccination in each study arm will be 
sequential as follows. The first 20 participants will be enrolled and 
dosed on OL-D1 with the mRNA-1273.351 50 µg dose. Upon 
completion of the first 50 µg dose arm, 20 participants will be enrolled 
in the second arm and will receive the mRNA-1273/mRNA-1273.351 
mixture (50 µg total dose). Following completion of the second arm, 
20 participants will be enrolled and dosed with the mRNA-1273.351 
20 µg dose. 

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Statistical 
Methods:
General Considerations: Data from Part A and Part B will be 
presented separately, as applicable. All analyses will be performed by 
treatment group overall (for the 2 cohorts combined) and for the 
2 cohorts separately, unless specified otherwise. Data from Part C may 
be presented separately, as appropriate.
For categorical variables, frequencies and percentages will be 
presented. Continuous variables will be summarized using descriptive 
statistics (number of participants, mean, median, standard deviation, 
minimum, and maximum).
Safety: Safety and reactogenicity will be assessed by clinical review 
of all relevant parameters including solicited ARs (local and systemic 
events), unsolicited AEs, SAEs, MAAEs, AEs leading to 
discontinuation, safety laboratory test results, vital signs, and physical 
examination findings. 
Solicited ARs and unsolicited AEs will be coded by system organ class 
and preferred term according to the Medical Dictionary for Regulatory 
Activities (MedDRA) for Adverse Reaction Terminology. The Toxicity 
Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled 
in Preventive Vaccine Clinical Trials is used in this study with 
modification for rash, solicited ARs, and vital signs. 
Rash will be graded in the following manner:
•
Grade 0 = no rash
•
Grade 1 = localized without associated symptoms
•
Grade 2 = maculopapular rash covering < 50% body surface area
•
Grade 3 = urticarial rash covering > 50% body surface area
•
Grade 4 = generalized exfoliative, ulcerative, or bullous dermatitis
All safety analyses will be based on the Safety Set, except summaries 
of solicited ARs, which will be based on the Solicited Safety Set. All 
safety analyses for Part A and Part B will be provided by age cohort 
unless otherwise specified. 
The number and percentage of participants with any solicited local AR, 
with any solicited systemic AR, and with any solicited AR during the 
7-day follow-up period after each injection will be summarized. A 
2-sided 95% exact confidence interval (CI) using the Clopper-Pearson 
method will be provided for the percentage of participants with any 
solicited AR.
Number and percentage of participants with unsolicited AEs, SAEs, 
MAAEs, Grade 3 or higher AEs, and AEs leading to discontinuation 
from study vaccine or participation in the study will be summarized. 

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Number of events of solicited ARs, unsolicited AEs/SAEs, and 
MAAEs will be reported in summarization tables accordingly. 
For all other safety parameters, descriptive summary statistics will be 
provided.
For treatment-emergent safety laboratory tests results, the raw values 
and change from baseline values will be summarized by age cohort (for 
Part A and Part B), treatment group, and visit at each timepoint. 
The number and percentage of participants who have chemistry, 
hematology, coagulation, and vital signs results below or above the 
laboratory normal ranges will be tabulated by timepoint. 
Demographic variables (eg, age, height, weight, and body mass index 
(BMI) and baseline characteristics will be summarized by treatment 
group for each age cohort (when appropriate) by descriptive statistics 
(mean, standard deviation for continuous variables, and number and 
percentage for categorical variables).
Data from Part C will be analyzed similarly.
Immunogenicity: The analyses of immunogenicity will be based on 
the Per-Protocol (PP) Set. For each age cohort (for Part A and Part B), 
if the number of participants in the Full Analysis Set (FAS) and PP Set 
differ (defined as the difference divided by the total number of 
participants in the PP Set) by more than 10%, supportive analyses of 
immunogenicity may be conducted using the FAS. 
For the primary immunogenicity endpoint (secondary immunogenicity 
in Part C), geometric mean (GM) of specific bAb with corresponding 
95% CI at each timepoint and geometric mean fold-rise (GMFR) of 
specific bAb with corresponding 95% CI at each post-baseline 
timepoint over pre-injection baseline at Day 1 will be provided by 
treatment group and age cohort (for Part A and Part B). Descriptive 
summary statistics including median, minimum, and maximum will 
also be provided. 
For the secondary immunogenicity endpoint (primary immunogenicity 
endpoint for Part C), geometric mean titer (GMT) of specific nAb with 
corresponding 95% CI at each timepoint and GMFR of specific nAb 
with corresponding 95% CI at each post-baseline timepoint over pre- 
injection baseline at Day 1 will be provided by treatment group and age 
cohort (for Part A and Part B). Descriptive summary statistics including 
median, minimum, and maximum will also be provided. For 
summarizations of GMT values, antibody values reported as below the 
lower limit of quantification (LLOQ) will be replaced 0.5 × LLOQ. 
Values that are greater than the upper limit of quantification (ULOQ) 
will be converted to the ULOQ. 

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The number and percentage of participants with fold-rise ≥ 2, 
fold-rise ≥3, and fold-rise ≥4 of serum SARS-CoV-2-specific nAb 
titers and participants with seroconversion from baseline will be 
provided with 2-sided 95% CI using the Clopper-Pearson method at 
each post-baseline timepoint. Seroconversion at a participant level is 
defined as a change of nAb titer from below the LLOQ to equal to or 
above LLOQ, or a 4-times or higher titer ratio in participants with pre- 
existing nAb titers.
Further 
details will be described in the Statistical Analysis Plan.
Data from Part C will be analyzed similarly.
Study Analyses 
A primary analysis of safety and immunogenicity data will be 
performed after participants have completed Day 57 study procedures 
for blinded Part A only. This primary analysis may be performed when 
all participants in Cohort 1 and the Cohort 2 sentinel group have 
completed Day 57 study procedures and/or when all participants in 
Cohort 1 and Cohort 2 have completed Day 57 study procedures. All 
data relevant to the primary study analysis through Day 57 visit will be 
cleaned (ie, data that are as clean as possible) and locked. A limited 
number of Sponsor and clinical research organization personnel will be 
unblinded to perform the primary study analysis and prepare a final 
Clinical Study Report (CSR), including individual listings. The study 
site staff, investigators, study monitors, and participants will remain 
blinded until initiation of the Open-Label Part B of the study. 
This protocol amendment will add an analysis at the end of Part A. An 
analysis of safety and immunogenicity data will be performed after all 
participants have completed Part A of the study. All data collected in 
Part A of the study will be cleaned (ie, data that are as clean as possible) 
and locked and a report may be generated. 
An interim analysis of the safety and immunogenicity data in Part B of 
the study may be performed after participants have completed the
OL-Day 29 and/or the OL-Day 57 study procedures. This analysis may 
be performed when all participants have completed OL-Day 29 and/or 
OL-Day 57 study procedures, or on a subset of participants who 
received a single booster dose at OL-Day 1 when they have completed 
OL-Day29 and/or OL-Day 57 study procedures. All data collected up 
to OL-D29 and/or OL-D57 in Part B, will be cleaned (ie, data that are 
as clean as possible) and locked, and a report may be generated. 
An interim analysis of the safety and immunogenicity data in Part C of 
the study may be performed after participants have completed the
OL-D8, OL-D15, OL-Day 29 and/or the OL-Day 57 study procedures.

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Date of Protocol
All data collected up to OL-D29 and/or OL-D57 in Part C, will be 
cleaned (i.e., data that are as clean as possible) and locked, and a report 
may be generated.
Additional analyses may be performed to support regulatory requests, 
as appropriate.
The EOS analysis of all endpoints will be performed after all 
participants
have
completed Month 13 (Blinded Part
A), or 
OL-Month 6 and OL-Month 7 (Open-Label Part B), or OL-Month 6 
(Part C) study procedures and after the database is cleaned and locked. 
Results of this analysis will be presented in an EOS CSR, including 
individual listings.
Amendment 5:
22 Apr 2021

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List of Abbreviations
Abbreviation
Definition
AE
adverse event
ALP
alkaline phosphatase
ALT
alanine aminotransferase
AR
adverse reaction
AST
aspartate aminotransferase
bAb
binding antibody
BMI
body mass index
BUN
blood urea nitrogen
CBC
complete blood count
CBER
Center for Biologics and Evaluation Research
CDC
US Centers for Disease Control and Prevention
CFR
Code of Federal Regulations
CI
confidence interval
CMV
cytomegalovirus
CONSORT
Consolidated Standards of Reporting Trials
CoV
coronavirus
CRO
contract research organization
CSR
clinical study report
DHHS
Department of Health and Human Services
DMID
Division of Microbiology and Infectious Diseases
DSPC
1,2-distearoyl-sn-glycero-3-phosphocholine
eCRF
electronic case report form
EDC
electronic data capture
eDiary
electronic diary
ELISA
enzyme-linked immunoabsorbent assay
EOS
end of study
EUA
Emergency Use Authorization
FAS
full analysis set
FDA
Food and Drug Administration
FSH
follicle-stimulating hormone
GCP
Good Clinical Practice
GLP
Good Laboratory Practice
GM
geometric mean

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Abbreviation
Definition
GMFR
geometric mean fold-rise
GMP
Good Manufacturing Practice
GMT
geometric mean titer
HCP
healthcare practitioner
hDPP4
dipeptidyl peptidase 4 
HIV
human immunodeficiency virus
hMPV
human metapneumovirus
IB
investigator’s brochure
ICF
informed consent form
ICH
International Council for Harmonisation
Ig
immunoglobulin
IM
intramuscular
IRB
institutional review board
IRT
interactive response technology
LLOQ
lower limit of quantification
LNP
lipid nanoparticle
MAAE
medically attended adverse event
MedDRA
Medical Dictionary for Regulatory Activities
MERS-CoV
Middle East Respiratory Syndrome coronavirus
mRNA
messenger RNA
nAb
neutralizing antibody
NIAID
National Institute of Allergy and Infectious Diseases
NOAEL
no adverse effect level
OL
open-label
PCR
polymerase chain reaction
PEG2000-DMG
1-monomethoxypolyethyleneglycol-2,3-dimyristylglycerol
with polyethylene glycol of average molecular weight 2000
PIV3
parainfluenza virus type 3 
PP
per-protocol
PT
prothrombin time
PTT
partial thromboplastin time
S 
spike
S-2P
spike protein with 2 proline residues introduced for stability 
in a prefusion conformation 

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Abbreviation
Definition
SAE
serious adverse event
SAP
statistical analysis plan
SARS-CoV
Severe Acute Respiratory Syndrome coronavirus
SM-102
heptadecan-9-yl 8-((2-hydroxyethyl) (6-oxo-6- 
(undecyloxy)hexyl) amino) octanoate 
SMC
Safety Monitoring Committee
SOP
standard operating procedure
TEAE
treatment-emergent adverse event
ULN
upper limit of normal
ULOQ
upper limit of quantification
USP
United States Pharmacopeia
VE
vaccine efficacy
VRC
Vaccine Research Center
WHO
World Health Organization

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1
INTRODUCTION
1.1 Background
Coronaviruses (CoVs) are a large family of viruses that cause illness ranging from the common 
cold to more severe diseases, such as Middle East Respiratory Syndrome (MERS-CoV) and Severe 
Acute Respiratory Syndrome (SARS-CoV). Coronaviruses are zoonotic, meaning they are 
transmitted between animals and people.
An outbreak of the CoV disease (COVID-19) caused by SARS-CoV-2 began in Wuhan, Hubei 
Province, China in December 2019 and has spread throughout China and to over 200 other 
countries and territories, including the United States (WHO 2020). A CoV ribonucleic acid was 
quickly identified in some of these patients. 
As of 20 Apr 2020, the World Health Organization (WHO) reported more than 2,314,621 
confirmed cases and 157,847 deaths globally and have therefore made the assessment that 
COVID-19 can be characterized as a pandemic (WHO 2020). As of 20 Apr 2020, the US Centers 
for Disease Control and Prevention (CDC) reported 746,625 confirmed and probable cases of 
COVID-19 in all 50 states and 5 jurisdictions, with 39,083 attributed and probable deaths 
(CDC 2020a). The CDC have reported that the highest risk of disease burden is in older adults and 
populations with certain underlying comorbid conditions such as heart disease, diabetes, and lung 
disease (CDC 2020b).
There is currently no vaccine against SARS-CoV-2. Global efforts to evaluate novel antivirals and 
therapeutic strategies to treat severe SARS-CoV-2 infections have intensified, but no proven 
therapeutic currently exists. Therefore, there is an urgent public health need for rapid development 
of novel interventions to prevent the spread of this disease. 
ModernaTX, Inc. has developed a rapid-response, proprietary vaccine platform based on a 
messenger RNA (mRNA) delivery system. The platform is 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. The delivered mRNA does not enter the cellular nucleus or interact with the genome, 
is nonreplicating, and is expressed transiently. mRNA vaccines have been used to induce immune 
responses against infectious pathogens such as cytomegalovirus (CMV) (NCT03382405), human 
metapneumovirus (hMPV) and parainfluenza virus type 3 (PIV3) (NCT03392389), and influenza 
virus (NCT03076385 and NCT03345043). 
The Sponsor is using its mRNA-based platform to develop a novel lipid nanoparticle (LNP)- 
encapsulated mRNA-based vaccine against SARS-CoV-2 (mRNA-1273). mRNA-1273 encodes 
for the full-length spike (S) protein of SARS-CoV-2, modified to introduce 2 proline residues to

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stabilize the S protein (S-2P) into a prefusion conformation. The CoV S protein mediates 
attachment and entry of the virus into host cells (by fusion), making it a primary target for 
neutralizing antibodies that prevent infection (Johnson et al 2016; Wang et al 2015; Wang et al 
2018; Chen et al 2017; Corti et al 2015; Yu et al 2015; Kim et al 2019; Widjaja et al 2019). It has 
been confirmed that the stabilized SARS-CoV-2 S-2P expresses well and is in the prefusion 
conformation (Wrapp et al 2020).
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 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 (Wu et al 2021; Wang 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 and Mallapaty 2021; Cohen 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. ModernaTX, Inc. is developing a 
mRNA vaccine (mRNA-1273.351) that is similar to the mRNA-1273 vaccine available under the 
Emergency Use Authorization (EUA), but in which the mRNA encodes for the S protein of the
B.1.351 variant.
Nonclinical studies have demonstrated that CoV S proteins are immunogenic and S protein-based 
vaccines, including those based on mRNA delivery platforms, are protective in animals. Prior 
clinical studies of vaccines targeting related CoVs and other viruses have demonstrated that 
mRNA-based vaccines are safe and immunogenic. It is therefore anticipated that mRNA-1273 will 
generate robust immune responses to the SARS-CoV-2 S protein. 
The mRNA-1273 vaccine is currently being evaluated for safety and immunogenicity in a 
dose-ranging Phase 1 study (NCT04283461) sponsored and conducted by the Division of 
Microbiology and Infectious Diseases (DMID) of the National Institute of Allergy and Infectious 
Diseases (NIAID). Two dose levels will be chosen for evaluation in this Phase 2 study, based on 
the data from the Phase 1 DMID study (Section 3.1.2). The development of this vaccine is being 
accelerated as, if it is demonstrated safe and immunogenic, it may be used to address the current 
COVID-19 outbreak as a result of the uniquely rapid and scalable manufacturing process for 
mRNA-1273.

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1.2 Nonclinical Studies in Development of mRNA-1273
Nonclinical studies have demonstrated that CoV S proteins are immunogenic and S protein-based 
vaccines, including those based on mRNA delivery platforms, are protective in animals. Prior 
clinical studies of vaccines targeting related CoVs and other viruses have demonstrated that 
mRNA-based vaccines are safe and immunogenic. It is therefore anticipated that mRNA-1273 will 
generate robust immune responses to the SARS-CoV-2 S protein and will be well tolerated. In 
addition, mRNA-1273 has shown preliminary evidence of protection against SARS-CoV-2 in a 
murine model of infection (data on file).
In support of development of mRNA-1273 for prophylaxis against SARS-CoV-2 infection, 
nonclinical immunogenicity, biodistribution, and safety studies have been completed with similar 
mRNA-based  vaccines  formulated  in  LNPs  containing  SM-102  (heptadecan-9-yl  8 
((2 hydroxyethyl)(6 oxo 6-(undecyloxy)hexyl)amino)octanoate), the novel proprietary lipid used 
in the mRNA-1273 LNP formulation. Non-clinical studies with mRNA-1273.351 and the 
mRNA-1273/mRNA-1273.351 mixture are also planned in mice, Syrian golden hamsters, and 
non-human primates. 
A detailed review of nonclinical experience with mRNA-1273 vaccine is provided in the 
investigator’s brochure (IB). 
1.3 Clinical Studies
The mRNA-1273 vaccine is currently being evaluated for safety and immunogenicity in the dose- 
ranging Phase 1 DMID study of healthy adults at least 18 years of age (Section 3.1.2). The Phase 1 
DMID study is an open-label dose-ranging study of mRNA-1273 in healthy adult male and non- 
pregnant female participants in 3 age groups: age 18 to 55 years, inclusive (45 participants); age 
56 to 70 years, inclusive (30 participants); and ≥71 years (30 participants). Each participant will 
receive an intramuscular (IM) injection (0.5 mL) of mRNA-1273 on Days 1 and 29 in the deltoid 
muscle and will be followed for 13 months after the second injection. 
As of 26 October 2020, 120 participants were enrolled. All participants received the first injection 
of mRNA-1273, and 116 participants received the second injection. Three mRNA-1273 dose levels 
(25, 100, and 50 µg) administered 28 days apart have been assessed in participants 18 to 55 years, 
56 to 70 years, and ≥71 years of age. The mRNA-1273 250 µg dose was not evaluated in 
participants 56 to 70 years and ≥71 years of age due to reactogenicity observed in 4 participants 
in the 250 µg (18 to 55 years) dose cohort. Across all age groups, solicited adverse reactions (ARs) 
were predominantly mild or moderate in severity and most commonly included fatigue, chills,

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headache, myalgia, and pain at the injection site. The incidence and severity of solicited ARs were 
generally dose dependent and increases in incidence and severity were generally observed after 
the second injection. The incidence of systemic reactions increased after the second injection, 
particularly at the highest (250 µg) dose. Four (27%) participants in the 250 μg dose cohort 
reported at least 1 severe solicited AR after the second injection, including feverishness, fatigue, 
fever, headache, myalgia, nausea, and erythema/redness. No serious adverse events (SAEs) have 
been reported through Day 119, and no pause rules were triggered during the study. 
This Phase 2a study (mRNA-1273-P201), conducted by the Sponsor under IND 19745, will 
expand the safety and immunogenicity database by testing 2 two dose levels (50 µg and 100 µg) 
in 400 adults. As of 05 November 2020, 200 (100%) participants each in the mRNA-1273 50 μg 
group, mRNA-1273 100 μg group, and placebo group received the first dose, and 195 (97.5%) 
participants in the mRNA-1273 50 μg group, 198 participants (99.0%) in the mRNA-1273 100 μg 
group, and 194 (97.0%) participants in the placebo group received the second injection 
(mRNA-1273-P201). In this study, 2 mRNA-1273 dose levels (50 and 100 µg) or placebo 
administered 28 days apart were assessed in participants ≥ 18 to < 55 years and ≥ 55 years of age. 
No protocol-specified pause rules were met during the study. In addition, the study initiated with 
a sentinel group of 50 participants ≥ 55 years of age; after review of the safety data by the 
independent SMC, the cohort was expanded to include the remaining 250 participants ≥ 55 years 
of age.

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2
STUDY OBJECTIVES
2.1 Primary Objectives (Part A, Blinded)
2.1.1
Primary Safety Objective
The primary safety objective is to evaluate the safety and reactogenicity of 2 dose levels of 
mRNA-1273 vaccine, each administered in 2 doses 28 days apart. 
2.1.2
Primary Immunogenicity Objective
The primary immunogenicity objective is to evaluate the immunogenicity of 2 dose levels of 
mRNA-1273 vaccine, each administered in 2 doses 28 days apart, as assessed by the level of 
specific binding antibody (bAb). 
2.2 Secondary Objective (Part A, Blinded)
The secondary objective is to evaluate the immunogenicity of 2 dose levels of mRNA-1273 
vaccine, each administered in 2 doses 28 days apart, as assessed by the titer of neutralizing 
antibody (nAb). 
2.3 Exploratory Objectives (Part A, Blinded)
The exploratory objectives are the following:

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2.4
Primary Objectives (Part B, Open Label)
2.4.1
Primary Safety Objective
The primary safety objective is to evaluate the safety and reactogenicity of 50 µg of mRNA-1273 
vaccine administered as a single booster dose or 100 µg of mRNA-1273 administered as 2 doses 
28 days apart. 
2.4.2
Primary Immunogenicity Objective
The primary immunogenicity objective is to evaluate the immunogenicity of 50 µg of mRNA-1273 
vaccine administered as a single booster dose or 100 µg of mRNA-1273 administered as 2 doses 
28 days apart, as assessed by the level of specific bAb. 
2.5 Secondary Objective (Part B, Open Label)
The secondary objective is to evaluate the immunogenicity of 50 µg of mRNA-1273 vaccine 
administered as a single booster dose or 100 µg of mRNA-1273 100µg administered as 2 doses 28 
days apart, as assessed by the titer of nAb. 
2.6 Exploratory Objectives (Part B, Open Label)
The exploratory objectives are the following:

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2.7 Primary Objectives (Part C, Open Label)
2.7.1
Primary Safety Objective
The primary safety objective is to evaluate the safety and reactogenicity of 2 dose levels (20 and 
50 µg) of mRNA-1273.351 or one dose level of a mixture of 25 µg mRNA-1273 and 25 µg mRNA- 
1273.351 (mRNA-1273/mRNA-1273.351 mixture) (50 µg total) vaccine administered as a single 
booster dose after completing a two-dose vaccination schedule of mRNA-1273 at least 6 months 
earlier.
2.7.2
Primary Immunogenicity Objective
The primary immunogenicity objective is to evaluate the immunogenicity of 2 dose levels (20 and 
50 µg) of mRNA-1273.351 or one dose level of mRNA-1273/mRNA-1273.351 mixture (50 µg 
total) vaccine administered as a single booster dose after completing a two-dose vaccination 
schedule of mRNA-1273 at least 6 months earlier, as assessed by the level of specific nAb directed 
against the S2P antigen derived from B.1.351 variant. 
2.8 Secondary Immunogenicity Objective (Part C, Open Label)
The secondary immunogenicity objective is to evaluate the immunogenicity of 2 dose levels (20 
and 50 µg) of mRNA-1273.351 or one dose level of mRNA-1273/mRNA-1273.351 mixture 
(50 µg total) vaccine administered as a single booster dose after completing a two-dose vaccination 
schedule of mRNA-1273 at least 6 months earlier, as assessed by the level of specific bAb directed 
against the S2P antigen derived from B.1.351 variant. 
2.9 Exploratory Objectives (Part C, Open Label)
The exploratory objectives are the following:

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3
INVESTIGATIONAL PLAN
3.1 General Study Design
This is a three-part, Phase 2a study: Part A, Part B, and Part C. Participants in Part A, the Blinded 
Phase of the study, are blinded to their treatment assignment. Given that the primary efficacy 
endpoint for mRNA-1273 against COVID-19 was met in a separate Phase 3 efficacy study (COVE 
study) conducted by the Sponsor, this Phase 2a study will move to Part B, Open Label 
Interventional Phase. 
Part B, the Open-label Interventional Phase of this study is designed to offer participants who 
received placebo in Part A of this study an option to receive 2 injections of open-label mRNA-1273 
(Figure 3). Participants who received 1 or 2 injections of mRNA-1273 (50 µg or 100 µg) in Part A 
of this study will proceed to Part B, open label, and will be offered a single booster dose of 
mRNA-1273 (50 µg). This study will be conducted in compliance with the protocol, Good Clinical 
Practice (GCP), and all applicable regulatory requirements.
Part C will be a proof-of-concept rollover study of approximately 60 participants, who are 
currently enrolled in Moderna’s Phase 3 mRNA-1273-P301 COVE study and have previously 
received 2 doses of mRNA-1273 at least 6 months earlier. Upon enrollment into Part C of this 
study, they will receive a single IM injection of mRNA-1273.351 (20 µg or 50 µg) or 
mRNA-1273/mRNA-1273.351 mixture (50 µg total) at least 6 months after receiving the second 
vaccination in the mRNA-1273-P301 COVE study. At enrollment into this study, their 
participation in mRNA-1273-P301 COVE study will be terminated. 
3.1.1
Part A, the Blinded Phase
The Blinded Phase of this study is a randomized, observer-blind, and placebo-controlled, with 
adult participants at least 18 years of age. The study schematic is presented in Figure 1 and the 
Schedule of Events is presented in Table 9. 
Two dose levels, 50 µg and 100 µg, will be evaluated in this study, based in part on initial safety 
data from the Phase 1 DMID study of mRNA-1273. The study will include 2 age cohorts: Cohort 1 
with 300 participants (≥ 18 to < 55 years old) and Cohort 2 with 300 participants (≥ 55 years old). 
Approximately 600 participants will receive either mRNA-1273 vaccine or saline placebo control 
according to a 1:1:1 randomization ratio; ie, within each age cohort, 100 participants will receive 
mRNA-1273 50 µg, 100 participants will receive mRNA-1273 100 µg, and 100 participants will 
receive saline placebo (Figure 1).

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The study will be initiated with a parallel enrollment of all 300 participants in Cohort 1 (≥ 18 to
< 55 years old) and a sentinel group of 50 participants in Cohort 2 (≥ 55 years old) receiving study 
treatment (Figure 2). Before initiating study treatment of the remaining participants in Cohort 2, 
safety data through Day 7 from the sentinel group of Cohort 2 and all available data from Cohort 1 
will be reviewed by the Safety Monitoring Committee (SMC; Section 6.1.1).
If no safety concerns are found, expansion enrollment (N=250) of Cohort 2 will proceed.
Figure 1:   Study Flow Schema (Part A, Blinded Phase)

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Figure 2:   Sentinel and Expansion Cohort Schema (Part A, Blinded Phase)
Part A, Blinded Phase of the study comprises up to 10 scheduled study site visits: Screening, Day 1, 
Day 8, Day 15, Day 29 (Month 1), Day 36, Day 43, Day 57 (Month 2), Day 209 (Month 7), and 
Day 394 (Month 13) or initiation of Part B, whichever is earlier. There are also scheduled 
participant contacts approximately every 2 weeks after Day 57 to collect MAAEs, AEs leading to 
withdrawal, SAEs, concomitant medications associated with these events, receipt of non-study 
vaccinations, exposure to someone with known COVID19 or SARS-CoV-2 infection, and 
participant experience of COVID-19 symptoms (Table 9). Every 4 weeks from Day 71 through 
Day 183 and from Day 223 through Day 363, each participant will complete a questionnaire in an 
electronic diary (eDiary) that will be reviewed by study site personnel. Safety telephone calls will 
occur every 4 weeks from Day 85 through Day 197 and from Day 237 through Day 377. The study 
duration will be approximately 14 months for each participant: a screening period of up to 1 month

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and a study period of 13 months that includes the first dose of vaccine on Day 1 and the second 
dose on Day 29. The participant's final visit will be on Day 394 (Month 13), 12 months after the 
second dose of vaccine on Day 29 (Month 1), or at the initiation of Part B, whichever is earlier. 
To test for the presence of SARS-CoV-2, nasopharyngeal swab samples will be collected at Day 1, 
Day 29, and Day 57. During the course of the study, participants meeting pre-specified disease 
criteria that suggest possible SARS-CoV-2 infection will be asked to contact the study site to 
arrange for a prompt, thorough, and careful assessment (Section 3.4.1).
Each participant will receive 2 injections of mRNA-1273 or placebo by 0.5 mL IM injection on 
Day 1 and Day 29. Vaccine accountability, dose preparation, and vaccine administration will be 
performed by unblinded pharmacy personnel who will not participate in any other aspects of the 
study during Part A, the Blinded Phase. The remainder of the study staff, all participants, and 
Sponsor personnel (or its designees) will remain blinded to dosing assignment (Section 3.3.5).
All participants will be followed for safety and reactogenicity and provide pre- and post-injection 
blood specimens for immunogenicity through 12 months after the last dose of investigational 
product. Section 4.7 describes the planned study analyses. 
The end of Part A is defined as the earlier of Visit 9, the completion of the last participant’s last 
visit, or initiation of Part B. Participants are considered to have completed Part A of the study if 
they complete the final visit on Day 394 (Month 13) or initiated Part B of the study. 
The end of study (EOS) is defined as date of last visit of Part A, Part B or Part C of the study, 
whichever occurs later. Participants are considered to have completed the study if they complete
the final visit on Day 394 (Month 13), 12 months after the second injection on Day 29 (Month 1).
At each dosing visit, participants will be instructed (Day 1) or reminded (Day 29) how to document 
and report solicited ARs within a provided eDiary. Solicited ARs will be assessed for 7 days (the 
day of injection and the following 6 days) after each injection and unsolicited AEs will be assessed 
for 28 days after each injection; SAEs and MAAEs will be assessed throughout the study. 
Participants will have blood sampled at scheduled study visits during the study for safety and 
immunogenicity assessments or other medical concerns, according to the investigator’s judgment. 
In addition, participants may have blood sampled at unscheduled visits for acute respiratory 
symptoms.
Detailed information on all statistical analysis of data is presented in Section 4.6.2. 

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3.1.2
Part B, Open-Label Interventional Phase
Part B, the Open-Label Interventional Phase of the study, is prompted by the authorization of a 
COVID-19 vaccine under an EUA. Transitioning the study to Part B permits all ongoing study 
participants to be informed of the availability and eligibility criteria of any COVID-19 vaccine 
made available under an EUA and the option to offer all ongoing study participants an opportunity 
to schedule a Participant Decision Visit to know their original treatment assignment (placebo vs. 
mRNA-1273 [50 µg or 100 µg] vaccine). 
Part B, the Open-Label Interventional Phase of the study, provides the opportunity for study 
participants who previously received placebo to actively request to receive 2 doses of mRNA-1273 
(100 µg) vaccine. In addition, all participants who previously received 1 or 2 injections of 
mRNA-1273 (50 µg or 100 µg) vaccine will be able to receive a single booster dose of 
mRNA-1273 (50 µg). All study participants will receive a Notification Letter summarizing the 
basis for a COVID-19 vaccine to receive an EUA and will be asked to schedule a Participant 
Decision Clinic Visit.
Figure 3:   Part B, Open-Label Schema
a All participants will proceed to Part B, Open-Label Interventional Phase; begins with the Participant Decision Visit.
b Participants who received 2 injections of mRNA-1273 100 µg during Blinded Part A.
c Participants who received 2 injections of mRNA-1273 50 µg during Blinded Part A.
d Participants who received 2 injections of mRNA-1273 in Part A and decline booster injection in Part B.
e Participants who received placebo in Part A and decline 2 injections of mRNA-1273 in Part B.
f Participants who received 2 injections of mRNA-1273 (50 µg or 100 µg) in Part A will receive one booster injection 
of mRNA-1273 50 µg in Part B.
g See Table 10 for directions for Part B schedule of events based on Participant status at end of Participant Decision 
Visit.

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At the Participant Decision Clinic Visit, all participants will:
•
Be given the option to be unblinded as to their original group assignment (placebo vs. 
mRNA-1273 vaccine [50 µg or 100 µg]), 
•
Be counselled about the importance of continuing other public health measures to limit the 
spread of disease including social distancing, wearing a mask, and hand-washing, 
•
Sign a revised ICF, and
•
Provide a nasopharyngeal (NP) swab for RT-PCR for SARS-CoV-2 and a blood sample for 
serology and immunogenicity. 
After the Participant Decision Clinic Visit (Table 10), all participants will proceed to the open-label 
Part B of the study and will follow the Part B Schedule of Events (Table 11 or Table 12) as follows 
(Figure 3):
•
Participants received placebo in Part A and consent to unblinding and to receiving
2 doses of mRNA-1273 in Part B: These participants will proceed to Part B and follow 
the schedule of events (SOE) in Table 11. 
•
Participants received 1 dose of mRNA-1273 in Part A (regardless of the initial dose 
level received) and consent to unblinding and to receiving another booster injection 
of mRNA-1273 in Part B: These participants will proceed to Part B and follow the SOE 
in Table 12. 
•
Participants received 2 doses of mRNA-1273 in Part A and consent to unblinding and 
to receiving another booster injection of mRNA-1273 dose in Part B: These participants 
will proceed to Part B and follow the SOE in Table 12 (note that these participants will 
receive 3 injections of mRNA-1273 during the course of the study). 
•
Participants received 2 doses of mRNA-1273 in Part A and consent to unblinding, but 
decline receiving another booster injection of mRNA-1273 in Part B: These 
participants will proceed to Part B and follow the schedule of events (SOE) in Table 12.
•
Received 1 dose of blinded study medication in Part A and decline unblinding: These 
participants will proceed to Part B and follow the SOE in Table 12.
•
Participants decline unblinding: These participants will proceed to Part B and follow the 
SOE in Table 12.
Note: After participant proceeds to the open-label Part B of the study at the 
Participant Decision Clinic Visit (Table 10), Part A schedule of events (Table 9) will 
no longer be followed and will become obsolete.

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3.1.3
Part C, Open-Label Interventional Phase of mRNA-1273.351 and mRNA- 
1273/mRNA-1273.351 Mixture Booster Vaccines
Part C, the Open-Label Interventional Phase of the study of mRNA-1273.351 and mRNA- 
1273/mRNA-1273.351 mixture booster vaccines, is prompted by the need to proactively prepare 
for vaccination strategies that induce a broader protection, including variants such as B.1.351. This 
part will be a proof-of-concept rollover design, where participants in Moderna’s Phase 3
mRNA-1273-P301 COVE study, who have previously received 2 doses of mRNA-1273 at least 6 
months previously, will be enrolled into Part C of this study. Upon consent to roll over, participants 
in Part C will receive a single booster dose of either mRNA-1273.351 (20 µg or 50 µg), or 
mRNA-1273/mRNA-1273.351 mixture (50 µg total). An additional booster dose may be added 
approximately 56 days after the first boost at OL-D1. This additional booster dose will be triggered 
following review of immunogenicity data up to OL-D15 of the initial mRNA-1273.351 (20 µg and 
50 µg) and mRNA-1273/mRNA-1273.351 mixture injections. The enrollment and vaccination in 
each study arm will be sequential. The first 20 participants will be enrolled and dosed on OL-D1 
with the mRNA-1273.351 50 µg dose. Upon completion of the first 50 µg dose arm, 20 participants 
will be enrolled in the second arm and will receive the mRNA-1273/mRNA-1273.351 mixture (50 
µg total dose). Following completion of the second arm, 20 participants will be enrolled and dosed 
with the mRNA-1273.351 20 µg dose. 
Figure 4:  Part
C,
Open-Label Schema for Boosting with mRNA-1273.351 and 
mRNA-1273/mRNA-1273.351 Mixture 
Note: *Only COVE study participants who are unblinded and have received 2 doses of mRNA-1273 at least 6 months 
earlier; in addition, the participants will have to meet all other specified eligibility criteria to be rolled over into Part C 
of the mRNA-1273-P201 study.

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3.1.4
Rationale for Dose Selection
In the Blinded Part A of this study, the 2 dose levels of mRNA-1273 tested in participants will be 
50 μg and 100 μg, based on assessment of available safety and immunogenicity data from the 
Phase 1 DMID study and Phase 1 studies of mRNA-1647 and mRNA-1443 (Section 1).
The Phase 1 DMID study, an open-label dose-ranging study of mRNA-1273 in healthy adult male 
and non-pregnant female participants in 3 age groups: age 18 to 55 years, inclusive 
(45 participants); age 56 to 70 years, inclusive (30 participants); and ≥71 years (30 participants) 
is currently ongoing. Participants in each age cohort will be randomly assigned to 1 of 3 dose levels 
of mRNA-1273: 25 μg, 100 μg, and 250 μg. Each participant will receive an IM injection (0.5 mL) 
of mRNA-1273 on Days 1 and 29 in the deltoid muscle and will be followed for 12 months after 
the second injection. 
As of 14 May 2020, 15 participants in each of the 3 dose levels of the 18 to 55-year age cohort 
received at least 1 dose of mRNA-1273. Recruitment of participants in the 2 older age cohorts is 
ongoing. There have been no SAEs and no triggering of study pause rules. A review of preliminary 
solicited local and systemic ARs in participants in the 18 to 55-year age cohort after the second 
injection showed 3 participants in the 100 µg dose group who reported severe local ARs (Grade 3 
erythema and induration) and 3 participants in the 250 µg dose group who reported severe systemic 
ARs (fever, fatigue, feverishness, myalgia, and nausea). These ARs resolved within 24 hours and 
were not assessed as serious.
The 50 μg and 100 μg doses proposed for this Phase 2a study fall within the doses being evaluated 
in the Phase 1 DMID study. Specifically, in Part B of the amended study, the decision to provide a 
booster dose to those participants who received two doses of 50 or 100 µg is, in part, to address 
the waning neutralizing antibody titers seen in the Phase 1 DMID study beginning 4 months after 
the first vaccination (Widge et al 2021). Furthermore, the choice of a 50 µg dose level as a booster 
is supported by data from Phase 2 studies indicating that the immune response is largely 
indistinguishable between 50 and 100 µg. 
In Part C of the amended study, participants will receive a single booster dose of either 
mRNA-1273.351 (20 µg or 50 µg) or mRNA-1273/mRNA-1273.351 mixture (50 µg total; 25 µg 
of mRNA-1273 and 25 µg of mRNA-1273.351). The dose ranging will help assess the potential 
for cross-priming by the variant vaccine. In addition, the inclusion of the choice of the 20-µg dose 
level as a booster is intended to help assess the stability of the 50 µg dose of the vaccine at the 
limits of the anticipated expiration.

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3.1.5
Rationale for Study Design
The 2 age cohorts in this Phase 2a study, ≥ 18 to < 55 years old and ≥ 55 years old, were established 
to better understand the relationships among dose, tolerability, and immunogenicity in different 
age groups, one being healthy older adults. The older cohort in this Phase 2a study corresponds to 
the 2 older age cohorts in the Phase 1 DMID study. 
Because there are currently no licensed SARS-CoV-2 vaccines available, 0.9% sodium chloride 
will be used as a placebo control for the safety and immunogenicity assessments. Consequently, 
the mRNA-1273 vaccine and placebo injections will look different, so administration will be 
blinded in Part A of the study (Section 3.3.5).
The Phase 1 DMID study is small (105 participants at 3 dose levels) and does not incorporate a 
placebo. Having a sample size of 600 participants in this Phase 2a study and including a placebo 
will help to improve understanding of AEs.
With SARS-CoV-2 expected to be circulating in the general population during the study, all 
participants will provide pre-injection blood samples and post-injection blood samples for 
antibody analysis through 12 months after the last dose of investigational product. In addition, 
participants will have nasopharyngeal swab samples collected at Day 1 and Day 29, before the 
injections, and at Day 57. Furthermore, with any signs or symptoms or MAAE suggesting
SARS-CoV-2 infection in a participant, an additional nasopharyngeal swab sample and a blood 
sample will be taken to confirm the diagnosis of SARS-CoV-2 via serology and polymerase chain 
reaction (PCR). Additionally, clinical information will be carefully collected to evaluate the 
severity of the clinical case.
Since it is possible that participants are naturally exposed to SARS-CoV-2 through community 
exposure, the nasopharyngeal swab samples collected before study injection may help discriminate 
between natural infection and vaccine-induced antibody responses, should such discrimination be 
needed.
Following authorization of a COVID-19 vaccine under EUA, this study amendment is designed 
to transition to Part B, the Open-Label Interventional Phase (Figure 3). Transitioning the study to 
Part B, Open-Label Interventional Phase, permits all ongoing study participants to (a) be 
informed of the availability and eligibility criteria of any COVID-19 vaccine made available 
under an EUA and (b) the option to offer all ongoing study participants who request unblinding 
an opportunity to schedule a study visit to know their original group assignment (placebo vs. 
mRNA-1273 [50 µg or 100 µg vaccine]). Part B, Open-Label Interventional Phase, also provides 
the opportunity for study participants who previously received placebo to request to receive 2 
doses of mRNA-1273 (100 µg) vaccine. Participants who originally received mRNA-1273 

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(50 µg or 100 µg vaccine) will have the opportunity to request to receive a single booster dose of 
mRNA-1273 (50 µg). 
As SARS-CoV-2 variants with mutations in the S protein have emerged, we are learning about 
the clinical significance to ongoing global vaccination efforts based on strains derived from the 
Wuhan virus. 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 
et al 2020). The development and testing of vaccines targeting this SARS-CoV-2 variant is 
urgently needed. 
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. Part C of this study will evaluate the immunological benefit of boosting 
participants previously vaccinated with mRNA-1273 (mRNA-1273-P301 COVE study) with the
B.1.351 strain-specific S protein (mRNA-1273.351) and the mRNA-1273/mRNA-1273.351 
mixture, which incorporates 25 µg of each of the Wuhan -1 and B.1.315 representative sequences, 
for a total dose of 50 µg. 
Healthy male or female participants will be enrolled at study sites in the US or its territories.
3.1.6
Inclusion Criteria
Each participant must meet all of the following criteria during the screening period and at 
Day 1/OL-D1, unless noted otherwise, to be enrolled in this study: 
Male or female, 18 years of age or older at the time of consent (Screening Visit, Day 0). For Part B, 
participants must have been previously enrolled in the mRNA-1273 P201 study. For Part C, 
participants must have been previously enrolled in the mRNA-1273-P301 COVE study, must have 
received two doses of mRNA-1273 in Part A of that study (ie, already unblinded and aware of their 
actual treatment), with their second dose at least 6 months prior to enrollment in this part, and must 
be currently enrolled and compliant in that study (ie, not have withdrawn or discontinued early). 
Understands and agrees to comply with the study procedures and provides written informed 
consent.
According to the assessment of the investigator, is in good general health and can comply with 
study procedures. 

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3.1.6.1
Inclusion criterion specific for Parts A and B:
1. Female participants of nonchildbearing potential may be enrolled in the study. 
Nonchildbearing potential is defined as surgically sterile (history of bilateral tubal ligation, 
bilateral oophorectomy, hysterectomy) or postmenopausal (defined as amenorrhea for
≥ 12 consecutive months prior to Screening (Day 0) without an alternative medical cause). 
A follicle-stimulating hormone (FSH) level may be measured at the discretion of the 
investigator to confirm postmenopausal status. 
2. Female participants of childbearing potential may be enrolled in the study if the participant 
fulfills all the following criteria:
•
Has a negative pregnancy test at Screening (Day 0) and on the day of the first 
injection (Day 1). 
•
Has practiced adequate contraception or has abstained from all activities that could 
result in pregnancy for at least 28 days prior to the first injection (Day 1). 
•
Has agreed to continue adequate contraception through 3 months following the 
second injection (Day 29). 
•
Is not currently breastfeeding.
Adequate female contraception is defined as consistent and correct use of a Food and Drug 
Administration (FDA) approved contraceptive method in accordance with the product label. 
For example:
•
Barrier method (such as condoms, diaphragm, or cervical cap) used in conjunction 
with spermicide
•
Intrauterine device
•
Prescription hormonal contraceptive taken or administered via oral (pill), transdermal 
(patch), subdermal, or IM route 
•
Sterilization of a female participant’s monogamous male partner prior to entry into 
the study 
Note: periodic abstinence (eg, calendar, ovulation, symptothermal, post-ovulation methods) 
and withdrawal are not acceptable methods of contraception.
3. Male participants engaging in activity that could result in pregnancy of sexual partners must 
agree to practice adequate contraception and refrain from sperm donation from the time of 
the first injection and through 3 months after the last injection.

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Adequate contraception for male participants is defined as:
•
Monogamous relationship with a female partner using an intrauterine device or 
hormonal contraception (described above) 
•
Use of barrier methods and spermicide
•
History of surgical sterilization
•
Male participants with partners who have become pregnant prior to Screening are 
eligible to participate in the study. 
3.1.6.2
Inclusion criterion specific for Part C:
1. Female participants of nonchildbearing potential may be enrolled in the study. 
Nonchildbearing potential is defined as surgically sterile (history of bilateral tubal ligation, 
bilateral oophorectomy, hysterectomy) or postmenopausal (defined as amenorrhea for
≥ 12 consecutive months prior to Screening (Day 0) without an alternative medical cause). 
The FSH level may be measured at the discretion of the investigator to confirm 
postmenopausal status.
2. Female participants of childbearing potential may be enrolled in the study if the participant 
fulfills all the following criteria:
•
Has a negative pregnancy test at Part C OL-Day 1 and on the day of injection.
•
Has practiced adequate contraception or has abstained from all activities that could
result in pregnancy for at least 28 days prior to the injection (OL-Day 1).
•
Has agreed to continue adequate contraception through 3 months following the second 
injection (OL-Day 57), as applicable.
•
Is not currently breastfeeding.
3. Adequate female contraception is defined as consistent and correct use of a Food and Drug 
Administration (FDA) approved contraceptive method in accordance with the product label. 
For example:
•
Barrier method (such as condoms, diaphragm, or cervical cap) used in conjunction with 
spermicide
•
Intrauterine device

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•
Prescription hormonal contraceptive taken or administered via oral (pill), transdermal 
(patch), subdermal, or IM route 
•
Sterilization of a female participant’s monogamous male partner prior to entry into the 
study
•
Note: periodic abstinence (eg, calendar, ovulation, symptothermal, post-ovulation 
methods) and withdrawal are not acceptable methods of contraception. 
4. Adequate contraception for male participants is defined as:
•
Monogamous relationship with a female partner using an intrauterine device or 
hormonal contraception (described above) 
•
Use of barrier methods and spermicide
•
History of surgical sterilization
•
Male participants with partners who have become pregnant prior to Screening are 
eligible to participate in the study.
5. Healthy adults or adults with pre-existing medical conditions who are in stable condition. A 
stable medical condition is defined as disease not requiring significant change in therapy or 
hospitalization for worsening disease during the 3 months before enrollment. 
6. For Part C, participants must have provided SARS-CoV 2 serology samples at Day 1, Day 29, 
Day 57, and at the Participant Decision Visit (OL-D1) in Moderna’s COVE study. 
3.1.7
Exclusion Criteria
3.1.7.1
Exclusion Criteria (Part A and Part B)
Participants meeting any of the following criteria for Parts A and B at the Screening Visit (Day 0) 
or at Day 1, unless noted otherwise, will be excluded from the study: 
1. Pregnant or breastfeeding.
2. Is acutely ill or febrile 24 hours prior to or at the Screening Visit (Day 0). Fever is defined 
as a body temperature ≥ 38.0°C/100.4°F. Participants meeting this criterion may be 
rescheduled within the relevant window periods. Afebrile participants with minor illnesses 
can be enrolled at the discretion of the investigator. 
3. Current treatment with investigational agents for prophylaxis against COVID-19.

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4. Has a medical, psychiatric, or occupational condition that may pose additional risk as a 
result of participation, or that could interfere with safety assessments or interpretation of 
results according to the investigator’s judgment. 
5. Is a healthcare worker or a member of an emergency response team.
6. Current use of any inhaled substance (eg, tobacco or cannabis smoke, nicotine vapors).
7. History of chronic smoking (≥1 cigarette a day) within 1 year of the Screening Visit
(Day 0).
8. History of illegal substance use or alcohol abuse within the past 2 years. This exclusion 
does not apply to historical cannabis use that was formerly illegal in the participant's state 
but is legal at the time of Screening.
9. Known history of hypertension, or systolic blood pressure > 150 mm Hg in participants in 
Cohort 1 (≥18 to < 55 years old) or systolic blood pressure > 160 mm Hg in participants 
in Cohort 2 (≥ 55 years old) at the Screening Visit (Day 0).
10. Known history of hypotension or systolic blood pressure < 85 mm Hg at the Screening 
Visit (Day 0). 
11. Diabetes mellitus.
12. Diagnosis of chronic pulmonary disease (eg, chronic obstructive pulmonary disease, 
asthma).
13. Chronic cardiovascular disease.
14. Resides in a nursing home.
15. Grade 1 or higher toxicity on clinical safety laboratory testing at the Screening Visit 
(Day 0).
16. Current or previous diagnosis of immunocompromising condition, immune-mediated 
disease, or other immunosuppressive condition. 
17. Received systemic immunosuppressants or immune-modifying drugs for > 14 days in total 
within 6 months prior to the Screening Visit (Day 0) (for corticosteroids ≥ 20 mg/day of 
prednisone equivalent). Topical tacrolimus is allowed if not used within 14 days prior to 
the Screening Visit (Day 0). 
18. Anticipating the need for immunosuppressive treatment at any time during participation in 
the study. 

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19. Positive serology for hepatitis B virus surface antigen, hepatitis C virus antibody, or human 
immunodeficiency virus (HIV) type 1 or 2 antibodies identified at the Screening Visit 
(Day 0).
20. History of anaphylaxis, urticaria, or other significant AR requiring medical intervention 
after receipt of a vaccine.
21. Bleeding disorder considered a contraindication to IM injection or phlebotomy.
22. Diagnosis of malignancy within previous 10 years (excluding non-melanoma skin cancer).
23. Has received or plans to receive a licensed vaccine ≤ 28 days prior to the first injection 
(Day 1) or plans to receive a licensed vaccine within 28 days before or after any study 
injection. Licensed influenza vaccines may be received more than 14 days before or after 
any study injection. 
24. Receipt of systemic immunoglobulins or blood products within 3 months prior to the 
Screening Visit (Day 0) or plans for receipt during the study. 
25. Has donated ≥450 mL of blood products within 28 days prior to the Screening Visit (Day 0) 
or plans to donate blood products during the study. 
26. Participated in an interventional clinical study, other than mRNA-1273-P301 COVE, 
within 28 days prior to the Screening Visit (Day 0) or plans to do so while participating in 
this study. 
27. Is an immediate family member or household member of study personnel.
3.1.7.2
Exclusion Criteria (Part C)
Participants meeting any of the following criteria for Part C at OL-D1, unless noted otherwise, will 
be excluded from the study: 
1. Is acutely ill or febrile 24 hours prior to or at the Screening Visit (Day 0). Fever is defined 
as a body temperature ≥ 38.0°C/100.4°F. Participants meeting this criterion may be 
rescheduled within the relevant window periods. Afebrile participants with minor illnesses 
can be enrolled at the discretion of the investigator. 
2. Current treatment with investigational agents for prophylaxis against COVID-19.
3. Has a medical, psychiatric, or occupational condition that may pose additional risk as a 
result of participation, or that could interfere with safety assessments or interpretation of 
results according to the investigator’s judgment.

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4. History of illegal substance use or alcohol abuse within the past 2 years. This exclusion 
does not apply to historical cannabis use that was formerly illegal in the participant's state 
but is legal at the time of Screening.
5. Known history of hypotension or systolic blood pressure < 85 mm Hg at the Screening 
Visit (Day 0).
6. Current or previous diagnosis of immunocompromising condition, immune-mediated 
disease, or other immunosuppressive condition. 
7. Received systemic immunosuppressants or immune-modifying drugs for > 14 days in total 
within 6 months prior to the Screening Visit (Day 0) (for corticosteroids ≥ 20 mg/day of 
prednisone equivalent). Topical tacrolimus is allowed if not used within 14 days prior to 
the Screening Visit (Day 0). 
8. Anticipating the need for immunosuppressive treatment at any time during participation in 
the study. 
9. History of anaphylaxis, urticaria, or other significant AR requiring medical intervention 
after receipt of a vaccine.
10. Bleeding disorder considered a contraindication to IM injection or phlebotomy.
11. Has received or plans to receive a licensed vaccine ≤ 28 days prior to the first injection 
(Day 1) or plans to receive a licensed vaccine within 28 days before or after any study 
injection. Licensed influenza vaccines may be received more than 14 days before or after 
any study injection. 
12. Receipt of systemic immunoglobulins or blood products within 3 months prior to the 
Screening Visit (Day 0) or plans for receipt during the study. 
13. Has donated ≥450 mL of blood products within 28 days prior to the Screening Visit (Day 0) 
or plans to donate blood products during the study. 
14. Participated in an interventional clinical study, other than mRNA-1273-P301 COVE, 
within 28 days prior to the Screening Visit (Day 0) or plans to do so while participating in 
this study. 
15. Is an immediate family member or household member of study personnel.
16. Is SARS-CoV-2 positive by RT-PCR (central or local testing) at baseline or at any time 
during the mRNA-1273-P301 COVE study regardless of the presence or absence of 
symptoms consistent with COVID-19. 
17. Had any SAE in the mRNA-1273-P301 COVE study.

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3.1.8
Screen Failures (Part A: Blinded Phase Only)
Screen failures are defined as participants who consent to participate in the study but are not 
subsequently randomly assigned to study intervention. A minimal set of screen failure information 
is required to ensure transparent reporting of screen failure participants to meet the Consolidated 
Standards of Reporting Trials (CONSORT) publishing requirements and to respond to queries 
from regulatory authorities. Minimal information includes demography, screen failure details, 
eligibility criteria, and any SAE. In the event an eligible participant was not enrolled as a result of 
a cohort being full and the participant having surpassed their 28-day screening period, the 
investigator may rescreen the participant for enrollment by assigning the participant a new 
identification number and repeating all screening procedures (Section 3.2.4).
3.1.9
Participant Restrictions During the Study
3.1.9.1
General and Dietary
Participants must not eat or drink anything hot or cold within 10 minutes before oral temperature 
is taken.
3.2 Withdrawal of Participants From the Study or Study Dosing
3.2.1
Participant Withdrawal From the Study
Participants can withdraw consent and discontinue from the study at any time, for any reason, 
without prejudice to further treatment the participant may need to receive.
If participant desires to withdraw from the study because of an AE, the investigator will try to 
obtain agreement to follow up with the participant until the event is considered resolved or stable 
and will then complete the EOS electronic case report form (eCRF).
Potential reasons for withdrawing a participant from the study include the following:
•
SAE
•
AE (non-SAE)
•
Protocol violation (specify)
•
Consent withdrawal (document reason); this includes participants who, at the Participant 
Decision Visit, withdraw consent from continuing in the study. 
•
Lost to follow-up
•
Other (specify)

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3.2.2
Handling Withdrawal From the Study
When a participant withdraws or is withdrawn from the study, the reason(s) for withdrawal will be 
recorded by the investigator on the relevant page of the eCRF. These participants will be requested 
to complete the EOS assessments at the study completion visit as outlined in the respective SoE 
for each study part. 
3.2.3
Lost to Follow-up
A participant will be considered lost to follow-up if he or she repeatedly fails to return for 
scheduled visits without stating an intention to withdraw consent and is unable to be contacted by 
the study site. The following actions must be taken if a participant fails to return to the study site 
for a required study visit: 
•
The site must attempt to contact the participant and reschedule the missed visit as soon as 
possible, counsel the participant on the importance of maintaining the assigned visit 
schedule and ascertain whether the participant wishes to and/or should continue in the study.
•
Before a participant is deemed lost to follow-up, the investigator or designee must make 
every effort to regain contact with the participant (where possible, 3 telephone calls and, if 
necessary, a certified letter to the participant’s last known mailing address or local 
equivalent methods). These contact attempts (eg, dates of telephone calls and registered 
letters) should be documented in the participant’s study source document. 
•
Should the participant continue to be unreachable, he/she will be considered to have 
withdrawn from the study. 
•
A participant should not be considered lost to follow-up until due diligence has been 
completed. Date of withdrawal/lost to follow-up should be the date of last contact with the 
participant where safety status of the participant was assessed (eg, study site visit, 
telephone call).
3.2.4
Replacements (Part A, Blinded Phase Only)
Any participant who is withdrawn, who is significantly outside the allowed injection window, or 
who is lost to follow-up from the study may be replaced at the Sponsor’s discretion. 
3.2.5
Participant Withdrawal From Study Dosing
Every reasonable attempt will be made to follow up with participants for safety throughout the 
entire study period, even if further injection is withheld or the participant misses one or more visits.

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Unless consent is withdrawn, a participant who withdraws or is withheld from receiving the second 
dose of study vaccine will remain in the study and complete all scheduled visits and assessments.
The investigator, in consultation with the Sponsor’s medical monitor, may withhold a participant 
from further injection if the participant experiences any of the following: 
•
Becomes pregnant
•
Develops, during the course of the study, symptoms or conditions listed in the exclusion 
criteria (Section 3.1.7) 
•
Experiences an AE (other than reactogenicity) after injection that is considered by the 
investigator to be related to investigational product (Section 3.4.8.10) and is of Grade 3 
(severe) or greater severity (Appendix 2) 
•
Experiences an AE or SAE that, in the judgment of the investigator, requires study vaccine 
withdrawal due to its nature, severity, or required treatment, regardless of the causal 
relationship to vaccine 
•
Experiences a clinically significant change in clinical laboratory test results, vital sign 
measurements, or general condition that, in the judgment of the investigator, requires 
vaccine withdrawal
•
Experiences anaphylaxis clearly attributed to study vaccine
•
Experiences generalized urticaria related to the study vaccine 
The reason(s) for withdrawal from further injection will be recorded.
3.3 Study Dosing Groups
3.3.1
Method of Assigning Participants to Dosing Groups (Part A and Part C)
There are 2 age cohorts in Part A of this study: participants ≥ 18 to < 55 years old in Cohort l and 
participants ≥ 55 years old in Cohort 2. During Part A, the Blinded Phase of the study, within each 
age cohort, approximately 300 participants will be randomly assigned in 1:1:1 ratio to receive 
mRNA-1273 50 µg, mRNA-1273 100 µg, or placebo. The randomization will be in a blinded 
manner using a centralized Interactive Response Technology (IRT), in accordance with pre- 
generated randomization schedules. Only the unblinded pharmacy personnel (Section 3.3.5) will 
have controlled access to which arm the participant is randomly assigned. 
Part C will be open label and the IRT system will not be utilized. The enrollment and vaccination 
in each study arm will be sequential. The first 20 participants will be enrolled and dosed on OL- 

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D1 with the mRNA-1273.351 50 µg dose. Upon completion of the first 50 µg dose arm, 20 
participants will be enrolled in the second arm and will receive the mRNA-1273/mRNA-1273.351 
mixture (50 µg total dose). Following completion of the second arm, 20 participants will be 
enrolled and dosed with the mRNA-1273.351 20 µg dose. In addition to the single dose of 
investigational product at OL-D1 (Day 1), a second booster dose of mRNA-1273.351 (20 µg or 50 
µg) or mRNA 1273/mRNA-1273.351 mixture may be administered approximately 56 days after 
the first dose. The administration of a second dose of IP will be based on the magnitude of the 
immune response on either OL-Day 15 or OL-Day 29 after a single dose. Specifically, if the 
immune response is lower than the response observed after two priming doses of mRNA-1273 in 
study P201 or P301, a second dose of either mRNA-1273.351 or mRNA-1273/mRNA 1273.351 
mixture may be considered. 
Dose group assignment in each cohort and stratification within each cohort for Part A and Part C 
is summarized in Table 1 and Table 2, respectively.
Table 1:    Dose Group Assignment (Part A)
Cohort
Treatment Groups
Investigational Product
Number of Participants
Cohort 1 
≥18 to < 55 years old
mRNA-1273 Arm
mRNA-1273 50 µg
100
mRNA-1273 Arm
mRNA-1273 100 µg
100
Placebo Arm
Placebo
100
Cohort 2 
≥55 years old
mRNA-1273 Arm
mRNA-1273 50 µg
100
mRNA-1273 Arm
mRNA-1273 100 µg
100
Placebo Arm
Placebo
100
Total
600
Table 2:    Dose Group Assignment (Part C)
Treatment Groups
Investigational Product
Number of Participants
mRNA-1273.351 Arm
mRNA-1273.351 20 µg
20
mRNA-1273.351 Arm
mRNA-1273.351 50 µg
20
mRNA-1273/mRNA-1273.351
mixture Arm
25 µg mRNA-1273 and 25 µg
mRNA-1273.351 mixture (50 µg total)
20
Total
60

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3.3.2
Investigational Product Administration
In the Blinded Part A of the study, investigational product will be administered as an IM injection 
into the deltoid muscle on a 2-dose injection schedule on Day 1 and Day 29, with a 28-day interval 
between doses. Each injection will have a volume of 0.5 mL and contain mRNA-1273 50 µg, 
mRNA-1273 100 µg, or saline placebo. Preferably, vaccine should be administered into the 
nondominant arm. 
In the open-label Part B of the study, mRNA-1273 vaccine will be administered as an IM injection 
into the deltoid muscle following the injection schedule for each group based on the product 
received: participants who received 1 or 2 doses of mRNA-1273 (50 µg and 100 µg) will receive 
a single booster dose of mRNA-1273 50 µg on OL-Day 1 in Part B (Table 11); participants who 
received placebo in Part A will receive 2 doses of mRNA-1273 100 µg on open-label (OL)-Day 
1 and OL-Day 29 of Part B (Table 11). In addition, participants who received only 1 dose of 
mRNA-1273 (50 µg or 100 µg) in Part A, will be receive a single booster dose of mRNA-1273 
(50µg) on OL-D1 in Part B (Table 12).
In the open-label Part C of the study, the investigational product will be administered as a single 
IM injection into the deltoid muscle on the day of the participant’s consent (OL-D1). Each injection 
will have variable dose volumes; the 20-µg dose of mRNA-1273.351 is 0.2 mL, the 50-µg dose of 
mRNA-1273.351 is 0.5 mL, and the 50-µg dose of pharmacy
prepared mixture of 
mRNA-1273/mRNA-1273.351 is 0.5 mL. 
In Part A, the investigational product will be prepared for injection as a single 0.5 mL dose for 
each participant based on the cohort and randomization assignment, as detailed in the 
mRNA-1273-P201 Pharmacy Manual. In Part B, the investigational product will be prepared for 
injection as a single 0.5 mL dose volumes for each participant as detailed in the mRNA-1273-P201 
Pharmacy Manual. In Part C, the investigational product will be prepared for injection as a single 
dose with varied volumes for each participant as detailed in mRNA1273-P201 Pharmacy Manual 
addendum for Part C. Unblinded pharmacy personnel, who will not participate in any other aspect 
of the study during Part A, the Blinded Phase, will perform investigational product accountability, 
dose preparation, and investigational product administration. The investigator will designate an 
unblinded clinical team member to provide oversight to the administration of investigational 
product so that it proceeds according to the procedures stipulated in this study protocol and the 
mRNA-1273-P201 Pharmacy Manual. Study-specific training will be provided. 
At each visit when investigational product is administered, participants will be monitored for a 
minimum of 30 minutes after administration. Assessments will include vital sign measurements 
and monitoring for local or systemic reactions (Schedule of Events, Table 9).

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Eligibility for subsequent investigational product injection is determined by following the criteria 
outlined in Section 3.3.2.2. 
The study site will be appropriately staffed, staff will be trained on emergency resuscitation, and 
will have stocked rescue medications (such as epinephrine, steroids, antihistamines, and 
intravenous fluids) should any severe reaction (eg, anaphylaxis or urticaria) occur that requires 
immediate intervention.
The rules for pausing dosing are provided in Section 3.3.2.1. 
3.3.2.1
Pause Rules
During Part A of the study, the investigators, study medical monitor, and Sponsor will monitor for 
events that could trigger a study pause (Table 3). Although these pause rules are not applicable 
during Part B and Part C, participants will continue to be monitored for the events in Table 3, and 
the Sponsor will be notified if any of these events occur. 
Table 3:    Pause Rule Criteria, Events, and Thresholds
Pause 
Rule 
Criterion
Event
Participant Threshold 
for Triggering Study 
Pause
1
Any death due to SARS-CoV-2 infection
≥1
2 
Any SAE or Grade 4 AE that cannot be reasonably 
attributed to a cause other than injection
≥ 3 
3
ICU admissions in Cohort 1 due to SARS-CoV-2 infection
≥3
4 
ICU admissions in Cohort 2 due to SARS-CoV-2 infection
≥ 6 
Abbreviations: AE = adverse event; ICU = intensive care unit; SAE = serious adverse event; SARS-Cov-2 = severe 
acute respiratory syndrome coronavirus that causes COVID-19.
If any of the thresholds for a study pause is met during Part A, the Sponsor will immediately 
suspend further enrollment and/or study dosing by notifying all investigators. Such a suspension 
will remain in force until the threshold event is adjudicated by the Safety Monitoring Committee 
(SMC; Section 6.1.1).
The investigator or designee is responsible for reporting to the Sponsor, via the electronic data 
capture (EDC) system within 24 hours of observation, each event potentially meeting any pause 
rule criterion. The Sponsor will inform the SMC (Section 6.1.1) of any event potentially meeting 
any pause rule criterion. The SMC will review all available study data to adjudicate such events in 
accordance with the SMC charter.

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The Sponsor will also actively monitor the following and provide them to the SMC for review as 
they become available:
•
Instances of study halting rules triggered in the Phase 1 DMID study (NCT04283461)
•
Histopathological data suggestive of vaccine-enhanced disease in ongoing nonclinical 
studies
The Sponsor will notify the Center for Biologics and Evaluation Research (CBER) within 48 hours 
in the event of a study pause. In the event of a study pause, all safety and immunogenicity 
assessments will continue per protocol. The window allowance for injection visits may be extended 
by an additional 7 days for affected participants at the discretion of the Sponsor. 
During Part B and Part C of the study, the Sponsor will continue to inform the SMC of the 
occurrence of any of the events in Table 3. The SMC will review all available relevant study data 
to adjudicate such events in accordance with the SMC charter.
3.3.2.2
Contraindications to Subsequent Injection
Prior to receiving a second injection, participants will be reassessed to ensure that they continue 
to meet eligibility requirements as outlined below. For Part C, if the option to administer a second 
injection is exercised, prior to receiving a second injection, participants will be reassessed to ensure 
they continue to meet eligibility requirements as outlined below. 
The following events in a participant constitute absolute contraindications to any further 
administration of the investigational product to that participant. If any of these events occur during 
the study, the participant must not receive additional doses of vaccine but will be encouraged to 
continue study participation for safety through 6 months following last injection (Section 3.2.5).
•
Symptomatic COVID-19 at the time of a second injection. If COVID-19 is suspected 
on or prior to administration of a second injection, further administration of 
investigational product must be withheld, as applicable, until COVID-19 test results 
are available.
•
Anaphylaxis or systemic hypersensitivity reaction following the administration of vaccine.
•
Any SAE judged by investigator or Sponsor to be related to study vaccine.
•
Pregnancy
•
Any clinically significant medical condition that, in the opinion of the investigator, poses 
an additional risk to the participant if he/she continues to participate in the study. 

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The following events constitute contraindications to administration of study vaccine at certain 
points in time, and if any of these events occur at the time scheduled for injection, the participant 
may be injected at a later date, within the time window specified in the Schedule of Events 
(Section 7.1), or the participant may be withdrawn from dosing at the discretion of the investigator 
(Section 3.2.5):
•
Acute moderate or severe infection with or without fever at the time of injection
•
Fever, defined as body temperature ≥ 38.0°C (100.4°F) at the time of injection
Participants with a minor illness without fever, as assessed by the investigator, can be administered 
investigational product. Participants with a fever of 38.0°C (100.4°F) or higher will be contacted 
within the time window acceptable for participation and reevaluated for eligibility. 
3.3.3
Identity of Investigational Product
The mRNA-1273 vaccine dosed in Part A and Part B of this study is an LNP dispersion of an 
mRNA encoding the prefusion stabilized S protein of SARS-CoV-2. The mRNA-1273.351 vaccine 
dosed in Part C of this study is an LNP dispersion of an mRNA encoding the prefusion stabilized 
S protein of SARS-CoV-2 variant B1.351. The mRNA-1273/mRNA-1273.351 mixture vaccine 
dosed in Part C of this study utilizes a mixture of mRNA-1273 and mRNA-1273.351 drug products 
to administer a single dose containing both vaccines. All vaccines are formulated in LNPs 
composed of 4 lipids (1 proprietary and 3 commercially available): the proprietary ionizable lipid 
SM-102;   cholesterol;   1,2-distearoyl-sn-glycero-3-phosphocholine   (DSPC);   and
1-monomethoxypolyethyleneglycol-2,3-dimyristylglycerol with polyethylene glycol of average 
molecular weight 2000 (PEG2000-DMG).
The mRNA-1273, mRNA-1273.351, and mRNA-1273/mRNA-1273.351 mixture vaccines are 
provided as sterile liquids for injection, white to off white dispersion in appearance. The 
mRNA-1273 vaccine dosed in Part A and Part B is in 20 mM Tris buffer containing 87 mg/mL 
sucrose and 10.7 mM sodium acetate at pH 7.5 and is provided at a concentration of 0.5 mg/mL. 
The mRNA-1273 vaccine dosed in Part C is in 20 mM Tris buffer containing 4.3 mM of sodium 
acetate at pH 7.5 and is provided at a concentration of 0.5 mg/mL. The mRNA-1273.351 vaccine 
in Part C is in 20 mM Tris buffer containing 10.7 mM of sodium acetate at pH 7.5 and provided at 
a concentration of 0.2 mg/mL. mRNA-1273 and mRNA-1273.351 vaccines will be mixed at the 
clinical site to enable dosing of the mRNA-1273/mRNA-1273.351 (50 µg total) arm. 
The placebo is 0.9% sodium chloride (normal saline) injection, USP.

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3.3.4
Management of Investigational Product
3.3.4.1
Delivery and Receipt
The Sponsor or designee is responsible for the following:
•
Supplying the investigational product
•
Confirming the appropriate labeling of mRNA-1273, mRNA-1273.351, and mRNA- 
1273/mRNA-1273.351 mixture Injection, so that it complies with the legal requirements 
of the US 
The investigator is responsible for acknowledging the receipt of the investigational product by a 
designated staff member at the site, including the following: 
•
Confirming that the investigational product was received in good condition
•
Confirming that the temperature during shipment from the Sponsor to the investigator’s 
designated storage location was appropriate 
•
Confirming whether the Sponsor has authorized the investigational product for use
•
Ensuring the appropriate dose level of mRNA-1273, mRNA-1273.351, and mRNA- 
1273/mRNA-1273.351 mixture Injection is properly prepared using aseptic technique 
Further description of the investigational product and instructions for the receipt, storage, 
preparation, administration, accountability, and destruction of the investigational product are 
described in the mRNA-1273-P201 Pharmacy Manual addendum for Part C. 
3.3.4.2
Packaging and Labeling
The Sponsor will provide the investigator and study site with adequate quantities of mRNA-1273, 
mRNA-1273.351, and mRNA-1273/mRNA-1273.351 mixture. The sterile vaccine product used 
in Part A and Part B is packaged in a 2-mL glass vial with a 0.6-mL fill volume. The mRNA-1273 
vaccine used in Part C is packaged in a 10-mL vial with a 6.3-mL fill volume. The mRNA- 
1273.351 vaccine used in Part C is packaged in a 2-mL vial with a 0.8-mL fill volume. The vaccines 
will have all required labeling per regulations and will be supplied to the pharmacy in an unblinded 
manner. Each vial will be individually labeled for future participant identification purposes. 
The mRNA-1273 and mRNA-1273.351 injections will be packaged and labeled in accordance 
with the standard operating procedures (SOPs) of the Sponsor or of its designee, Code of Federal 
Regulations Title 21 (CFR), Good Manufacturing Practice (GMP) guidelines, International

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Council for Harmonisation (ICH) Good Clinical Practice (GCP) guidelines, guidelines for Quality 
System Regulations, and applicable regulations. 
The Sponsor or Sponsor’s designee will supply the 0.9% sodium chloride injection for use as both 
a placebo and a diluent to mRNA-1273 and mRNA-1273.351. The 0.9% sodium chloride bears a 
commercial label and does not contain study-specific identification.
3.3.4.3
Storage
The mRNA-1273 vaccine in Part A and Part B must be stored at -90°C to -60°C (-130°F to -76°F). 
The mRNA-1273 vaccine in Part C must be stored at -25°C to -15°C. The mRNA-1273.351 
vaccine used in Part C must be stored at -90°C to -60°C (-130°F to -76°F). Freezers must be in a 
secure area with limited access (unblinded pharmacy staff only) and protected from moisture and 
light until it is prepared for administration (Section 3.3.2). The freezer should have automated 
temperature recording and a 24-hour alert system in place that allows for rapid response in case of 
freezer malfunction. There must be an available back-up freezer. The freezers must be connected 
to a back-up generator. In addition, vaccine accountability study staff (eg, the unblinded pharmacy 
personnel) are required to keep a temperature log to establish a record of compliance with these 
storage conditions. The site is responsible for reporting any mRNA-1273 and mRNA-1273.351 
vaccine that was not temperature controlled during shipment or during storage to the unblinded 
site monitor. Such vaccines will be retained for inspection by the unblinded monitor and disposed 
of according to approved methods. 
The 0.9% sodium chloride injection (USP) should be stored at 20ºC to 25ºC (68ºF to 77ºF) in a 
restricted access area.
3.3.4.4
Investigational Product Accountability
It is the investigator’s responsibility that the unblinded pharmacy personnel maintain accurate 
records in an investigational product accountability log of receipt of all investigational product, 
inventory at the site, dispensing of mRNA-1273, mRNA-1273.351, and placebo, study injections, 
and return to the Sponsor or alternative disposition of used/unused products. 
An unblinded site monitor will review the inventory and accountability log during site visits and 
after the completion of treatment. Additional details are found in the mRNA-1273-P201 Pharmacy 
Manual (Part A and Part B) and the mRNA-1273-P201 Pharmacy Manual Addendum for Part C. 

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3.3.4.5
Handling and Disposal
An unblinded site monitor will reconcile the investigational product during the conduct and at the 
end of the study for compliance. Once fully reconciled at the site at the end of the study, the 
investigational product can be destroyed at the investigational site or at a Sponsor-selected third 
party, as appropriate.
Investigational product may be destroyed at the study site only if permitted by local regulations 
and authorized by the Sponsor. A Certificate of Destruction must be completed and sent to the 
Sponsor or designee. 
3.3.5
Blinding
See Section 3.1.2 regarding the addition of a participant decision visit as part of this protocol 
amendment.
Part A of this study is observer blind. The investigator, study staff, study participants, site monitors, 
and Sponsor personnel (or its designees) will be blinded to the investigational product administered 
until study end or initiation of Part B, with the following exceptions: 
•
Unblinded pharmacy personnel (of limited number) will be assigned to vaccine 
accountability procedures and will prepare and administer mRNA-1273 (or placebo) to all 
participants. These pharmacy personnel will have no study functions other than study 
vaccine management, documentation, accountability, preparation, and administration. 
They will not be involved in participant evaluations and will not reveal the identity of 
investigational product to either the participant or the blinded study site personnel involved 
in the conduct of the study unless this information is necessary in the case of an emergency.
•
Unblinded site monitors, not involved in other aspects of monitoring, will be assigned as 
the investigational product accountability monitors. They will have responsibilities to 
ensure that sites are following all proper investigational product accountability, preparation, 
and administration procedures. 
•
A primary analysis of safety and immunogenicity data will be performed after participants 
have completed Day 57 study procedures. This primary analysis may be performed when 
all participants in Cohort 1 and the Cohort 2 sentinel group have completed Day 57 study 
procedures and/or when all participants in Cohort 1 and Cohort 2 have completed Day 57 
study procedures. All data relevant to the primary study analysis through Day 57 will be 
cleaned (ie, data that are as clean as possible) and locked. A limited number of Sponsor and 
clinical research organization (CRO) personnel will be unblinded to perform the primary 
study analysis and prepare a final Clinical Study Report (CSR), including individual 

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listings. The study site staff, investigators, study monitors, and participants will remain 
blinded until the initiation of Open-Label Part B.
In Part A, the dosing assignment will be concealed by having the unblinded pharmacy personnel 
prepare the investigational product in a secure location that is not accessible or visible to other 
study staff. A blinding label over the syringe used for injection will maintain the blind at the time 
of injection, as the doses containing mRNA-1273 will look different than placebo. Only delegated 
unblinded site staff will conduct the injection procedure. Once the injection is completed, only the 
blinded study staff will perform further assessments and interact with the participants. Access to 
the randomization code will be strictly controlled at the pharmacy.
Part B and Part C of the study will be open label.
3.3.6
Breaking the Blind 
A participant or participants may be unblinded in the event of an SAE or other severe event, or if 
there is a medical emergency requiring the identity of the product to be known to properly treat a 
participant. If a participant becomes seriously ill or pregnant during the study, the blind will be 
broken if knowledge of the administered vaccine will affect that participant’s dosing options. In 
the event of a medical emergency requiring identification of the vaccine administered to an 
individual participant, the investigator will make every attempt to contact the Sponsor medical 
lead to explain the need for opening the code within 24 hours of opening the code. The investigator 
will be responsible for documenting the time, date, reason for the code break, and the names of the 
personnel involved. 
In addition to the aforementioned situations where the blind may be broken, the data will also be 
unblinded to a statistical team at specified time points for the primary study analysis as outlined in 
Section 4.7. 
3.3.7
Dosing Compliance
All doses of investigational product will be administered at the study site under direct observation 
of unblinded pharmacy personnel and appropriately recorded (date and time) in the eCRF. 
Unblinded pharmacy personnel will confirm that the participant has received the entire dose of 
vaccine. If a participant does not receive vaccine or does not receive all of the planned doses, the 
reason for the missed dose will be recorded.
Participants who miss the second injection due to noncompliance with the visit schedule and not 
due to a safety pause will still be required to follow the original visit and testing schedule as 
described in the protocol. Unless consent is withdrawn, a participant who withdraws or is withheld

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from receiving the second dose of study vaccine will remain in the study and complete all safety 
and immunogenicity assessments required through the scheduled EOS. 
The study site is responsible for ensuring participants comply with the study windows allowed. If 
a participant misses a visit, every effort should be made to contact the participant and complete a 
visit within the defined visit window (Part A Table 9, Part B Table 11, and Table 12, and Part C 
Table 12). If a participant does not complete a visit within the time window, that visit will be 
classified as a missed visit and the participant will continue with subsequent scheduled study visits. 
All safety requirements of the missed visit will be captured and included in the subsequent visit 
(eg, clinical laboratory testing, eDiary review for reactogenicity, immunologic testing, as 
applicable).
3.3.8
Prior and Concomitant Medications
3.3.8.1
Prior Medications and Therapies
Information about prior medications (including any prescription or over-the-counter medications, 
vaccines, or blood products) taken by the participant within the 28 days before providing informed 
consent (or as designated in the inclusion/exclusion requirements) will be recorded in the 
participant’s eCRF.
3.3.8.2
Concomitant Medications and Therapies
At each study visit, study site staff must question the participant regarding any medications taken 
and vaccinations received by the participant and record the following information in the eCRF: 
•
All non-study vaccinations administered within the period starting 28 days before the first 
study injection. 
•
All concomitant medications and non-study vaccinations taken through 28 days after each 
injection. Antipyretics and analgesics taken prophylactically (ie, taken in the absence of 
any symptoms in anticipation of an injection reaction) will be recorded as such. 
•
Any concomitant medications relevant to or for the treatment of an SAE or a MAAE.
•
Participant will be asked in the eDiary if they have taken any antipyretic or analgesic to 
treat or prevent fever or pain within 7 days after each study injection, including the day of 
injection. Reported antipyretic or analgesic medications should be recorded in the source 
document by the site staff during the post-injection study visits or via other participant 
interactions (eg, telephone calls).

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The use of the following concomitant medications and/or vaccines will not require withdrawal of 
the participant from the study but may determine a participant’s eligibility to receive a second dose 
or evaluability in the per-protocol analysis (analysis sets are described in Section 4.4):
•
Any investigational or nonregistered product (drug or vaccine) other than the study vaccine 
used during the study period. 
•
Immunosuppressants or other immune-modifying drugs administered chronically (ie, more 
than 14 days in total) during the study period. For corticosteroids, this will mean that 
prednisone ≥ 20 mg/day or the equivalent is not permitted. Inhaled, nasal, and topical 
steroids are allowed.
•
Long-acting immune-modifying drugs administered at any time during the study period 
(eg, infliximab). 
•
A licensed vaccine administered during the period from 28 days before through 28 days 
after each study injection, except for any licensed influenza vaccine that was administered 
more than 14 days before or after any study injection. 
•
Immunoglobulins and/or any blood products administered during the study period.
Concomitant medications (including vaccinations) will be coded using the WHO Drug Dictionary. 
If a participant takes a prohibited drug therapy, the investigator and the CRO’s medical monitor 
will make a joint decision about continuing or withholding further injection of the participant based 
on the time the medication was administered, the drug’s pharmacology and pharmacokinetics, and 
whether use of the medication will compromise the participant’s safety or interpretation of the data. 
It is the investigator’s responsibility to ensure that details regarding the concomitant medications 
are adequately recorded in the eCRF.
3.4 Study Procedures
Before performing any study procedures, all potential participants will sign an informed consent 
form (ICF) (as detailed in Section 5.3). Participants will undergo study procedures at the time 
points specified in the Schedule of Events (Table 9).
After participant proceeds to the open-label Part B of the study at the Participant Decision Clinic 
Visit (Table 10), Part A schedule of events (Table 9) will no longer be followed and become 
obsolete.
Upon the participant’s decision to end participation in Moderna’s mRNA-1273-P301 COVE study, 
and consent to enrolling into Part C of this study, they will follow study procedures as specified in 
the Schedule of Events (Table 12).

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A participant also can be seen for an unscheduled visit at any time during the study. An unscheduled 
visit may be prompted by reactogenicity issues or new or ongoing AEs. The site also has the 
discretion to make reminder telephone calls or send text messages to inform the participant about 
visits, review eDiary requirements, or follow up on ongoing or outstanding issues. 
In accordance with “FDA Guidance on Conduct of Clinical Trials of Medical Products during 
COVID-19 Public Health Emergency” (DHHS 2020), investigators may convert study site visits 
to telemedicine visits with the approval of the Sponsor. Such action should be taken to protect the 
safety and well-being of study participants and study site staff or to comply with state or municipal 
mandates.
3.4.1
Assessment for SARS-CoV-2 Infection
Study participants will have nasopharyngeal swab samples collected for SARS-CoV-2 testing at 
time points specified in the Schedule of Events (Part A Table 9 and Part B Table 10, Table 11 and 
Table 12, and Part C Table 12).
For Part A, Part B, and Part C of this study, a study illness visit or a consultation will be arranged 
within 24 hours or as soon as possible to collect a nasopharyngeal swab sample to ascertain the 
presence of SARS-CoV-2 via PCR if a participant experiences any of the following: 
•
Signs or symptoms of SARS-CoV-2 infection as defined by the CDC (CDC 2020c) 
•
Exposure to an individual confirmed to be infected with SARS-CoV-2 
•
MAAE suggesting a SARS-CoV-2 infection
Additionally, clinical information will be carefully collected to evaluate the severity of the clinical 
case. All findings will be recorded in the eCRF.
If scheduled, a study site illness visit may include assessments such as medical history, physical 
examination, blood sampling for clinical laboratory testing, and nasopharyngeal swab sampling 
for viral PCR (including multiplex PCR for respiratory viruses including SARS-CoV-2) to evaluate 
the severity of the clinical case. Radiologic imaging studies may be conducted. Blood samples will 
be collected at all illness visits for potential future immunologic assessment of SARS-CoV-2 
infection.
If participants are confirmed to have SARS-CoV-2 infection, the investigator will notify the 
participant’s primary care physician of the diagnosis. Additionally, a convalescent visit will be 
scheduled approximately 28 days after diagnosis. At this visit, a blood sample will be collected for 
potential future immunologic assessment of SARS-CoV-2 infection. 

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If participants are confirmed to have SARS-CoV-2 infection, and are asymptomatic, the 
investigator will notify the participant’s primary care physician and local health authority, as per 
local regulations. If the participant had known exposure to COVID-19 (eg, exposure to someone 
with confirmed COVID-19 disease), it will be captured in the COVID-19 exposure form, and the 
participant will be discontinued from future study treatment only, and will continue to follow all 
other study assessments as outlined in the protocol. Additionally, a convalescent visit will be 
scheduled approximately 28 days after diagnosis. At this visit, a blood sample will be collected for 
potential immunologic assessment of SARS-CoV-2 infection. 
Any confirmed SARS-CoV-2 infection occurring in participants, except asymptomatic infection 
diagnosed at Day 1, will be captured as an MAAE along with relevant concomitant medications 
and details about severity, seriousness, and outcome. 
3.4.2
Use of Electronic Diaries
At the time of consent, the participants must confirm they will be willing to complete an eDiary 
using either an application downloaded to their smartphone or using a device that is provided at 
the time of enrollment. Before enrollment on Day 1, the participant will be instructed to download 
the eDiary application or will be provided an eDiary device to record solicited ARs
(Section 3.4.8.4) beginning on Day 1 or at the Participant Decision Visit in the open-label Part B 
of the study. 
In Part A, at each injection visit, participants will be instructed (Day 1) or reminded (Day 29) on 
thermometer usage to measure body temperature, ruler usage to measure injection site erythema 
and swelling/induration (hardness), and self-assessment for localized axillary swelling or 
tenderness on the same side as the injection arm.
In Part B and Part C, at the respective injection visit, participants will be reminded on thermometer 
usage to measure body temperature, ruler usage to measure injection site erythema and 
swelling/induration (hardness), and self-assessment for localized axillary swelling or tenderness 
on the same side as the injection arm.
At each injection visit, participants will record data into the eDiary starting approximately 
30 minutes after injection under supervision of the study site staff to ensure successful entry of 
assessments. The site staff will perform any retraining as necessary. Study participants will 
continue to record data in the eDiary after they leave the study site, preferably in the evening and 
at the same time each day, on the day of injection and for 6 days following injection. 

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Participants will record the following data in the eDiary:
•
Solicited local and systemic reactogenicity ARs, as defined in Section 3.4.8.4, that occur 
on the day of each vaccine administration and during the 7 days after vaccine 
administration (ie, the day of injection and 6 subsequent days). Any solicited AR that is 
ongoing beyond Day 7 will be reported in the eDiary until resolution. Adverse reactions 
recorded in diaries beyond Day 7 should be reviewed by study site staff either during the 
next scheduled telephone call or at the next study site visit (Table 9, Table 11, and Table
12).
•
Daily oral body temperature measurement should be performed at approximately the same 
time each day using the thermometer provided by the study site. If body temperature is 
taken more than once in a given day, only the highest temperature reading should be 
recorded.
•
Measurement, as applicable, for solicited local ARs (injection site erythema and 
swelling/induration); the size measurements will be performed using the ruler provided by 
the study site. 
•
Participants will be queried by the eDiary whether any medications were taken to treat or 
prevent pain or fever on a day of injection or for the 6 subsequent days. 
The eDiary will be the only source documents allowed for solicited systemic or local ARs 
(including body temperature measurements). Participants will be instructed to complete eDiary 
entries daily. The participant will have a limited window on the following day to complete 
assessments for the previous day; quantitative temperature recordings and measurement of any 
injection site erythema or swelling/induration reported on the following day may be excluded from 
the analyses of solicited ARs.
Any new safety information reported during safety telephone calls or at site visits (including a 
solicited reaction) that is not already captured in the eDiary will be described in the source 
documents as a verbally reported event. Any AR reported in this manner must be described as an 
unsolicited event and therefore entered on the AE eCRF. 
Study site staff will review eDiary data with participants at the Day 8 and Day 36 visits in the 
blinded Part A of the study. In the open-label Part B of the study, eDiary data will be reviewed in 
person on open-label (OL) Day 8 for participants receiving a single booster (Table 12) and via 
phone call 7 days after each vaccination for those participants receiving 2 doses of 100 µg 
mRNA-1273 (Table 11). In Part C of the study, eDiary data will be reviewed in person on open- 
label Day 8 (Table 12).

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The eDiary will also be used after the Day 57 visit (including OL-Day 57 in Part B and Part C) to 
capture the occurrence of AEs, MAAEs, SAEs, or AEs leading to study withdrawal, every 4 weeks 
from Day 71 through Day 183 in Part A (Table 9), from OL-Day 71 through OL- Day 155 in Part B 
(Table 11 and Table 12) and Part C (Table 12), and from Day 223 through Day 363 in Part A only 
(Table 9).
The eDiary will prompt the participant to complete an eDiary questionnaire that collects the 
following data: 
•
Changes in health since last completing the questionnaire or since last in contact with the 
study site. 
•
Known exposure to someone with known COVID-19 or SARS-CoV-2 infection.
•
Any experience of symptoms of COVID-19.
•
Any MAAEs or SAEs.
If an eDiary record results in identification of relevant safety events according to the study period 
or of symptoms of COVID-19, the site will follow up with the participant via telephone and assess 
the need for an unscheduled visit. 
Completion of eDiary questionnaires will alternate with safety telephone calls (Section 3.4.3) as 
the procedure for safety follow-up approximately every 2 weeks after the Day 57 (Table 9) or the 
OL-Day 57 visit (Table 11 and Table 12).
3.4.3
Safety Telephone Calls
A safety telephone call is a telephone call made to the participant by trained site personnel. This 
call will follow a script, which will facilitate the collection of relevant safety information. 
In blinded Part A, safety telephone calls are scheduled to occur every 4 weeks from Day 85 through 
Day 197 and from Day 237 through Day 377 (Table 9).
In the open-label Part B, the safety telephone calls are scheduled to occur every 4 weeks (Table 11
and Table 12).
In the open-label Part C, the safety telephone calls are scheduled to occur every 4 weeks (Table
12).
The participant will be interviewed according to the script about occurrence of AEs, MAAEs, 
SAEs, AEs leading to study withdrawal, concomitant medications associated with those events, 
and any non-study vaccinations (Section 3.4.8.6). In addition, study personnel will collect 
information on known participant exposure to someone with known COVID-19 or SARS-CoV-2 

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infection and on participant experience of COVID-19 symptoms. All safety information collected 
from the telephone contact must be documented in source documents as described by the 
participant and not documented on the script used for the safety telephone contact. 
3.4.4
Safety Laboratory Assessments
In the blinded Part A of the study, laboratory tests will be performed by the central laboratory 
unless otherwise specified. Screening safety laboratory tests will include complete blood count 
with differential, alanine aminotransferase (ALT), aspartate aminotransferase (AST), total and 
direct bilirubin, alkaline phosphatase (ALP), blood urea nitrogen/creatinine, prothrombin time 
(PT), and partial thromboplastin time (PTT). These safety laboratory tests are to be repeated at 
Day 29 and Day 57 only for Cohort 2 (≥ 55 years of age).
Additional tests include the following:
In both Parts A and B, a point-of-care urine pregnancy test will be performed at the Screening 
Visit (Day 0) or Participant Decision Visit (OL-Day 1) and before each vaccine 
administration. In Part C, a point-of-care urine pregnancy test will be performed at the 
OL-Day 1 prior to vaccine administration. 
At any time, a pregnancy test either via blood or point-of-care urine can be performed, at the 
discretion of the investigator. 
•
If not documented in a female participant’s medical records, an FSH test may be performed 
at the Screening Visit (Day 0, Part A, Blinded Phase only), as necessary and at the 
discretion of the investigator, to confirm postmenopausal status. 
•
Hepatitis B surface antigen, hepatitis C virus antibody, and HIV virus (types 1 and 2) 
antibody at the Screening Visit (Day 0, Part A, Blinded Phase only). 
3.4.5
Immunogenicity Assessments
Blood samples for immunogenicity assessments will be collected at the time points indicated in 
the Schedule of Events for each study part, Table 9 for the blinded Part A, and Table 10, Table 11
and Table 12 for open-label Part B, and Table 12 for Part C. On Day 1 and Day 29 (Table 9), and 
on OL-Day 1 (Table 12) and on OL-Day 1 and OL-Day 29 (Table 11), blood samples for 
immunogenicity assessment will be collected before administration of vaccine. The following 
analytes will be measured:
•
Serum bAb level against SARS-CoV-2 as measured by enzyme-linked immunosorbent 
assay (ELISA) specific to the SARS-CoV-2 S protein 

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•
Serum nAb titer against SARS-CoV-2 as measured by pseudovirus and/or live virus 
neutralization assays
In Part C, serum samples for immunogenicity assessment will be analyzed for the following:
•
Serum nAb against SARS-CoV-2 as measured by pseudovirus (and/or live virus) using 
the B.1.351 and the D614G variant sequences of SARS-CoV-2 S protein (and/or variant 
strains)
•
Serum bAb against SARS-CoV-2 as measured by ELISA against the B.1.351 and the 
D614G variant sequences of SARS-CoV-2 S protein 
Sample aliquots will be designed to ensure that backup samples are available and that adequate 
vial volumes may allow further testing needs. The actual time and date of each sample collected 
will be recorded in the eCRF, and unique sample identification will be utilized to maintain the 
blind at the laboratory at all times and to allow for automated sample tracking and housing. 
Handling and preparation of the samples for analysis, as well as shipping and storage requirements, 
will be provided in a separate study manual.
The ELISA and measurement of nAb titers will be performed in a laboratory designated by the 
Sponsor.
For participants who provide consent (Section 5.3), serum from immunogenicity testing may be 
used for future research, which may be performed at the discretion of the Sponsor to further 
characterize the immune response to SARS-CoV-2, additional assay development, and the immune 
response across the coronaviruses. 
3.4.6
Blood Sampling Volumes
In Part A, the maximum planned volumes of blood sampled per participant are 66 mL for 1 day, 
182 mL for 28 days, and 398 mL for the complete study (Table 4).

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Table 4: 
Maximum Blood Sampling Volumes per Participant by Visit (Part A, 
Blinded)
Study Visit Day
D0
D1
D15
D29
D43
D57
D209
D394
Total
Safety laboratory tests
16 mL
161 mL
161 mL
48 mL
Immunogenicity 
assays
50 mL
50 mL
50 mL
50 mL
50 mL
50 mL
50 mL
350 mL
Total
16 mL
50 mL
50 mL
66 mL
50 mL
66 mL
50 mL
50 mL
398 mL
Abbreviation: D = Day.
1Only participants in Cohort 2 will have blood sampled for safety laboratory tests at Day 29 and Day 57.
In Parts B and C, the maximum planned volumes of blood sampled per participant are 20 mL per 
visit, 80 mL for 28 days, and a total of 120 mL (Table 5).
Table 5: 
Maximum Blood Sampling Volumes per Participant by Visit (Part B and 
Part C Open-label)
Study Visit Day
OL-D1
OL-D8
OL-D15
OL-D29
OL-D57
OL-M6-71
Total
Immunogenicity assays
20 mL
20 mL
20 mL
20 mL
20 mL
20 mL
120 mL
Abbreviation: OL = Open-Label; D = Day; M = month.
1 OL-M6-7 is calculated based on the participant’s last vaccination day, ie, for participants receiving a single booster 
dose this will be OL-M6, and for participants; who receive 2 injections, this visit will be based off of the day of second 
injection (ie, OL-Day 29), and will be OL-M7. In Part C, the last blood sample collection will be at OL-M6.
3.4.7
Safety Assessments
In Part A (blinded), Part B (open-label), and Part C (open-label), safety assessments will include 
monitoring and recording of the following for each participant:
•
Solicited local and systemic ARs (Section 3.4.8.4) that occur during the 7 days following 
each injection (ie, the day of injection and 6 subsequent days). Solicited ARs will be 
recorded daily using eDiaries (Section 3.4.2).
•
Unsolicited AEs observed or reported during the 28 days following each injection (ie, the 
day of injection and 27 subsequent days). Unsolicited AEs are AEs that are not included in 
the protocol-defined solicited ARs (Section 3.4.8.4).
•
AEs leading to discontinuation from dosing and/or study participation from Day 1 through 
Day 394 (Part A), OL-Month 6 or 7 (Part B), and OL-Month 6 (Part C) or withdrawal from 
the study. 
•
MAAEs from Day 1 through Day 394 (Part A), OL-Month 6 or 7 (Part B), and OL-Month 6 
(Part C) or withdrawal from the study. 

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•
SAEs from Day 1 through Day 394 (Part A), OL-Month 6 or 7 (Part B), and OL-Month 6 
(Part C) or withdrawal from the study. 
•
Results of safety laboratory tests (Part A).
•
Vital sign measurements.
•
Physical examination findings.
•
Assessments for SARS-CoV-2 infection from Day 1 through study completion 
(Section 3.4.1).
3.4.8
Safety Definitions
3.4.8.1
Adverse Event
AnAE is defined as any untoward medical occurrence associated with the use of a drug in humans, 
whether or not considered drug related. 
A treatment-emergent AE (TEAE) is defined as any event not present before exposure to vaccine 
or any event already present that worsens in intensity or frequency after exposure. 
Events Meeting the Adverse Event Definition
•
Any abnormal laboratory test result (hematology, clinical chemistry, or PT/PTT) or other 
safety assessment (eg, electrocardiogram, radiological scan, vital sign measurement), 
including one that worsens from baseline and is considered clinically significant in the 
medical and scientific judgment of the investigator.
•
Exacerbation of a chronic or intermittent pre-existing condition including either an increase 
in frequency and/or intensity of the condition. 
•
New conditions detected or diagnosed after mRNA-1273 vaccine administration even 
though it may have been present before the start of the study. 
Events NOT Meeting the Adverse Event Definition
•
Medical or surgical procedure (eg, endoscopy, appendectomy): the condition that leads to 
the procedure is the AE.
•
Situations in which an untoward medical occurrence did not occur (social and/or 
convenience admission to a hospital). 
An AR is any AE for which there is a reasonable possibility that the investigational product caused 
the AE (Section 3.4.8.4). For the purposes of investigational new drug safety reporting,

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“reasonable possibility” means that there is evidence to suggest a causal relationship between the 
investigational product and the AE. 
An unsolicited AE is any AE reported by the participant that is not specified as a solicited AR in 
the protocol or is specified as a solicited AR in the protocol but starts outside the protocol-defined 
post-injection period for reporting solicited ARs (ie, for the 7 days after each injection). 
3.4.8.2
Medically Attended Adverse Event
An MAAE is an AE that leads to an unscheduled visit to a healthcare practitioner (HCP). This 
would include visits to a study site for unscheduled assessments (eg, rash assessment, abnormal 
laboratory follow-up, SARS-CoV-2 infection [Section 3.4.1]) and visits to HCPs external to the 
study site (eg, urgent care, primary care physician). Investigators will review unsolicited AEs for 
the occurrence of any MAAEs. All MAAEs must be fully reported on the MAAE page of the eCRF. 
3.4.8.3
Serious Adverse Event
An AE (including an AR) is considered an SAE if, in the view of either the investigator or Sponsor, 
it results in any of the following outcomes: 
•
Death
A death that occurs during the study or that comes to the attention of the investigator during 
the protocol-defined follow-up period must be reported to the Sponsor, whether or not it is 
considered related to study vaccine.
•
Is life-threatening
An AE is considered life-threatening if, in the view of either the investigator or the 
Sponsor, its occurrence places the participant at immediate risk of death. It does not 
include an AE that, had it occurred in a more severe form, might have caused death.
•
Inpatient hospitalization or prolongation of existing hospitalization
In general, inpatient hospitalization indicates the participant was admitted to the hospital 
or emergency ward for at least one overnight stay for observation and/or treatment that 
would not have been appropriate in the physician’s office or outpatient setting. The 
hospital or emergency ward admission should be considered an SAE regardless of 
whether opinions differ as to the necessity of the admission. Complications that occur 
during inpatient hospitalization will be recorded as an AE; however, if a complication/AE 
prolongs hospitalization or otherwise fulfills SAE criteria, the complication/AE will be 
recorded as a separate SAE.

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•
Persistent or significant incapacity or substantial disruption of the ability to conduct 
normal life functions 
This definition is not intended to include experiences of relatively minor medical 
significance such as uncomplicated headache, nausea/vomiting, diarrhea, influenza, and 
accidental trauma (eg, sprained ankle) which may interfere with or prevent everyday life 
functions but do not constitute a substantial disruption. 
•
Congenital anomaly or birth defect
•
Medically important event
Medical judgment should be exercised in deciding whether SAE reporting is appropriate 
in other situations, such as important medical events that may not be immediately life- 
threatening or result in death or hospitalization but may jeopardize the participant or 
require medical or surgical intervention to prevent one of the other outcomes listed in the 
above definition. These events should usually be considered serious. 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. 
3.4.8.4
Solicited Adverse Reactions
The term “reactogenicity” refers to the occurrence and intensity of selected signs and symptoms 
(ARs) occurring after vaccine administration. The eDiary (Section 3.4.2) will solicit participant 
reporting of ARs using a structured checklist. Participants will record such occurrences in an 
eDiary on the day of each vaccine administration and for the 6 days after a day of injection. 
The following local ARs will be solicited by the eDiary: pain at injection site, erythema (redness) 
at injection site, swelling/induration (hardness) at injection site, and localized axillary swelling or 
tenderness ipsilateral to the injection arm.
The following systemic ARs will be solicited by the eDiary: headache, fatigue, myalgia (muscle 
aches all over the body), arthralgia (aching in several joints), nausea/vomiting, rash, body 
temperature (potentially fever), and chills. 
The study site staff will contact the participant within 24 hours of becoming aware of the event if 
any of the following occurs within 7 days after study injection: 
•
Severe (Grade 3) local or systemic ARs (Table 6) 
•
Presence of any rash

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The purpose of the contact is to assess the nature of AR, including assessment of potential pause 
rules. In the event that rash is reported, the participant will be asked to return to the study site for 
assessment by the investigator. 
The investigator will review, confirm, and grade reactogenicity according to the grading scales 
presented in Table 6, modified from the Toxicity Grading Scale for Healthy Adult and Adolescent 
Volunteers Enrolled in Preventive Vaccine Clinical Trials (DHHS 2007).
If a solicited local or systemic AR continues beyond 7 days after injection, the participant will be 
prompted to capture solicited local or systemic ARs in the eDiary until resolution. Adverse 
reactions recorded in eDiaries beyond Day 7 should be reviewed either via telephone call or at the 
following study visit. All solicited ARs (local and systemic) will be considered causally related to 
injection.

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Table 6:
Solicited Adverse Reactions and Grades
Reaction
Grade 0 
Grade 1 
Grade 2 
Grade 3 
Grade 4*
Injection site pain
None
Does not interfere with 
activity
Repeated use of over-the- 
counter pain reliever > 24 
hours or interferes with 
activity
Any use of prescription 
pain reliever or prevents 
daily activity
Requires emergency room 
visit or hospitalization
Injection site erythema 
(redness)
< 25 mm/
< 2.5 cm
25 - 50 mm/
2.5 - 5 cm
51 - 100 mm/
5.1 - 10 cm
> 100 mm/
> 10 cm
Necrosis or exfoliative 
dermatitis
Injection site 
swelling/induration 
(hardness)
< 25 mm/
< 2.5 cm
25 - 50 mm/
2.5 - 5 cm
51 - 100 mm/
5.1 - 10 cm
> 100 mm/
> 10 cm
Necrosis
Axillary (underarm) 
swelling or tenderness 
ipsilateral to the side of 
injection
None
No interference with 
activity
Repeated use of over-the- 
counter (non-narcotic) 
pain reliever > 24 hours or 
some interference with 
activity
Any use of prescription 
(narcotic) pain reliever 
or prevents daily activity
Requires emergency room 
visit or hospitalization
Headache
None
No interference with 
activity
Repeated use of over-the- 
counter pain reliever > 24 
hours or some interference 
with activity
Significant; any use of 
prescription pain reliever 
or prevents daily activity
Requires emergency room 
visit or hospitalization
Fatigue
None
No interference with 
activity
Some interference with 
activity
Significant; prevents 
daily activity
Requires emergency room 
visit or hospitalization
Myalgia (muscle aches all 
over body)
None
No interference with 
activity
Some interference with 
activity
Significant; prevents 
daily activity
Requires emergency room 
visit or hospitalization
Arthralgia (joint aches in 
several joints)
None
No interference with 
activity
Some interference with 
activity
Significant; prevents 
daily activity
Requires emergency room 
visit or hospitalization

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Reaction
Grade 0 
Grade 1 
Grade 2 
Grade 3 
Grade 4*
Nausea/vomiting
None
No interference with 
activity or 1-2 episodes/ 
24 hours
Some interference with 
activity or
> 2 episodes/24 hours
Prevents daily activity, 
requires outpatient 
intravenous hydration
Requires emergency room 
visit or hospitalization for 
hypotensive shock
Chills
None
No interference with 
activity
Some interference with 
activity not requiring 
medical intervention
Prevents daily activity 
and requires medical 
intervention
Requires emergency room 
visit or hospitalization
Fever (oral)
< 38.0°C
< 100.4°F
38.0 – 38.4°C
100.4 – 101.1°F
38.5 – 38.9°C
101.2 – 102.0°F
39.0 – 40.0°C
102.1 – 104.0°F
> 40.0°C
> 104.0°F
Rash*
No rash
Localized rash, without 
associated symptoms
Maculopapular rash, 
covering < 50% body 
surface area
Generalized urticarial, 
covering > 50% body 
surface area
Generalized exfoliative, 
ulcerative or bullous 
dermatitis, eg, Stevens- 
Johnson syndrome or 
erythema multiforme
* Grading for rash and Grade 4 events per Investigator assessment (with exception of fever).
Sources: Guidance for Industry – Toxicity Grading Scale for Heathy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials; tables for clinical 
abnormalities (DHHS 2007). Division of AIDS Grading the Severity of Adult and Pediatric Adverse Events (DHHS 2014). 

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In case of any rash episode observed within 7 days after study injection, the participant will be 
instructed to contact the study site within 24 hours. During participant evaluation, the investigator 
should categorize the rash as one of the following: 
•
Rash no longer present and history not consistent with urticaria.
•
Rash no longer present but history is consistent with urticaria.
•
Rash present but clinical findings are not consistent with urticaria. Alternative diagnosis 
should be specified as an AE. 
•
Rash present and clinical findings consistent with urticaria.
Any solicited AR that meets any of the following criteria must be entered into the participant’s 
source document and must also be recorded as an AE in the participant’s Adverse Event eCRF:
•
Solicited local or systemic AR that results in a visit to an HCP (MAAE)
•
Solicited local or systemic AR leading to the participant withdrawing from the study or the 
participant being withdrawn from the study by the investigator (AE leading to withdrawal)
•
Solicited local or systemic AR lasting beyond 7 days post-injection
•
Solicited local or systemic AR that leads to participant withdrawal from vaccine 
administration
•
Solicited local or systemic AR that otherwise meets the definition of an SAE
•
Solicited AR with a toxicity score of Grade 3 or greater
An unsolicited AE is any AE reported by the participant that is either not specified as a solicited 
AR in the protocol or is specified as a solicited AR in the protocol, but starts outside the
protocol-defined post-injection period for reporting solicited ARs (ie, for the 7 days after each 
injection).
3.4.8.5
Pregnancy
Pregnancies occurring in participants after enrollment must be reported to Sponsor or designee 
within 72 hours of the site learning of its occurrence. If the participant agrees to submit this 
information, the pregnancy must be followed to determine the outcome, including spontaneous or 
voluntary termination, details of the birth, and the presence or absence of any birth defects, 
congenital abnormalities, or maternal and/or newborn complications. This follow-up should occur 
even if intended duration of the safety follow-up for the study has ended. Pregnancy report forms 
will be distributed to the study site to be used for this purpose. The investigator must immediately

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(within 24 hours of awareness) report to the Sponsor any pregnancy resulting in an abnormal 
outcome according to the procedures described for SAEs (Section 3.4.8.8).
3.4.8.6
Definition and Reporting of Adverse Events Consistent with Anaphylaxis
All suspected cases of anaphylaxis should be recorded as MAAEs and reported as an SAE, based 
on criteria for medically important event, unless the event meets other serious criteria. As an SAE 
the event should be reported to the Sponsor or designee immediately and in all circumstances 
within 24 hours as per Section 3.4.8.8 Reporting AEs. The investigator will submit any updated 
anaphylaxis case data to the Sponsor within 24 hours of it being available. For reporting purposes, 
a participant who displays signs/symptoms consistent with anaphylaxis as shown below should be 
reported as a potential case of anaphylaxis. This is provided as general guidance for investigators 
and is based on the Brighton Collaboration case definition (Ruggeberg et al 2007).
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:
•
sudden onset AND
•
rapid progression of signs and symptoms AND
•
involving two or more organ systems, as follows:
Skin/mucosal: urticaria (hives), generalized erythema, angioedema, generalized pruritus with skin 
rash, generalized prickle sensation, red and itchy eyes 
Cardiovascular: measured hypotension, clinical diagnosis of uncompensated shock, loss of 
consciousness or decreased level of consciousness, evidence of reduced peripheral circulation 
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 
Gastrointestinal: diarrhea, abdominal pain, nausea, vomiting

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3.4.8.7
Eliciting and Documenting Adverse Events
The investigator is responsible for ensuring that all AEs and SAEs are recorded in the eCRF and 
reported to the Sponsor. Unsolicited AEs will be captured from Day 1 through 28 days after each 
dose up to Day 57 visit in Part A (Table 9), up to OL-Day 57 visit in Part B (Table 11 and Table
12), and up to 28 days after the last injection in Part C (Table 12). Both MAAEs and SAEs will be 
captured from blinded (Part A) and open-label (Part B) Day 1 throughout entire study duration 
(Day 394 for Part A, or 6 months post-last vaccination for Part B and C for all participants), as 
specified in the respective SOEs (Table 9, Table 11, and Table 12). Any AEs occurring before 
receipt of the vaccine will be analyzed separately from TEAEs.
At every study site visit or telephone contact, participants will be asked a standard question to 
elicit any medically-related changes in their well-being according to the scripts provided. 
Participants will also be asked if they have been hospitalized, had any accidents, used any new 
medications, changed concomitant medication regimens (both prescription and over-the-counter 
medications), or had any non-study vaccinations. 
In addition to participant observations, data from clinical laboratory test results, physical 
examination findings, or other documents relevant to participant safety classified as an AE will be 
documented on the AE page of the eCRF. 
3.4.8.8
Reporting Adverse Events
The investigator is responsible for reporting all AEs that are observed or reported during the study, 
regardless of their relationship to vaccine or their clinical significance. If there is any doubt as to 
whether a clinical observation is an AE, the event should be reported. 
All unsolicited AEs reported or observed during the study will be recorded on the AE page of the 
eCRF. Information to be collected includes cohort, type of event, time of onset, investigator- 
specified assessment of severity and relationship to vaccine, time of resolution of the event, 
seriousness, as well as any required treatment or evaluations, and outcome. The unsolicited AEs 
resulting from concurrent illnesses, reactions to concurrent illnesses, reactions to concurrent 
medications, or progression of disease states must also be reported. All AEs will be followed until 
they are resolved or stable or judged by the investigator to be not clinically significant. The 
Medical Dictionary for Regulatory Activities (MedDRA) will be used to code all unsolicited AEs.
Any medical condition that is present at the time that the participant is screened but does not 
deteriorate should not be reported as an unsolicited AE. However, if it deteriorates at any time 
during the study, it should be recorded as an unsolicited AE.

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Any AE considered serious by the investigator or that meets SAE criteria (Section 3.4.8.3) must 
be reported to the Sponsor immediately (within 24 hours of becoming aware of the SAE). The 
investigator will assess whether there is a reasonable possibility that the vaccine caused the SAE. 
The Sponsor will be responsible for notifying the relevant regulatory authorities of any SAE as 
outlined in the 21 US CFR Parts 312 and 320. The investigator is responsible for notifying the 
institutional review board (IRB) directly.
If the eCRF is unavailable at the time of the SAE, the following contact information is to be used 
for SAE reporting:
•
SAE Mailbox: 
•
SAE Hotline (USA and Canada):
•
SAE Fax line (USA and Canada):
3.4.8.9
Assessment of Severity
An event is defined as “serious” when it meets at least one of the predefined outcomes as described 
in the definition of an SAE (Section 3.4.8.3), NOT when it is rated as severe.
The severity (or intensity) of an AR or AE refers to the extent to which it affects the participant’s 
daily activities and will be classified as mild (Grade 1), moderate (Grade 2), severe (Grade 3), or 
Grade 4 using the following criteria: 
•
Mild (Grade 1): These events do not interfere with the participant’s daily activities.
•
Moderate (Grade 2): These events cause some interference with the participant’s daily 
activities but do not require medical intervention.
•
Severe (Grade 3): These events prevent the participant’s daily activity and require medical 
intervention.
•
Grade 4 (solicited ARs): These events require an emergency room visit or hospitalization.
Changes in the severity of an AE should be documented to allow an assessment of the duration of 
the event at each level of intensity to be performed. An AE characterized as intermittent requires 
documentation of onset and duration of each episode. 
The Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive 
Vaccine Clinical Trials (DHHS 2007) will be used to categorize local and systemic solicited ARs 
(Table 6), clinical laboratory test results, and vital sign measurements observed during this study. 
Specific criteria for clinical and laboratory abnormalities are presented in Appendix 2 (Table 13
and Table 14, respectively) and will be graded if outside of the reference range for the laboratory 
utilized.

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3.4.8.10 Assessment of Causality
The investigator’s assessment of an AE’s relationship to vaccine is part of the documentation 
process but is not a factor in determining what is or is not reported in the study. 
The investigator will assess causality (ie, whether there is a reasonable possibility that the vaccine 
caused the event) for all AEs and SAEs. The relationship will be characterized using the following 
classification:
•
Not related: There is not a reasonable possibility of a relationship to the investigational 
product. Participant did not receive the investigational product OR temporal sequence of 
the AE onset relative to administration of the investigational product is not reasonable OR 
the AE is more likely explained by another cause than the investigational product. 
•
Related: There is a reasonable possibility of a relationship to the investigational product. 
There is evidence of exposure to the investigational product. The temporal sequence of the 
AE onset relative to the administration of the investigational product is reasonable. The AE 
is more likely explained by the investigational product than by another cause. 
3.4.8.11 Follow-up of Adverse Events
All AEs, SAEs, and MAAEs must be reported in detail on the appropriate page of the eCRF and 
followed until the event is resolved or stable or judged by the investigator to be not clinically 
significant.
3.4.9
Vital Sign Measurements
Vital sign measurements will include systolic and diastolic blood pressure, heart rate, respiratory 
rate, and body temperature (preferred route is oral). The participant will be seated for at least 
5 minutes before all measurements are taken. Vital signs will be measured at the time points 
indicated in the Schedule of Events (Table 9, Table 11, and Table 12). In all parts, blinded and open 
label, on Day 1 and Day 29 (as applicable), vital sign measurements will be collected once before 
vaccine administration and at least 30 minutes (Part A) and 30 minutes (Parts B and C) after 
vaccine administration (before participants are discharged from the study site). 
Febrile participants at Day 1 and Day 29 (Parts A, B, and C) visits (fever is defined as a body 
temperature ≥38.0°C/100.4°F) may be rescheduled within the relevant window periods. Afebrile 
participants with minor illnesses may be injected at the discretion of the investigator.
When procedures overlap and are scheduled to occur at the same time point, the order of 
procedures should be vital sign measurements and then the blood collection. 

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If any of the vital sign measurements meet the toxicity grading criteria for clinical abnormalities 
(Table 13) of Grade 3 or greater, the abnormal value and grade will be documented on the AE page 
of the eCRF (unless there is another known cause of the abnormality that would result in an AE 
classification). The investigator will continue to monitor the participant with additional 
assessments until the vital sign value has reached the reference range, returns to the vital sign value 
at baseline, is considered stable, or until the investigator determines that follow-up is no longer 
medically necessary.
3.4.10 Physical Examinations
A symptom-directed physical examination, including height and weight, will be performed at 
scheduled time points as indicated in the Schedule of Events (Table 9, Table 11, and Table 12). 
The physical examination may include assessment of skin, head, ears, eyes, nose, throat, neck, 
thyroid, lungs, heart, cardiovascular, abdomen, lymph nodes, and musculoskeletal 
system/extremities. Any clinically significant finding identified during a study visit should be 
reported as a MAAE.
Symptom-directed physical examinations may be performed at other timepoints at the discretion 
of the investigator. On each injection day before injection and again 7 days after injection, the arm 
receiving the injection should be examined and the associated lymph nodes should be evaluated. 
Body mass index will be calculated at the Screening Visit (Day 0) only.

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4
STATISTICALANALYSIS PLAN
This section summarizes the planned statistical analysis strategy and procedures for the study. The 
details of statistical analysis will be provided in the statistical analysis plan (SAP), which will be 
finalized before the clinical database lock for the study and treatment unblinding. If, after the study 
has begun, but prior to any unblinding, changes are made to primary and/or key secondary 
objectives/hypotheses, or the statistical methods related to those hypotheses, then the protocol will 
be amended (consistent with ICH Guideline E9). Changes to other secondary or exploratory 
analyses made after the protocol has been finalized, along with an explanation as to when and why 
they occurred, will be listed in the SAP or CSR for the study. Ad hoc exploratory analyses, if any, 
will be clearly identified in the CSR.
4.1
Blinding and Responsibility for Analyses
Blinding during the Part A of the study will be managed as described in Section 3.3.5. The Sponsor 
Biostatistics department or designee will generate the randomized allocation schedule(s) for study 
treatment assignment. Randomization will be implemented via an IRT.
Details regarding unblinded SMC review are described in Section 6.1. 
A limited number of Sponsor and CRO personnel will be unblinded to perform the primary analysis 
and prepare a final CSR after participants have completed Day 57 visit study procedures in Part A 
(Section 3.3.5). This primary analysis may be performed when all participants in Cohort 1 and the 
Cohort 2 sentinel group have completed Day 57 study procedures and/or when all participants in 
Cohort 1 and Cohort 2 have completed Day 57 study procedures. The study site staff, investigators, 
study monitors, and participants will remain blinded until the initiation of Part B.
Planned study analyses and data presentation for unblinded SMC review are described in
Section 4.7 and Section 6.1, respectively. At each analysis, pre-identified Sponsor members will 
be unblinded to review treatment level results as defined in the study Data Blinding Plan. 
Unblinded data presentation or analysis for SMC review will be handled by the CRO unblinded 
team of statisticians and programmers, who are not involved in study design. A strict firewall 
between the CRO blinded and unblinded teams will be maintained during study conduct. Sponsor 
personnel who have access to review unblinded results will be documented. Sponsor and CRO 
personnel involved in the ongoing review and oversight of safety and immunogenicity will remain 
blinded until the initiation of Part B, as will study investigators and personnel at the study sites. 
The results of the primary analysis will not be shared with the investigators before completion of 
Part A of the study. 
Part B and Part C will be open label.

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4.2
Hypothesis Testing
There is no hypothesis testing in this study.
4.3
Analysis Endpoints
4.3.1
Part A, Blinded
4.3.1.1
Primary Endpoints
4.3.1.1.1 Primary Safety Endpoints
The primary safety objective will be evaluated by the following safety endpoints:
•
Solicited local and systemic ARs through 7 days after each injection.
•
Unsolicited AEs through 28 days after each injection.
•
MAAEs through the entire study period.
•
SAEs throughout the entire study period.
•
Safety laboratory abnormalities at Day 29 and Day 57 (Cohort 2 only).
•
Vital sign measurements and physical examination findings.
4.3.1.1.2 Primary Immunogenicity Endpoint
•
Level of SARS-CoV-2-specific bAb measured by ELISA on Day 1, Day 29 (Month 1), 
Day 43, Day 57 (Month 2), Day 209 (Month 7), and Day 394 (Month 13), as 
applicable.
4.3.1.2
Secondary Endpoints
The secondary objective will be evaluated by the following endpoints:
•
Titer of SARS-CoV-2-specific nAb on Day 1, Day 29 (Month 1), Day 43, 
Day 57 (Month 2), Day 209 (Month 7), and Day 394 (Month 13), as applicable. 
•
Seroconversion on Day 29 (Month 1), Day 43, Day 57 (Month 2), Day 209 (Month 7), 
and Day 394 (Month 13), as applicable. 

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4.3.1.3
Exploratory Endpoints
The exploratory endpoints are the following:
4.3.2
Part B, Open Label
4.3.2.1
Primary Endpoints (Part B, Open Label)
4.3.2.1.1 Primary Safety Endpoints
The primary safety objective will be evaluated by the following safety endpoints:
•
Solicited local and systemic ARs through 7 days after each injection.
•
Unsolicited AEs through 28 days after each injection.
•
MAAEs through the entire study period.
•
SAEs throughout the entire study period.
•
Vital sign measurements and physical examination findings.
4.3.2.1.2 Primary Immunogenicity Endpoint
•
For participants receiving 100 µg of mRNA-1273 as 2 doses 28 days apart: Level of 
SARS-CoV-2-specific bAb measured by ELISA on OL-Day 1, OL-Day 8, OL-Day 15, 
OL-Day 29 (OL-Month 1), OL-Day 57 (OL-Month 2), and OL-Day 209 (OL-Month 7). 
•
For participants receiving 50 µg of mRNA-1273 as a single booster: Level of 
SARS-CoV-2-specific bAb measured by ELISA on OL-Day 1, OL-Day 8, OL-Day 15, 
OL-Day 29 (OL-Month 1), OL-Day 57 (OL-Month 2), and OL-Day 181 (OL-Month 6). 

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4.3.2.2
Secondary Endpoints (Part B, Open Label)
The secondary objective will be evaluated by the following endpoints:
•
For participants receiving 100 µg of mRNA-1273 as 2 doses 28 days apart: Titer of 
SARS-CoV-2-specific nAb on OL- Day 1, OL-Day 8, OL- Day 15, OL- Day 29 (OL- 
Month 1), OL- Day 57 (OL-Month 2), and OL- Day 209 (OL-Month 7). 
•
For participants receiving 50 µg of mRNA-1273 as a single booster: Titer of 
SARS-CoV-2-specific nAb on OL-Day 1, OL-Day 8, OL-Day 15, OL-Day 29 (OL- 
Month 1), OL-Day 57 (OL-Month 2), and OL-Day 181 (OL-Month 6). 
•
For participants receiving 100 µg of mRNA-1273 as 2 doses 28 days apart: 
Seroconversion  on  OL-Day  8,  OL-Day  15,  OL-Day  29  (OL-Month 1), 
OL-Day 57 (OL-Month 2), and OL-Day 209 (OL-Month 7). 
•
For participants receiving 50 µg of mRNA-1273 as a single booster: Seroconversion 
on OL-Day 8, OL-Day 15, OL-Day 29 (OL-Month 1), OL-Day 57 (OL-Month 2), and 
OL-Day 181 (OL-Month 6), and the proportion of participants with a ≥2-, ≥3-, or 
≥4-fold rise in antibody titer from open-label baseline.
4.3.2.3
Exploratory Endpoints (Part B, Open Label)
The exploratory endpoints are the following:

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4.3.3
Part C, Open Label
4.3.3.1
Primary Endpoints (Part C, Open Label)
4.3.3.1.1 Primary Safety Endpoints
The primary safety objective will be evaluated by the following safety endpoints:
•
Solicited local and systemic ARs through 7 days after injection.
•
Unsolicited AEs through 28 days after injection.
•
MAAEs through the entire study period.
•
SAEs throughout the entire study period.
•
Vital sign measurements and physical examination findings.
4.3.3.1.2 Primary Immunogenicity Endpoints (Part C, Open Label)
The primary objective will be evaluated by the following endpoints:
•
For participants receiving 2 dose levels (20 and 50 µg) of mRNA-1273.351 or one dose 
level (50 µg total) of mRNA-1273/mRNA-1273.351 mixture as a single booster: titer 
of serum neutralizing antibody against SARS-CoV2 as measured by pseudovirus 
(and/or live virus) using the B.1.351 and D614G variant sequences of SARS-CoV-2 
protein (and/or variant strains) on OL-Day 1, OL-Day 8, OL-Day 15, and OL-Day 29 
(OL-Month 1), OL-Day 57 (OL-Month 2), and OL-Day 181 (OL-Month 6). 
•
For participants receiving 2 dose levels (20 and 50 µg) of mRNA-1273.351 or one dose 
level (50 µg total) of mRNA-1273/mRNA-1273.351 mixture as a single booster: 
seroconversion on OL-Day 8, OL-Day 15, and OL-Day 29 (OL-Month 1), OL-Day 57 
(OL Month 2), and OL-Day 181 (OL-Month 6) and the proportion of participants with 
a ≥2-, ≥3-, or ≥4-fold rise in antibody titer from the open-label baseline.
4.3.3.2
Secondary Immunogenicity Endpoint
•
For participants receiving 2 dose levels (20 and 50 µg) of mRNA-1273.351 or one dose 
level (50 µg total) of mRNA-1273/mRNA-1273.351 mixture as a single booster: level of 
SARS-CoV-2-specific serum binding antibody against the B.1.351 and D614G variant 
sequences of SARS-CoV-2 protein on OL-Day 1, OL-Day 8, OL-Day 15, OL-Day 29 
(OL-Month 1), OL-Day 57 (OL-Month 2), and OL-Day 181 (OL-Month 6). 

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4.3.3.3
Exploratory Endpoints (Part C, Open Label)
The exploratory endpoints are the following:
4.4
Analysis Populations
4.4.1
Randomized Set
The Randomized Set consists of all participants who are randomly assigned in the study, regardless 
of the participants’ treatment status in the study. This analysis set will be used for analyses of 
Part A.
4.4.2
Solicited Safety Set
The Solicited Safety Set consists of all participants who are randomly assigned and received any 
study injection, and contribute any solicited AR data; ie, have at least one post-baseline solicited 
safety (eDiary) assessment. The Solicited Safety Set will be used for the analyses of solicited ARs 
and participants will be included in the treatment group corresponding to the study injection they 
actually received. This analysis set will be used for analyses in Part A, Part B and Part C. 
4.4.3
Safety Set
The Safety Set consists of all randomly assigned participants who received any study injection. 
The Safety Set will be used for analysis of safety except for the solicited ARs. Participants will be 
included in the treatment group corresponding to the study injection they actually received for the 
analysis of safety data using the Safety Set. This analysis set will be used for analyses in Part A, 
Part B, and Part C.

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4.4.4
Full Analysis Set
The Full Analysis Set (FAS) consists of all randomly assigned participants who a) receive any 
study injection, b) have baseline (Day 1 or OL-Day 1, as appropriate) data available for those 
analyses that require baseline data, and c) have at least one post-injection assessment for the 
analysis endpoint. Participants will be included in the treatment group to which they were 
randomly assigned. This analysis set will be used for analyses in Part A, Part B, and Part C. 
4.4.5
Per-Protocol Set
The Per-Protocol (PP) Set consists of all FAS participants who meet all of the following criteria:
•
Complied with the injection schedule
•
Complied with the timings of immunogenicity blood sampling to have post-injection 
results available for at least one assay component corresponding to the immunogenicity 
analysis objective 
•
Did not have SARS-CoV-2 infection
•
Have had no major protocol deviations that impact immune response during the period 
corresponding to the immunogenicity analysis objective 
The PP Set will serve as the primary population for the analysis of immunogenicity data in Part A, 
Part B, and Part C of this study. Participants will be included in the treatment group to which they 
were randomly assigned. 
4.5
Sample Size Determination
There is no hypothesis testing in this study. The number of proposed participants is considered 
sufficient to provide a descriptive summary of the safety and immunogenicity of different dose 
levels of mRNA-1273. 
In the blinded Part A, approximately 600 participants will be randomly assigned in a 1:1:1 ratio to 
mRNA-1273 50 µg, mRNA-1273 100 µg, or placebo. A total of 400 participants will receive 
mRNA-1273, 200 participants in each dose level, or 100 participants in each age cohort and dose 
level. Table 7 presents the 95% confidence interval (CI) for 1 participant with an AE and the lowest 
AE rate detectable with at least 95% probability for each selected sample size. The 2-sided 95% CI 
was calculated using the Clopper-Pearson method for one proportion in SAS 9.4 software. The
2-sided 95% CI is estimated (0.01%, 1.4%) at sample size of 400 with 1 participant reporting an 
AE. Furthermore, a sample size of 400 has at least a 95% probability to observe at least

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1 participant with an AE at a true 0.75% AE rate. Participants who received any injection in Part 
A will have the opportunity to enter Part B provided that they meet the eligibility criteria.
In the open-label Part C, approximately 60 participants from Moderna’s mRNA-1273-P301 COVE 
study will be enrolled and will be assigned to receive a single IM injection of mRNA-1273.351 
(20 µg or 50 µg) or mRNA-1273/mRNA-1273.351 mixture (50 µg total). The enrollment and 
vaccination in each study arm will be sequential. The first 20 participants will be enrolled and 
dosed on OL-D1 with the mRNA-1273.351 50 µg dose. Upon completion of the first 50 µg dose 
arm,
20
participants
will
be
enrolled
in
the
second
arm
and
will
receive
the 
mRNA-1273/mRNA-1273.351 mixture (50 µg total dose). Following completion of the second 
arm, 20 participants will be enrolled and dosed with the mRNA-1273.351 20 µg dose. 
Table 7:  95% Confidence Interval for One Participant with AE and the Lowest 
Detectable Incidence Rate at 95% Probability in Selected Sample Size
Sample Size 
Receiving 
mRNA-1273
Rate and 95% CI (%) at One Participant with AE
Lowest Detectible Rate 
(%) with ≥95% Probability
AE Rate
Lower CI
Upper CI
100
1.00
0.03
5.45
2.95
200
0.50
0.01
2.75
1.49
400
0.25
0.01
1.38
0.75
Abbreviations: AE = adverse event; CI = confidence interval.
4.6
Statistical Methods
Data from Part A, Part B, and Part C will be presented separately as applicable.
For Part A and Part B of the study, there are 2 age cohorts: Cohort 1 with 300 participants (≥ 18 to
< 55 years old) and Cohort 2 with 300 participants (≥ 55 years old). All analyses will be performed 
by treatment group overall (for the 2 cohorts combined) and for the 2 cohorts separately, unless 
specified otherwise.
4.6.1
Summary of Baseline Characteristics and Demographics
Demographic variables (eg, age, height, weight, and BMI) and baseline characteristics will be 
summarized by treatment group for each age cohort (when appropriate) by descriptive statistics 
(mean, standard deviation for continuous variables, and number and percentage for categorical 
variables).

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4.6.2
Safety Analyses
Safety and reactogenicity will be assessed by clinical review of all relevant parameters including 
solicited ARs (local and systemic events), unsolicited AEs, SAEs, MAAEs, AEs leading to 
discontinuation, safety laboratory test results (Part A only), vital signs, and physical examination 
findings.
Solicited ARs and unsolicited AEs will be coded by system organ class and preferred term 
according to the MedDRA for adverse reaction terminology. The Toxicity Grading Scale for 
Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials (DHHS
2007) is used in this study with modification for rash, solicited ARs, and vital signs (Table 6).
Rash will be graded as:
•
Grade 0 = no rash
•
Grade 1 = localized without associated symptoms
•
Grade 2 = maculopapular rash covering < 50% body surface area
•
Grade 3 = urticarial rash covering > 50% body surface area
•
Grade 4 = generalized exfoliative, ulcerative, or bullous dermatitis
All safety analyses will be based on the Safety Set, except summaries of solicited ARs which will 
be based on the Solicited Safety Set. All safety analyses will be provided by age cohort (for Part 
A and Part B) unless otherwise specified.
The number and percentage of participants with any solicited local AR, with any solicited systemic 
AR, and with any solicited AR during the 7-day follow-up period after each injection will be 
summarized. A 2-sided 95% exact CI using the Clopper-Pearson method will be provided for the 
percentage of participants with any solicited AR. 
Number and percentage of participants with unsolicited AEs, SAEs, MAAEs, Grade 3 or higher 
AEs, and AEs leading to discontinuation from study vaccine or participation in the study will be 
summarized.
Number of events of solicited ARs, unsolicited AEs/SAEs, and MAAEs will be reported in 
summarization tables accordingly. 
For all other safety parameters, descriptive summary statistics will be provided. Table 8
summarizes the analysis strategy for safety parameters.

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Table 8:    Analysis Strategy for Safety Parameters
Safety Endpoint
Number and Percentage of 
Participants, Number of Events
95% CI
Any Solicited AR (overall and by local, systemic)
X
X
Any Unsolicited AE
X
Any SAE
X
Any Unsolicited MAAE
X
Any Unsolicited Treatment-Related AE
X
Any Treatment-Related SAE
X
Discontinuation due to AE
X
Any Grade 3 and above AE
X
Any Treatment-Related Grade 3 and above AE
X
Abbreviations: AE = adverse event; AR = adverse reaction; CI = confidence interval; MAAE = medically attended adverse event; 
SAE = serious adverse event.
Notes: 95% CI using the Clopper-Pearson method, X = results will be provided. Unsolicited AEs will be summarized by system 
organ class and preferred term coded by the Medical Dictionary for Regulatory Activities.
For treatment-emergent safety laboratory tests results in Part A and Part B of the study, the raw 
values and change from baseline values will be summarized by age cohort, treatment group, and 
visit at each timepoint.
The number and percentage of participants who have chemistry, hematology, coagulation, and 
vital signs results below or above the laboratory normal ranges will be tabulated by timepoint.
Data from Part C will be analyzed similarly. 
Further details will be described in the SAP.
4.6.3
Immunogenicity Analyses
The analyses of immunogenicity will be based on the PP Set. For each age cohort (for Part A 
and Part B), if the number of participants in the FAS and PP Set differ (defined as the difference 
divided by the total number of participants in the PP Set) by more than 10%, supportive 
analyses of immunogenicity may be conducted using the FAS. 
For the primary immunogenicity endpoint (secondary immunogenicity endpoint in Part C) 
(Section 4.3.1.1.2), geometric mean (GM) of specific bAb with corresponding 95% CI at each 
timepoint and geometric mean fold-rise (GMFR) of specific bAb with corresponding 95% CI 
at each post-baseline timepoint over pre-injection baseline will be provided by treatment group 
and age cohort (for Part A and Part B). Descriptive summary statistics including median, 
minimum, and maximum will also be provided. 

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For the secondary immunogenicity endpoint (primary immunogenicity endpoint in Part C) 
(Section 4.3.1.2), geometric mean titer (GMT) of specific nAb with corresponding 95% CI at 
each timepoint and GMFR of specific nAb with corresponding 95% CI at each post-baseline 
timepoint over pre-injection baseline will be provided by treatment group and age cohort (for 
Part A and Part B). Descriptive summary statistics including median, minimum, and maximum 
will also be provided. For summarizations of GMT values, antibody values reported as below 
the LLOQ will be replaced by 0.5 × LLOQ. Values that are greater than the upper limit of 
quantification (ULOQ) will be converted to the ULOQ. 
The number and percentage of participants with fold-rise ≥2, fold-rise ≥3, and fold-rise ≥ 4 
of serum SARS-CoV-2-specific nAb titers and participants with seroconversion from baseline 
will be provided with 2-sided 95% CI using the Clopper-Pearson method at each post-baseline 
timepoint. Seroconversion at a participant level is defined as a change of nAb titer from below 
the LLOQ to equal to or above LLOQ, or a 4-times or higher titer ratio in participants with 
pre-existing nAb titers.
Data from Part C will be analyzed similarly for each strain included in each assay.
Details for immunogenicity analyses on data collected in the open-label phase will be provided 
in the SAP. 
4.6.4
Exploratory Analyses
Exploratory analyses may include the following:

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4.7
Study Analyses
4.7.1
Primary Study Analysis for Blinded Part A Only
A primary analysis of safety and immunogenicity data will be performed after participants have 
completed Day 57 study procedures. This primary analysis may be performed when all participants 
in Cohort 1 and the Cohort 2 sentinel group have completed Day 57 study procedures and/or when 
all participants in Cohort 1 and Cohort 2 have completed Day 57 study procedures. All data 
relevant to the primary study analysis through the Day 57 visit will be cleaned (ie, data that are as 
clean as possible) and locked. Results of this analysis will be presented in a final CSR, including 
individual listings.
4.7.2
Analysis at End of Blinded Part A Only
An analysis of safety and immunogenicity data will be performed after all participants have 
completed Part A of the study. All data collected in Part A of the study will be cleaned (ie, data that 
are as clean as possible) and locked and a report may be generated as needed.
4.7.3
Interim Study Analysis for Open-Label Part B Only
An interim analysis of the safety and immunogenicity data in Part B of the study may be performed 
after participants have completed the OL-Day 29 and/or the OL-Day 57 study procedures. This 
analysis may be performed when all participants have completed OL-Day 29 and/or OL-Day 57 
study procedures, or on a subset of participants who received a single booster dose at OL-Day 1 
when they have completed OL-Day 29 and/or OL-Day 57 study procedures. All data collected in 
Part B of the study will be cleaned (ie, data that are as clean as possible) and locked and a report 
may be generated as needed. Results of this analysis may be presented in a CSR. 
4.7.4
Interim Study Analysis for Open-Label Part C Only
An interim analysis of the safety and immunogenicity data in Part C of the study may be performed 
after participants have completed the OL-D8, OL-D15, OL-Day 29 and/or the OL-Day 57 study 
procedures. All data collected in Part C of the study will be cleaned (ie, data that are as clean as 
possible) and locked and a report may be generated as needed. Results of this analysis may be 
presented in a CSR.
4.7.5
Additional Study Analyses
Additional analyses may be performed to support regulatory request as appropriate.

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4.7.6
End of Study Analysis
The EOS analysis of all endpoints will be performed after all participants have completed
Month 13 (Blinded Part A), OL-M6 and OL-M7 (Open-Label Part B), or OL-Month 6 (Part C) 
study procedures and after the database is cleaned and locked. Results of this analysis will be 
presented in an EOS CSR, including individual listings. 
Additional information can be found in the SAP.
4.8
Data Quality Assurance
All aspects of the study will be monitored for compliance with applicable government regulations 
with respect to current ICH harmonized tripartite guideline E6(R2): GCP and current SOPs. The 
eCRFs will be utilized and accessed through iMedidata® via the internet. This EDC system is 
validated and compliant with US Title 21 of CFR Part 11. Each person involved with the study 
will have an individual identification code and password that allow for record traceability. There 
may be an internal quality review audit of the data and additional reviews by the clinical monitor.
Due to safety review requirements, study sites must follow the data entry and availability 
instructions provided by the Sponsor in the study readiness trainings. As a quality measure, 
timeliness of data entry and data query resolution will be followed closely. Other issues of data 
quality that may hinder safety review or pose a concern with patient safety will be brought to the 
attention of the Sponsor or CRO, with appropriate awareness to the SMC if needed. 

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5
INVESTIGATOR OBLIGATIONS
The following administrative items are meant to guide the investigator in the conduct of the study 
and may be pursuant to change based on industry and government SOPs, working practice
documents, or guidelines. Changes will be reported to the IRB but will not result in protocol 
amendments.
5.1
Confidentiality
All laboratory specimens, evaluation forms, reports, and other records will be identified in a 
manner designed to maintain participant confidentiality. All records will be kept in a secure storage 
area with limited access. Clinical information will not be released without the written permission 
of the participant, except as necessary for monitoring and auditing by the Sponsor, its designee, 
relevant regulatory authority, or the IRB. 
The investigator and all employees and coworkers involved with this study may not disclose or 
use for any purpose other than performance of the study, any data, record, or other unpublished, 
confidential information disclosed to those individuals for the purpose of the study. Prior written 
agreement from the Sponsor or its designee must be obtained for the disclosure of any said 
confidential information to other parties. 
5.2
Institutional Review
Federal regulations and the ICH E6(R2) guidelines require that approval be obtained from an IRB 
before participation of human participants in research studies. Before study onset, the protocol, 
informed consent, advertisements to be used for the recruitment of study participants, and any 
other written information regarding this study to be provided to the participant must be approved 
by the IRB. Documentation of all IRB approvals and of the IRB compliance with the ICH E6(R2) 
guidelines will be maintained by the site and will be available for review by the Sponsor or its 
designee.
All IRB approvals should be signed by the IRB chairman or designee and must identify the IRB 
name and address, the clinical protocol by title or protocol number or both, and the date approval 
or a favorable opinion was granted. 
5.3
Participant Consent
Written informed consent in compliance with US Title 21 CFR Part 50 shall be obtained from each 
participant before he or she enters the study or before any unusual or nonroutine procedure that 
involves risk to the participant is performed. If any institution-specific modifications to study- 

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related procedures are proposed or made by the site, the consent should be reviewed by the Sponsor 
or its designee or both before IRB submission. Once reviewed, the investigator will submit the 
ICF to the IRB for review and approval before the start of the study. If the ICF is revised during 
the course of the study, all active participating participants must sign the revised form. 
Before recruitment and enrollment, each prospective participant will be given a full explanation of 
the study, be allowed to read the approved ICF, and be given answers to any questions. Once the 
investigator is assured that the participant understands the implications of participating in the study, 
the participant will be asked to give his or her consent to participate in the study by signing the 
ICF. Separate counseling and consent may be provided for HIV testing as applicable per local laws 
or regulations. 
The ICF will also explain that excess serum from immunogenicity testing may be used for future 
research, which may be performed at the discretion of the Sponsor to further characterize the 
immune response to SARS-CoV-2, additional assay development, and the immune response across 
the coronaviruses. 
The investigator or designee will provide a copy of the ICF to the participant. The original form 
shall be maintained in the participant’s medical records at the site.
5.4
Study Reporting Requirements
By participating in this study, the investigator agrees to submit reports of SAEs to Sponsor 
according to the timeline and method outlined in this protocol. In addition, the investigator agrees 
to submit annual reports to his or her IRB as appropriate. 
5.5
Financial Disclosure and Obligations
The investigator is required to provide financial disclosure information to allow the Sponsor to 
submit the complete and accurate certification or disclosure statements required under 21 CFR 54. 
In addition, the investigator must provide to the Sponsor a commitment to promptly update this 
information if any relevant changes occur during the course of the investigation and for 1 year 
following the completion of the study. 
Neither the Sponsor, the CRO, nor the study site is financially responsible for further testing or 
treatment of any medical condition that may be detected during the screening process. In addition, 
in the absence of specific arrangements, neither the Sponsor, the CRO, nor the study site is 
financially responsible for further treatment of the disease under study. 

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5.6
Investigator Documentation
Prior to beginning the study, the investigator will be asked to comply with ICH E6(R2) 8.2 and 
Title 21 of the CFR by providing the following essential documents, including but not limited to:
•
IRB approval,
•
An original investigator-signed investigator agreement page of the protocol,
•
Form FDA 1572, fully executed, and all updates on a new fully executed Form FDA 1572,
•
Curriculum vitae for the principal investigator and each subinvestigator listed on Form 
FDA 1572. Current licensure must be noted on the curriculum vitae. The curriculum vitae 
will be signed and dated by the principal investigators and subinvestigators at study start-up, 
indicating that they are accurate and current,
•
Financial disclosure information to allow the Sponsor to submit complete and accurate 
certification or disclosure statements required under 21 CFR 54. In addition, the 
investigators must provide to the Sponsor a commitment to promptly update this 
information if any relevant changes occur during the course of the investigation and for 
1 year after the completion of the study, 
•
An IRB-approved ICF, samples of site advertisements for recruitment for this study, and 
any other written information about this study that is to be provided to the participant, and
•
Laboratory certifications and reference ranges for any local laboratories used by the site, 
in accordance with 42 CFR 493. 
5.7
Study Conduct
The investigator agrees that the study will be conducted according to the principles of ICH E6(R2). 
The investigator will conduct all aspects of this study in accordance with all national, state, and 
local laws or regulations. The study will be conducted in compliance with the protocol, current 
GCP guidelines – adopting the principles of the Declaration of Helsinki – and all applicable 
regulatory requirements. 

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5.8
Data Collection
5.8.1
Case Report Forms and Source Documents
As part of the responsibilities assumed by participating in the study, the investigator agrees to 
maintain adequate case histories for participants treated as part of the research under this protocol. 
The investigator agrees to maintain accurate eCRFs and source documentation as part of the case 
histories. These source documents may include laboratory reports and similar sources. 
Electronic case report forms are accessed through iMedidata® via the internet. This EDC system is 
validated and compliant with 21 CFR 11. Each person involved with the study will have an 
individual identification code and password that allows for record traceability. Thus, the system, 
and subsequently any investigative reviews, can identify coordinators, investigators, and 
individuals who have entered or modified records, as well as the time and date of any modifications. 
There may be internal quality review audit of the data and additional reviews by the clinical 
monitor.
Each eCRF is presented as an electronic copy, allowing data entry by site personnel, who can add 
and edit data, add new participants, identify and resolve discrepancies, and view records. This 
system provides immediate direct data transfer to the database, as well as immediate detection of 
discrepancies, enabling site coordinators to resolve and manage discrepancies in a timely manner.
5.9
Adherence to Protocol
The investigator agrees to conduct the study as outlined in this protocol in accordance with ICH 
E6(R2) and all applicable guidelines and regulations. 
5.10 Reporting Adverse Events
By participating in this study, the investigator agrees to submit reports of SAEs according to the 
timeline and method outlined in this protocol. In addition, the investigator agrees to submit annual 
reports to his or her IRB as appropriate. The investigator also agrees to provide the Sponsor with 
an adequate report, if applicable, shortly after completion of the investigator’s participation in the 
study.
5.11 Investigator’s Final Report
Upon completion of the study, the investigator, where applicable, should inform the institution; the 
investigator/institution should provide the IRB with a summary of the study’s outcome, and the 
Sponsor and regulatory authority(ies) with any reports required. 

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5.12 Records Retention
Essential documents should be retained until at least 2 years after the last approval of a marketing 
application in an ICH region and until there are no pending or contemplated marketing applications 
in an ICH region or at least 2 years have elapsed since the formal discontinuation of clinical 
development of the vaccine. These documents should be retained for a longer period, however, if 
required by the applicable regulatory requirements or by an agreement with the Sponsor. It is the 
Sponsor’s responsibility to inform the investigator/institution as to when these documents no 
longer need to be retained. 
5.13 Publications
After completion of the study, the data may be considered for reporting at a scientific meeting or 
for publication in a scientific journal. In these cases, the Sponsor will be responsible for these 
activities and will work with the investigators to determine how the manuscript is written and 
edited, the number and order of authors, the publication to which it will be submitted, and other 
related issues. The Sponsor has final approval authority over all such issues. 
Data are the property of the Sponsor and cannot be published without their prior authorization, but 
data and publication thereof will not be unduly withheld. 

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6
STUDY MANAGEMENT
6.1
Monitoring
Ongoing safety monitoring will be performed in a blinded manner by the CRO’s medical monitor, 
the Sponsor’s medical monitor, and the individual site investigators throughout the study. 
6.1.1
Safety Monitoring Committee
Safety oversight will be under the direction of an SMC composed of external independent 
consultants with relevant expertise. Members of the SMC will be independent from the study 
conduct and free of conflict of interest. The SMC will meet on a regular basis to assess safety 
throughout the study conduct. The SMC will operate under the rules of an approved charter that 
will be written and reviewed at the organizational meeting of the SMC. Details regarding the SMC 
composition, responsibilities, procedures, and frequency of data review will be defined in its 
charter.
The SMC will convene on an ad hoc basis if any of the pause rules, described in Section 3.3.2.1, 
are met. The SMC will review all available unblinded study data to adjudicate any potential study 
pauses and make recommendations on further study conduct, including requesting additional 
information, recommending stopping the study, recommending changes to study conduct and/or 
the protocol, or recommending additional operational considerations due to safety issues that arise 
during the study. 
6.1.2
Monitoring of the Study
The study monitor, as a representative of the Sponsor, is obligated to follow the study closely. In 
doing so, the monitor will visit the investigator and study facility at periodic intervals, in addition 
to maintaining necessary telephone and letter contact. The monitor will maintain current personal 
knowledge of the study through observation, review of study records and source documentation, 
and discussion of the conduct of the study with the investigator and staff. The monitor will be 
blinded to dose assignments. A separate unblinded study monitor will be responsible for vaccine 
accountability.
All aspects of the study will be carefully monitored by the Sponsor or its designee for compliance 
with applicable government regulation with respect to current ICH E6(R2) guidelines and SOPs. 

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6.1.3
Inspection of Records
The investigator and institution involved in the study will permit study-related monitoring, audits, 
IRB review, and regulatory inspections by providing direct access to all study records. In the event 
of an audit, the investigator agrees to allow the Sponsor, their representatives, the FDA, or other 
regulatory agency access to all study records. 
The investigator should promptly notify the Sponsor of any audits scheduled by any regulatory 
authorities and promptly forward copies of any audit reports received to the Sponsor. 
6.2
Management of Protocol Amendments and Deviations
6.2.1
Modification of the Protocol
Any changes in this research activity, except those necessary to remove an apparent, immediate 
hazard to the participant, must be reviewed and approved by the Sponsor or designee. 
Amendments to the protocol must be submitted in writing to the investigator’s IRB for 
approval before participants are enrolled into an amended protocol. 
6.2.2
Protocol Deviations
A protocol deviation is any change, divergence, or departure from the study design or 
procedures of a study protocol. A protocol deviation may be a reason to remove data from an 
analysis set at the time of analysis. Major protocol deviations are defined as exclusionary from 
the analysis according to the protocol objectives and endpoints. Protocol deviations will be 
documented by the study monitor throughout the course of monitoring visits. The investigator 
will be notified in writing by the monitor of such deviations. 
After a participant proceeds to the open-label Part B of the study at the Participant Decision 
Clinic Visit (Table 10), Part A schedule of events (Table 9) will no longer be followed and 
become obsolete.
6.3
Study Termination
Although the Sponsor has every intention of completing the study, they reserve the right to 
discontinue it at any time for clinical or administrative reasons.
The EOS is defined as the date on which the last participant completes the last visit (includes 
the EOS Visit and any additional long-term follow-up). Any additional long-term follow-up 
that is required to monitor the resolution of a finding or AE may be reported through an 
amendment to the CSR. 

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6.4
Clinical Study Reports
Whether the study is completed or prematurely terminated, the Sponsor will ensure that CSRs 
are prepared and provided to the regulatory agency(ies) as required by the applicable regulatory 
requirement(s). The Sponsor will also ensure that CSRs in marketing applications meet the 
standards of the ICH harmonized tripartite guideline E3: Structure and Content of Clinical 
Study Reports. 
Where required by applicable regulatory requirements, an investigator signatory will be 
identified for the approval of the CSRs. The investigator will be provided reasonable access to 
statistical tables, figures, and relevant reports and will have the opportunity to review complete 
study results. 
The final CSR will be prepared based on the primary analysis of safety and immunogenicity 
data, which is based on cleaned and locked data collected from participants from Day 0 through 
the Day 57 visit (Section 4.7.1). Reports after Part B and Part C interim analyses may be 
generated. All data collected up to OL-D29 and/or OL-D57 in each Part B and Part C, will be 
cleaned (i.e., data that are as clean as possible) and locked. Results of these analysis may be 
presented in a CSR.
The EOS CSR will be based on an analysis of all data collected from Day 0 through Day 394 
(Blinded Part A), OL-M6 or OL-M7 (Open-Label Part B), and OL-M6 (Open-Label Part C).
The Sponsor will provide the investigator(s) with the final approved EOS CSR. 

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7
APPENDICES
7.1
Appendix 1: Schedule of Events
The Schedules of Events are presented in Table 9 for Part A, and Table 11 and Table 12 for Part B, 
and Table 12 for Part C. Reasons and procedures for possible unscheduled visits are provided in 
Section 3.4 and Section 3.4.1. 
If a participant cannot attend a study site visit (scheduled or unscheduled) with the exception of 
Screening, Day 1, and Day 29 visits, a home visit is acceptable if performed by appropriately 
delegated study site staff or a home healthcare service provided by the Sponsor. If neither a 
participant visit to the study site nor a home visit to the participant is possible (with the exception 
of Screening, Day 1, and Day 29 visits), a safety telephone call should be performed that includes 
the assessments scheduled for the safety telephone calls.
After the Participant Decision Clinic Visit, all participants will proceed with Part B SOEs as 
described in (Table 10).

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Table 9:
Schedule of Events (Part A, Blinded Phase only)
Visit Number
0
1
2
3
4
5
6
7
8
9
Type of Visit
C
C
C
C
C
C
C
C
SFU
C
SFU
C
Month Timepoint
M0
M1
M2
eDiary
SC
M7
eDiary
SC
M13
Study Visit Day
D01
(Screening)
D1 (Baseline)
D82
D152
D293
D362, 3 
D432, 3 
D572, 3 
Every 4 weeks 
D71 – D1833, 4
Every 4 weeks
D85– D1973, 5
D2092, 3
Every 4 weeks
D223– D3633, 4
Every 4 weeks
D237– D3773, 5
D3942, 3
Window Allowance (Days)
-28
+3
±3
+7
+3
±3
-3/
+7
±2
±3
±14
±2
±3
±14
Days Since Most Recent Injection
-
0
7
14
28/0
7
14
28
-
-
180
-
-
365
ICF, demographics, concomitant medications, 
medical history
X
Confirm participant meets inclusion and exclusion 
criteria
X
X
Blood for safety laboratory tests6
X
X4 
X4 
Blood for viral serology (hepatitis B, hepatitis C, 
HIV [1 and 2])
X
Physical examination including vital signs7
X
X
X
X
X
X
X
X
X
X
Pregnancy testing8
X
X
X
Randomization
X
Study injection
(including 30-minute post-dosing observation 
period)
X
X
Blood for vaccine immunogenicity9
X
X
X
X
X
X
X
Nasopharyngeal swab sample for SARS-CoV-210
X
X
X
eDiary activation for recording solicited adverse 
reactions (7 days)11
X
X
Review of eDiary
X
X

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Visit Number
0
1
2
3
4
5
6
7
8
9
Type of Visit
C
C
C
C
C
C
C
C
SFU
C
SFU
C
Month Timepoint
M0
M1
M2
eDiary
SC
M7
eDiary
SC
M13
Study Visit Day
D01
(Screening)
D1 (Baseline)
D82
D152
D293
D362, 3 
D432, 3 
D572, 3 
Every 4 weeks 
D71 – D1833, 4
Every 4 weeks
D85– D1973, 5
D2092, 3
Every 4 weeks
D223– D3633, 4
Every 4 weeks
D237– D3773, 5
D3942, 3
Window Allowance (Days)
-28
+3
±3
+7
+3
±3
-3/
+7
±2
±3
±14
±2
±3
±14
Days Since Most Recent Injection
-
0
7
14
28/0
7
14
28
-
-
180
-
-
365
Follow-up safety calls12
X
X
Recording of unsolicited AEs
X
X
X
X
X
X
X
Recording of MAAEs and concomitant medications 
relevant to or for the treatment of the MAAE
X
X
X
X
X
X
X
X12
X
X
X12
X
X
Recording of SAEs and concomitant medications 
relevant to or for the treatment of the SAE
X
X
X
X
X
X
X
X12
X
X
X12
X
X
Recording of concomitant medications and non- 
study vaccinations13
X
X
X
X
X
X
X
Study completion
X
Abbreviations: AE = adverse event; ALT = alanine aminotransferase; AST = aspartate aminotransferase; BUN = blood urea nitrogen; C = clinic visit; 
CBC = complete blood count; D = day; HIV = human immunodeficiency virus; ICF = informed consent form; M = month; MAAE = medically attended AE; 
SC = safety (telephone) call; SFU = Safety Follow Up; PCR = polymerase chain reaction; PT = prothrombin time; PTT = partial thromboplastin time; 
SAE = serious adverse event.
Note: In accordance with “FDA Guidance on Conduct of Clinical Trials of Medical Products during COVID-19 Public Health Emergency” (DHHS 2020), 
investigators may convert study site visits to telemedicine visits with the approval of the Sponsor.
1.  The Day 0 visit may be performed over multiple visits if within the 28-day screening window.
2.  All scheduled study visits should be completed within the respective visit windows. If the participant is not able to come on site for a study site visit as a result 
of the COVID-19 pandemic (self-quarantine or disruption of study site activities following business continuity plans and/or local government mandates for 
“stay at home” or “shelter in place”), a safety call to the participant should be made in place of the study site visit. The safety call should encompass all 
scheduled visit assessments that can be completed remotely, such as assessment for adverse events and concomitant medications (eg, as defined in scheduled 
safety telephone calls). Home visits will be permitted for all non-dosing visits except for Screening if a participant cannot come to the study site as a result of

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the COVID-19 pandemic. Home visits must be permitted by the site IRB and the participant via informed consent and have prior approval from the Sponsor 
(or its designee).
3. If the visit for the second dose (Day 29) is disrupted and cannot be completed at Day 29 +7 days as a result of the COVID-19 pandemic (self-quarantine or 
disruption of clinical site activities following business continuity plans and/or local government mandates for “stay at home” or “shelter in place”), the window 
may be extended to Day 29 + 21 days. When the extended window is used, the remaining study visits should be rescheduled to follow the inter-visit interval 
from the actual date of the second dose.
4.  Safety follow-up via eDiary questionnaire will be performed every 4 weeks starting at Day 71 to Day 183 and again starting at Day 223 to Day 363. These 
study days are relative to Day 1 vaccine administration and are not affected by the timing of the second vaccine administration.
5.
Safety follow-up via a safety telephone call will be performed every 4 weeks starting at Day 85 to Day 197 and again starting at Day 237 to Day 377. There is 
potential overlap of the Day 197 safety telephone call and Visit 8 due to their respective visit windows. As such, the safety telephone call on Day 197 only 
needs to be performed if the participant is scheduled to complete Visit 8 after Day 200.
6.  Safety laboratory tests include the following: CBC with differential, AST, ALT, total and direct bilirubin, ALP, BUN/creatinine, PT/PTT. Safety laboratory 
tests are to be repeated at Day 29 and Day 57 only for Cohort 2 (≥ 55 years old).
7.  Physical examination: A full physical examination, including height and weight, will be performed at Day 1, Day 29, and Day 57. Symptom-directed physical 
examinations may be performed at other time points at the discretion of the investigator. On each injection day before injection and again 7 days after injection, 
the arm receiving the injection should be examined and the associated lymph nodes should be evaluated. Any clinically significant finding identified during a 
study visit should be reported as an MAAE. Vital signs are to be collected pre- and post-dosing on days of injection (Day 1 and Day 29). When applicable, 
vital sign measurements should be performed before blood collection. Participants who are febrile (body temperature ≥ 38.0°C/100.4°F) before injection on 
Day 1 or Day 29 must be rescheduled within the relevant window period to receive the injection. Afebrile participants with minor illnesses can be administered 
investigational product at the discretion of the investigator.
8.
Pregnancy test at Screening and Day 1 and before the second study injection will be a point-of-care urine test. At the discretion of the investigator a pregnancy 
test either via blood or point-of-care urine test can be performed. Follicle-stimulating hormone level may be measured to confirm menopausal status at the 
discretion of the investigator.
9.  Sample must be collected prior to dosing on days of injection (Day 1 and Day 29).
10.  The nasopharyngeal swab sample, collected prior to vaccination on days of injection (Day 1 and Day 29), will be used to ascertain the presence of SARS-CoV-2 
via PCR.
11. Diary entries will be recorded by the participant starting approximately 1 hour after injection while at the study site with instruction provided by study staff. 
Study participants will continue to record in the eDiary each day after they leave the study site, preferably in the evening and at the same time each day, on 
the day of injection and for 6 days following injection. Any solicited AR that is ongoing beyond Day 7 will be reported in the eDiary until resolution. 
Adverse reactions recorded in eDiaries beyond Day 7 should be reviewed either during the next telephone call or at the next study site visit.
12. Trained site personnel will call all participants to collect information relating to any AEs, MAAEs, SAEs, AEs leading to study withdrawal, information on 
concomitant medications associated with those events, and any non-study vaccinations. In addition, study personnel will collect information on known 
participant exposure to someone with known COVID-19 or SARS-CoV-2 infection and on participant experience of COVID-19 symptoms. Sites will collect 
this information for diary days only if diary responses indicate the need for follow-up via telephone.
13.
All concomitant medications and non-study vaccinations will be recorded through 28 days after each injection; all concomitant medications relevant to or for 
the treatment of an SAE or MAAE will be recorded from Day 1 through the final visit (Day 394).

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Table 10:
Part B: Participant Decision Clinic Visit
All Participants
Return to clinic for Participant Decision Clinic Visit
X
Sign revised Informed Consent Form
X
Confirm participant’s choice to be unblinded or not to be unblinded
X
Confirm participant’s choice to receive open-label mRNA-1273
X
Nasopharyngeal swab
X
Blood for immunologic analysis
X
Counsel about social distancing practices1
X
Participant Status at end of Participant Decision Clinic Visit
Part B Schedule of Events
Consents to unblinding and to receiving either 2 doses of mRNA-1273, 28 days apart, 
or a single booster of mRNA-1273 (50 µg) at OL-D1 in Part B
Received placebo in Part A
Table 11
Received 1 dose of mRNA-1273 in Part A
Table 12
Received 2 doses of mRNA-1273 in Part A
Table 12
Consents to unblinding but declines to receiving either 2 doses of mRNA-1273, 28 days 
apart, or a single booster of mRNA-1273 (50 µg) in Part B
Received 1 or 2 doses of placebo in Part A
Table 12
Received 1 dose of mRNA-1273 in Part A2
Table 12
Received 2 doses of mRNA-1273 in Part A
Table 12
Declines unblinding and mRNA-1273 or booster in Part B
Table 12
1.
All participants are counselled about the importance of continuing other public health measures to limit the spread of disease including physical-social 
distancing, wearing a mask, and hand-washing.
2.
Applies to participants in Part A who received 50 µg or 100 µg mRNA-1273.

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Table 11:
Part B: Open-label Schedule of Events: ONLY for Participants Receiving 2 Doses of mRNA-1273 28 Days Apart
Visit Number
0
OL-1 
OL-2 
OL-3 
OL-4 
OL-5 
OL-6 
Type of Visit
C
C
C
C
C
SC
C
SFU
C
Month Timepoint
OL-M0
OL-M1
OL-M2
eDiary
SC
OL-M7
Study Visit Day
OL-D11
Participant 
Decision 
Visit
OL-D8
OL-D15
OL-D29
OL-D36
OL-D57
Every 4 
weeks 
OL-D71– 
OL-D1552
Every 4 
weeks 
OL-D85– 
OL-D169
OL- 
D209
Window Allowance (Days)
7
+3
±3
+7
+3
-3/+7
±2
±3
±14
Days Since Most Recent Injection
0
7
14
28
7
28
-- 
-- 
180
Informed consent form
X
Confirm participant meets inclusion 
and exclusion criteria
X
Physical examination including vital 
signs3
X
X
X
X
Pregnancy testing
X
X
Study injection (including 30- 
minute post-dosing observation 
period)
X
X
Blood for serology9 and 
immunogenicity4
X
X
X
X
X
X
Nasopharyngeal swab sample for 
SARS-CoV-25
X
X
X
eDiary activation for recording 
solicited adverse reactions (7 days)6
X
X
Review of eDiary
X
X
X
Follow-up safety calls7
X
X
Recording of unsolicited AEs
X
X
X
X
X
X
Recording of MAAEs and 
concomitant medications relevant to 
or for the treatment of the MAAE8
X
X
X
X
X
X
X
X
X

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Visit Number
0
OL-1 
OL-2 
OL-3 
OL-4 
OL-5 
OL-6 
Type of Visit
C
C
C
C
C
SC
C
SFU
C
Month Timepoint
OL-M0
OL-M1
OL-M2
eDiary
SC
OL-M7
Study Visit Day
OL-D11
Participant 
Decision 
Visit
OL-D8
OL-D15
OL-D29
OL-D36
OL-D57
Every 4 
weeks 
OL-D71– 
OL-D1552
Every 4 
weeks 
OL-D85– 
OL-D169
OL- 
D209
Window Allowance (Days)
7
+3
±3
+7
+3
-3/+7
±2
±3
±14
Days Since Most Recent Injection
0
7
14
28
7
28
-- 
-- 
180
Recording of SAEs and concomitant 
medications8 relevant to or for the 
treatment of the SAE
X
X
X
X
X
X
X8 
X
X
Recording of concomitant 
medications and non-study 
vaccinations8
X
X
X
X
X
X
Study Completion
X
Abbreviations: AE = adverse event; C = clinic visit; M = month; MAAE = medically attended AE; SC = safety (telephone) call; SFU = Safety Follow Up; 
SAE = serious adverse event.
Note: In accordance with “FDA Guidance on Conduct of Clinical Trials of Medical Products during COVID-19 Public Health Emergency” (DHHS 2020), 
investigators may convert study site visits to telemedicine visits with the approval of the Sponsor
1.
The Participant Decision Visit may be performed over multiple visits if within the given window.
2.
Safety follow-up via eDiary questionnaire will be performed every 4 weeks starting at OL-Day 71 to OL-Day 155. These study days are relative to OL- 
Day 1 vaccine administration and are not affected by the timing of the second vaccine administration.
3.
Physical examination: A symptom-directed physical examination, including height and weight, will be performed at OL-Day 1, OL-Day 29, and OL- 
Day 57. Symptom-directed physical examinations may be performed at other time points at the discretion of the investigator. Any clinically significant 
finding identified during a study visit should be reported as an MAAE. Vital signs are to be collected pre- and post-dosing on days of injection (Day 1 and 
Day 29). When applicable, vital sign measurements should be performed before blood collection. Participants who are febrile (body temperature
≥38.0°C/100.4°F) before injection on OL-Day 1 or OL-Day 29 must be rescheduled within the relevant window period to receive the injection. Afebrile 
participants with minor illnesses can be administered investigational product at the discretion of the investigator.
4.
Sample must be collected prior to dosing on days of injection.
5.
The nasopharyngeal swab sample, collected prior to vaccination on days of injection, will be used to ascertain the presence of SARS-CoV-2 via PCR.
6.
Diary entries will be recorded by the participant starting approximately 30 minutes after injection while at the study site with instruction provided by study 
staff. Study participants will continue to record in the eDiary each day after they leave the study site, preferably in the evening and at the same time each 
day, on the day of injection and for 6 days following injection. Any solicited AR that is ongoing beyond Day 7 will be reported in the eDiary until 
resolution. Adverse reactions recorded in eDiaries beyond Day 7 should be reviewed either during the next telephone call or at the next study site visit.

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7.
Trained site personnel will call all participants to collect information relating to any AEs, MAAEs, SAEs, AEs leading to study withdrawal, information 
on concomitant medications associated with those events, and any non-study vaccinations. In addition, study personnel will collect information on known 
participant exposure to someone with known COVID-19 or SARS-CoV-2 infection and on participant experience of COVID-19 symptoms. Sites will 
collect this information for diary days only if diary responses indicate the need for follow-up via telephone.
8.
All concomitant medications and non-study vaccinations will be recorded through 28 days injection; all concomitant medications relevant to or for the 
treatment of an SAE or MAAE will be recorded from Day 1 through the final visit (OL-Day 209).
9.
Blood sample for serology will be collected only at the Participant Decision Visit.

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Table 12:
Part B and Part C: Open-label Schedule of Events (Participants Receiving a Booster Dose)9
Visit Number
0
OL-1 
OL-2 
OL-3 
OL-4
OL-5 
OL-6 
Type of Visit
C
C
C
C
C
C
SC
SFU
C
Month Timepoint
OL-M0
OL-M1
OL-M2
eDiary
SC
OL-M6
Study Visit Day
OL-D1/
Participant 
Decision 
Visit1,2
OL-D8
OL-D15
OL-D29
OL-D57
OL-D6412
Every 4 
weeks 
OL-D71–
OL-D1553
Every 4 
weeks 
OL-D85– 
OL-D169
OL-D181
Window Allowance (Days)
+3
±3
+7
-3/+7
+3
±2
±3
±14
Days Since Most Recent Injection
0
7
14
28
56
7
-- 
-- 
180
Informed consent form
X
Confirm participant meets inclusion 
and exclusion criteria
X
Physical examination including 
vital signs4
X
X
X
X
Pregnancy testing
X
Study injection (including
30-minute post-dosing observation 
period)
X
X11
Blood for serology10 and 
immunogenicity5
X
X
X
X
X
X
Nasopharyngeal swab sample for 
SARS-CoV-26
X
X
X
eDiary activation for recording 
solicited adverse reactions (7 days)7
X
X12
Review of eDiary
X
X12
Follow-up safety calls8
X
Recording of unsolicited AEs
X
X
X
X
X12
X12

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Visit Number
0
OL-1 
OL-2 
OL-3 
OL-4
OL-5 
OL-6 
Type of Visit
C
C
C
C
C
C
SC
SFU
C
Month Timepoint
OL-M0
OL-M1
OL-M2
eDiary
SC
OL-M6
Study Visit Day
OL-D1/
Participant 
Decision 
Visit1,2
OL-D8
OL-D15
OL-D29
OL-D57
OL-D6412
Every 4 
weeks 
OL-D71–
OL-D1553
Every 4 
weeks 
OL-D85– 
OL-D169
OL-D181
Window Allowance (Days)
+3
±3
+7
-3/+7
+3
±2
±3
±14
Days Since Most Recent Injection
0
7
14
28
56
7
-- 
-- 
180
Recording of MAAEs and 
concomitant medications relevant to 
or for the treatment of the MAAE9
X
X
X
X
X
X
X
X
X
Recording of SAEs and
concomitant medications relevant to 
or for the treatment of the SAE9
X
X
X
X
X
X
X
X
X
Recording of concomitant 
medications and non-study 
vaccinations9
X
X
X
X
X12
X12
Study Completion
X
Abbreviations: AE = adverse event; C = clinic visit; ICF = informed consent form; M = month; MAAE = medically attended AE; SC = safety (telephone) call; 
SFU = Safety Follow Up; SAE = serious adverse event.
Note: In accordance with “FDA Guidance on Conduct of Clinical Trials of Medical Products during COVID-19 Public Health Emergency” (DHHS 2020), 
investigators may convert study site visits to telemedicine visits with the approval of the Sponsor.
1.
The Participant Decision Visit is only applicable to Part B and may be performed over multiple visits if within the given window.
2.
Participants who received 1 dose of mRNA-1273 (50 or 100ug) in Part A and agree to receive 1 dose of mRNA-1273 in Part B, will follow Table 11
Schedule of Events.
3.
Safety follow-up via eDiary questionnaire will be performed every 4 weeks starting at OL-Day 71 to OL-Day 155. These study days are relative to 
OL-Day 1 vaccine administration.
4.
Physical examination: A symptom-directed physical examination, including height and weight, will be performed at OL-Day 1, OL-Day 29, and 
OL-Day 57. Symptom-directed physical examinations may be performed at other time points at the discretion of the investigator. On the day of injection 
before injection and again 7 days after injection, the arm receiving the injection should be examined and the associated lymph nodes should be evaluated. 
Any clinically significant finding identified during a study visit should be reported as an MAAE. Vital signs are to be collected pre- and post-dosing on 
days of injection (OL-Day 1). When applicable, vital sign measurements should be performed before blood collection. Participants who are febrile (body

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temperature ≥ 38.0°C/100.4°F) before injection on OL-Day 1 must be rescheduled within the relevant window period to receive the injection. Afebrile 
participants with minor illnesses can be administered investigational product at the discretion of the investigator.
5.
Sample must be collected prior to dosing on days of injection.
6.
The nasopharyngeal swab sample, collected prior to vaccination on days of injection, will be used to ascertain the presence of SARS-CoV-2 via PCR.
7.
Diary entries will be recorded by the participant starting approximately 30 minutes after injection while at the study site with instruction provided by study 
staff. Study participants will continue to record in the eDiary each day after they leave the study site, preferably in the evening and at the same time each 
day, on the day of injection and for 6 days following injection. Any solicited AR that is ongoing beyond Day 7 will be reported in the eDiary until 
resolution. Adverse reactions recorded in eDiaries beyond Day 7 should be reviewed either during the next telephone call or at the next study site visit.
8.
Trained site personnel will call all participants to collect information relating to any AEs, MAAEs, SAEs, AEs leading to study withdrawal, information 
on concomitant medications associated with those events, and any non-study vaccinations. In addition, study personnel will collect information on known 
participant exposure to someone with known COVID-19 or SARS-CoV-2 infection and on participant experience of COVID-19 symptoms. Sites will 
collect this information for diary days only if diary responses indicate the need for follow-up via telephone.
9.
All concomitant medications and non-study vaccinations will be recorded through 28 days injection; all concomitant medications relevant to or for the 
treatment of an SAE or MAAE will be recorded from OL-Day 1 through the final visit (OL-Day 181).
NOTE: The following participants will complete the described assessments in this SOE at OL-Day 1, and will skip OL-D8, OL-D15, OL-Day 29, and OL-D57:
•
Participants who received 1 or 2 doses of mRNA-1273 in Part A and decline receiving booster mRNA-1273 in Part B.
•
Participants who decline unblinding
•
Participants who received placebo in Part A, but decline to receive 2 doses of mRNA-1273 in Part B 
Participants who decline receiving booster mRNA-1273, decline unblinding, or decline to receive 2 doses of mRNA-1273 in Part B will not receive study 
vaccination at OL-D1 (or OL-D29), will not perform a pregnancy test, or eDiary activation at OL-D1.
10. Blood sample for serology will be collected only at the Participant Decision Visit (OL-D1).
11. In Part C, an additional booster dose may be added approximately 56 days after the first boost at OL-D1. This additional booster dose will be triggered 
following review of immunogenicity data up to OL-D15 of the initial mRNA1273.351 (20 µg and 50 µg) and mRNA-1273/mRNA-1273.351 mixture 
injections.
12. If the additional booster dose is given at OL-D57, an eDiary for reactogenicity will be completed for 7 days post-injection. Additionally, unsolicited AEs 
will continue to be collected for 28 days post last injection.

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7.2
Appendix 2: Toxicity Grading Scale Tables
The toxicity grading scales for clinical and laboratory abnormalities are presented in Table 13 and 
Table 14, respectively. Note that for laboratory abnormalities, grading only occurs if the values are 
outside of the normal values established by the clinical laboratory. For study-specific laboratory 
normal ranges and associated toxicity grades, refer to the laboratory manual and provided toxicity 
grade communications. 
Table 13:
Tables for Clinical Abnormalities
Local Reaction to Injectable 
Product
Mild 
(Grade 1)
Moderate 
(Grade 2)
Severe 
(Grade 3)
Potentially 
Life-threatening
(Grade 4)
Pain
Does not 
interfere with 
activity
Repeated use of 
non-narcotic 
pain reliever
> 24 hours or 
interferes with 
activity
Any use of 
narcotic pain 
reliever or 
prevents daily 
activity
ER visit or 
hospitalization
Tenderness
Mild discomfort 
to touch
Discomfort with 
movement
Significant 
discomfort at 
rest
ER visit or 
hospitalization
Erythema/Redness * 
2.5 – 5 cm
5.1 – 10 cm
> 10 cm
Necrosis or 
exfoliative 
dermatitis
Induration/Swelling **
2.5 – 5 cm and 
does not
interfere with 
activity
5.1 – 10 cm or 
interferes with
activity
> 10 cm or 
prevents daily 
activity
Necrosis
Abbreviation: ER = emergency room.
* 
In addition to grading the measured local reaction at the greatest single diameter, the measurement should be recorded as 
a continuous variable.
**  Induration/swelling should be evaluated and graded using the functional scale as well as the actual measurement. 
Source: Guidance for industry – Toxicity Grading Scale for Heathy Adult and Adolescent Volunteers Enrolled in Preventive
Vaccine Clinical Trials; tables for clinical abnormalities (DHHS 2007).

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Vital Signs * 
Mild 
(Grade 1)
Moderate 
(Grade 2)
Severe 
(Grade 3)
Potentially 
Life-threatening
(Grade 4)
Tachycardia (beats per 
minute)
101 – 115
116 – 130
> 130
ER visit or 
hospitalization 
for arrhythmia
Bradycardia (beats per 
minute)**
50 – 54
45 – 49
< 45
ER visit or 
hospitalization 
for arrhythmia
Hypertension (systolic) 
(mm Hg)
141 – 150
151 – 155
> 155
ER visit or 
hospitalization 
for malignant 
hypertension
Hypertension (diastolic) 
(mm Hg)
91 – 95
96 – 100
> 100
ER visit or 
hospitalization 
for malignant 
hypertension
Hypotension (systolic) 
(mm Hg)
85 – 89
80 – 84
< 80
ER visit or 
hospitalization 
for hypotensive 
shock
Respiratory rate (breaths per 
minute)
17 – 20
21 – 25
> 25
Intubation
Abbreviation: ER = emergency room.
Note that fever is classified under systemic reactions for grading purposes.
*
Participant should be at rest for all vital sign measurements.
**
When resting heart rate is between 60 – 100 beats per minute. Use clinical judgment when characterizing bradycardia 
among some healthy participant populations, for example, conditioned athletes.
Source: Guidance for industry – Toxicity Grading Scale for Heathy Adult and Adolescent Volunteers Enrolled in Preventive 
Vaccine Clinical Trials; tables for clinical abnormalities (DHHS 2007). 

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Systemic (General)
Mild 
(Grade 1)
Moderate 
(Grade 2)
Severe 
(Grade 3)
Potentially 
Life-threatening
(Grade 4)
Fever (°C) * 
(°F) *
38.0 – 38.4
100.4 – 101.1
38.5 – 38.9
101.2 – 102.0
39.0 – 40.0
102.1 – 104.0
> 40.0
> 104.0
Nausea/vomiting
No interference 
with activity or 1 to 
2 episodes/24 hours
Some interference 
with activity or
> 2 episodes/
24 hours
Prevents daily 
activity, requires 
outpatient IV 
hydration
ER visit or 
hospitalization 
for hypotensive 
shock
Diarrhea
2 – 3 loose stools or
< 400 g/24 hours
4 – 5 stools or
400 – 800 g/
24 hours
6 or more watery 
stools or > 800 g/ 
24 hours or 
requires 
outpatient IV 
hydration
ER visit or 
hospitalization
Headache
No interference 
with activity
Repeated use of 
non-narcotic pain 
reliever > 24 hours 
or some interference
with activity
Significant; any 
use of narcotic 
pain reliever or 
prevents daily 
activity
ER visit or 
hospitalization
Fatigue/malaise 
(unusual tiredness)
No interference 
with activity
Some interference 
with activity
Significant; 
prevents daily 
activity
ER visit or 
hospitalization
Generalized myalgia 
(muscle ache or pain)
No interference 
with activity
Some interference 
with activity
Significant; 
prevents daily 
activity
ER visit or 
hospitalization
Generalized arthralgia 
(joint ache or pain)
No interference 
with activity
Some interference 
with activity not 
requiring medical 
intervention
Prevents daily 
activity and 
requires medical 
intervention
ER visit or 
hospitalization
Abbreviations: ER = emergency room; IV = intravenous.
*
Oral temperature; no recent hot or cold beverages or smoking.
Sources: Guidance for industry – Toxicity Grading Scale for Heathy Adult and Adolescent Volunteers Enrolled in Preventive 
Vaccine Clinical Trials; tables for clinical abnormalities (DHHS 2007). Division of AIDS Grading the Severity of Adult 
and Pediatric Adverse Events (DHHS 2014). 

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Table 14:
Tables for Laboratory Abnormalities
Serum Chemistry*
Mild 
(Grade 1)
Moderate 
(Grade 2)
Severe 
(Grade 3)
Potentially 
Life-threatening
(Grade 4)**
BUN (mg/dL)
23 – 26
27 – 31
> 31
Requires dialysis
Creatinine (mg/dL)
1.5 – 1.7
1.8 – 2.0
2.1 – 2.5
> 2.5 or requires dialysis
ALP; increase by factor
1.1 – 2.0 × 
ULN
2.1 – 3.0 × 
ULN
3.1 – 10 × 
ULN
> 10 × ULN
Liver function tests – ALT and AST; 
increase by factor
1.1 – 2.5 x 
ULN
2.6 – 5.0 × 
ULN
5.1 – 10 × 
ULN
> 10 × ULN
Bilirubin – when accompanied by 
any increase in liver function test; 
increase by factor
1.1 – 1.25 × 
ULN
1.26 – 1.5 × 
ULN
1.51 – 1.75
× ULN
> 1.75 × ULN
Bilirubin – when liver function test is 
normal; increase by factor
1.1 – 1.5 × 
ULN
1.6 – 2.0 × 
ULN
2.0 – 3.0 × 
ULN
> 3.0 × ULN
Abbreviations: ALP = alkaline phosphatase; ALT = alanine aminotransferase; AST = aspartate aminotransferase; 
BUN = blood urea nitrogen; ULN = upper limit of the normal range.
*
The laboratory values provided in the tables serve as guidelines and are dependent upon institutional normal parameters.
Institutional normal reference ranges should be provided to demonstrate that they are appropriate.
**
The clinical signs or symptoms associated with laboratory abnormalities might result in characterization of the laboratory 
abnormalities as potentially life-threatening (Grade 4). For example, a low sodium value that falls within a Grade 3 
parameter (125 – 129 mEq/L) should be recorded as a Grade 4 hyponatremia event if the participant had a new seizure 
associated with the low sodium value.
Source: Guidance for industry – Toxicity Grading Scale for Heathy Adult and Adolescent Volunteers Enrolled in Preventive 
Vaccine Clinical Trials; tables for laboratory abnormalities (DHHS 2007). 

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Hematology * 
Mild 
(Grade 1)
Moderate 
(Grade 2)
Severe 
(Grade 3)
Potentially Life- 
Threatening 
(Grade 4)
Hemoglobin (female) (g/dL)
11.0 – 12.0
9.5 – 10.9
8.0 – 9.4
< 8.0
Hemoglobin (female) change 
from baseline value (g/dL)
Any decrease – 
1.5
1.6 – 2.0
2.1 – 5.0
> 5.0
Hemoglobin (male) (g/dL)
12.5 – 13.5
10.5 – 12.4
8.5 – 10.4
< 8.5
Hemoglobin (male) change 
from baseline value (g/dL)
Any decrease – 
1.5
1.6 – 2.0
2.1 – 5.0
> 5.0
WBC increase (cell/mm3) 
10,800 – 15,000
15,001 – 20,000
20,001 – 25,000
> 25,000
WBC decrease (cell/mm3) 
2,500 – 3,500
1,500 – 2,499
1,000 – 1,499
< 1,000
Lymphocytes decrease 
(cell/mm3) 
750 – 1,000
500 – 749
250 – 499
< 250
Neutrophils decrease 
(cell/mm3) 
1,500 – 2,000
1,000 – 1,499
500 – 999
< 500
Eosinophils (cell/mm3) 
650 – 1,500
1,501 – 5,000
> 5,000
Hypereosinophilic
Platelets decreased (cell/mm3) 
125,000 – 
140,000
100,000 – 
124,000
25,000 – 99,000
< 25,000
PT; increase by factor
> 1.0 – 1.10 × 
ULN
1.11 – 1.20 × 
ULN
1.21 – 1.25 × 
ULN
> 1.25 × ULN
PTT; increase by factor
> 1.0 – 1.2 × 
ULN
1.21 – 1.4 × ULN
1.41 – 1.5 × 
ULN
> 1.5 × ULN
Abbreviations: PT = prothrombin time; PTT = partial thromboplastin time; ULN = upper limit of normal; WBC = white blood cell.
*
The laboratory values provided in the tables serve as guidelines and are dependent upon institutional normal parameters. 
Institutional normal reference ranges should be provided to demonstrate that they are appropriate. Laboratory abnormality 
grading occurs only when the values fall beyond the normal ranges established by the local laboratory.
Source: Guidance for industry – Toxicity Grading Scale for Heathy Adult and Adolescent Volunteers Enrolled in Preventive 
Vaccine Clinical Trials; tables for laboratory abnormalities (DHHS 2007). Note that the criteria for Grade 1 PT and PTT have 
been adjusted from the source table: instead of ≥ 1.0 x ULN, both criteria are > 1.0 x ULN. Grade 1 will not be used for 
hematology values due to the large overlap with normal values at the central laboratory.
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7.3
Appendix 3: Protocol Amendment History
The document history table for this protocol and the Protocol Amendment Summary of 
Changes table for the current Amendment 5 is located directly before the Table of Contents. 
Descriptions of Amendments 1, 2, 3, 4, and 5 are presented in this appendix.
7.3.1
Amendment 5, 19 Feb 2021 
Main Rationale for the Amendment:
There is an urgent need for vaccination strategies against SARS-CoV2 that induce broader 
protection that includes variants such as B.1.351 to decrease morbidity and mortality. 
ModernaTX, Inc. is developing a mRNA vaccine (mRNA-1273.351) that is similar to the 
mRNA-1273 vaccine available under the Emergency Use Authorization (EUA), but in which 
the mRNA encodes for mutations included in the S protein of the B.1.351 variant. 
This protocol amendment will add Part C to the protocol, which will be an amendment to 
investigate the proof of concept of a single dose booster of two dose levels of the 
mRNA-1273.351 variant and a mixture formulation of mRNA-1273/mRNA-1273.351 
administered to approximately 60 participants who received primary vaccination during the 
mRNA-1273-P301 COVE study. The COVE study participants will be offered enrollment in 
this new site-specific sub study, Part C of mRNA-1273-P201, based on pre-determined 
eligibility criteria. If they choose to enroll in this protocol amendment, the participants will 
be discontinued from the mRNA-1273-P301 COVE study. The participants would have had 
to be originally randomized to the mRNA-1273 group and have previously received 2 doses 
of mRNA-1273, 28 days apart, to be enrolled in this amendment. The unblinding visit should 
also have occurred. In this protocol amendment, enrolled participants will be allocated 1:1:1 
to receive a single intramuscular injection of mRNA-1273.351 (20 µg or 50 µg) or mRNA- 
1273/mRNA-1273.351 mixture (50 µg) as a booster injection. 
The summary of changes table provided here describes the major changes made in 
Amendment 5 relative to Amendment 4, including the sections modified and the 
corresponding rationales. The synopsis of Amendment 5 has been modified to correspond to 
changes in the body of the protocol. 

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Summary of Major Changes in Protocol Amendment 5:
Section # and Name
Description of Change
Brief Rationale
Title Page, Protocol Approval Page,
Headers, Protocol Amendment 
Summary of Changes
Updated the protocol version 
and date.
To reflect the new version and 
date of the protocol.
Protocol Synopsis – Objectives and 
Section 2.7 (Primary Objectives 
[Part C, Open Label]), Section 2.8 
(Secondary Immunogenicity 
Objective [Part C, Open Label]), and 
Section 2.9 (Exploratory Objectives 
[Part C, Open Label]
The description of the Part C 
primary, secondary, and 
exploratory objectives was 
added to the Protocol Synopsis. 
The description of Part C was 
included in Section 2 (Study 
Objectives). Section 2.7,
Section 2.8, and Section 2.9 
were added to encompass the 
addition of Part C primary, 
secondary, and exploratory 
objectives.
The addition of Part C was the 
main purpose of this amendment.
Protocol Synopsis – Study Design 
and Methodology and Section 3.1 
(General Study Design)
A description of the general 
design of Part C was added to
the synopsis. The description 
was also added to Section 3.1 for 
consistency.
The addition of Part C was the 
main purpose of this amendment. 
Language was included for 
consistency and clarity.
Protocol Synopsis – Study Design 
and Methodology and Section 3.1.3 
(Part C, Open-Label Interventional 
Phase of mRNA-1273.351 and 
mRNA-1273/mRNA-1273.351
Mixture Booster Vaccines)
A further description of the 
methodology for Part C was 
included in the synopsis and 
Section 3.1.3 for consistency and 
clarity. Figure 4 was added to 
Section 3.1.3 as a visual aid for 
the structure of Part C.
The addition of Part C was the 
main purpose of this amendment. 
Language was included for 
consistency and clarity.
Protocol Synopsis – Safety 
Assessments and Section 3.4.7 
(Safety Assessments)
Applicable safety assessments 
for Part C were indicated in the 
safety sections of the synopsis 
and body for consistency.
The addition of Part C was the 
main purpose of this amendment.
Protocol Synopsis – Immunogenicity 
assessments, Section 3.4.5 
(Immunogenicity Assessments)
Part C immunogenicity 
assessments were included for 
clarity.
The addition of Part C was the 
main purpose of this amendment. 
Language added for clarity.
Protocol Synopsis – Investigational 
Product, Dosage, and Route of 
Administration and Section 3.3.3 
(Identity of Investigational Product)
The investigational product, 
dosage, and route of 
administration information was 
provided for Part C.
The addition of Part C was the 
main purpose of this amendment. 
Language was included for clarity.
Protocol Synopsis – Investigational 
Product, Dosage, and Route of 
Administration and Section 3.3.5 
(Blinding)
Specified that Part B and Part C 
of the study will be open label.
The addition of Part C was the 
main purpose of this amendment. 
Language was added for clarity 
and consistency.

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Section # and Name
Description of Change
Brief Rationale
Protocol Synopsis – Sample Size 
and Section 4.5 (Sample Size 
Determination)
Clarified that patients in Part A 
will have the opportunity to 
enter Part B provided they meet 
the eligibility criteria.
A description of the Part C 
sample size and enrollment 
process was provided.
Language was updated for clarity. 
The description for Part C was 
included as the addition of Part C 
was the main purpose of this 
amendment.
Protocol Synopsis – Statistical 
Methods and Section 4.6 Statistical 
Methods.
Indicated that Part C data may 
be presented separately, as 
appropriate.
Specified when analyses were 
specific to Part A and Part B.
Indicated that Part C will be 
similarly analyzed (when not 
specific to Part A and Part B).
Language was included as the 
addition of Part C was the main 
purpose of this amendment. Other 
language updated for clarity and 
consistency.
Protocol Synopsis – Study Analyses 
and Section 4.7.3 (Interim Study 
Analysis for Open-Label Part C 
Only)
Indicated that an interim analysis 
of the safety and
immunogenicity data in Part C
of the study may be performed 
after participants have
completed OL-D8, OL-D15,
OL-Day 29 and/or the OL- 
Day 57 study procedures.
Section 4.7.3 added, and 
language included for 
consistency and clarity.
The addition of Part C was the 
main purpose of this amendment. 
Language was included for clarity.
Section 3.1.6 (Inclusion Criteria)
Section 3.1.6 heading was 
created.
Inclusion criterion #7 was 
updated to #6 as there is no 
inclusion criterion #7.
A separate set of inclusion 
criteria for Part C was included. 
Headers separating Parts A and 
B from Part C were created.
Headings were created for clarity 
and readability.
Numbering was updated for 
clarity and accuracy.
Part C inclusion criteria was added 
to clarify what participants will be 
eligible for Part C.
Section 3.1.7 (Exclusion Criteria)
A separate set of exclusion 
criteria for Part C was included. 
Headers separating Parts A and 
B from Part C were created.
Part C exclusion criteria was 
added to clarify which participants 
will not be eligible for Part C.
Headers were created for clarity 
and readability.
Section 3.3.1 (Method of Assigning 
Participants to Dosing Groups [Part 
A and Part C])
Table 2 – Dose Group 
Assignment (Part C) added to 
clarify groups, investigational 
product, and number of 
participants.
The addition of Part C was the 
main purpose of this amendment. 
The table was added for clarity.

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Section # and Name
Description of Change
Brief Rationale
Section 3.3.2 (Investigational 
Product Administration)
Indicated that the Part C 
investigational product will be 
administered as a single 
intramuscular injection into the 
deltoid muscle on the day of the 
participants consent. Each 
injection will have variable dose 
volumes; the 20-µg dose of 
mRNA-1273.351 is 0.2 mL, the
50-µg dose of mRNA-1273.351 
is 0.5 mL, and the 50-µg dose of 
pharmacy prepared mixture of 
mRNA-1273/mRNA-1273.351
is 0.5 mL.
The addition of Part C was the 
main purpose for this amendment. 
This language was included for 
clarity.
Section 3.3.2.1 (Pause Rules)
Indicated that the pause rules 
described in this section are not 
applicable to Part C. Clarified 
for Part C, that the sponsor will 
continue to inform the SMC of 
any occurrence of the events in 
Table 3.
The addition of Part C was the 
main purpose for this amendment. 
This language was included for 
clarity.
Section 3.3.2.2 (Contraindications to 
Subsequent Injection)
Updated how long the patient 
will be encouraged to continue 
study participation from 12 
months to 6 months.
Existing safety data across
mRNA-1273 studies suggest that a 
safety follow up of 6 months after 
last vaccination is acceptable.
Section 3.3.4.2 (Packaging and 
Labeling)
Additional packaging and 
labeling information for Part C 
was included.
The addition of Part C was the 
main purpose of this amendment.
Section 3.3.4.3 (Storage)
Confirmed that the mRNA-1273 
vaccine in Part C must be stored 
at -25°C to -15°C. The mRNA- 
1273.351 vaccine used in Part C 
must be stored at -90°C to -60°C 
(-130°F to -76°F).
The addition of Part C was the 
main purpose of this amendment 
and other additional language was 
for clarity.
Section 3.8.5.6 (Definition and 
Reporting of Adverse Events 
Consistent With Anaphylaxis)
Section 3.8.5.6 describes the 
definitions and reporting 
procedures for Adverse Events 
(AEs) consistent with 
anaphylaxis.
This text is being added to all 
mRNA-1273 protocols based on 
recent reports of anaphylaxis in 
the post-Emergency Use 
Authorization setting.
Section 4.3.3 (Part C, Open Label)
Updated Section 4.3 to include 
Part C primary safety endpoints, 
primary immunogenicity 
endpoints, secondary 
immunogenicity endpoint, and 
exploratory endpoints.
The addition of Part C was the 
main purpose of this amendment.

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Section # and Name
Description of Change
Brief Rationale
Section 7.1 (Appendix 1: Schedule 
of Events) – Table 11 (Part B: 
Open-label Schedule of Events:
“Blood for vaccine 
immunogenicity4” updated to 
“Blood for serology9 and 
immunogenicity4” 
Added Footnote 9 “Blood 
sample for serology will be 
collected only at the Participant 
Decision Visit.”
Language updated and footnote 
added for clarity and specificity of 
serology timing.
ONLY for Participants Receiving 2
Doses of mRNA-1273 28 Days
Apart)

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Section # and Name
Description of Change
Brief Rationale
Section 7.1 (Appendix 1: Schedule 
of Events) – Table 12 (Part B and 
Part C: Open-label Schedule of 
Events (Participants Receiving a 
Booster Dose)9
Table title updated to remove 
“ONLY for” and “single.”
“Blood for vaccine 
immunogenicity5” updated to 
“Blood for serology10 and 
immunogenecity5” 
Updated note language to 
indicate the following, 
“Participants who decline 
receiving booster mRNA-1273, 
decline unblinding, or decline to 
receive 2 doses of mRNA-1273 
in Part B will not receive study 
vaccination at OL-D1 (or OL- 
D29), will not perform a 
pregnancy test, or eDiary 
activation at OL-D1.”
Added Footnote 10 “Blood 
sample for serology will be 
collected only at the Participant 
Decision Visit (OL-D1).”
Addition of Booster injection for 
Part C under OL-D57.
Added footnote 11 “In Part C, an 
additional booster injection may 
be added approximately 56 days 
after the first boost at OL-D1.
This additional booster dose will 
be triggered following review of 
immunogenicity data up to OL- 
D15 of the initial 
mRNA1273.351(20 and 50 µg)
and mRNA-1273/mRNA- 
1273.351 mixture injections.”
Added footnote 12 “If the 
additional booster dose is given 
at OL-D57, an eDiary for 
reactogenicity will be completed 
for 7 days post-injection.
Additionally, unsolicited AEs 
will continue to be collected for 
28 days post last injection.”
Title update made as this schedule 
of events applies to participants 
who choose to decline unblinding, 
but wish to remain in the study, 
decide to unblind but decline to 
receive further vaccination (either 
a single mRNA-1273 booster or 2 
doses of mRNA-1273, 28 days 
apart). Language updates made for 
clarity and specificity of serology 
timing.
An additional booster injection 
may be added approximately 56 
days after the first boost at OL- 
D1. This will be determined 
following review of 
immunogenicity data up to
OL-D15.
Additional footnotes included for 
clarity.

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Protocol mRNA-1273-P201 Amendment 6 
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7.3.2
Amendment 4, 15 Jan 2021 
Main Rationale for the Amendment:
Following authorization of a COVID-19 vaccine under an Emergency Use Authorization 
(EUA), this study amendment is designed to transition to Part B, the Open-Label Interventional 
Phase (Figure 3). Transitioning the study to Part B, Open-Label Interventional Phase permits 
all ongoing study participants to (a) be informed of the availability and eligibility criteria of 
any COVID-19 vaccine made available under an EUA, and (b) the option to offer all ongoing 
study participants who request unblinding an opportunity to schedule a study visit to know 
their original group assignment (placebo vs. mRNA-1273 [50µg or 100µg vaccine]). 
Part B, Open-label Interventional Phase, also provides the opportunity for study participants 
who previously received placebo, to request to receive 2 doses of the mRNA-1273 (100 µg) 
vaccine. Participants who originally received 1 or 2 doses of mRNA-1273 (50µg or 100µg 
vaccine) during Part A, will have the opportunity to request to receive a single booster dose of 
mRNA-1273 (50 µg). 
The summary of changes table provided here describes the major changes made in Amendment 
4 relative to Amendment 3, including the sections modified and the corresponding rationales. 
The synopsis of Amendment 4 has been modified to correspond to changes in the body of the 
protocol.
Summary of Major Changes in Protocol Amendment 4:
Section # and Name
Description of Change
Brief Rationale
Title Page, Protocol Approval Page, 
Headers, Protocol Amendment 
Summary of Changes
Updated the protocol version 
and date
To reflect the new version and date 
of the protocol
Synopsis (Objectives) and Section 2 
(Study Objectives)
Added objectives for Part B, 
Open Label
Added to specifically enumerate 
the objectives for the Open-Label 
part of the study, allowing for 
changes to study design and 
dosing.

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Section # and Name
Description of Change
Brief Rationale
Synopsis (Study Design), Section
3.1.2 (Part B, Open-Label 
Interventional Phase), Section 7.1 
(Appendix 1: Schedule of Events)
Added a “Participant Decision 
Clinic Visit”; instructions for 
transitioning to Part B, Open 
Label; Schedule of Events for 
the Participant Decision Clinic 
Visit; and Schedules of Events 
for Part B, Open-Label 
procedures.
This Participant Decision Clinic 
Visit provides the opportunity for 
study site personnel to discuss with 
and offer to participants, the
choice to be unblinded, as well as 
offering to participants who 
originally received placebo, the 
choice to receive active
vaccination with mRNA-1273 and 
possible vaccination against 
COVID-19, as well as offering 
those who received mRNA-1273 
during Part A, the choice to
receive a booster injection of 
mRNA-1273.
The new Schedules of Events 
distinguish Part B, Open Label 
from Part A, Blinded, since all 
participants will transition to Part
B. The Part B Schedules of Events 
provide procedural instructions for 
participants who will receive 2 
mRNA-1273 injections and for 
those who will receive 1
mRNA-1273 injection in Part B.
Section 1.2 (Nonclinical Studies in 
Development of mRNA-1273) and 
Section 1.3 (Clinical Studies 
 
Updated status of nonclinical 
studies, as well as ongoing 
clinical studies, including this 
study (mRNA-1273-P201) and 
the Phase 3 Study mRNA-1273- 
P301.
The status of the 3 clinical studies 
(one Phase 1, one Phase 2a, and 
the Phase 3 study) has changed 
since Amendment 3.
In addition, the results of the 
interim analyses in the Phase 3 
study of the primary efficacy 
endpoint (prevention of COVID- 
19 infection), a major secondary 
endpoint (prevention of severe 
COVID-19), and safety and 
reactogenicity endpoints are now 
available and are provided here. 
These results provide the 
justification for offering 
participants the opportunity to 
receive active investigational 
product (mRNA-1273) and the 
potential benefit of vaccination
against COVID-19.

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Section # and Name
Description of Change
Brief Rationale
Section 4.3.2 (Statistical Analyses, 
Part B, Open Label)
Addition of Part B, open-label 
statistical analyses
Lists the Part B, open-label 
endpoints. Major differences from 
the Part A endpoints/analyses were 
elimination of assessment of 
laboratory values, and 
distinguishing identical endpoints 
for 50 µg and 100 µg of
mRNA-1273.
Section 3.4.5 (Blinding)
The study site staff, 
investigators, study monitors, 
and participants will remain 
blinded until the conclusion of 
the study.
Changed to: The study site staff, 
investigators, study monitors, 
and participants will remain
blinded until the initiation of
Open-Label Part B.
Previous language is no longer 
applicable, since the study will be 
unblinded for Part B.
Section 3.4.2.1 (Pause Rules)
The pause-triggering rules that 
have been in effect for Part A, 
will not be applicable for Part B; 
however, participants will 
continue to be monitored for the 
pause rule criteria.
In December 2020, after review of 
both safety and efficacy data 
observed to date, the FDA granted 
Emergency Use Authorization 
(EUA) to Moderna’s mRNA-1273 
vaccine. Given this, the current 
pause rules as outlined cannot be 
applied effectively, as it is more 
likely that any serious safety signal 
would emerge from the ongoing 
large public vaccination 
campaigns. Moderna will still 
monitor for safety events in this 
study and will report to the Safety 
Monitoring Committee as 
appropriate.
Section 4.7.2 (Interim Analysis for 
Open-Label Part B Only)
Added an option IA following 
completion of OL-Day 29 
and/or OL-Day 57 study
procedures.
The IA would help inform of the 
benefit of participant receiving a 
booster dose.

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Protocol mRNA-1273-P201 Amendment 6 
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7.3.3
Amendment 3, 02 Sep 2020
The main purpose of this amendment was to clarify that data can be analyzed in multiple 
batches based on availability of participants who have reached the Day 57 visit. The 
summary of changes table describes the major changes made in Amendment 3 relative to 
Amendment 2, including the sections modified and the corresponding rationales. Minor 
editorial or formatting changes are not included in this summary table. 
Summary of Major Changes in Protocol Amendment 3:
Section # and Name
Description of Change
Brief Rationale
Title page, Signature page, 
Synopsis, and header
Updated the protocol version and date
Reflect the new version and 
date of the protocol.
Synopsis, Section 3.1 Study 
Design
Deleted repeated text about Safety 
Monitoring Committee review before 
expansion in Cohort 2.
Editorial removal of redundant 
text.
Synopsis,
Section 3.4.5 Blinding, 
Section 4.1 Blinding and 
Responsibility for Analyses, 
Section 4.7.1 Primary Study
Analysis
Added information about potential 
participant populations to be included in 
the primary analysis of safety and 
immunogenicity after completion of 
Day 57 procedures.
Clarification that data can be 
analyzed in multiple batches 
based on availability of 
participants who have reached 
the Day 57 visit.
Synopsis, Section 4.6.2 
Safety Analyses
Revisions to clarify that separate 
summaries of Grade 3 or higher solicited 
ARs are not planned.
Clarification of planned safety 
analyses.
Section 3.5.2 Use of 
Electronic Diaries, 
Section 7.1 Appendix 1:
Schedule of Events (Table 7)
Added clarification about site follow-up of 
relevant safety events from eDiary entries 
(includes revisions to Footnote 12).
Clarification that follow-up by 
telephone of relevant safety 
events from eDiary entries is 
not the same as scheduled
safety follow-up telephone 
calls.
Section 7.1 Appendix 1: 
Schedule of Events (Table 7)
The acceptable window around the Day 29 
visit has been clarified as + 7 days with no 
negative visit window.
Correction to reflect the 
minimum interval between 
vaccine administrations of 
28 days.
Section 7.1 Appendix 1: 
Schedule of Events (Table 7)
The footnotes and footnote numbering 
have been updated to accommodate the 
footnotes that were added with
Amendment 2.
Editorial clarification.
Section 7.1 Appendix 1: 
Schedule of Events (Table 7)
Footnote 4 has been revised to clarify that
study days for safety follow-up are relative 
to Day 1 vaccine administration.
Editorial clarification.
Section 7.1 Appendix 1: 
Schedule of Events (Table 7)
Footnote 5 has been revised to explain 
how to handle potential visit window 
overlap related to Visit 8.
Editorial clarification.
Section 7.1 Appendix 1: 
Schedule of Events (Table 7)
Footnote 10 has been revised to clarify the 
timing of nasopharyngeal swab samples on 
vaccination days.
Editorial clarification.
Abbreviations: AE = adverse event; AR = adverse reaction; MAAE = medically attended adverse event; SAE = serious 
adverse event.

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Protocol mRNA-1273-P201 Amendment 6 
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7.3.4
Amendment 2, 01 Jul 2020 
Main Rationale for the Amendment:
The main purpose of this amendment was to change the statistical analysis plan by removing 
interim analyses and defining the Primary Study Analysis and EOS Analysis. The summary of 
changes table describes the major changes made in Amendment 2 relative to Amendment 1, 
including the sections modified and the corresponding rationales. Minor editorial or formatting 
changes are not included in this summary table. 
Summary of Major Changes in Protocol Amendment 2:
Section # and Name
Description of Change
Brief Rationale
Title page, Signature page, 
and header
Updated the protocol version and date
Reflect the new version and 
date of the protocol.
Synopsis, Section 3.1 Study 
Design, Section 3.5.2 Use of 
Electronic Diaries, Section
3.5.3 Safety Telephone Calls, 
Section 7.1 Appendix 1: 
Schedule of Events
(including text, Table 7, and 
footnotes to Table 7)
Added eDiary questionnaires to the 
procedure for safety follow-up after the 
Day 57 visit, with completion of eDiary
questionnaires alternating with safety 
telephone calls approximately every
2 weeks after the Day 57 visit.
Reduce the burden on study 
site personnel of completing 
safety follow-up by telephone.
Synopsis, Section 3.1 Study 
Design, Section 3.5.3 Safety 
Telephone Calls, Section 7.1
Appendix 1: Schedule of 
Events (footnote 12)
Added exposure to someone with known 
COVID-19 or SARS-CoV-2 infection and 
participant experience of COVID-19
symptoms to the list of events queried 
during scheduled safety telephone calls.
Improve surveillance for 
incidence of COVID-19 during 
the study.
Synopsis, Section 3.1 Study 
Design
End of Study definition was amended.
Minor clarification to define 
the End of Study.
Synopsis, Section 3.4.5
Blinding, Section 4.1 
Blinding and Responsibility 
for Analyses, Section 4.7 
Study Analyses,
Section 4.7.1 Primary Study 
Analysis, Section 4.7.2 End 
of Study Analysis,
Section 6.4 Clinical Study 
Reports
Added descriptions of the Primary Study 
Analysis and End of Study Analysis and 
respective clinical study reports, replacing 
descriptions of interim analyses and 
reports. The synopsis contains a new 
section.
Eliminate interim analyses in 
favor of a focus on the primary 
analysis.
Synopsis, Section 4.6 
Statistical Methods
Stated that all analyses will be performed 
by treatment group overall (for the
2 cohorts combined) and for the 2 cohorts 
separately, unless specified otherwise.
Previous versions of the 
protocol had not included the 
overall analysis in statement of 
the standard scope of analysis.
Synopsis, Section 4.6.3 
Immunogenicity Analyses
For the primary immunogenicity endpoint, 
geometric mean titer was changed to 
geometric mean.
Assays for bAb are under 
development. The reported 
values may or may not be
titers; hence the protocol 
wording has been modified.

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Section # and Name
Description of Change
Brief Rationale
Section 3.5.1 Assessment for 
SARS-CoV-2 Infection
Added instructions for asymptomatic 
patients who have a confirmed SARS- 
CoV-2 infection.
To clarify the steps for the 
investigator to follow when a 
participant is confirmed to have 
SARS-CoV-2 infection but is 
asymptomatic.
Section 3.5.8.8 Assessment 
of Severity
Decoupled life-threatening and Grade 4 in 
the severity assessment.
To adhere to CDISC guidance 
and align with case report form 
page.
Section 3.5.8.8 Assessment 
of Severity
Added clarification on when an AE is 
defined as serious.
To clarify when an AE is 
defined as serious.
Abbreviations: AE = adverse event; bAb = binding antibody; CDISC = Clinical Data Interchange Standards Consortium; 
eDiary = electronic diary; SARS-Cov-2 = Severe Acute Respiratory Syndrome coronavirus that causes COVID-19.
7.3.5
Amendment 1, 18 May 2020 
Main Rationale for the Amendment:
The main purpose of this amendment was to incorporate the following modifications 
requested by the FDA Center for Biologics Evaluation and Research: 
•
Enhance monitoring of participants who are confirmed to have SARS-CoV-2 
infection.
•
Include a convalescent visit for participants with confirmed SARS-CoV-2 infection.
•
Explore the mRNA-1273 vaccine efficacy in preventing asymptomatic SARS-CoV-2 
infection.
•
Update the Month 7 and Month 13 visits to Day 209 and Day 394, respectively, to 
extend the follow-up to a full 12-month period after the second injection on Day 29 
(Month 1). 
•
Decrease the highest dose of mRNA-1273 in the study from 250 µg to 100 µg.
The summary of changes table describes the major changes made in Amendment 1, including 
the sections modified and the corresponding rationale. Minor editorial or formatting changes 
are not included in this summary table. 
Summary of Major Changes in Protocol Amendment 1:
Section # and Name
Description of Change
Brief Rationale
Title page, Signature page, 
and header
Updated protocol version and date.
Revised version and date of 
protocol.
Title page, Signature page, 
and header
Updated the protocol title.
Revised to reflect the current 
purpose of the study.
Synopsis and
Section 2.3 Exploratory 
Objectives
Request from the Health 
Authority.

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Protocol mRNA-1273-P201 Amendment 6 
mRNA-1273
Section # and Name
Description of Change
Brief Rationale
Synopsis,
Section 2.3 Exploratory
Objectives, Section 4.3.3 
Exploratory Endpoints, 
Section 4.6.4 Exploratory 
Analyses
Editorial change.
Synopsis, Section 3.1 Study 
Design, Study Flow Schema 
(Figure 1), Sentinel and 
Expansion Cohort Schema 
(Figure 2),
Section 3.1.1 Rationale for 
Dose Selection, 3.4.1 Method 
of Assigning Participants to 
Dosing Groups. Dose Group 
Assignment (Table 1),
3.4.2 Investigational Product 
Administration, 4.5 Sample 
Size Determination
Decreased the highest dose of mRNA- 
1273 in the study from 250 µg to 100 µg.
Decreased based on the 
preliminary findings of the 
Phase 1 DMID study.
Synopsis and
Section 3.1 Study Design
Deleted collection of nasopharyngeal swab 
samples at the Screening Visit (Day 0).
Editorial update for
consistency with Schedule of 
Events (Table 7).
Synopsis and
Section 3.1 Study Design
Deleted the number of visits at which 
participants will have blood samples 
collected.
Editorial update to avoid 
confusion as blood samples 
will be collected at different
visits for safety and vaccine 
immunogenicity assessments.
Synopsis; Section 3.1 Study 
Design, Section 3.5.6 Blood 
Sampling Volumes (Table 3), 
Section 3.5.7 Safety 
Assessments,
Section 3.5.8.6 Eliciting and 
Documenting Adverse 
Events,
Section 4.3.1.2 Primary 
Immunogenicity Endpoint, 
Section 4.3.2 Secondary 
Endpoints,
Section 4.7 Interim Analyses, 
Section 6.4 Clinical Study 
Reports, and
Section 7.1 Appendix 1: 
Schedule of Events (Table 7)
Updated Month 7 and Month 13 visits to 
Day 209 and Day 394, respectively, to 
allow for 6-month and 12-month intervals, 
respectively, after the second injection on 
Day 29 (Month 1). 
Request from the Health 
Authority.
Synopsis, Section 3.1 Study 
Design, and
Section 7.1 Appendix 1: 
Schedule of Events (Table 7)
Updated the biweekly safety telephone 
calls from Day 211 through Day 351 to 
Day 223 through Day 377.
Consequent to the change 
made to the Day 209 Visit
(Request from the Health 
Authority).

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Protocol mRNA-1273-P201 Amendment 6 
mRNA-1273
Section # and Name
Description of Change
Brief Rationale
Synopsis, Section 3.1 Study 
Design,
Section 3.1.2 Rationale for 
Study Design,
Section 3.5.1 Assessment for 
SARS-CoV-2 Infection, and 
Section 7.1 Appendix 1:
Schedule of Events (Table 7)
Updated nasal swab to nasopharyngeal 
swab.
Clarified the type of swab to be 
performed.
Section 3.1.1 Rationale for 
Dose Selection
Updated enrollment and preliminary safety
data from the ongoing Phase 1 DMID 
study.
Updated based on the
preliminary findings of the 
Phase 1 DMID study.
Section 3.2.1 Inclusion 
Criteria
Updated inclusion criterion #7 to exclude 
sperm donations through 3 months after 
the last injection.
Update to align with the 
informed consent form on 
refraining male participants 
from sperm donation through
3 months after the last injection 
based on IRB feedback to the 
ICF.
Section 3.3.2 Handling 
Withdrawal From the Study
Updated the scheduled end of study 
assessments at Day 394 (Month 13) to 
allow for a 12-month interval after the
second vaccination on Day 29 (Month 1).
Request from the Health 
Authority.
Section 3.4.5 Blinding
Updated the method to maintain the blind 
of the dosing assignment from opaque 
sleeve to blinding label.
Operational change in cases for 
which opaque sleeves are not 
used.
Section 3.5.1 Assessment for 
SARS-CoV-2 Infection
•
Added more intense monitoring of 
participants who are confirmed to 
have SARS-CoV-2 infection (ie, 
notification of the participant’s 
primary care physician by the 
investigator and recording of 
confirmed SARS-CoV-2 infection as 
an MAAE along with relevant 
concomitant medications and details 
about severity, seriousness, and 
outcome).
•
Added a convalescent visit with blood 
collection after diagnosis of
SARS-CoV-2 infection.
Request from the Health 
Authority.
Section 3.5.1 Assessment for 
SARS-CoV-2 Infection and 
Section 3.5.8.2 Medically
Attended Adverse Event
Deleted “or COVID-19.”
Editorial update for internal 
consistency.
Section 4.3.3 Exploratory 
Endpoints
Request from the Health 
Authority.

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28 Apr 2021
Protocol mRNA-1273-P201 Amendment 6 
mRNA-1273
Section # and Name
Description of Change
Brief Rationale
Section 7.1 Appendix 1: 
Schedule of Events (Table 7)
Deleted that Day 0 and Day 1 visits may 
be combined the same day.
Editorial update of template 
text, which did not apply to 
this protocol.
Corrected sequential footnote numbering 
in the schedule of events (Table 7).
Editorial update.
Included a header row titled “Days Since 
Most Recent Vaccination.”
Update to clarify that the visits 
are relative to the most recent 
injection.
Abbreviation: DMID = Division of Microbiology and Infectious Diseases; ICF = informed consent form; IRB = Institutional 
Review Board; MAAE = medically attended adverse event; SARS-Cov-2 = Severe Acute Respiratory Syndrome
coronavirus that causes COVID-19.

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Protocol mRNA-1273-P201 Amendment 6 
mRNA-1273
8
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