A Phase 2/3, Randomized, Observer-blind, Active-controlled, Multicenter Study to Evaluate the Immunogenicity and Safety of Omicron Variant Vaccines in Comparison With mRNA-1273 (Prototype) Booster Vaccine
Phase: PHASE2
Conditions: SARS-CoV-2
Sponsor: ModernaTX, Inc.

ModernaTX, Inc. 
mRNA-1273-P305 Protocol Amendment 2 
mRNA-1273 
Confidential 
Page 1 
CLINICAL STUDY PROTOCOL 
Protocol Title: 
A Phase 2/3, Randomized, Observer-blind, Active-controlled, 
Multicenter Study to Evaluate the Immunogenicity and Safety 
of Omicron Variant Vaccines in Comparison with mRNA-1273 
(Prototype) Booster Vaccine 
Protocol Number: 
mRNA-1273-P305 Amendment 2 
Sponsor Name: 
ModernaTX, Inc.  
Legal Registered Address: 
200 Technology Square 
Cambridge, MA 02139 
Sponsor Contact and 
Medical Monitor: 
 
 
ModernaTX, Inc. 
Telephone: 
 
e-mail: 
Regulatory Agency 
Identifier Number: 
EudraCT: 2022-000063-51 
Date of Protocol 
Amendment 2: 
Date of Protocol 
Amendment 1: 
26 Aug 2022 
03 Mar 2022 
Date of Original Protocol: 
26 Jan 2022 
CONFIDENTIAL 
All financial and nonfinancial support for this study will be provided by ModernaTX, Inc. 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 the 
International Council for Harmonisation (ICH) of Technical Requirements for Registration of 
Pharmaceuticals for Human Use, E6(R2) Good Clinical Practice (GCP) Guidance. 
NCT05249829
PPD
PPD
PPD

ModernaTX, Inc. 
mRNA-1273-P305 Protocol Amendment 2 
mRNA-1273 
Confidential 
Page 2 
PROTOCOL APPROVAL – SPONSOR SIGNATORY 
Study Title: 
A Phase 2/3, Randomized, Observer-blind, Active-controlled, 
Multicenter Study to Evaluate the Immunogenicity and Safety of 
Omicron Variant Vaccines in Comparison with mRNA-1273 
(Prototype) Booster Vaccine 
Protocol Number: 
mRNA-1273-P305 Amendment 2 
Date of Protocol 
Amendment 2: 
26 Aug 2022 
  
Protocol accepted and approved by: 
 
See eSignature and date signed on 
the last page of this document. 
 
 
ModernaTX, Inc. 
200 Technology Square 
Cambridge, MA 02139 
Telephone: 
 
 
 
Date 
 
 
 
 
 
 
 
 
PPD
PPD

ModernaTX, Inc. 
mRNA-1273-P305 Protocol Amendment 2 
mRNA-1273 
Confidential 
Page 3 
DECLARATION OF INVESTIGATOR 
I have read and understood all sections of the protocol entitled “A Phase 2/3, Randomized, 
Observer-blind, Active-controlled, Multicenter Study to Evaluate the Immunogenicity and Safety 
of Omicron Variant Vaccines in Comparison with mRNA-1273 (Prototype) Booster Vaccine” 
and the most recent version of the investigator’s brochure. 
I agree to supervise all aspects of the protocol and to conduct the clinical investigation in 
accordance with the current protocol, the International Council for Harmonisation (ICH) of 
Technical Requirements for Registration of Pharmaceuticals for Human Use, E6(R2) Good 
Clinical Practice (GCP) Guidance, and all applicable government regulations. I will not make 
changes to the protocol before consulting with ModernaTX, Inc. or implement protocol changes 
without independent ethics committee (IEC) approval except to eliminate an immediate risk to 
participants. 
I agree to administer study vaccine only to participants under my personal supervision or the 
supervision of a subinvestigator. I will not supply study vaccine to any person not authorized to 
receive it. I also agree that persons debarred from conducting or working on clinical studies by 
any court or regulatory agency will not be allowed to conduct or work on studies for the Sponsor 
or a partnership in which the Sponsor is involved. I will immediately disclose it in writing to the 
Sponsor if any person who is involved in the study is debarred, or if any proceeding for 
debarment is pending, or to the best of my knowledge threatened. 
I will not disclose confidential information contained in this document including participant 
information, to anyone other than the recipient study staffs and members of the IEC. I agree to 
ensure that this information will not be used for any purpose other than the evaluation or conduct 
of the clinical investigation without the prior written consent from ModernaTX, Inc. I will not 
disclose information regarding this clinical investigation or publish results of the investigation 
without authorization from ModernaTX, Inc. 
The signature below provides the necessary assurance that this study will be conducted 
according to all stipulations of the protocol, including statements regarding confidentiality, and 
according to local legal and regulatory requirements and ICH E6(R2) GCP guidelines. 
 
Signature of Principal Investigator 
 
 
Date 
 
 
 
 
 
Printed Name of Principal Investigator  
 
 
 
 

ModernaTX, Inc. 
mRNA-1273-P305 Protocol Amendment 2 
mRNA-1273 
Confidential 
Page 4 
PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE 
DOCUMENT HISTORY 
Document 
Date 
Amendment 2 
26 Aug 2022 
Amendment 1 
03 Mar 2022 
Original Protocol 
26 Jan 2022 
Amendment 2, 26 Aug 2022: Current Amendment 
This amendment is considered to be substantial based on the criteria set forth in Article 10(a) of 
Directive 2001/20/EC of the European Parliament and the Council of the European Union. 
Main Rationale for the Amendment: 
Following authorization of the messenger ribonucleic acid (mRNA)-1273.214 booster in the 
United Kingdom, this amendment will incorporate an optional unblinding for participants who 
report eligibility to receive an additional coronavirus disease 2019 (COVID-19) booster outside of 
the study.  
The summary of changes table provided below describes the major changes made to Amendment 2 
relative to Amendment 1, including the sections modified and the corresponding rationales. The 
synopsis of the protocol has been modified to correspond to changes in the body of the protocol. 
Minor copy edits and administrative updates were made throughout the protocol to align with new 
content as well as for clarity, readability, consistency, and/or accuracy. 
Summary of Major Changes in Protocol Amendment 2: 
Section # and Name 
Description of Change 
Brief Rationale 
3 (Objectives and Endpoints) 
Deleted secondary objective in Table 
3 and Table 4 for evaluating 
immunogenicity of messenger 
ribonucleic acid (mRNA)-1273.529 
or mRNA-1273.214 booster 
administered in Part 1 or Part 2 of 
the study as a 3rd or 4th dose 
Removed objective 
since only a few 
participants were 
randomized in either 
part to receive a 
booster as the 3rd dose 
Modified Table 4 to remove the 
Month 6 timepoint from all primary 
Optional unblinding to 
occur after Month 3 
visit resulting in 
Month 6 and 

ModernaTX, Inc. 
mRNA-1273-P305 Protocol Amendment 2 
mRNA-1273 
Confidential 
Page 5 
Section # and Name 
Description of Change 
Brief Rationale 
and secondary objectives and 
endpoints in Part 2 
subsequent visits to 
fall under open-label, 
observational study 
Phase B for unblinded 
participants 
Added exploratory objective to 
Table 4 to evaluate immunogenicity 
of mRNA-1273.214 booster 
compared to mRNA-1273 booster 
administered as a 4th dose study 
vaccine in participants at Month 6  
To account for 
assessing 
immunogenicity in the 
Part 2 participants 
who are unblinded or 
remain blinded  
4 (Study Design) 
Modified the study design to include 
2 Phases for each part: the 
randomized, blinded phase (Phase A) 
and the open-label, observational 
phase (Phase B) 
Two phases were 
included for each part 
to differentiate 
between the original, 
observer-blind phase 
of the study (Phase A) 
and the open-label, 
observational Phase B 
for eligible unblinded 
participants to obtain 
an additional booster 
outside of the study 
6.2 (Randomization and 
Blinding), 8.5 
(Randomization) 
Updated text to reflect that 
randomization occurred during the 
original, observer-blinded Phase A 
Added to clarify that 
Phase A was the phase 
during which 
randomization 
occurred  
6.2 (Randomization and 
Blinding), Section 9.1 
(Blinding and Responsibility 
for Analyses) 
Updated text in accordance with 
Section 6.3.7 
For alignment 
6.3.7 (Unblinding) 
Updated section to describe optional 
unblinding for participants who 
report eligibility for an additional 
booster outside of the study 
Provided clarification 
of optional unblinding 
plan 

ModernaTX, Inc. 
mRNA-1273-P305 Protocol Amendment 2 
mRNA-1273 
Confidential 
Page 6 
Section # and Name 
Description of Change 
Brief Rationale 
6.5.3 (Concomitant 
Medications and Vaccines 
That May Lead to the 
Elimination of a Participant 
from Per-protocol Analyses) 
Added text, “Any COVID-19 
vaccine received outside of the study 
after the study vaccination” 
For clarification 
8.9.2 (Assessments for 
SARS-CoV-2 Infection) 
Updated text describing assessments 
for severe acute respiratory 
syndrome coronavirus 2 (SARS-
CoV-2) infection 
For clarification 
9 (Statistical Analysis Plan) 
Updated text in relevant sections and 
Table 10 in accordance with Section 
3, Section 4 and Section 6.3.7 
For alignment 
 
 

ModernaTX, Inc. 
mRNA-1273-P305 Protocol Amendment 2 
mRNA-1273 
Confidential 
Page 7 
1. 
PROTOCOL SUMMARY 
1.1. 
Protocol Synopsis 
Name of Sponsor/Company: ModernaTX, Inc. 
Name of Investigational Products: mRNA-1273.529, mRNA-1273.214 
Protocol Title: A Phase 2/3, Randomized, Observer-blind, Active-controlled, Multicenter 
Study to Evaluate the Immunogenicity and Safety of Omicron Variant Vaccines in 
Comparison with mRNA-1273 (Prototype) Booster Vaccine 
Protocol Number: mRNA-1273-P305, Amendment 2 
Study Duration: Approximately 13 months 
Phase of Development: Phase 2/3 
Estimated Date First Participant Enrolled: 07 Feb 2022  
Estimated Date Last Participant Completed: 07 Apr 2023 
Site Locations: Multicenter study in the UK 
Objectives and Endpoints 
Part 1: mRNA-1273.529 and mRNA-1273 
Objectives 
Endpoints 
Primary  
To demonstrate non-
inferiority of the immune 
response of 
mRNA-1273.529 
compared to mRNA-1273 
booster administered as a 
4th dose against the 
B.1.1.529 strain at Day 29 
or Month 3 
• 
Geometric mean titer (GMT) of mRNA-1273.529 and mRNA-
1273 against the B.1.1.529 strain at Day 29 and Month 3 after 
study vaccine administration 
• 
Ratio of GMTmRNA-1273.529/GMTmRNA-1273 against the B.1.1.529 
strain at Day 29 and Month 3 after study vaccine administration 
To evaluate the safety and 
reactogenicity of mRNA-
1273.529 and 
• 
Solicited local and systemic reactogenicity ARs during a 7-day 
follow up period after vaccination 

ModernaTX, Inc. 
mRNA-1273-P305 Protocol Amendment 2 
mRNA-1273 
Confidential 
Page 8 
mRNA-1273 administered 
as a booster dose 
• 
Unsolicited AEs during the 28-day follow-up period after 
vaccination 
• 
SAEs, medically attended AEs (MAAEs), AEs leading to 
withdrawal, and AEs of special interest (AESIs) from Day 1 to 
end of study 
Secondary  
Key Secondary 
To demonstrate 
superiority of the immune 
response of 
mRNA-1273.529 
compared to mRNA-1273 
administered as a 4th dose 
against the B.1.1.529 
strain at Day 29 or 
Month 3 
• 
GMT of mRNA-1273.529 and mRNA-1273 against the 
B.1.1.529 strain at Day 29 and Month 3 after study vaccine 
administration 
• 
Ratio of GMTmRNA-1273.529/GMTmRNA-1273 against the B.1.1.529 
strain at Day 29 and Month 3 after study vaccine administration 
 
Other Secondary 
To demonstrate 
non-inferiority of the 
immune response of 
mRNA-1273.529 
compared to mRNA-1273 
booster administered as a 
4th dose against both the 
B.1.1.529 and the 
prototype strain at all 
evaluable time points 
• 
GMT of mRNA-1273.529 and mRNA-1273 against both the 
B.1.1.529 and the prototype strain at all evaluable time points 
after study vaccine administration 
• 
Ratio of GMTmRNA-1273.529/GMTmRNA-1273 against both the 
B.1.1.529 and the prototype strain at all evaluable time points 
after study vaccine administration 
 
To evaluate the 
seroresponse rate (SRR) 
of mRNA-1273.529 and 
mRNA-1273 boosters 
administered as a 4th dose 
• 
SRR against the B.1.1.529 strain 
• 
SRR against the prototype strain  
Exploratory Objectives 
To assess for symptomatic 
and asymptomatic 
SARS-CoV-2 infection 
after vaccination with 
mRNA-1273.529 booster 
or mRNA-1273 booster 
Reverse transcriptase polymerase-chain reaction (RT-PCR)-confirmed 
symptomatic or asymptomatic SARS-CoV-2 infection will be defined 
in participants based on the following criteria: 
• 
Protocol-defined COVID-19 case definition 
o The participant must have experienced at least TWO of 
the following systemic symptoms: Fever (≥ 38ºC), 
chills, myalgia, headache, sore throat, new olfactory 
and taste disorder(s), OR 
o The participant must have experienced at least ONE of 
the following respiratory signs/symptoms: cough, 

ModernaTX, Inc. 
mRNA-1273-P305 Protocol Amendment 2 
mRNA-1273 
Confidential 
Page 9 
shortness of breath or difficulty breathing, OR clinical 
or radiographical evidence of pneumonia; AND 
o The participant must have at least one nasopharyngeal 
(NP) swab, nasal swab, or saliva sample (or respiratory 
sample, if hospitalized) positive for SARS-CoV-2 by 
RT-PCR 
• 
Center for Disease Control (CDC) defined COVID-19 
definition based on the CDC criteria: the presence of one of the 
CDC listed symptoms (https://www.cdc.gov/coronavirus/2019-
ncov/symptoms-testing/symptoms.html) and a positive RT-
PCR test on a respiratory sample 
• 
Asymptomatic SARS-CoV-2 infection is defined as a positive 
RT-PCR test on a respiratory sample in the absence of 
symptoms or a positive serologic test for antinucleocapsid 
antibody after a negative test at time of enrollment 
To evaluate the 
immunogenicity of 
mRNA-1273.529 booster 
against other variant 
strains 
• 
GMT of mRNA-1273.529 against other variant strains (eg, 
Alpha, Beta, Delta) after study vaccine administration 
• 
Ratio of GMTmRNA-1273.529/GMTmRNA-1273 against other variant 
strains after study vaccine administration 
• 
GMFR of mRNA-1273.529 against other variant strains after 
study vaccine administration 
• 
SRR against other variant strains 
To evaluate the genetic 
and/or phenotypic 
relationships of isolated 
SARS-CoV-2 strains to 
the vaccine sequence 
• 
Characterize the SARS-CoV-2 spike genetic sequence of viral 
isolates and compare with the vaccine sequence 
• 
Characterize the immune responses to vaccine breakthrough 
isolates 
Abbreviations: AE = adverse event; AESI = adverse event of special interest; AR = adverse reaction; CDC = 
Centers for Disease Control and Prevention; GMFR = geometric mean fold rise; GMR = geometric mean titer 
ratio; GMT = geometric mean titer; MAAE = medically attended adverse event; mRNA = messenger ribonucleic 
acid; NP = nasopharyngeal; RT-PCR = reverse transcription polymerase chain reaction; SAE = serious adverse 
event; SARS-CoV-2 = severe acute respiratory syndrome coronavirus 2; SRR = seroresponse rate. 
Part 2: mRNA-1273.214 and mRNA-1273 
Objectives 
Endpoints 
Primary  

ModernaTX, Inc. 
mRNA-1273-P305 Protocol Amendment 2 
mRNA-1273 
Confidential 
Page 10 
To demonstrate 
non-inferiority of the 
immune response of 
mRNA-1273.214 
compared to mRNA-
1273 booster 
administered as a 4th dose 
against the B.1.1.529 
strain at Day 29 or 
Month 3 
• 
Geometric mean titer (GMT) of mRNA-1273.214 and 
mRNA-1273 against the B.1.1.529 strain at Day 29 or Month 3 
after study vaccine administration 
• 
Ratio of GMTmRNA-1273.214/GMTmRNA-1273 against the B.1.1.529 
strain at Day 29 or Month 3 after study vaccine administration 
To demonstrate 
non-inferiority of the 
immune response of 
mRNA-1273.214 
compared to mRNA-
1273 booster 
administered as a 4th dose 
against the prototype 
strain at Day 29 or 
Month 3 
• 
GMT of mRNA-1273.214 and mRNA-1273 against the 
prototype strain at Day 29 or Month 3 after study vaccine 
administration 
• 
Ratio of GMTmRNA-1273.214/GMTmRNA-1273 against the prototype 
strain at Day 29 or Month 3 after study vaccine administration 
To demonstrate 
superiority of the 
immune response of 
mRNA-1273.214 
compared to 
mRNA-1273 booster 
administered as a 4th dose 
against the B.1.1.529 
strain at Day 29 or 
Month 3 
• 
GMT of mRNA-1273.529 and mRNA-1273 against the 
B.1.1.529 strain at Day 29 or Month 3 after study vaccine 
administration 
• 
Ratio of GMTmRNA-1273.529/GMTmRNA-1273 against the B.1.1.529 
strain at Day 29 or Month 3 after study vaccine administration 
To evaluate the safety 
and reactogenicity of 
mRNA-1273.214 and 
mRNA-1273 
administered as a booster 
dose 
• 
Solicited local and systemic reactogenicity ARs during a 7-day 
follow-up period after vaccination 
• 
Unsolicited AEs during the 28-day follow-up period after 
vaccination 
• 
SAEs, medically attended AEs (MAAEs), AEs leading to 
withdrawal, and AEs of special interest (AESIs) from Day 1 to 
end of study 
Secondary 
To evaluate the 
seroresponse rate (SRR) 
of mRNA-1273.214 and 
mRNA-1273 boosters 
administered as a 4th dose 
• 
SRR against the B.1.1.529 strain  
• 
SRR against the prototype strain  
 

ModernaTX, Inc. 
mRNA-1273-P305 Protocol Amendment 2 
mRNA-1273 
Confidential 
Page 11 
To evaluate the immune 
response of mRNA-
1273.214 compared to 
mRNA-1273 booster 
administered as a 4th dose 
against other variant 
strains at Day 29 or 
Month 3  
• 
GMT of mRNA-1273.214 and mRNA-1273 against other 
variant strains at Day 29 or Month 3 
• 
Ratio of GMTmRNA-1273.214/GMTmRNA-1273 against other variant 
strains at Day 29 or Month 3 
• 
SRR against other variant strains 
To assess for 
symptomatic and 
asymptomatic 
SARS-CoV-2 infection 
after vaccination with 
mRNA-1273.214 booster 
or mRNA-1273 booster 
Reverse transcriptase polymerase-chain reaction (RT-PCR)-confirmed 
symptomatic or asymptomatic SARS-CoV-2 infection will be defined in 
participants based on the following criteria: 
• 
Protocol-defined COVID-19 case definition 
o The participant must have experienced at least TWO of 
the following systemic symptoms: Fever (≥ 38ºC), 
chills, myalgia, headache, sore throat, new olfactory 
and taste disorder(s), OR 
o The participant must have experienced at least ONE of 
the following respiratory signs/symptoms: cough, 
shortness of breath or difficulty breathing, OR clinical 
or radiographical evidence of pneumonia; AND 
o The participant must have at least one nasopharyngeal 
(NP) swab, nasal swab, or saliva sample (or respiratory 
sample, if hospitalized) positive for SARS-CoV-2 by 
RT-PCR. 
• 
Center for Disease Control (CDC) defined COVID-19 
definition based on the CDC criteria: the presence of one of the 
CDC listed symptoms (https://www.cdc.gov/coronavirus/2019-
ncov/symptoms-testing/symptoms.html) and a positive RT-PCR 
test on a respiratory sample 
• 
Asymptomatic SARS-CoV-2 infection is defined as a positive 
RT-PCR test on a respiratory sample in the absence of 
symptoms or a positive serologic test for antinucleocapsid 
antibody after a negative test at time of enrollment 
Exploratory Objectives 
To evaluate cellular 
immunogenicity in a 
subset of participants 
• 
Frequency, magnitude, and phenotype of virus-specific T-cell 
and B-cell responses measured by flow cytometry or other 
methods, and to perform targeted repertoire analysis of T-cells 
and B-cells after vaccination 
To evaluate the genetic 
and/or phenotypic 
relationships of isolated 
SARS-CoV-2 strains to 
the vaccine sequence 
• 
Characterize the SARS-CoV-2 spike genetic sequence of viral 
isolates and compare with the vaccine sequence 
• 
Characterize the immune responses to vaccine breakthrough 
isolates 

ModernaTX, Inc. 
mRNA-1273-P305 Protocol Amendment 2 
mRNA-1273 
Confidential 
Page 12 
To evaluate the 
immunogenicity of 
mRNA-1273.214 booster 
compared to mRNA-
1273 booster 
administered as a 4th dose 
study vaccine in 
participants at Month 6 
• 
GMT of mRNA-1273.214 against both the B.1.1.529 and the 
prototype strain at Month 6 after study vaccine administration 
• 
Ratio of GMTmRNA-1273.214/GMTmRNA-1273 against the B.1.1.529 
strain at Month 6 after study vaccine administration 
• 
Ratio of GMTmRNA-1273.214/GMTmRNA-1273 against the prototype 
strain at Month 6 after study vaccine administration 
• 
GMFR of mRNA-1273.214 and mRNA-1273 against the 
B.1.1.529 and prototype strain at all evaluabletimepoints after 
study vaccine administration 
• 
SRR against both the B.1.1.529 and prototype strain at Month 6 
Abbreviations: AE = adverse event; AESI = adverse event of special interest; AR = adverse reaction; CDC = 
Centers for Disease Control and Prevention; GMFR = geometric mean fold rise; GMR = geometric mean titer 
ratio; GMT = geometric mean titer; MAAE = medically attended adverse event; mRNA = messenger 
ribonucleic acid; NP = nasopharyngeal; RT-PCR = reverse transcription polymerase chain reaction; SAE = 
serious adverse event; SARS-CoV-2 = severe acute respiratory syndrome coronavirus 2; SRR = seroresponse 
rate. 
Overall Study Design 
The study is a Phase 2/3, 2-part, randomized, observer-blind, active-controlled, multicenter 
study to evaluate the immunogenicity and safety of mRNA-1273.529 and mRNA-1273.214 
booster vaccine in medically stable individuals 16 years and older. The mRNA-1273.529 
vaccine contains mRNAs encoding for the S-2P of the SARS-CoV-2 Omicron variant 
(B.1.1.529). The mRNA-1273.214 vaccine contains mRNAs encoding for both the S-2P of the 
SARS-CoV-2 Wuhan Hu-1 strain and the S-2P of the SARS-CoV-2 Omicron variant 
(B.1.1.529), formulated in the same LNP. 
The study consists of 2 parts with 2 phases each:  
In Part 1, approximately 600-1000 participants will be randomized in a 1:1 ratio to 1 of 
2 study arms to receive a single dose of either 50 μg of mRNA-1273.529 or 50 μg of 
mRNA-1273 (active control). Randomization will be stratified by age groups (16 to < 65 years 
or ≥ 65 years) and number of booster doses received (to receive study vaccine as the 4th dose 
or to receive study vaccine as the 3rd dose). At least ≥ 90% of participants will receive the 
study vaccine as the 4th dose. The potential number of participants in each arm and the 
randomization ratio can be found in the table below. 
In Part 2, approximately 2,924 participants will be randomized in a 1:1 ratio to 1 of 2 study 
arms to receive a single dose of either 50 μg of mRNA-1273.214 or 50 μg of mRNA-1273 
(active control). Randomization will be stratified by age groups (16 to < 65 years or ≥ 
65 years) and number of booster doses received (to receive study vaccine as the 4th dose or to 
receive study vaccine as the 3rd dose). At least ≥ 90% of participants will receive the study 

ModernaTX, Inc. 
mRNA-1273-P305 Protocol Amendment 2 
mRNA-1273 
Confidential 
Page 13 
vaccine as the 4th dose. The potential number of participants in each arm and the 
randomization ratio can be found in the table below. 
Each part has a Phase A (randomized, blinded) and Phase B (open-label, observational). Phase 
B was designed to offer eligible participants in either treatment arms in Part 1 to obtain an 
additional booster after their Month 6 assessment and eligible participants in either treatment 
arms in Part 2 the option to obtain an additional booster after their Month 3 assessment. The 
additional booster may be obtained outside the study. 
Part 1: Study Arm and Dose Levels 
Vaccination 
Group 
Vaccination 
Received 
Total 
Dose 
N 
(total) 
Study 
vaccine as 
the 3rd dose 
Study vaccine as 
the 4th dose 
1 
mRNA-1273.529 
50 µg 
300-500a 
30-50 
270-450 
2 
mRNA-1273 
(Active Control) 
50 µg 
300-500a 
30-50 
270-450 
Abbreviations: mRNA = messenger ribonucleic acid; N = number. 
a Part 1 will end enrollment when Part 2 starts enrollment. The number of participants in Part 1 will be 
determined by the start date of Part 2. 
Part 2: Study Arm and Dose Levels 
Vaccination 
Group 
Vaccination 
Received 
Total 
Dose 
N 
(total) 
Study vaccine 
as the 3rd 
dose 
Study vaccine 
as the 4th dose 
1 
mRNA-1273.214 
50 µg 
1462 
134 
1328 
2 
mRNA-1273 
(Active Control) 
50 µg 
1462 
134 
1328 
Abbreviations: mRNA = messenger ribonucleic acid; N = number. 
All participants will have previously received 2 or 3 doses of an authorized/approved 
COVID-19 vaccine. Participants who previously received 2 doses of a COVID-19 vaccine as a 
primary series will receive mRNA-1273.529, mRNA-1273.214, or mRNA-1273 as the third 
dose, and participants who have previously received a primary series and 1 booster dose will 
receive mRNA-1273.529, mRNA-1273.214, or mRNA-1273 as the 4th dose. Participants who 
will receive the 4th dose as part of the study must have previously received a mRNA vaccine 
as the 3rd dose of a COVID-19 vaccine. Participants who will receive the 3rd dose as part of the 
study may have previously received 2 doses of a mRNA or a non-mRNA COVID-19 vaccine 
(a mixed approach is acceptable). 
Medically stable individuals, ages 16 and above (to include 2 age groups: 16 to < 65 and 
≥ 65 years) will be screened and enrolled. Participants with chronic diseases requiring ongoing 
medical intervention or within the last 2 months prior to enrollment will be excluded. 

ModernaTX, Inc. 
mRNA-1273-P305 Protocol Amendment 2 
mRNA-1273 
Confidential 
Page 14 
Participants with immunocompromising conditions or medications, or malignancy within 
10 years (excluding nonmelanoma skin cancer) will also be excluded. Participants who 
received a COVID-19 vaccine within 90 days prior to enrollment or had positive 
SARS-CoV-2 testing by an authorized/approved lateral flow/rapid antigen or polymerase 
chain reaction (PCR) within 90 days prior to enrollment will be excluded as well. 
Except for appropriately delegated unblinded pharmacists, vaccine administrators and 
monitors, all personnel involved in the conduct of the trial will remain blinded to individual 
treatment assignment until study unblinding. Study visits will consist of a Screening Visit (up 
to 28 days before the Day 1 visit), Vaccination Visit at Day 1 and subsequent study visits on 
Day 8 (for a subset of participants in Part 2 of the study), Day 29 (Month 1), Day 85 
(Month 3), Day 179 (Month 6), and Day 359 (Month 12), with up to 13 months of study 
participation in each part of the study. Unscheduled visits for potential symptoms of 
COVID-19 will include PCR testing. 
Safety Oversight: 
Safety monitoring for this study will include the blinded study team members, inclusive of at a 
minimum, the Sponsor medical monitor and CRO medical monitor, as well as safety reviews 
by an unblinded Data and Safety Monitoring Board (DSMB). The study team will conduct 
ongoing blinded safety reviews during the study and will be responsible for notifying the 
DSMB of potential safety signal events. The DSMB, composed of external, independent 
subject matter experts, including an unblinded statistician, will conduct unblinded reviews of 
safety data on a periodic basis, as defined in a DSMB charter, or as otherwise requested by the 
study team. 
An independent Cardiac Event Adjudication Committee (CEAC) comprised of medically 
qualified personnel, including cardiologists, will review suspected cases of myocarditis, 
pericarditis, and myopericarditis to determine if they meet CDC criteria for “probable” or 
“confirmed” events and provide the assessment to the Sponsor. The CEAC members will be 
blinded to study vaccine assignment. Details regarding the CEAC composition, 
responsibilities, procedures, and frequency of data review will be defined in the CEAC 
charter. 
Number of Participants:  
Part 1: Approximately 600-1000 participants will be randomized in a 1:1 ratio to 1 of 2 study 
arms to receive a single dose of either 50 μg of mRNA-1273.529 or 50 μg of mRNA-1273 
(active control). 

ModernaTX, Inc. 
mRNA-1273-P305 Protocol Amendment 2 
mRNA-1273 
Confidential 
Page 15 
Part 2: Approximately 2,924 participants will be randomized in a 1:1 ratio to 1 of 2 study arms 
to receive a single dose of either 50 μg of mRNA-1273.214 or 50 μg of mRNA-1273 (active 
control). 
Study Eligibility Criteria:  
Inclusion Criteria:  
Each participant must meet all of the following criteria during the screening period and at 
Day 1, unless noted otherwise, to be enrolled in this study:  
1. Male or female, at least 16 years of age at the time of consent (Screening Visit). 
2. Investigator’s assessment that the participant understands and is willing and physically 
able to comply with protocol-mandated follow-up, including all procedures. 
3. Participant has provided written informed consent for participation in this study, 
including all evaluations and procedures as specified in this protocol. 
4. Female participants of nonchildbearing potential may be enrolled in the study. 
Nonchildbearing potential is defined as postmenopausal or permanently sterilized 
(Section 11.2). A follicle stimulating hormone (FSH) level should be measured at the 
discretion of the investigator to confirm postmenopausal status, if necessary. 
5. 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 the Screening Visit and on the day of 
vaccination prior to vaccine dose being administered on 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 dose (Day 1). 
Adequate female contraception is defined as consistent and correct use of a 
local health authority approved contraceptive method in accordance with the 
product label. 
• Has agreed to continue adequate contraception through 90 days following 
vaccine administration. 
6. Has received 2 prior doses of one of the following approved/authorized COVID-19 
vaccines: Moderna, Pfizer/BioNTech, Oxford/AstraZeneca, Janssen. A heterologous 
vaccine regimen is acceptable.  
7. Participants who will receive the 4th dose as part of the study must have previously 
received a mRNA vaccine (Moderna or Pfizer/BioNTech) as the 3rd dose of a 

ModernaTX, Inc. 
mRNA-1273-P305 Protocol Amendment 2 
mRNA-1273 
Confidential 
Page 16 
COVID-19 vaccine. Participants who will receive the 3rd dose as part of the study may 
have previously received 2 doses of an approved/authorized mRNA or a non-mRNA 
COVID-19 vaccine (a heterologous vaccine regimen is acceptable). 
Exclusion Criteria:  
Participants meeting any of the following criteria, unless noted otherwise, will be excluded 
from the study: 
1. Had close contact (without personal protective equipment [PPE]) as defined by the 
CDC in the past 14 days to someone diagnosed with SARS-CoV-2 infection or 
COVID-19 within 10 days of the close contact. Participants may be rescreened after 
14 days provided that they remain asymptomatic.  
2. Participant is acutely ill or febrile (temperature ≥ 38.0°C/100.4°F) 72 hours prior to or 
at the Screening Visit or Day 1. Participants meeting this criterion may be rescheduled 
within the 28-day screening window and will retain their initially assigned participant 
number. 
3. Has tested positive for SARS-CoV-2 by an authorized/approved lateral flow/rapid 
antigen or PCR test within 90 days of Screening or later. 
4. Has received a COVID-19 vaccine within 90 days of the Screening Visit. 
5. Has received a total of 4 doses or more of COVID-19 vaccine. 
6. Has received a COVID-19 vaccine at a dose different from the authorized/approved 
dose. 
7. History of a diagnosis or condition that, in the judgment of the Investigator, is 
clinically unstable or may affect participant safety, assessment of safety endpoints, 
assessment of immune response, or adherence to study procedures. Clinically unstable 
is defined as a diagnosis or condition requiring significant changes in management or 
medication within the 2 months prior to screening and includes ongoing workup of an 
undiagnosed illness that could lead to a new diagnosis or condition.  
8. Reported history of congenital or acquired immunodeficiency, immunosuppressive 
condition, or immune-mediated disease requiring immunosuppressive treatment or 
other immunosuppressive condition. 
9. Dermatologic conditions that could affect local solicited AR assessments (eg, tattoos, 
psoriasis patches affecting skin over the deltoid areas). 
10. Reported history of anaphylaxis or severe hypersensitivity reaction after receipt of any 
components of mRNA vaccine. 

ModernaTX, Inc. 
mRNA-1273-P305 Protocol Amendment 2 
mRNA-1273 
Confidential 
Page 17 
11. Reported history of bleeding disorder that is considered a contraindication to 
intramuscular (IM) injection or phlebotomy. 
12. Any medical, psychiatric, or occupational condition, including reported history of 
substance abuse, that, in the opinion of the Investigator, might pose additional risk due 
to participation in the study or could interfere with the interpretation of study results.  
13. Has received systemic immunosuppressants or immune-modifying drugs for > 14 days 
in total within 181 days prior to screening (for corticosteroids ≥ 10 mg/day of 
prednisone equivalent) or is anticipating the need for immunosuppressive treatment at 
any time during participation in the study. 
14. Has received or plans to receive any licensed vaccine ≤ 28 days prior to the study 
injection (Day 1) or plans to receive a licensed vaccine within 28 days after the study 
injection (with the exception that approved seasonal influenza vaccine may be received 
by at least 7 days and preferably 14 days apart from the study injection). 
15. Has received systemic immunoglobulins or blood products within 90 days prior to the 
Screening Visit or plans to receive during the study. 
16. Diagnosis of malignancy within the previous 10 years (excluding nonmelanoma skin 
cancer). 
17. Has donated ≥ 450 mL of blood products within 28 days prior to the Screening Visit or 
plans to donate blood products during the study. 
18. Has participated in an interventional clinical study within 28 days prior to the 
Screening Visit based on the medical history interview or plans to do so while 
participating in this study. 
19. Is an immediate family member or household member of study personnel, study site 
staff, or Sponsor personnel. 
 
Study Treatments: 
The vaccines to be administered in this study are described in the table below. 
Investigational Product and Active Comparator Administered 
Study Arm: 
mRNA-1273 
mRNA-1273.529 
mRNA-1273.214 
Intervention 
Name: 
mRNA-1273 (aka, 
Moderna COVID-19 
vaccine) 
mRNA-1273.529 
mRNA-1273.214 

ModernaTX, Inc. 
mRNA-1273-P305 Protocol Amendment 2 
mRNA-1273 
Confidential 
Page 18 
Type: 
Vaccine 
Vaccine 
Vaccine 
Dosage 
Level(s): 
50 µg (mRNA) 
50 µg (mRNA) 
50 µg (mRNA) 
Route of 
Administration: 
IM injection 
IM injection 
IM injection 
Physical 
Description: 
Sterile liquid for 
injection, 
white-to-off-white 
dispersion 
Sterile liquid for 
injection, 
white-to-off-white 
dispersion 
Sterile liquid for 
injection, white-to-
off-white dispersion 
Source: 
Sourced locally by 
the sites  
Provided centrally by 
the Sponsor 
Provided centrally 
by the Sponsor 
Packaging and 
Labeling: 
mRNA-1273 will be 
provided in its 
commercial 
presentation  
mRNA-1273.529 will 
be provided in 
2R borosilicate glass 
vials. Vials will be 
labeled as required per 
local requirement. 
mRNA-1273.214 
will be provided in 
2R borosilicate glass 
vials. Vials will be 
labeled as required 
per local 
requirement.  
Abbreviations: IM = intramuscular; mRNA = messenger ribonucleic acid. 
mRNA-1273 is a LNP dispersion of an mRNA encoding the prefusion stabilized S protein of 
SARS-CoV-2.  
mRNA-1273.529 contains mRNA CX-031302 encoding for the S-2P of the SARS-CoV-2 
Omicron variant (B.1.1.529). mRNA-1273 contains mRNA CX-024414 encoding for the S-2P 
of Wuhan-Hu-1. mRNA-1273.529 and mRNA-1273 each consists of mRNAs formulated in a 
mixture of 4 lipids common to the Sponsor’s mRNA vaccine platform: SM-102, cholesterol, 
DSPC, and PEG 2000-DMG. 
mRNA-1273.214 contains CX-024414, the mRNA that encodes for the prefusion stabilized 
spike glycoprotein (S-2P) of the Wuhan-Hu-1 isolate of SARS-CoV-2, and CX-031302, the 
mRNA that encodes for the S-2P of the SARS-CoV-2 B.1.1.529 variant. The formulated 
mRNAs are mixed in a 1:1 ratio. mRNA-1273.214 consists of each mRNA formulated in a 
mixture of four lipids common to the Sponsor's mRNA vaccine platform: SM-102, cholesterol, 
DSPC, and PEG 2000-DMG. 
mRNA-1273.529, mRNA-1273.214, and mRNA-1273 will be administered at a 50 µg dose 
level as an IM injection into the deltoid muscle on Day 1.  
Procedures and Assessments:  

ModernaTX, Inc. 
mRNA-1273-P305 Protocol Amendment 2 
mRNA-1273 
Confidential 
Page 19 
Immunogenicity Assessments:  
Blood samples will be collected for the following parameters: 
• Serum binding antibody (bAb) level against SARS-CoV-2 as measured by ligand 
binding assay specific to the SARS-CoV-2 S protein and the S protein receptor-binding 
domain (RBD). 
• Serum neutralizing antibody (nAb) level against SARS-CoV-2 as measured by 
pseudovirus neutralization assays. 
• Testing for serologic markers for SARS-CoV-2 infection as measured by anti-
nucleocapsid antibodies detected by immunoassay. 
Safety Assessments: 
Safety assessments will include monitoring and recording of the following for each 
participant: 
• Solicited local and systemic adverse reactions (ARs) that occur during the 7 days 
following vaccination (ie, the day of injection and 6 subsequent days). Solicited ARs 
will be recorded daily using eDiaries. 
• Unsolicited adverse events (AEs) observed or reported during the 28 days following 
vaccination. Unsolicited AEs are AEs that are not included in the protocol-defined 
solicited ARs. 
• AEs leading to withdrawal from the study. 
• Medically attended AEs (MAAEs) from vaccination on Day 1 through end of study 
(EoS) or withdrawal from the study. 
• AEs of special interest (AESIs) from vaccination on Day 1 through EoS or withdrawal 
from the study. 
• Serious AEs (SAEs) from vaccination on Day 1 through EoS or withdrawal from the 
study. 
• Vital sign measurements before and after vaccination. 
• Physical examination findings (if performed). 
• Assessments for SARS-CoV-2 infection from Day 1 through study completion. 
• Details of all pregnancies in female participants will be collected after the start of study 
vaccine and until the end of their participation in the study. All pregnancies must be 

ModernaTX, Inc. 
mRNA-1273-P305 Protocol Amendment 2 
mRNA-1273 
Confidential 
Page 20 
followed to determine the outcome; however, pregnancy related data received after the 
end of the study may not be collected in the clinical database. 
Efficacy Assessments: 
Vaccine efficacy will be assessed as an exploratory endpoint in Part 1 and as a secondary 
endpoint in Part 2 of this study. Active surveillance for COVID-19 and SARS-CoV-2 
infection will be performed in both parts of the study. 
Statistical Methods: 
Statistical Hypotheses: 
Part 1: 
The primary objective on immune response in Part 1 of this study is based on the participants 
who will receive the 4th dose of the study vaccine.  
Primary Hypotheses:  
1) mRNA-1273.529, as a single booster dose, is non-inferior to mRNA-1273 based on 
GMT ratio against the B.1.1.529 strain with a non-inferiority margin of 1.5 at Day 29. 
2) mRNA-1273.529, as a single booster dose, is non-inferior to mRNA-1273 based on 
GMT ratio against the B.1.1.529 strain with a non-inferiority margin of 1.5 at Month 3. 
Key Secondary Hypothesis: 
mRNA-1273.529, as a single booster dose, is superior to mRNA-1273 based on GMT ratio 
against the B.1.1.529 strain at Day 29 or Month 3. 
For the primary objective of immune response, hypotheses testing based on participants 
receiving the 4th dose, alpha of 0.05 (2-sided) will be allocated to the 2 time points: alpha of 
0.01 (2-sided) will be allocated to Day 29, alpha of 0.04 (2-sided) will be allocated to Month 
3.  
The non-inferiority of mRNA-1273.529 as compared to mRNA-1273 against the B.1.1.529 
strain at Day 29 will be assessed using a non-inferiority margin of 1.5 at 2-sided alpha of 0.01. 
The primary immunogenicity objective is considered met if non-inferiority against the 
B.1.1.529 strain is demonstrated, ie, the lower bound of the 99% confidence interval (CI) of 
the GMT ratio of mRNA-1273.529 vs. mRNA-1273 against B.1.1.529 is ≥ 0.67 (1/1.5).  
The non-inferiority of mRNA-1273.529 as compared to mRNA-1273 against the B.1.1.529 
strain at Month 3 will be assessed using a non-inferiority margin of 1.5 at 2-sided alpha of 
0.04. The primary immunogenicity objective is considered met if non-inferiority against the 

ModernaTX, Inc. 
mRNA-1273-P305 Protocol Amendment 2 
mRNA-1273 
Confidential 
Page 21 
B.1.1.529 strain is demonstrated, ie, the lower bound of the 96% confidence interval (CI) of 
the GMT ratio of mRNA-1273.529 vs. mRNA-1273 against B.1.1.529 is ≥ 0.67 (1/1.5).  
Part 2: 
The primary objective on immune response in Part 2 of this study is based on the participants 
who will receive the 4th dose in Part 2 of the study. There are 6 hypotheses on immune 
response of mRNA-1273.214 listed below. Part 2 of this study is considered to have met its 
primary objective if non-inferiority of mRNA-1273.214 against the B.1.1.529 strain, non-
inferiority of mRNA-1273.214 against the prototype strain, and superiority of mRNA-
1273.214 against the B.1.1.529 strain are demonstrated as compared to mRNA-1273 at any of 
the following time points post-booster: Day 29, Month 3. The figure below depicts the 
hypotheses testing strategy. 
Primary Hypotheses:  
1) mRNA-1273.214, as a single booster dose, is non-inferior to mRNA-1273 based on 
GMT ratio against the B.1.1.529 strain with a non-inferiority margin of 1.5 at Day 29. 
2) mRNA-1273.214, as a single booster dose, is non-inferior to mRNA-1273 based on 
GMT ratio against the prototype strain with a non-inferiority margin of 1.5 at Day 29. 
3) mRNA-1273.214, as a single booster dose, is superior to mRNA-1273 based on GMT 
ratio against the B.1.1.529 strain at Day 29. 
4) mRNA-1273.214, as a single booster dose, is non-inferior to mRNA-1273 based on 
GMT ratio against the B.1.1.529 strain with a non-inferiority margin of 1.5 at Month 3. 
5) mRNA-1273.214, as a single booster dose, is non-inferior to mRNA-1273 based on 
GMT ratio against the prototype strain with a non-inferiority margin of 1.5 at Month 3. 
6) mRNA-1273.214, as a single booster dose, is superior to mRNA-1273 based on GMT 
ratio against the B.1.1.529 strain at Month 3. 

ModernaTX, Inc. 
mRNA-1273-P305 Protocol Amendment 2 
mRNA-1273 
Confidential 
Page 22 
Figure: Statistical Hypothesis Testing Strategy of mRNA-1273.214 vs. mRNA-1273 
(Part 2) 
 
 
Abbreviations: M = month; mRNA = messenger ribonucleic acid. 
For the primary objective of immune response, hypotheses testing based on participants 
receiving the 4th dose, alpha of 0.05 (2-sided) will be allocated to the two time points: alpha of 
0.01 (2-sided) will be allocated to Day 29, and alpha of 0.04 (2-sided) will be allocated to 
Month 3. 
For the primary immunogenicity objective, the non-inferiority of mRNA-1273.214 as 
compared to mRNA-1273 against the B.1.1.529 strain and the non-inferiority of 
mRNA-1273.214 as compared to mRNA-1273 against the prototype strain at Day 29 will be 
assessed using a non-inferiority margin of 1.5 at 2-sided alpha of 0.01. Non-inferiority against 
the B.1.1.529 strain and the prototype strain are both demonstrated if the lower bound of the 
99% confidence interval (CI) of the GMR of mRNA-1273.214 vs. mRNA-1273 against 
B.1.1.529 is ≥ 0.67 (1/1.5) and the lower bound of the 99% CI of the GMR of 
mRNA-1273.214 vs mRNA-1273 against prototype is ≥ 0.67. 
Superiority of mRNA-1273.214 as compared to mRNA-1273 against the B.1.1.529 strain will 
be evaluated at Day 29. Once the non-inferiority of mRNA-1273.214 as compared to 
mRNA-1273 against both the B.1.1.529 and the prototype strain at Day 29 is demonstrated, 

ModernaTX, Inc. 
mRNA-1273-P305 Protocol Amendment 2 
mRNA-1273 
Confidential 
Page 23 
the 99% CI of GMR (mRNA-1273.214 vs. mRNA-1273) will be used to assess superiority of 
mRNA-1273.214 as compared to mRNA-1273. If the lower bound of the GMR rules out (>) 1 
at Day 29, superiority of mRNA-1273.214 compared to mRNA-1273 against B.1.1.529 will be 
considered demonstrated. 
Hypotheses testing at Month 3 will be performed in the same manner, first testing two non-
inferiority hypotheses (one against the B.1.1.529 strain and one against the prototype strain) at 
alpha of 0.04 level (2-sided). Once non-inferiority is demonstrated for both B.1.1529 and 
prototype strains, then superiority testing against the B.1.1.529 at alpha of 0.04 level (2-sided) 
will be performed. 
Sample Size Justification: 
This study will include:  
1. Participants who received 2 doses of a COVID-19 vaccine as the primary series and the 
3rd dose of a COVID-19 vaccine and will receive the 4th dose as part of the study. 
2. Participants who received 2 doses of a COVID-19 vaccine as the primary series and will 
receive the 3rd dose as part of the study. 
Part 1 (50 µg mRNA-1273.529 and 50 µg mRNA-1273 in 1:1 randomization) 
The primary immunogenicity objective is to assess immune response of mRNA-1273.529 
against B.1.1.529 in participants who are receiving mRNA-1273.529 (or mRNA-1273) as the 
4th dose in Part 1 of this study.  
The target enrollment is up to 500 participants (minimum of 300) for each study arm (1:1). 
The assumptions are: 1) at least 
 participants will be in the 4th dose subgroup; and 2) 
 
of participants will be excluded from the PP set for immunogenicity, SARS-CoV-2 negative 
(eg, due to infection with the SARS-CoV-2 Omicron variant).  
Day 29: 
With approximately 
 evaluable participants per arm, there is 
 power to 
demonstrate non-inferiority of mRNA-1273.529 against the B.1.1.529 strain at 2-sided alpha 
of 1.0% at Day 29. With this range of sample sizes, the power to demonstrate superiority of 
mRNA-1273.529 against the B.1.1.529 variant strain at a 2-sided alpha of 1% at Day 29 
ranges from 
. The assumptions are: the true GMT ratio (mRNA-1273.529 vs 
mRNA-1273) ranges from 
, the standard deviation of the natural log-transformed 
titer is 
, with a non-inferiority margin of 1.5. 
CCI
CCI
CCI
CCI
CCI
CCI
CCI

ModernaTX, Inc. 
mRNA-1273-P305 Protocol Amendment 2 
mRNA-1273 
Confidential 
Page 24 
Month 3: 
With approximately 
 evaluable participants per arm, there is 
 power 
to demonstrate non-inferiority of mRNA-1273.529 against the B.1.1.529 strain at 2-sided 
alpha of 4.0% at Month 3. With this range of sample sizes, the power to demonstrate 
superiority of mRNA-1273.529 against the B.1.1.529 variant strain at a 2-sided alpha of 4% at 
Month 3 ranges from 
. The assumptions are: the true GMT ratio 
(mRNA-1273.529 vs mRNA-1273) ranges from 
, the standard deviation of the 
natural log-transformed titer is 
, with a non-inferiority margin of 1.5. Specific operating 
characteristics are presented in the table below. 
With approximately 
 participants receiving the 4th dose in each study arm, there is at 
least 90% probability to observe one participant reporting an AE in each study arm if the true 
incidence of AEs is 1%.  
Operating Characteristics for Part 1: 
True GMR  
 
(mRNA-1273.529 
vs. mRNA-1273 
against B.1.1.529) 
Number 
evaluable 
patients 
per arm 
(4th dose) 
Minimum empirical 
GMR for the primary 
objective 
Power 
Two-sided Type I Error (α) = 0.01 (Day 29) 
Primary Objective: Non-inferiority (lower bound of the (1-α) *100% of GMR ≥ 0.67) 
Key Secondary Objective: Superiority (lower bound of the (1-α) *100% of GMR rules out 1) 
Two-sided Type I Error (α) = 0.04 (Month 3) 
CCI
CCI
CCI
CCI
CCI
CCI
CCI
CCI

ModernaTX, Inc. 
mRNA-1273-P305 Protocol Amendment 2 
mRNA-1273 
Confidential 
Page 25 
Primary Objective: Non-inferiority (lower bound of the (1-α) *100% of GMR ≥ 0.67) 
Key Secondary Objective: Superiority (lower bound of the (1-α) *100% of GMR rules out 1) 
Abbreviations: GMR = geometric mean titer ratio; mRNA = messenger ribonucleic acid. 
Part 2 (50 µg mRNA-1273.214 and 50 µg mRNA-1273 in 1:1 randomization) 
The primary immunogenicity objective in Part 2 of this study is to assess immune response of 
mRNA-1273.214 against the B.1.1.529 and prototype strains in participants receiving mRNA-
1273.214 (or mRNA-1273) as the 4th dose. The sample size is driven by this subgroup. 
Hypotheses testing on immunogenicity data will be performed at 2 timepoints of interest (Day 
29 and Month 3 post-booster). To preserve family-wise alpha of 0.05 (2-sided), alpha will be 
allocated to Day 29 of 0.01 (2-sided) and Month 3 of 0.04 (2-sided). 
Statistical power for hypotheses testing at Day 29 (alpha=0.01, 2-sided): 
For the 4th dose subgroup, the target enrollment is approximately 1328 participants for each 
treatment arm (1:1). Assuming 
 of participants will be excluded from the PP Set for 
Immunogenicity, SARS-CoV-2 negative, with approximately 
 evaluable participants in 
each arm, there is 
 power to demonstrate non-inferiority of mRNA-1273.214 
against the B.1.1.529 and prototype strains at 2-sided alpha of 1.0%. With this sample size, 
there is approximately 
 power to demonstrate superiority of mRNA-1273.214 
against the B.1.1.529 variant strain at a 2-sided alpha of 1.0% at Day 29. The assumptions are: 
the true GMT ratio (mRNA-1273.214 vs. mRNA-1273) against the B.1.1.529 strain ranges 
from 
 and the true GMT ratio (mRNA-1273.214 vs. mRNA-1273) against the 
CCI
CCI
CCI
CCI
CCI
CCI
CCI

ModernaTX, Inc. 
mRNA-1273-P305 Protocol Amendment 2 
mRNA-1273 
Confidential 
Page 26 
prototype is , the standard deviation of the natural log-transformed titer is 
, with a non-
inferiority margin of 1.5.  
Statistical power for hypotheses testing at Month 3 (alpha=0.04, 2-sided): 
With approximately 
 evaluable participants in each arm, there is 
 power to 
demonstrate non-inferiority of mRNA-1273.214 against the B.1.1.529 strain and against 
prototype strain at 2-sided alpha of 4.0% at Month 3. With this sample size, there is 
approximately 
 power to demonstrate superiority of mRNA-1273.214 against the 
B.1.1.529 variant strain at a 2-sided alpha of 4.0% at Month 3. The assumptions are: the true 
GMT ratio (mRNA-1273.214 vs. mRNA-1273) against the B.1.1.529 strain ranges from 
 
and the true GMT ratio (mRNA-1273.214 vs. mRNA-1273) against the prototype is , 
the standard deviation of the natural log-transformed titer is 
, with a non-inferiority margin 
of 1.5. 
With approximately 1328 participants receiving the 4th dose in each study arm, there is at least 
90% probability to observe one participant reporting an AE in each study arm if the true rate 
incidence of AEs is 1%.  
The enrollment target of this study is approximately 1328 participants per arm to receive the 
4th dose. The Omicron VOC has spread quickly throughout the world as the predominant 
circulating SARS-CoV-2 strain globally. There may be an urgency to perform Day 29 or 
Month 3 analysis as early as possible. Depending on the operational feasibility, particularly 
the testing capability of assays of antibodies against B.1.1.529, the Sponsor may decide to 
perform the analysis of immunogenicity after immunogenicity data from a subset of the 
participants receiving the 4th dose becomes available. Such a decision will be documented 
prior to the planned analysis at Day 29 or Month 3.  
The power and operating characteristics for Part 2 under various GMT ratios and 2 different 
scenarios for the number of evaluable participants with immunogenicity data are provided in 
the table below. Based on 
 evaluable participants per arm (4th dose), under the same 
assumptions outlined above, there is 
 power to demonstrate non-inferiority of 
mRNA-1273.214 compared to mRNA-1273 against the- B.1.1.529 at Day 29 at α = 1% if true 
GMT ratio 
; and there is approximately 
 power to demonstrate superiority at α = 1% 
if the true ratio if 
 With this size, there is 
 power at Month 3 (primary 
objective) at α = 4% (2-sided) if the true GMT ratio is 
; and there is 
 power to 
demonstrate superiority at α = 4% (2-sided) if the true GMR is 
. 
CCI
CCI
CCI
CCI
CCI
CCI
CCI
CCI
CCI
CCI
CCI
CCI
CCI
CCI
CCI
CCI
CCI

ModernaTX, Inc. 
mRNA-1273-P305 Protocol Amendment 2 
mRNA-1273 
Confidential 
Page 27 
Operating Characteristics for Part 2: 
True GMR  
 
(mRNA-1273.214 
vs. mRNA-1273 
against 
B.1.1.529) 
Number 
evaluable 
patients per 
arm (4th 
dose) 
Minimum empirical GMR for the 
primary objective 
Power 
Two-sided Type I Error (α) = 0.01 (Day 29) 
Primary Objective: Non-inferiority (lower bound of the (1-α) *100% of GMR ≥ 0.67) 
Primary Objective: Superiority (lower bound of the (1-α) *100% of GMR rules out 1) 
Two-sided Type I Error (α) = 0.04 (Month 3) 
Primary Objective: Non-inferiority (lower bound of the (1-α) *100% of GMR ≥ 0.67) 
CCI
CCI

ModernaTX, Inc. 
mRNA-1273-P305 Protocol Amendment 2 
mRNA-1273 
Confidential 
Page 28 
Primary Objective: Superiority (lower bound of the (1-α) *100% of GMR rules out 1) 
Abbreviations: GMR = geometric mean titer ratio; mRNA = messenger ribonucleic acid. 
CCI
CCI

ModernaTX, Inc. 
mRNA-1273-P305 Protocol Amendment 2 
mRNA-1273 
Confidential 
Page 29 
Analysis Populations (Part 1 and Part 2): 
Set 
Description 
Full Analysis Set (FAS) 
The FAS consists of all randomized participants who receive the 
IP. Participants will be analyzed according to their randomized 
study arm. 
Modified Intent-to-Treat 
(mITT) Set 
The mITT Set consists of all participants in the FAS who have no 
serologic or virologic evidence of prior SARS-CoV-2 infection 
(both negative RT-PCR test for SARS-CoV-2 and negative 
serology test based on bAb specific to SARS-CoV-2 
nucleocapsid) prebooster, ie, all FAS participants with pre-
booster/baseline SARS-CoV-2 negative status. Participants will be 
analyzed according to their randomized study arm. 
PP Set for Immunogenicity 
(PPSI) 
The PPSI consists of all participants in the FAS who receive the 
planned dose of study vaccination and have no major protocol 
deviations that impact key or critical data. Participants will be 
analyzed according to their randomized study arm. 
PP Set for Immunogenicity –
SARS-CoV-2 negative (PPSI-
Neg) 
Participants in the PPSI who have no serologic or virologic 
evidence of SARS-CoV-2 infection up to day of visit analysis, ie, 
who are SARS-CoV-2 negative, defined by both negative RT-
PCR test for SARS-CoV-2 and negative serology test based on 
bAb specific to SARS-CoV-2 nucleocapsid. 
PPSI-Neg will be the primary analysis set for analyses of 
immunogenicity unless otherwise specified.  
Solicited Safety Set 
The Solicited Safety Set consists of all randomized participants 
who receive IP and contribute any solicited AR data. 
The Solicited Safety Set will be used for the analyses of solicited 
ARs. Participants will be included in the study arm that they 
actually received. 
Safety Set 
The Safety Set consists of all randomized participants who receive 
IP. The Safety Set will be used for all analyses of safety except for 
the solicited ARs. Participants will be included in the study arm 
that they actually received. 
PP Set for Efficacy (PPSE) 
The PPSE consists of all participants in the mITT who receive the 
planned study vaccination and have no major protocol deviations 
that impact key or critical data. 
Abbreviations: AR = adverse reaction; FAS = full analysis set; IP = investigational product; mITT = modified 
intent-to-treat; PP = Per protocol; RT-PCR = reverse transcription polymerase chain reaction; SARS-CoV-
2 = severe acute respiratory syndrome coronavirus 2. 

ModernaTX, Inc. 
mRNA-1273-P305 Protocol Amendment 2 
mRNA-1273 
Confidential 
Page 30 
Immunogenicity Analysis: 
Part 1: mRNA-1273.529 vs. mRNA-1273 
The primary objective on immune response in Part 1 of this study is based on the participants 
who will receive the 4th dose in the study. There is 1 hypothesis on immune response of 
mRNA-1273.529. Part 1 is considered to meet its primary objective if non-inferiority of 
mRNA-1273.529 against the B.1.1.529 strain is demonstrated as compared to mRNA-1273 
(primary hypothesis). 
An analysis of covariance (ANCOVA) model will be performed to assess the difference in 
immune response between mRNA-1273.529 and mRNA-1273 as the 4th dose in the subgroup 
of participants who received the 4th dose. This analysis will be carried out for immune 
response against the B.1.1.529 strain and the prototype virus strain separately in the PPSI-Neg 
analysis population. 
Specifically, for immune response against the B.1.1.529 strain, in the ANCOVA model, 
antibody titers at Day 29 post-booster against the B.1.1.529 strain will be a dependent 
variable, and a group variable (mRNA-1273.529 and mRNA-1273) will be the fixed effect, 
adjusting for age groups (< 65, ≥ 65 years) and pre-booster antibody titer level, if applicable. 
The GMT will be estimated by the geometric least square mean (GLSM) from the model and 
its corresponding 99% CIs will be provided for each group. The GMR (ratio of GMTs) for 
mRNA-1273.529 with respect to mRNA-1273 will be estimated by the ratio of GLSM from 
the model and the corresponding 99% CIs will be provided. The 99% CI for GMR will be 
used to assess the between group difference in immune response against the B.1.1.529 strain 
for mRNA-1273.529 at Day 29 compared to the mRNA-1273 as a booster for non-inferiority 
testing.  
Against the B.1.1.529 strain, the non-inferiority of immune response of mRNA-1273.529 as 
compared to mRNA-1273 will be considered demonstrated if the lower bound of the 
corresponding 99% CI is ≥ 0.67 (Day 29) based on a non-inferiority margin of 1.5. 
Once non-inferiority against B.1.1.529 is demonstrated, superiority of mRNA-1273.529 as 
compared to mRNA-1273 against B.1.1529 will be tested; if the lower bound of the 99% CI of 
the GMT ratio is > 1 (Day 29), superiority is demonstrated.  
The same ANCOVA model will be used to assess immune response of mRNA-1273.529 
against the B.1.1.529 strain at Month 3; 96% CI for GMR will be used to assess the between 
group difference in immune response against the B.1.1.529 strain for non-inferiority and 
superiority. For the immune response against the prototype virus strain, the same analysis 
method will be used. 

ModernaTX, Inc. 
mRNA-1273-P305 Protocol Amendment 2 
mRNA-1273 
Confidential 
Page 31 
Part 2: mRNA-1273.214 vs. mRNA-1273 
The primary objective on immune response in Part 2 of this study is based on the participants 
who will receive the 4th dose in Part 2 of the study. There are 6 hypotheses on the immune 
response of mRNA-1273.214 (see figure above). Part 2 is considered to meet its primary 
objective if non-inferiority of mRNA-1273.214 against the B.1.1.529 strain, non-inferiority of 
mRNA-1273.214 against the prototype, and superiority of mRNA-1273.214 against the 
B.1.1.529 strain are demonstrated as compared to mRNA-1273 at any of the following time 
points post-booster: Day 29, Month 3. 
An ANCOVA model will be carried out to assess the difference in immune response between 
mRNA-1273.214 and mRNA-1273 in the subgroup of participants who received the 4th dose. 
This analysis will be carried out for the immune response against the B.1.1.529 strain and the 
prototype virus strain separately using the PPSI-Neg analysis population. 
Specifically, for immune response against the B.1.1.529 strain, in the ANCOVA model, 
antibody titers at Day 29 post-booster against the B.1.1.529 strain will be a dependent 
variable, and a group variable (mRNA-1273.214 and mRNA-1273) will be the fixed effect, 
adjusting for age groups (< 65, ≥ 65 years) and pre-booster antibody titer level, if applicable. 
The GMT will be estimated by the geometric least square mean (GLSM) from the model and 
its corresponding 99% CIs will be provided for each group. The GMR (ratio of GMTs) for 
mRNA-1273.214 with respect to mRNA-1273 will be estimated by the ratio of GLSM from 
the model and the corresponding 99% CIs will be provided. The 99% CI for GMR will be 
used to assess the between group difference in immune response against the B.1.1.529 strain 
for mRNA-1273.529 at Day 29 compared to the mRNA-1273 as a booster for non-inferiority 
testing.  
Against the B.1.1.529 strain, the non-inferiority of immune response of mRNA-1273.214 as 
compared to mRNA-1273 will be considered demonstrated if the lower bound of the 
corresponding 99% CI is ≥ 0.67 based on a non-inferiority margin of 1.5. 
Once non-inferiority against B.1.1.529 is demonstrated, superiority of mRNA-1273.214 as 
compared to mRNA-1273 against B.1.1529 will be tested (at Day 29); if the lower bound of 
the 99% CI of the GMT ratio is > 1, superiority is demonstrated. 
The same ANCOVA model will be used to assess immune response of mRNA-1273.214 
against the B.1.1.529 strain at Month 3; 96% CI for GMR will be used to assess the between 
group difference in immune response against the B.1.1.529 strain for non-inferiority and 
superiority. For the immune response against the prototype virus strain, the same analysis 
method will be used. 

ModernaTX, Inc. 
mRNA-1273-P305 Protocol Amendment 2 
mRNA-1273 
Confidential 
Page 32 
As part of the secondary analysis to assess for immune response against other variants, the 
same analysis method described above will be used. A 95% CI for GMR will be used to assess 
for non-inferiority and superiority. 
The following section is applicable to both Part 1 and Part 2: 
Immunogenicity, SARS-CoV-2-specific bAb and nAb, will be assessed at multiple timepoints 
in this study. Mixed effects models will be used to analyze all post-booster/baseline measures. 
The models will include treatment group, analysis visit, treatment by visit interaction, and 
adjustment for age groups and pre-booster titer levels. An unstructured covariance structure 
will be used to model the within-participant errors. The GMT will be estimated from the 
model and its corresponding 95% CI will be provided for each group at each post-boost 
timepoint. The GMR (ratio of GMTs) for mRNA-1273.529 and for mRNA-1273.214 with 
respect to mRNA-1273 will be estimated from each model and the corresponding 95% CI will 
be provided at each post-boost time point. 
For each of the antibodies of interest (eg, levels of SARS-CoV-2–specific bAb and 
SARSCoV-2-specific nAb), the GMT or level with corresponding 95% CI at each time point, 
and GMFR of post-booster/pre-booster titers or levels with corresponding 95% CI at each post 
baseline time point will be provided for each arm. The 95% CIs will be calculated based on 
the t-distribution of the log-transformed values then back-transformed to the original scale for 
presentation. The following descriptive statistics will also be provided at each time point: 
number of participants (n), median, minimum, and maximum. PPSI will be used as the 
analysis population to summarize the immune responses (antibodies of interest) and the above 
summary statistics including GMT and GMFR will be provided by pre-booster/study baseline 
SARS-CoV-2 status. 
SRR definitions and analyses will be defined in the SAP. 
Planned Analyses  
The planned analyses of immunogenicity and safety will be conducted after participants have 
completed Day 29 and Month 3 visit assessments. Analyses of the Month 6 and Month 12 visit 
including the Phase B (open-label, observational) part of the study will be exploratory.  
The final analysis of all endpoints will be performed after all participants have completed or 
discontinued from the study. Results of this analysis will be presented in a final CSR. 
Efficacy Analyses: 
Number and incidence rates of symptomatic COVID-19 disease, asymptomatic SARS-CoV-2 
infection, as well as COVID-19 regardless of symptoms will be provided for each study arm. 
Vaccine efficacy may be estimated if the number of cases accrued is deemed to be sufficient. 

ModernaTX, Inc. 
mRNA-1273-P305 Protocol Amendment 2 
mRNA-1273 
Confidential 
Page 33 
Efficacy analyses will be performed using the mITT and PP Set for Efficacy analysis 
populations. The details will be provided in SAP. 
Safety Analyses: 
All safety analyses will be based on the Safety Set, except analyses of solicited ARs, which 
will be based on the Solicited Safety Set.  
Safety and reactogenicity will be assessed by clinical review of all relevant parameters 
including solicited ARs (local and systemic ARs), unsolicited AEs, and physical examination 
findings.  
The number and percentage of participants with any solicited local AR, with any solicited 
systemic AR, with any solicited AR during the 7-day follow-up period after vaccination, and 
with Grade 3 or higher solicited AR will be provided. A 2-sided 95% exact CI using the 
Clopper Pearson method will be provided for the percentage of participants with any solicited 
AR. 
The number and percentage of participants with unsolicited AEs, treatment-related AEs, 
severe AEs, SAEs, MAAEs, AESIs, and AEs leading to withdrawal will be summarized. 
Unsolicited AEs will be presented by MedDRA system organ class and preferred term. 
Unsolicited AEs will be coded according to the MedDRA Dictionary for Adverse Reaction 
Terminology. 
Pregnancy outcomes will also be summarized. 
 
 

ModernaTX, Inc. 
mRNA-1273-P305 Protocol Amendment 2 
mRNA-1273 
Confidential 
Page 34 
1.2. 
Study Schema 
The study schema is presented in Figure 1. 
Figure 1: 
Study Schema 
 
Abbreviations: COVID-19 = coronavirus disease 2019; mRNA = messenger ribonucleic acid; N = number.  
 

ModernaTX, Inc. 
mRNA-1273-P305 Protocol Amendment 2 
mRNA-1273 
Confidential 
Page 35 
1.3. 
Schedule of Events 
Table 1: 
Schedule of Events Part 1 
Visit Number 
 
1 
2 
 
 
3 
4 
5 
 
6 
USV 
Type of Visit 
C 
C 
SC 
SC 
SC 
C 
C 
C 
SC 
C 
C 
Month Timepoint 
 
M0 
 
 
 
M1 
M3 
M6 
M9 
M12 
Up to 
M12 
Study Visit Day  
Screening1 
D1 
(Baseline) 
D8 
D15 
D22 
D29 
D85 
D179 
D269 
D359/EoS 
USV 
Window Allowance 
(Days) 
-28 
 
+3 
+3 
+3 
-3/+7 
±7 
±14 
±7 
±14 
N/A 
Days Since Vaccination 
- 
0 
7 
14 
21 
28 
84 
178 
268 
358 
 
ICF, demographics, 
concomitant 
medications, medical 
history2  
X 
 
 
 
 
 
 
 
 
 
 
Confirm participant 
meets inclusion and 
exclusion criteria 
X 
X 
 
 
 
 
 
 
 
 
 
Physical examination3 
X 
X 
 
 
 
X 
X 
X 
 
X 
X 
Vital signs4 
X 
X 
 
 
 
 
 
 
 
 
X 
Pregnancy testing5 
X 
X 
 
 
 
 
 
 
 
 
 
Randomization 
 
X 
 
 
 
 
 
 
 
 
 
Dosing 
 
Study injection 
(including 15-minute 
post-dosing observation 
period) 
 
X 
 
 
 
 
 
 
 
 
 
Surveillance for COVID-19 
 

ModernaTX, Inc. 
mRNA-1273-P305 Protocol Amendment 2 
mRNA-1273 
Confidential 
Page 36 
Visit Number 
 
1 
2 
 
 
3 
4 
5 
 
6 
USV 
Type of Visit 
C 
C 
SC 
SC 
SC 
C 
C 
C 
SC 
C 
C 
Month Timepoint 
 
M0 
 
 
 
M1 
M3 
M6 
M9 
M12 
Up to 
M12 
Study Visit Day  
Screening1 
D1 
(Baseline) 
D8 
D15 
D22 
D29 
D85 
D179 
D269 
D359/EoS 
USV 
Window Allowance 
(Days) 
-28 
 
+3 
+3 
+3 
-3/+7 
±7 
±14 
±7 
±14 
N/A 
Days Since Vaccination 
- 
0 
7 
14 
21 
28 
84 
178 
268 
358 
 
Surveillance for 
COVID-19/Unscheduled 
visit6 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Nasopharyngeal swab6 
 
X 
 
 
 
X 
X 
X 
 
X 
X 
Blood for SARS-CoV-2 
surveillance  
 
X 
 
 
 
X 
X 
X 
 
X 
 
eDiary activation for 
surveillance for 
COVID-19/Unscheduled 
visit 
 
 
 
 
 
X 
 
 
 
 
 
eDiary prompts every 2 
weeks for surveillance 
for COVID-19 and 
major changes in health 
 
 
 
 
 
eDiary prompts every 2 weeks (Day 43 through 
Day 359/EoS) 
 
Immunogenicity Assessment 
 
Blood for humoral 
immunogenicity7 
 
X 
 
 
 
X 
X 
X 
 
X  
 

ModernaTX, Inc. 
mRNA-1273-P305 Protocol Amendment 2 
mRNA-1273 
Confidential 
Page 37 
Visit Number 
 
1 
2 
 
 
3 
4 
5 
 
6 
USV 
Type of Visit 
C 
C 
SC 
SC 
SC 
C 
C 
C 
SC 
C 
C 
Month Timepoint 
 
M0 
 
 
 
M1 
M3 
M6 
M9 
M12 
Up to 
M12 
Study Visit Day  
Screening1 
D1 
(Baseline) 
D8 
D15 
D22 
D29 
D85 
D179 
D269 
D359/EoS 
USV 
Window Allowance 
(Days) 
-28 
 
+3 
+3 
+3 
-3/+7 
±7 
±14 
±7 
±14 
N/A 
Days Since Vaccination 
- 
0 
7 
14 
21 
28 
84 
178 
268 
358 
 
Safety Assessments 
 
eDiary activation for 
recording solicited 
adverse reactions 
(7 days)8 
 
X 
 
 
 
 
 
 
 
 
 
Review of eDiary 
 
 
X 
 
 
 
 
 
 
 
 
Follow-up safety 
 
 
X 
X 
X 
 
 
 
X 
 
 
Recording of 
Unsolicited AEs  
 
X 
X 
X 
X 
X 
 
 
 
 
 
Recording of MAAEs, 
AESIs, AE leading to 
withdrawal and 
concomitant 
medications relevant to 
or for the treatment of 
these events9 
 
X 
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 
X 

ModernaTX, Inc. 
mRNA-1273-P305 Protocol Amendment 2 
mRNA-1273 
Confidential 
Page 38 
Visit Number 
 
1 
2 
 
 
3 
4 
5 
 
6 
USV 
Type of Visit 
C 
C 
SC 
SC 
SC 
C 
C 
C 
SC 
C 
C 
Month Timepoint 
 
M0 
 
 
 
M1 
M3 
M6 
M9 
M12 
Up to 
M12 
Study Visit Day  
Screening1 
D1 
(Baseline) 
D8 
D15 
D22 
D29 
D85 
D179 
D269 
D359/EoS 
USV 
Window Allowance 
(Days) 
-28 
 
+3 
+3 
+3 
-3/+7 
±7 
±14 
±7 
±14 
N/A 
Days Since Vaccination 
- 
0 
7 
14 
21 
28 
84 
178 
268 
358 
 
Recording of 
concomitant 
medications and non-
study vaccinations10 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Abbreviations: AE = adverse event; AESI = adverse event of special interest; AR = adverse reaction; C = clinic visit; COVID-19 = coronavirus disease 2019; 
D = day; eDiary = electronic diary; EoS = end of study; ICF = informed consent form; M = month; MAAE = medically attended AE; N/A = not applicable; 
NP = nasopharyngeal; SAE = serious adverse event; SARS-CoV-2 = severe acute respiratory syndrome coronavirus 2; SC = safety (phone) call; USV = 
unscheduled safety visit. 
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 AEs and concomitant medications. Home visits will be permitted for all non-dosing visits 
except for Screening if a participant cannot come to the study site. 
1. 
The Screening Visit and Day 1 may be performed on the same day or a different day. Additionally, the Screening visit may be performed over multiple visits 
if within the 28-day screening window. 
2. 
Verbal medical history is acceptable. 
3. 
Physical examination: a full physical examination, including vital signs, height, and weight, will be performed at Screening and Day 1. Body mass index 
will be calculated at the Screening Visit only. Symptom-directed physical examinations will be performed on Day 29, Day 85, Day 179, D359/EoS, and 
during USV visits. On the day of the vaccination, the arm receiving the injection should be examined and the associated lymph nodes should be evaluated. 
Any clinically significant finding identified by a healthcare professional during a study visit should be reported as a MAAE.  
4. 
Vital signs measurements: Systolic and diastolic blood pressures, heart rate, respiratory rate, and body temperature. The preferred route of temperature 
assessment is oral. On the day of vaccination, vital signs will be collected once before vaccination and once 15 minutes after vaccination. When applicable, 
vital sign measurements should be performed before blood collection. Participants who are febrile (body temperature ≥ 38.0°C/100.4°F) before dosing must 
be rescheduled within the relevant window period to receive the injection. Afebrile participants with minor illnesses can be enrolled at the discretion of the 
investigator. Vital signs may be collected at other clinic visits in conjunction with a symptom-directed physical examination. A pulse oximeter measurement 
may be performed at the unscheduled visit, if applicable/available. 

ModernaTX, Inc. 
mRNA-1273-P305 Protocol Amendment 2 
mRNA-1273 
Confidential 
Page 39 
5. 
A point-of-care urine pregnancy test will be performed at the Screening Visit and before the vaccine dose on Day 1, if Day 1 is not on the same day as the 
Screening Visit. At the discretion of the investigator, a pregnancy test either via blood or point-of-care urine can be performed at any time. The participant’s 
follicle stimulating hormone level should be measured at the Screening Visit, as necessary, and at the discretion of the investigator, to confirm postmenopausal 
status. 
6. 
An unscheduled visit may be prompted by reactogenicity issues, illness visit for COVID-19, or new or ongoing AEs. If a participant experiences symptoms 
suggestive of COVID-19, the participant will be directed as soon as possible and within 24 hours to undergo testing as outlined in Section 8.9.2. An 
unscheduled study illness visit will be arranged as soon as possible and within 72 hours for participants who test positive for SARS-CoV-2 as per testing as 
outlined in Section 8.9.2. At this visit, an NP swab will be collected to evaluate for the presence of SARS-CoV-2 infection. If a study site visit is not possible, 
a home visit may be arranged to collect a swab sample and conduct clinical evaluations. Additionally, clinical information will be collected to evaluate the 
severity of the clinical case. 
7. 
Samples for humoral immunogenicity must be collected prior to receipt of vaccination on Day 1. All participants will have blood drawn for humoral 
immunogenicity.  
8. 
The participant will record data in the eDiary approximately 15 minutes after dosing 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, on the day of dosing, and for 6 days 
following. Any solicited AR that is ongoing beyond Day 7 will be reported verbally by participants at the scheduled Safety Calls, until resolution. Adverse 
reactions recorded in eDiaries beyond Day 7 should be reviewed either via phone call or at the following study visit. Participants will be given 
thermometers to record their body temperatures and rulers to measure any injection site reactions. 
9. 
Trained study personnel will call all participants to collect information relating to any MAAEs, AEs leading to study discontinuation, SAEs, AESIs, 
information on concomitant medications associated with those events, and any non-study vaccinations.  
10. All concomitant medications and non-study vaccinations will be recorded through 28 days after vaccination, except authorized or investigational 
COVID-19 vaccine(s) given at any time during the study period should be recorded (Day 29 through EoS). 
 
 

ModernaTX, Inc. 
mRNA-1273-P305 Protocol Amendment 2 
mRNA-1273 
Confidential 
Page 40 
Table 2: 
Schedule of Events Part 2 
Visit Number 
 
1 
2 
 
 
3 
4 
5 
 
6 
USV 
Type of Visit 
C 
C 
C/SC 
SC 
SC 
C 
C 
C 
SC 
C 
C 
Month Timepoint 
 
M0 
 
 
 
M1 
M3 
M6 
M9 
M12 
Up to 
M12 
Study Visit Day  
Screening1 
D1 
(Baseline) 
D8 
D15 
D22 
D29 
D85 
D179 
D269 
D359/EoS 
USV 
Window Allowance 
(Days) 
-28 
 
+3 
+3 
+3 
-3/+7 
±7 
±14 
±7 
±14 
N/A 
Days Since Vaccination 
- 
0 
7 
14 
21 
28 
84 
178 
268 
358 
 
ICF, demographics, 
concomitant 
medications, medical 
history2  
X 
 
 
 
 
 
 
 
 
 
 
Confirm participant 
meets inclusion and 
exclusion criteria 
X 
X 
 
 
 
 
 
 
 
 
 
Physical examination3 
X 
X 
X 
 
 
X 
X 
X 
 
X 
X 
Vital signs4 
X 
X 
 
 
 
 
 
 
 
 
X 
Pregnancy testing5 
X 
X 
 
 
 
 
 
 
 
 
 
Randomization 
 
X 
 
 
 
 
 
 
 
 
 
Dosing 
 
Study injection 
(including 15-minute 
post-dosing observation 
period) 
 
X 
 
 
 
 
 
 
 
 
 

ModernaTX, Inc. 
mRNA-1273-P305 Protocol Amendment 2 
mRNA-1273 
Confidential 
Page 41 
Visit Number 
 
1 
2 
 
 
3 
4 
5 
 
6 
USV 
Type of Visit 
C 
C 
C/SC 
SC 
SC 
C 
C 
C 
SC 
C 
C 
Month Timepoint 
 
M0 
 
 
 
M1 
M3 
M6 
M9 
M12 
Up to 
M12 
Study Visit Day  
Screening1 
D1 
(Baseline) 
D8 
D15 
D22 
D29 
D85 
D179 
D269 
D359/EoS 
USV 
Window Allowance 
(Days) 
-28 
 
+3 
+3 
+3 
-3/+7 
±7 
±14 
±7 
±14 
N/A 
Days Since Vaccination 
- 
0 
7 
14 
21 
28 
84 
178 
268 
358 
 
Surveillance for COVID-19 
 
Surveillance for 
COVID-19/Unscheduled 
visit6 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Nasopharyngeal swab6 
 
X 
 
 
 
X 
X 
X 
 
X 
X 
Blood for SARS-CoV-2 
surveillance  
 
X 
 
 
 
X 
X 
X 
 
X 
 
eDiary activation for 
surveillance for 
COVID-19/Unscheduled 
visit 
 
 
 
 
 
X 
 
 
 
 
 
eDiary prompts every 2 
weeks for surveillance 
for COVID-19 and 
major changes in health 
 
 
 
 
 
eDiary prompts every 2 weeks (Day 43 through 
Day 359/EoS) 
 
Immunogenicity Assessment 
 
Blood for humoral 
immunogenicity7  
 
X  
 
 
 
X  
X  
X  
 
X  
 

ModernaTX, Inc. 
mRNA-1273-P305 Protocol Amendment 2 
mRNA-1273 
Confidential 
Page 42 
Visit Number 
 
1 
2 
 
 
3 
4 
5 
 
6 
USV 
Type of Visit 
C 
C 
C/SC 
SC 
SC 
C 
C 
C 
SC 
C 
C 
Month Timepoint 
 
M0 
 
 
 
M1 
M3 
M6 
M9 
M12 
Up to 
M12 
Study Visit Day  
Screening1 
D1 
(Baseline) 
D8 
D15 
D22 
D29 
D85 
D179 
D269 
D359/EoS 
USV 
Window Allowance 
(Days) 
-28 
 
+3 
+3 
+3 
-3/+7 
±7 
±14 
±7 
±14 
N/A 
Days Since Vaccination 
- 
0 
7 
14 
21 
28 
84 
178 
268 
358 
 
Blood for cellular 
immunogenicity in a 
subset of participants7 
 
X 
X 
 
 
 
 
 
 
 
 
Safety Assessments 
 
eDiary activation for 
recording solicited 
adverse reactions 
(7 days)8 
 
X 
 
 
 
 
 
 
 
 
 
Review of eDiary 
 
 
X 
 
 
 
 
 
 
 
 
Follow-up safety 
 
 
X 
X 
X 
 
 
 
X 
 
 
Recording of 
Unsolicited AEs  
 
X 
X 
X 
X 
X 
 
 
 
 
 
Recording of MAAEs, 
AESIs, AE leading to 
withdrawal and 
concomitant 
medications relevant to 
or for the treatment of 
these events9 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 

ModernaTX, Inc. 
mRNA-1273-P305 Protocol Amendment 2 
mRNA-1273 
Confidential 
Page 43 
Visit Number 
 
1 
2 
 
 
3 
4 
5 
 
6 
USV 
Type of Visit 
C 
C 
C/SC 
SC 
SC 
C 
C 
C 
SC 
C 
C 
Month Timepoint 
 
M0 
 
 
 
M1 
M3 
M6 
M9 
M12 
Up to 
M12 
Study Visit Day  
Screening1 
D1 
(Baseline) 
D8 
D15 
D22 
D29 
D85 
D179 
D269 
D359/EoS 
USV 
Window Allowance 
(Days) 
-28 
 
+3 
+3 
+3 
-3/+7 
±7 
±14 
±7 
±14 
N/A 
Days Since Vaccination 
- 
0 
7 
14 
21 
28 
84 
178 
268 
358 
 
Recording of SAEs and 
concomitant 
medications relevant to 
or for the treatment of 
the SAE9 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Recording of 
concomitant 
medications and non-
study vaccinations10 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Abbreviations: AE = adverse event; AESI = adverse event of special interest; AR = adverse reaction; C = clinic visit; COVID-19 = coronavirus disease 2019; 
D = day; eDiary = electronic diary; EoS = end of study; ICF = informed consent form; M = month; MAAE = medically attended AE; N/A = not applicable; 
NP = nasopharyngeal; SAE = serious adverse event; SARS-CoV-2 = severe acute respiratory syndrome coronavirus 2; SC = safety (phone) call; USV = 
unscheduled safety visit. 
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 AEs and concomitant medications. Home visits will be permitted for all non-dosing visits 
except for Screening if a participant cannot come to the study site. 
1. 
The Screening Visit and Day 1 may be performed on the same day or a different day. Additionally, the Screening visit may be performed over multiple visits 
if within the 28-day screening window. 
2. 
Verbal medical history is acceptable. 
3. 
Physical examination: a full physical examination, including vital signs, height, and weight, will be performed at Screening and Day 1. Body mass index 
will be calculated at the Screening Visit only. Symptom-directed physical examinations will be performed on Day 8 (if applicable), Day 29, Day 85, Day 179, 
D359/EoS, and during USV visits. On the day of the vaccination, the arm receiving the injection should be examined and the associated lymph nodes should 
be evaluated. Any clinically significant finding identified by a healthcare professional during a study visit should be reported as a MAAE.  

ModernaTX, Inc. 
mRNA-1273-P305 Protocol Amendment 2 
mRNA-1273 
Confidential 
Page 44 
4. 
Vital signs measurements: Systolic and diastolic blood pressures, heart rate, respiratory rate, and body temperature. The preferred route of temperature 
assessment is oral. On the day of vaccination, vital signs will be collected once before vaccination and once 15 minutes after vaccination. When applicable, 
vital sign measurements should be performed before blood collection. Participants who are febrile (body temperature ≥ 38.0°C/100.4°F) before dosing must 
be rescheduled within the relevant window period to receive the injection. Afebrile participants with minor illnesses can be enrolled at the discretion of the 
investigator. Vital signs may be collected at other clinic visits in conjunction with a symptom-directed physical examination. A pulse oximeter measurement 
may be performed at the unscheduled visit, if applicable/available. 
5. 
A point-of-care urine pregnancy test will be performed at the Screening Visit and before the vaccine dose on Day 1, if Day 1 is not on the same day as the 
Screening Visit. At the discretion of the investigator, a pregnancy test either via blood or point-of-care urine can be performed at any time. The participant’s 
follicle stimulating hormone level should be measured at the Screening Visit, as necessary, and at the discretion of the investigator, to confirm postmenopausal 
status. 
6. 
An unscheduled visit may be prompted by reactogenicity issues, illness visit for COVID-19, or new or ongoing AEs. If a participant experiences symptoms 
suggestive of COVID-19, the participant will be directed as soon as possible and within 24 hours to undergo testing as outlined in Section 8.9.2. An 
unscheduled study illness visit will be arranged as soon as possible and within 72 hours for participants who test positive for SARS-CoV-2 as per testing as 
outlined in Section 8.9.2. At this visit, an NP swab will be collected to evaluate for the presence of SARS-CoV-2 infection. If a study site visit is not possible, 
a home visit may be arranged to collect a swab sample and conduct clinical evaluations. Additionally, clinical information will be collected to evaluate the 
severity of the clinical case. 
7. 
Samples for humoral immunogenicity and cellular immunogenicity (if applicable) must be collected prior to receipt of vaccination on Day 1. All 
participants will have blood drawn for humoral immunogenicity. Only a subset of participants who will receive the 4th dose as the study vaccine will have 
blood drawn for cellular immunogenicity. 
8. 
The participant will record data in the eDiary approximately 15 minutes after dosing 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, on the day of dosing, and for 6 days 
following. Any solicited AR that is ongoing beyond Day 7 will be reported verbally by participants at the scheduled Safety Calls, until resolution. Adverse 
reactions recorded in eDiaries beyond Day 7 should be reviewed either via phone call or at the following study visit. Participants will be given 
thermometers to record their body temperatures and rulers to measure any injection site reactions. 
9. 
Trained study personnel will call all participants to collect information relating to any MAAEs, AEs leading to study discontinuation, SAEs, AESIs, 
information on concomitant medications associated with those events, and any non-study vaccinations.  
10. All concomitant medications and non-study vaccinations will be recorded through 28 days after vaccination, except authorized or investigational 
COVID-19 vaccine(s) given at any time during the study period should be recorded (Day 29 through EoS). 
 

ModernaTX, Inc. 
mRNA-1273-P305 Protocol Amendment 2 
mRNA-1273 
Confidential 
Page 45 
TABLE OF CONTENTS 
 
CLINICAL STUDY PROTOCOL ..................................................................................................1 
PROTOCOL APPROVAL – SPONSOR SIGNATORY ................................................................2 
DECLARATION OF INVESTIGATOR .........................................................................................3 
1. 
PROTOCOL SUMMARY ............................................................................................7 
1.1. 
Protocol Synopsis .........................................................................................................7 
1.2. 
Study Schema .............................................................................................................34 
1.3. 
Schedule of Events .....................................................................................................35 
TABLE OF CONTENTS ...............................................................................................................45 
LIST OF TABLES .........................................................................................................................50 
LIST OF FIGURES .......................................................................................................................51 
LIST OF ABBREVIATIONS ........................................................................................................52 
2. 
INTRODUCTION ......................................................................................................55 
2.1. 
Study Rationale ...........................................................................................................55 
2.2. 
Background and Overview .........................................................................................55 
2.2.1. 
mRNA-1273, mRNA-1273.529, and mRNA-1273.214 .............................................57 
2.2.2. 
Nonclinical Studies .....................................................................................................57 
2.2.3. 
Clinical Studies ...........................................................................................................57 
2.3. 
Benefit/Risk Assessment ............................................................................................58 
2.3.1. 
Known Potential Benefits ...........................................................................................58 
2.3.2. 
Risks from Study Participation and Their Mitigation .................................................58 
2.3.3. 
Overall Benefit/Risk Conclusion ................................................................................60 
3. 
OBJECTIVES AND ENDPOINTS ............................................................................61 
4. 
STUDY DESIGN .......................................................................................................67 
4.1. 
General Design ...........................................................................................................67 
4.2. 
Scientific Rationale for Study Design ........................................................................69 
4.3. 
Justification for Dose and Control Product ................................................................69 
4.4. 
End of Study Definition ..............................................................................................70 
5. 
STUDY POPULATION .............................................................................................71 
5.1. 
Inclusion Criteria ........................................................................................................71 
5.2. 
Exclusion Criteria .......................................................................................................72 
5.3. 
Lifestyle Restrictions ..................................................................................................73 

ModernaTX, Inc. 
mRNA-1273-P305 Protocol Amendment 2 
mRNA-1273 
Confidential 
Page 46 
5.4. 
Screen Failures ............................................................................................................73 
6. 
STUDY TREATMENT ..............................................................................................74 
6.1. 
Investigational Product and Active Comparator Administered ..................................74 
6.2. 
Randomization and Blinding ......................................................................................75 
6.3. 
Preparation/Handling/Storage/Accountability ............................................................76 
6.3.1. 
Clinical Study Material Preparation ...........................................................................76 
6.3.2. 
Clinical Study Material Administration......................................................................76 
6.3.3. 
Clinical Study Material Packaging and Labeling .......................................................76 
6.3.4. 
Clinical Study Material Storage ..................................................................................77 
6.3.5. 
Clinical Study Material Accountability ......................................................................77 
6.3.6. 
Clinical Study Material Handling and Disposal .........................................................78 
6.3.7. 
Unblinding ..................................................................................................................78 
6.4. 
Study Intervention Compliance ..................................................................................78 
6.5. 
Prior and Concomitant Medications ...........................................................................79 
6.5.1. 
Prior Medications and Therapies ................................................................................79 
6.5.2. 
Concomitant Medications and Therapies .....................................................................79 
6.5.3. 
Concomitant Medications and Vaccines That May Lead to the Elimination of 
a Participant from Per-protocol Analyses ....................................................................80 
7. 
DELAY OR DISCONTINUATION OF STUDY INTERVENTION AND 
PARTICIPANT DISCONTINUATION/WITHDRAWAL .......................................81 
7.1. 
Participant Discontinuation/Withdrawal from the Study ...........................................81 
7.2. 
Lost to Follow-up .......................................................................................................82 
8. 
STUDY ASSESSMENTS AND PROCEDURES ......................................................83 
8.1. 
Screening ....................................................................................................................83 
8.2. 
Confirm Inclusion and Exclusion Criteria ..................................................................83 
8.3. 
Demographic and Baseline Data ................................................................................83 
8.4. 
Medical History ..........................................................................................................83 
8.5. 
Randomization ............................................................................................................83 
8.6. 
Physical Examination and Vital Signs ........................................................................83 
8.7. 
Study Vaccine Administration ....................................................................................84 
8.8. 
Immunogenicity and Efficacy Assessments ...............................................................84 
8.8.1. 
Immunogenicity Assessments ....................................................................................84 
8.8.2. 
Vaccine Efficacy and Surveillance for COVID-19 Symptoms ..................................85 

ModernaTX, Inc. 
mRNA-1273-P305 Protocol Amendment 2 
mRNA-1273 
Confidential 
Page 47 
8.9. 
Safety Assessments .....................................................................................................85 
8.9.1. 
Pregnancy Screen and Testing ....................................................................................85 
8.9.2. 
Assessments for SARS-CoV-2 Infection ....................................................................86 
8.9.3. 
Safety Telephone Calls ...............................................................................................88 
8.9.4. 
Use of Electronic Diaries ............................................................................................88 
8.9.5. 
Blood Sampling Volumes ...........................................................................................89 
8.9.6. 
Ancillary Supplies for Participant Use .......................................................................89 
8.10. 
Safety Definitions .......................................................................................................89 
8.10.1. 
Adverse Event .............................................................................................................89 
8.10.2. 
Serious Adverse Events ..............................................................................................90 
8.10.3. 
Solicited Adverse Reactions .......................................................................................91 
8.10.4. 
Medically Attended Adverse Events ..........................................................................93 
8.10.5. 
Adverse Event of Special Interest ...............................................................................94 
8.10.6. 
Recording and Follow-up of Pregnancy .....................................................................95 
8.10.7. 
Recording and Follow-up of an AE and/or SAE ........................................................96 
8.10.8. 
Assessment of Intensity ..............................................................................................97 
8.10.9. 
Assessment of Causality .............................................................................................97 
8.10.10. 
Reporting Adverse Events ..........................................................................................98 
8.10.11. 
Reporting Serious Adverse Events .............................................................................98 
8.10.12. 
Time Period and Frequency for Collecting AE and SAE Information .......................99 
8.10.13. 
Method of Detecting AEs and SAEs ........................................................................100 
8.10.14. 
Follow-up of AEs and SAEs .....................................................................................100 
8.10.15. 
Regulatory Reporting Requirements for SAEs .........................................................101 
8.11. 
Safety Oversight .......................................................................................................101 
8.12. 
Treatment of Overdose .............................................................................................102 
8.13. 
Pharmacokinetics ......................................................................................................102 
8.14. 
Pharmacodynamics ...................................................................................................102 
8.15. 
Biomarkers ................................................................................................................102 
9. 
STATISTICAL ANALYSIS PLAN .........................................................................103 
9.1. 
Blinding and Responsibility for Analyses ................................................................103 
9.2. 
Statistical Hypotheses ...............................................................................................103 
9.3. 
Sample Size and Power Calculation .........................................................................106 
9.4. 
Multiplicity ...............................................................................................................112 

ModernaTX, Inc. 
mRNA-1273-P305 Protocol Amendment 2 
mRNA-1273 
Confidential 
Page 48 
9.5. 
Analyses Populations ................................................................................................112 
9.6. 
Statistical Analyses ...................................................................................................113 
9.6.1. 
Immunogenicity Analyses ........................................................................................114 
9.6.2. 
Efficacy Analyses .....................................................................................................116 
9.6.3. 
Safety Analyses ........................................................................................................116 
9.6.4. 
Exploratory Analyses ................................................................................................117 
9.7. 
Planned Analyses ......................................................................................................117 
10. 
REFERENCES .........................................................................................................118 
11. 
SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS ................................................................................................120 
11.1. 
APPENDIX 1: Study Governance Considerations ...................................................121 
11.1.1. 
Regulatory and Ethical Considerations ....................................................................121 
11.1.2. 
Study Monitoring ......................................................................................................121 
11.1.3. 
Audits and Inspections ..............................................................................................123 
11.1.4. 
Financial Disclosure .................................................................................................123 
11.1.5. 
Recruitment Procedures ............................................................................................123 
11.1.6. 
Informed Consent Process ........................................................................................123 
11.1.7. 
Protocol Amendments ..............................................................................................125 
11.1.8. 
Protocol Deviations ..................................................................................................125 
11.1.9. 
Data Protection .........................................................................................................125 
11.1.10. 
Sample Retention and Future Biomedical Research ................................................126 
11.1.11. 
Data and Safety Monitoring Board ...........................................................................127 
11.1.12. 
Dissemination of Clinical Study Data ......................................................................127 
11.1.13. 
Data Quality Assurance and Quality Control ...........................................................127 
11.1.14. 
Data Collection and Management ............................................................................128 
11.1.15. 
Source Documents ....................................................................................................129 
11.1.16. 
Retention of Records ................................................................................................129 
11.1.17. 
Study and Site Closure..............................................................................................129 
11.1.18. 
Publication Policy .....................................................................................................130 
11.2. 
APPENDIX 2: Contraceptive Guidance ...................................................................131 
11.3. 
APPENDIX 3: Adverse Events of Special Interest ..................................................133 

ModernaTX, Inc. 
mRNA-1273-P305 Protocol Amendment 2 
mRNA-1273 
Confidential 
Page 49 
11.4. 
APPENDIX 4: CDC Working Case Definitions of Pericarditis, Myocarditis, 
and Myopericarditis Occurring After Receipt of COVID-19 mRNA 
Vaccines ....................................................................................................................136 
11.5. 
APPENDIX 5: Protocol Amendment History ..........................................................138 
11.5.1. 
Amendment 1, 03 Mar 2022 .....................................................................................138 
 
 
 

ModernaTX, Inc. 
mRNA-1273-P305 Protocol Amendment 2 
mRNA-1273 
Confidential 
Page 50 
LIST OF TABLES 
Table 1: 
Schedule of Events Part 1 ...........................................................................................35 
Table 2: 
Schedule of Events Part 2 ...........................................................................................40 
Table 3: 
Study Objectives and Endpoints for Part 1 (mRNA-1273.529 and mRNA-
1273) ...........................................................................................................................61 
Table 4: 
Study Objectives and Endpoints for Part 2 (mRNA-1273.214 and mRNA-
1273) ...........................................................................................................................64 
Table 5: 
Part 1 Study Arm and Dose Levels .............................................................................68 
Table 6: 
Part 2 Study Arm and Dose Levels .............................................................................68 
Table 7: 
Investigational Product and Active Comparator Administered ..................................74 
Table 8: 
Solicited Adverse Reactions and Grades ....................................................................92 
Table 9:  
Operating Characteristics and Power for the Primary and Key Secondary 
Objectives Under Various GMR and the Number of Evaluable Participants 
with Immunogenicity Data Who Receives the 4th Dose in this Study (Part 1) ........108 
Table 10: Operating Characteristics and Power for the Primary and Key Secondary 
Objectives Under Various GMR and the Number of Evaluable Participants 
with Immunogenicity Data Who Receives the 4th Dose in this Study (Part 2) ........111 
Table 11: Populations for Analyses ..........................................................................................113 
Table 12: Analysis Strategy for Safety Parameters ..................................................................117 
Table 13: Adverse Events of Special Interest ...........................................................................133 
Table 14: Case Definitions of Probable and Confirmed Myocarditis, Pericarditis, and 
Myopericarditis .........................................................................................................136 
 
 
 

ModernaTX, Inc. 
mRNA-1273-P305 Protocol Amendment 2 
mRNA-1273 
Confidential 
Page 51 
LIST OF FIGURES 
Figure 1: 
Study Schema .............................................................................................................34 
Figure 2: 
Statistical Hypothesis Testing Strategy of mRNA-1273 vs. mRNA-1273 
(Part 2) ......................................................................................................................105 
 

ModernaTX, Inc. 
mRNA-1273-P305 Protocol Amendment 2 
mRNA-1273 
Confidential 
Page 52 
LIST OF ABBREVIATIONS 
The following abbreviations and terms are used in this study protocol. 
Abbreviation or Specialist Term 
Definition 
AE 
adverse event 
AESI 
adverse event of special interest 
ANCOVA 
analysis of covariance 
AR 
adverse reaction 
bAb 
binding antibody 
CDC 
Centers for Disease Control and Prevention 
CEAC 
Cardiac Event Adjudication Committee 
CI 
confidence interval 
cMRI 
cardiac magnetic resonance imaging 
COVID-19 
coronavirus disease 2019 
CRO 
contract research organization 
CSR 
clinical study report 
DHHS 
Department of Health and Human Services 
DSMB 
Data and Safety Monitoring Board 
ECG or EKG 
electrocardiogram 
eCRF 
electronic case report form 
eDiary 
electronic diary 
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 
GLSM 
geometric least square mean 
GMFR 
geometric mean fold rise 
GMR 
geometric mean ratio 

ModernaTX, Inc. 
mRNA-1273-P305 Protocol Amendment 2 
mRNA-1273 
Confidential 
Page 53 
Abbreviation or Specialist Term 
Definition 
GMT 
geometric mean titer 
HCP 
healthcare practitioner 
HRT 
hormonal replacement therapy 
IB 
investigator’s brochure 
ICF 
informed consent form 
ICH 
International Council for Harmonisation 
IEC 
Independent Ethics Committee 
IM 
intramuscular(ly) 
IP 
investigational product 
IRT 
interactive response technology  
LNP 
lipid nanoparticle 
LTFU 
lost to follow-up 
MAAE 
medically attended adverse event 
MedDRA 
Medical Dictionary for Regulatory Activities 
mITT 
modified intent-to-treat 
mRNA 
messenger ribonucleic acid 
nAb 
neutralizing antibody 
NHS 
National Health Service 
NP 
nasopharyngeal 
PP  
per protocol 
PPE 
personal protective equipment 
PPSE 
per protocol set for efficacy 
PPSI 
per protocol set for immunogenicity 
PPSI-neg 
per protocol set for immunogenicity –SARS-CoV-2 negative 
QA 
quality assurance 
RBD 
receptor-binding domain 
RT-PCR 
reverse transcription polymerase chain reaction 
S 
spike 

ModernaTX, Inc. 
mRNA-1273-P305 Protocol Amendment 2 
mRNA-1273 
Confidential 
Page 54 
Abbreviation or Specialist Term 
Definition 
SAE 
serious adverse event 
SAP 
statistical analysis plan 
SARS 
severe acute respiratory syndrome 
SARS-CoV-2 
severe acute respiratory syndrome coronavirus 2 
SoE 
schedule of events 
SRR 
seroresponse rate 
TEAE 
treatment-emergent adverse event 
USP 
United States Pharmacopeia 
USV 
unscheduled safety visit 
VOC 
variants of concern 
WHO 
World Health Organization 
WOCBP 
women of childbearing potential 
 

ModernaTX, Inc. 
mRNA-1273-P305 Protocol Amendment 2 
mRNA-1273 
Confidential 
Page 55 
2. 
INTRODUCTION 
2.1. 
Study Rationale 
There is an urgent need for vaccination strategies that induce broader protection against severe 
acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOC), including 
the Omicron variant, to decrease morbidity and mortality. In addition, it is currently not known 
whether breakthrough infections could occur long term due to waning antibody titers 
(Doria-Rose et al 2021, Pegu et al 2021). Based on the experience of mRNA-1273, available 
under Emergency Use Authorization (EUA), and leveraging the flexible nature of the messenger 
ribonucleic acid (mRNA) technology, ModernaTX, Inc (the Sponsor) is evaluating mRNA 
vaccines to address the Omicron variant. 
2.2. 
Background and Overview 
Coronaviruses are a large family of viruses that cause illness ranging from the common cold to 
more severe diseases, such as Middle East Respiratory Syndrome and severe acute respiratory 
syndrome (SARS). An outbreak of a novel coronavirus (later designated SARS-CoV-2) initially 
emerged in Wuhan, Hubei Province, China in December 2019. The World Health Organization 
(WHO) declared coronavirus disease 2019 (COVID-19) a pandemic on 11 Mar 2020 with nearly 
265 million confirmed cases and 5.2 million deaths by 05 December 2021 (WHO 2021).  
The Sponsor’s scalable mRNA/lipid nanoparticle (LNP) technology platform allowed for a rapid 
response to the pandemic and was used to develop mRNA-1273, a novel LNP-encapsulated 
mRNA-based vaccine against SARS-CoV-2. mRNA-1273 contains a single mRNA 
(CX-024414) that encodes for the full-length SARS-CoV-2 spike (S) protein of the Wuhan-Hu-1 
SARS-CoV-2 virus, modified with 2 proline substitutions within the heptad repeat 1 domain 
(S-2P) to stabilize the S protein into a prefusion conformation. In December 2020, mRNA-1273 
was granted EUA for the prevention of COVID-19 in individuals 18 years of age and older based 
on the demonstration of efficacy and safety in a Phase 3 pivotal trial conducted in persons at high 
risk for SARS-CoV-2 infection (Baden et al 2021). On January 31, 2022, the FDA announced 
the approval of mRNA-1273 marketed as Spikevax (FDA News Release 2022). 
Over the course of the pandemic, SARS-CoV-2 variants have emerged and are likely to continue 
to emerge, some of which may prove to have some level of escape from immunity associated 
with previous infection or vaccination. Recently, newer variants have raised concern, due to 
reports of increased infectivity or reduction in the ability of convalescent sera or sera from 
vaccinated subjects to neutralize these emergent strain variants. Mutations occurring in the 
receptor-binding domain (RBD) are of particular concern, as this site includes the dominant 
neutralization epitopes on the S protein and these mutations could impact the effectiveness of 
antibodies elicited by infection or vaccination in neutralizing the virus (Greaney et al 2021). 

ModernaTX, Inc. 
mRNA-1273-P305 Protocol Amendment 2 
mRNA-1273 
Confidential 
Page 56 
These recent evolutionary events indicate that SARS-CoV-2 has the capacity to develop more 
efficient transmission between human hosts (Martin et al 2021) and vaccination strategies to 
control the virus need to be responsive to this evolution. A SARS-CoV-2 variant, Alpha 
(B.1.1.7), rapidly spread from southeast England around the globe. The Beta (B.1.351) variant 
emerged in South Africa, and the Gamma (P.1 lineage) variant was initially reported in Brazil. 
The Delta (B.1.617.2) variant, which contains 2 mutations in the RBD (L452R and T478K), 
circulated globally in 2021. In vitro characterization of sera from individuals recently vaccinated 
with the 2-dose regimen of the Moderna COVID-19 vaccine at the 100 µg dose showed that the 
Moderna COVID-19 vaccine produced neutralizing titers against key emerging variants tested, 
including Alpha, Beta, and Delta (Wang et al 2021, Wu et al 2021, Choi et al 2021). The studies 
showed no significant reduction in neutralizing titers against the Alpha variant relative to the 
prototype Wuhan-Hu-1 strain and a 2.1-fold reduction versus the Delta variant; however, a 
greater than 6-fold reduction in neutralizing titers was observed against the Beta variant relative 
to the Wuhan-Hu-1. Evidence from adenovirus vector SARS-CoV-2 vaccines based on the 
Wuhan-Hu-1 sequence suggests reduced vaccine efficacy against moderate to severe COVID-19 
in South Africa where the Beta variant circulated (Madhi et al 2021, Sadoff et al 2021). A real-
world effectiveness study that the Sponsor conducted with Kaiser Permanente found that vaccine 
effectiveness against the Delta variant declined from 94.1% 14-60 days after vaccination to 
80.0% 151-180 days after vaccination (Bruxvoort et al 2021). 
In November 2021, the SARS-CoV-2 Omicron variant (B.1.1.529) was detected in South Africa 
and epidemiological information about its spread in other regions is being evaluated. Available 
evidence suggests that the Omicron variant has transmission advantage over prior variants. The 
Omicron variant has significant antigenic change with a potential growth advantage. In addition, 
it contains potential antibody escape site mutations (such as K417N, T478K, E484A, N501Y). 
Results from the Sponsor show that 1 month after completing the primary series, 
mRNA-1273-elicited serum neutralization of Omicron variant pseudovirus was not detectable. 
However, neutralization was observed at 2 weeks after an mRNA-1273 booster dose, although 
activity was reduced relative to the prototype D614G strain and remained lower than that 
observed against the prototype D614G strain at 1 month after the primary series. Further 
evaluation of the in vitro neutralization of the Omicron variant, using sera from vaccinees, is 
currently in progress.  
Overall, this study will assess whether a single booster dose of the mRNA vaccine boosts 
antibody responses to the Omicron variant and the prototype strain. Participants who previously 
received 2 or 3 doses of a COVID-19 vaccine will receive a single booster dose of the 
mRNA-1273.529, mRNA-1273.214, or mRNA-1273 vaccines in this study. 

ModernaTX, Inc. 
mRNA-1273-P305 Protocol Amendment 2 
mRNA-1273 
Confidential 
Page 57 
2.2.1. 
mRNA-1273, mRNA-1273.529, and mRNA-1273.214 
The Sponsor has developed a rapid response, proprietary vaccine platform based on a 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-1273 
mRNA-1273 encodes for the full-length S protein of SARS-CoV-2, modified to introduce 
2 proline residues to stabilize the S-2P in 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 (nAbs) that prevent infection (Corbett et al 2020). It has been confirmed 
that the stabilized SARS-CoV-2 S2P antigen presents in the correct prefusion conformation 
(Wrapp et al 2020). 
In December 2020, mRNA-1273 was granted EUA for the prevention of COVID-19 for 
individuals 18 years of age and older. It is currently being evaluated for safety, immunogenicity, 
and efficacy in ongoing Phase 1 (NCT04283461), Phase 2 (NCT04405076), and Phase 3 
(NCT04470427) trials. All 3 trials have been modified to allow for unblinding and crossover of 
placebo subjects and/or to assess safety and immunogenicity of booster doses of vaccine. 
mRNA-1273.529 
Developed similarly to mRNA-1273 on the Sponsor’s platform, mRNA-1273.529 contains 
mRNA CX-031302 encoding for the S-2P of B.1.1.529. 
mRNA-1273.214 
mRNA-1273.214 contains CX-024414, the mRNA that encodes for the prefusion stabilized spike 
glycoprotein (S-2P) of the Wuhan-Hu-1 isolate of SARS-CoV-2 and CX-031302, the mRNA that 
encodes for the S-2P of the SARS-CoV-2 B.1.1.529 variant. 
2.2.2. 
Nonclinical Studies 
Nonclinical study data for mRNA-1273 is available in the Investigator’s Brochure (IB). 
Nonclinical studies of mRNA-1273.529 and mRNA-1273.214 are ongoing. 
2.2.3. 
Clinical Studies 
Clinical study data for mRNA-1273 is available in the IB. mRNA-1273.529 and mRNA-
1273.214 are also being evaluated in the Sponsor’s trial, mRNA-1273-P205, a Phase 2/3, open-
label study to evaluate the immunogenicity and safety of boosters for SARS-CoV-2 variants. 
Data from the Sponsor’s Phase 2 trials suggest that mRNA-1273.211, a bivalent vaccine that 

ModernaTX, Inc. 
mRNA-1273-P305 Protocol Amendment 2 
mRNA-1273 
Confidential 
Page 58 
contains mRNA encoding for the S-2P of Wuhan-Hu-1 and mRNA encoding for the S-2P of 
B.1.351 at a 1:1 ratio, induced numerically similar or higher and more durable 
neutralizing responses against both vaccine-matched and unmatched strains compared to the 
monovalent mRNA-1273 and mRNA-1273.351 (encodes for S-2P of B.1.351) vaccine. This 
supports the hypothesis that the bivalent mRNA-1273.214 vaccine to be tested in this study may 
generate more durable neutralizing responses against the Omicron variant strain and the 
prototype strain compared to mRNA-1273. 
2.3. 
Benefit/Risk Assessment 
2.3.1. 
Known Potential Benefits 
The following benefits may accrue to participants that will receive the mRNA-1273.529, mRNA-
1273.214, or mRNA-1273 booster vaccines: 
• The mRNA-1273.529, mRNA-1273.214, or mRNA-1273 vaccine as a booster dose 
may provide improved protection against COVID-19 VOC.  
• Participants will have a baseline (Day 1) evaluation for SARS-CoV-2 infection and 
ongoing surveillance for COVID-19 throughout the study. 
• The study will contribute to the development of a vaccine against COVID-19 VOC, a 
current pandemic disease. 
2.3.2. 
Risks from Study Participation and Their Mitigation 
The safety profile of mRNA-1273 is largely based on data from the pivotal Phase 3 study 
(Study mRNA-1273-P301). It is expected that the safety profile of mRNA-1273.529 and 
mRNA-1273.214 will be similar to mRNA-1273. 
Solicited adverse reactions (ARs) were reported more frequently among vaccine participants 
than among placebo participants. The most frequently reported ARs after any dose in the vaccine 
group were pain at the injection site, fatigue, headache, myalgia, and chills. The most common 
solicited local AR was pain. Solicited systemic ARs were reported more frequently by vaccine 
participants after dose 2 (fatigue, 65.3%, headache, 58.6%, myalgia, 58% and arthralgia, 42.8%) 
than after dose 1 (fatigue, 37.2%, headache, 32.7%, myalgia, 22.7% and arthralgia,16.6%). 
Grade 3 systemic ARs were also reported more frequently after dose 2 than after dose 1. The 
majority of local and systemic ARs had a median duration of 1 to 3 days.  
Overall, there was a higher reported rate of some ARs in younger age groups: the incidence of 
axillary swelling/tenderness, fatigue, headache, myalgia, arthralgia, chills, nausea/vomiting, and 
fever was higher in adults aged 18 to < 65 years than in those aged 65 years and above. 
Grade 3 solicited local ARs were more frequently reported after dose 2 than after dose 1.  

ModernaTX, Inc. 
mRNA-1273-P305 Protocol Amendment 2 
mRNA-1273 
Confidential 
Page 59 
Unsolicited adverse events (AEs) that occurred within 28 days following each vaccination were 
reported by 23.9% of participants who received mRNA-1273 and 21.6% of participants who 
received placebo. Unsolicited AEs that occurred in ≥ 1% of study participants who received 
mRNA-1273 and at a rate at least 1.5-fold higher rate than placebo, were lymphadenopathy 
related events (1.1% vs. 0.6%). All of the lymphadenopathy events are similar to the axillary 
swelling/tenderness in the injected arm reported as solicited ARs. Several participants reported 
injection site reactions after Day 7 that were characterized by erythema, induration, and often 
pruritus. Consultation with a dermatopathologist suggested that these were most likely dermal 
hypersensitivity and were unlikely to represent a long-term safety concern.  
Hypersensitivity AEs were reported in 1.5% of vaccine recipients and 1.1% of placebo 
recipients. Hypersensitivity events in the vaccine group included injection site rash and injection 
site urticaria, which are likely related to vaccination. There have been no cases of severe 
hypersensitivity or anaphylactic reactions reported immediately after vaccination in the trial to 
date. 
There were 3 reports of Bell’s palsy in the mRNA-1273 vaccine group (one of which was a 
serious AE [SAE]), which occurred 22, 28, and 32 days after vaccination, and 1 in the placebo 
group which occurred 17 days after vaccination. Currently available information on Bell’s palsy 
is insufficient to determine a causal relationship with the vaccine.  
SAEs were reported at the same rates in participants who received mRNA-1273 and placebo 
from the first dose until the last observation. There were 2 SAEs of facial swelling in vaccine 
recipients with a history of injection of dermatological fillers. The onset of swelling was reported 
1 and 2 days, respectively, after vaccination and was likely related to vaccination. There was 
1 SAE of intractable nausea and vomiting in a participant with prior history of severe headache 
and nausea requiring hospitalization. This event occurred 1 day after vaccination and was likely 
related to vaccination.  
There were no other notable patterns or numerical imbalances between study arms for specific 
categories of AEs (including other neurologic, neuro-inflammatory, and thrombotic events) that 
would suggest a causal relationship to mRNA-1273.  
In the post-authorization period, there have been very rare reports of anaphylaxis following 
mRNA-1273 administration. In addition, there have been very rare reports of myocarditis and 
pericarditis occurring after vaccination with COVID-19 mRNA vaccines. The majority of the 
cases have been reported in young males shortly after the second dose of the vaccine. These are 
typically mild cases and individuals tend to recover within a short time following standard 
treatment and rest. Investigators and study participants should be alert to the signs and symptoms 
of myocarditis and pericarditis. Safety will be monitored throughout the study. 

ModernaTX, Inc. 
mRNA-1273-P305 Protocol Amendment 2 
mRNA-1273 
Confidential 
Page 60 
2.3.3. 
Overall Benefit/Risk Conclusion 
The evolving antigenic variation of SARS-CoV-2 underscores the urgent need for vaccination 
strategies that induce broader protection, specifically against VOC with attendant risk of viral 
escape. The Sponsor is developing monovalent and multivalent mRNA vaccines 
(mRNA-1273.529 and others) that are similar to the mRNA-1273 vaccine, but in which the 
mRNA encodes for mutations included in the S protein of both the prototype strain 
(Wuhan-Hu-1) and VOC. It is not yet known the degree to which currently available 
authorized/approved mRNA-1273 vaccine and variant-targeted mRNA-1273 vaccines are 
protective against new variants. 
Considering the safety data for mRNA-1273 to date and the similarities of mRNA-1273 to 
mRNA-1273.529 and mRNA-1273.214, the Sponsor considers the potential benefits of 
participation in this study to exceed the risks. 
 

ModernaTX, Inc. 
mRNA-1273-P305 Protocol Amendment 2 
mRNA-1273 
Confidential 
Page 61 
3. 
OBJECTIVES AND ENDPOINTS 
The objectives which will be evaluated in this study and endpoints associated with each objective 
in Part 1 and Part 2 are provided in Table 3 and Table 4, respectively. 
Table 3: 
Study Objectives and Endpoints for Part 1 (mRNA-1273.529 and mRNA-
1273) 
Objectives 
Endpoints 
Primary  
To demonstrate non-
inferiority of the immune 
response of mRNA-
1273.529 compared to 
mRNA-1273 booster 
administered as a 4th dose 
against the B.1.1.529 
strain at Day 29 or Month 
3 
• 
Geometric mean titer (GMT) of mRNA-1273.529 and mRNA-
1273 against the B.1.1.529 strain at Day 29 and Month 3 after 
study vaccine administration 
• 
Ratio of GMTmRNA-1273.529/GMTmRNA-1273 against the B.1.1.529 
strain at Day 29 and Month 3 after study vaccine 
administration 
 
To evaluate the safety and 
reactogenicity of mRNA-
1273.529 and mRNA-1273 
administered as a booster 
dose 
• 
Solicited local and systemic reactogenicity ARs during a 7-day 
follow up period after vaccination 
• 
Unsolicited AEs during the 28-day follow-up period after 
vaccination 
• 
SAEs, medically attended AEs (MAAEs), AEs leading to 
withdrawal, and AEs of special interest (AESIs) from Day 1 to 
end of study 
Secondary  
 Key Secondary 
To demonstrate superiority 
of the immune response of 
mRNA-1273.529 
compared to mRNA-1273 
administered as a 4th dose 
against the B.1.1.529 
strain at Day 29 or Month 
3  
• 
GMT of mRNA-1273.529 and mRNA-1273 against the 
B.1.1.529 strain at Day 29 and Month 3 after study vaccine 
administration 
• 
Ratio of GMTmRNA-1273.529/GMTmRNA-1273 against the B.1.1.529 
strain at Day 29 and Month 3 after study vaccine 
administration 

ModernaTX, Inc. 
mRNA-1273-P305 Protocol Amendment 2 
mRNA-1273 
Confidential 
Page 62 
 Other Secondary 
To demonstrate non-
inferiority of the immune 
response of mRNA-
1273.529 compared to 
mRNA-1273 booster 
administered as a 4th dose 
against both the B.1.1.529 
and the prototype strain at 
all evaluable time points 
• 
GMT of mRNA-1273.529 and mRNA-1273 against both the 
B.1.1.529 and the prototype strain at all evaluable time points 
after study vaccine administration 
• 
Ratio of GMTmRNA-1273.529/GMTmRNA-1273 against both the 
B.1.1.529 and the prototype strain at all evaluable time points 
after study vaccine administration 
 
To evaluate the 
seroresponse rate (SRR) of 
mRNA-1273.529 and 
mRNA-1273 boosters 
administered as a 4th dose 
• 
SRR against the B.1.1.529 strain  
• 
SRR against the prototype strain  
Exploratory Objectives 
To assess for symptomatic 
and asymptomatic 
SARS-CoV-2 infection 
after vaccination with 
mRNA-1273.529 booster 
or mRNA-1273 booster 
Reverse transcriptase polymerase-chain reaction (RT-PCR)-confirmed 
symptomatic or asymptomatic SARS-CoV-2 infection will be defined 
in participants based on the following criteria: 
• 
Protocol-defined COVID-19 case definition 
o The participant must have experienced at least TWO of 
the following systemic symptoms: Fever (≥ 38ºC), 
chills, myalgia, headache, sore throat, new olfactory 
and taste disorder(s), OR 
o The participant must have experienced at least ONE of 
the following respiratory signs/symptoms: cough, 
shortness of breath or difficulty breathing, OR clinical 
or radiographical evidence of pneumonia; AND 
o The participant must have at least one nasopharyngeal 
(NP) swab, nasal swab, or saliva sample (or respiratory 
sample, if hospitalized) positive for SARS-CoV-2 by 
RT-PCR. 
• 
Center for Disease Control (CDC)-defined COVID-19 
definition based on the CDC criteria: the presence of one of the 
CDC-listed symptoms 
(https://www.cdc.gov/coronavirus/2019-ncov/symptoms-
testing/symptoms.html) and a positive RT-PCR test on a 
respiratory sample 
• 
Asymptomatic SARS-CoV-2 infection is defined as a positive 
RT-PCR test on a respiratory sample in the absence of 
symptoms or a positive serologic test for antinucleocapsid 
antibody after a negative test at time of enrollment 

ModernaTX, Inc. 
mRNA-1273-P305 Protocol Amendment 2 
mRNA-1273 
Confidential 
Page 63 
To evaluate the 
immunogenicity of 
mRNA-1273.529 booster 
against other variant 
strains 
• 
GMT of mRNA-1273.529 against other variant strains (eg, 
Alpha, Beta, Delta) after study vaccine administration 
• 
Ratio of GMTmRNA-1273.529/GMTmRNA-1273 against other variant 
strains after study vaccine administration 
• 
GMFR of mRNA-1273.529 against other variant strains after 
study vaccine administration 
• 
SRR against other variant strains 
To evaluate the genetic 
and/or phenotypic 
relationships of isolated 
SARS-CoV-2 strains to the 
vaccine sequence 
• 
Characterize the SARS-CoV-2 spike genetic sequence of viral 
isolates and compare with the vaccine sequence 
• 
Characterize the immune responses to vaccine breakthrough 
isolates 
Abbreviations: AE = adverse event; AESI = adverse event of special interest; AR = adverse reaction; CDC = Centers 
for Disease Control and Prevention; GMFR = geometric mean fold rise; GMR = geometric mean titer ratio; GMT = 
geometric mean titer; MAAE = medically attended adverse event; mRNA = messenger ribonucleic acid; NP = 
nasopharyngeal; RT-PCR = reverse transcription polymerase chain reaction; SAE = serious adverse event; SARS-
CoV-2 = severe acute respiratory syndrome coronavirus 2; SRR = seroresponse rate. 

ModernaTX, Inc. 
mRNA-1273-P305 Protocol Amendment 2 
mRNA-1273 
Confidential 
Page 64 
Table 4: 
Study Objectives and Endpoints for Part 2 (mRNA-1273.214 and mRNA-
1273) 
Objectives 
Endpoints 
Primary  
To demonstrate non-inferiority of 
the immune response of mRNA-
1273.214 compared to mRNA-1273 
booster administered as a 4th dose 
against the B.1.1.529 strain at Day 
29 or Month 3 
• 
Geometric mean titer (GMT) of mRNA-1273.214 and 
mRNA-1273 against the B.1.1.529 strain at Day 29 or 
Month 3 after study vaccine administration 
• 
Ratio of GMTmRNA-1273.214/GMTmRNA-1273 against the 
B.1.1.529 strain at Day 29 or Month 3 after study 
vaccine administration 
To demonstrate non-inferiority of 
the immune response of 
mRNA-1273.214 compared to 
mRNA-1273 booster administered 
as a 4th dose against the prototype 
strain at Day 29 or Month 3 
• 
Geometric mean titer (GMT) of mRNA-1273.214 and 
mRNA-1273 against the prototype strain at Day 29 or 
Month 3 after study vaccine administration 
• 
Ratio of GMTmRNA-1273.214/GMTmRNA-1273 against the 
prototype strain at Day 29 or Month 3 after study 
vaccine administration 
To demonstrate superiority of the 
immune response of mRNA-
1273.214 compared to mRNA-1273 
booster administered as a 4th dose 
against the B.1.1.529 strain at Day 
29 or Month 3 
• 
GMT of mRNA-1273.529 and mRNA-1273 against the 
B.1.1.529 strain at Day 29 or Month 3 after study 
vaccine administration 
• 
Ratio of GMTmRNA-1273.529/GMTmRNA-1273 against the 
B.1.1.529 strain at Day 29 or Month 3 after study 
vaccine administration 
To evaluate the safety and 
reactogenicity of mRNA-1273.214 
and mRNA-1273 administered as a 
booster dose 
• 
Solicited local and systemic reactogenicity ARs during a 
7-day follow up period after vaccination 
• 
Unsolicited AEs during the 28-day follow-up period 
after vaccination 
• 
SAEs, medically attended AEs (MAAEs), AEs leading 
to withdrawal, and AEs of special interest (AESIs) from 
Day 1 to end of study 
Secondary  
To evaluate the seroresponse rate 
(SRR) of mRNA-1273.214 and 
mRNA-1273 boosters administered 
as a 4th dose 
• 
SRR against the B.1.1.529 strain  
• 
SRR against the prototype strain  
To evaluate the immune response of 
mRNA-1273.214 compared to 
mRNA-1273 booster administered 
as a 4th dose against other variant 
strains at Day 29 or Month 3  
• 
GMT of mRNA-1273.214 and mRNA-1273 against 
other variant strains at Day 29 or Month 3 
• 
Ratio of GMTmRNA-1273.214/GMTmRNA-1273 against other 
variant strains at Day 29 or Month 3 
• 
SRR against other variant strains 

ModernaTX, Inc. 
mRNA-1273-P305 Protocol Amendment 2 
mRNA-1273 
Confidential 
Page 65 
To assess for symptomatic and 
asymptomatic SARS-CoV-2 
infection after vaccination with 
mRNA-1273.214 booster or 
mRNA-1273 booster 
Reverse transcriptase polymerase-chain reaction (RT-PCR)-
confirmed symptomatic or asymptomatic SARS-CoV-2 infection 
will be defined in participants based on the following criteria: 
• 
Protocol-defined COVID-19 case definition 
o The participant must have experienced at least 
TWO of the following systemic symptoms: 
Fever (≥ 38ºC), chills, myalgia, headache, sore 
throat, new olfactory and taste disorder(s), OR 
o The participant must have experienced at least 
ONE of the following respiratory 
signs/symptoms: cough, shortness of breath or 
difficulty breathing, OR clinical or 
radiographical evidence of pneumonia; AND 
o The participant must have at least one 
nasopharyngeal (NP) swab, nasal swab, or saliva 
sample (or respiratory sample, if hospitalized) 
positive for SARS-CoV-2 by RT-PCR. 
• 
Center for Disease Control (CDC) defined COVID-19 
definition based on the CDC criteria: the presence of one 
of the CDC listed symptoms 
(https://www.cdc.gov/coronavirus/2019-ncov/symptoms-
testing/symptoms.html) and a positive RT-PCR test on a 
respiratory sample 
• 
Asymptomatic SARS-CoV-2 infection is defined as a 
positive RT-PCR test on a respiratory sample in the 
absence of symptoms or a positive serologic test for 
antinucleocapsid antibody after a negative test at time of 
enrollment 
Exploratory Objectives 
To evaluate cellular immunogenicity 
in a subset of participants 
• 
Frequency, magnitude, and phenotype of virus-specific 
T-cell and B-cell responses measured by flow cytometry 
or other methods, and to perform targeted repertoire 
analysis of T-cells and B-cells after vaccination 
To evaluate the genetic and/or 
phenotypic relationships of isolated 
SARS-CoV-2 strains to the vaccine 
sequence 
• 
Characterize the SARS-CoV-2 spike genetic sequence of 
viral isolates and compare with the vaccine sequence 
• 
Characterize the immune responses to vaccine 
breakthrough isolates 

ModernaTX, Inc. 
mRNA-1273-P305 Protocol Amendment 2 
mRNA-1273 
Confidential 
Page 66 
To evaluate the immunogenicity of 
mRNA-1273.214 booster compared 
to mRNA-1273 booster 
administered as a 4th dose study 
vaccine in participants at Month 6 
• 
GMT of mRNA-1273.214 against both the B.1.1.529 
and the prototype strain at Month 6 after study vaccine 
administration 
• 
Ratio of GMTmRNA-1273.214/GMTmRNA-1273 against the 
B.1.1.529 strain at Month 6 after study vaccine 
administration 
• 
Ratio of GMTmRNA-1273.214/GMTmRNA-1273 against the 
prototype strain at Month 6 after study vaccine 
administration 
• 
GMFR of mRNA-1273.214 and mRNA-1273 against the 
B.1.1.529 and prototype strain at all evaluable timepoints 
after study vaccine administration 
• 
SRR against both the B.1.1.529 and prototype strain at 
Month 6 
Abbreviations: AE = adverse event; AESI = adverse event of special interest; AR = adverse reaction; CDC = Centers 
for Disease Control and Prevention; GMFR = geometric mean fold rise; GMR = geometric mean titer ratio; GMT = 
geometric mean titer; MAAE = medically attended adverse event; mRNA = messenger ribonucleic acid; NP = 
nasopharyngeal; RT-PCR = reverse transcription polymerase chain reaction; SAE = serious adverse event; SARS-
CoV-2 = severe acute respiratory syndrome coronavirus 2; SRR = seroresponse rate. 

ModernaTX, Inc. 
mRNA-1273-P305 Protocol Amendment 2 
mRNA-1273 
Confidential 
Page 67 
4. 
STUDY DESIGN 
4.1. 
General Design 
The study is a Phase 2/3, 2-part, randomized, observer-blind, active-controlled, multicenter study 
to evaluate the immunogenicity and safety of mRNA-1273.529 and mRNA-1273.214 booster 
vaccine in medically stable individuals 16 years and older. The mRNA-1273.529 vaccine to be 
tested in this study contain mRNAs encoding for the S-2P of the SARS-CoV-2 Omicron variant 
(B.1.1.529). The mRNA-1273.214 vaccine contains the Wuhan Hu-1 and B.1.1.529 mRNAs (2 
mRNAs: CX024414 encoding for the S-2P of Wuhan Hu-1 and CX-031302 encoding for the S-
2P of B.1.1.529) and formulated in the same LNP. 
The study consists of 2 parts with 2 phases each:  
In Part 1, approximately 600-1000 participants will be randomized in a 1:1 ratio to 1 of 2 study 
arms to receive a single dose of either 50 μg of mRNA-1273.529 or 50 μg of mRNA-1273 
(active control. Randomization will be stratified by age groups (16 to < 65 years or ≥ 65 years) 
and number of booster doses received (to receive study vaccine as the 4th dose or to receive study 
vaccine as the 3rd dose). At least ≥ 90% of participants will receive study vaccine as the 4th dose. 
The potential number of participants in each arm and the randomization ratio can be found in 
Table 5. 
In Part 2, approximately 2,924 participants will be randomized in a 1:1 ratio to 1 of 2 study arms 
to receive a single dose of either 50 μg of mRNA-1273.214 or 50 μg of mRNA-1273 (active 
control). Randomization will be stratified by age groups (16 to < 65 years or ≥ 65 years) and 
number of booster doses received (to receive study vaccine as the 4th dose or to receive study 
vaccine as the 3rd dose). At least ≥ 90% of participants will receive study vaccine as the 4th dose. 
The potential number of participants in each arm and the randomization ratio can be found in 
Table 6. 
Each part has a Phase A (randomized, blinded) and Phase B (open-label, observational). Phase B 
was designed to offer eligible participants in either treatment arms in Part 1 to obtain an 
additional booster after their Month 6 assessment and eligible participants in either treatment 
arms in Part 2 the option to obtain an additional booster after their Month 3 assessment. The 
additional booster may be obtained outside the study. 

ModernaTX, Inc. 
mRNA-1273-P305 Protocol Amendment 2 
mRNA-1273 
Confidential 
Page 68 
Table 5: 
Part 1 Study Arm and Dose Levels 
Vaccination 
Group 
Vaccination 
Received 
Total 
Dose 
N 
(total) 
Study vaccine 
as the 3rd dose 
Study vaccine as 
the 4th dose 
1 
mRNA-1273.529 
50 µg 
300-500a 
30-50 
270-450 
2 
mRNA-1273 
(Active Control) 
50 µg 
300-500a 
30-50 
270-450 
Abbreviations: mRNA = messenger ribonucleic acid; N = number. 
a Part 1 will end enrollment when Part 2 starts enrollment. The number of participants in Part 1 will be determined 
by the start date of Part 2. 
Table 6: 
Part 2 Study Arm and Dose Levels
Vaccination 
Group 
Vaccination 
Received 
Total 
Dose 
N 
(total) 
Study Vaccine 
as the 3rd Dose 
Study Vaccine 
as the 4th Dose 
1 
mRNA-1273.214 
50 µg 
1462 
134 
1328 
2 
mRNA-1273 
(Active control) 
50 µg 
1462 
134 
1328 
Abbreviations: mRNA = messenger ribonucleic acid; N = number. 
All participants will have previously received 2 or 3 doses of an authorized/approved COVID-19 
vaccine. Participants who had previously received 2 doses of a COVID-19 vaccine as a primary 
series will receive mRNA-1273.529, mRNA-1273.214, or mRNA-1273 as the third dose, and 
participants who have previously received a primary series and 1 booster dose will receive 
mRNA-1273.529, mRNA-1273.214, or mRNA-1273 as the 4th dose. Participants who will 
receive the 4th dose as part of the study must have previously received a mRNA vaccine as the 
3rd dose of a COVID-19 vaccine. Participants who will receive the 3rd dose as part of the study 
may have previously received 2 doses of a mRNA or a non-mRNA COVID-19 vaccine (a mixed 
approach is acceptable). 
Medically stable individuals, ages 16 and above (to include 2 age groups: 16 to < 65 and 
≥ 65 years) will be screened and enrolled. Participants with chronic diseases requiring ongoing 
medical intervention or within the last 2 months prior to enrollment will be excluded. 
Participants with immunocompromising conditions or medications, or malignancy within 
10 years (excluding nonmelanoma skin cancer) will also be excluded. Participants who received 
a COVID-19 vaccine within 90 days prior to enrollment or had positive SARS-CoV-2 testing by 
an authorized/approved lateral flow/rapid antigen or polymerase chain reaction (PCR) within 
90 days prior to enrollment will be excluded as well. 
Except for appropriately delegated unblinded pharmacists, vaccine administrators and monitors, 
all personnel involved in the conduct of the trial will remain blinded to individual treatment 
assignment until study unblinding. Study visits will consist of a Screening Visit (up to 28 days 
before the Day 1 visit), Vaccination Visit at Day 1 and subsequent study visits on Day 8 (for a 
subset of participants in Part 2), Day 29 (Month 1), Day 85 (Month 3), Day 179 (Month 6), and 

ModernaTX, Inc. 
mRNA-1273-P305 Protocol Amendment 2 
mRNA-1273 
Confidential 
Page 69 
Day 359 (Month 12), with up to 13 months of study participation. Unscheduled visits for 
potential symptoms of COVID-19 will include PCR testing. 
4.2. 
Scientific Rationale for Study Design 
This 2-phase study includes a randomized, blinded phase (Phase A) and an open-label, 
observational phase (Phase B). Phase A is designed as a 2-part, randomized, stratified, observer-
blind, active-controlled study to demonstrate the immunogenicity and safety of the 
mRNA-1273.529 and mRNA-1273.214 vaccine in medically stable individuals 16 years and 
older. Participants will receive a single dose of either mRNA-1273.529/mRNA-1273.214 or 
mRNA-1273 (active comparator) booster vaccine as the 3rd or 4th dose of a COVID-19 vaccine. 
Because it is possible that participants are exposed to SARS-CoV-2 through community 
exposure, NP swab samples and the serologic assays will be collected before vaccination on 
Day 1 to help discriminate between natural infection and vaccine-induced antibody responses, 
should such discrimination be needed. Furthermore, NP swab specimen(s) for assessment of 
pathogens including SARS-CoV-2, will also be collected at any time during the study period if 
participants have symptoms suggestive of COVID-19 or other upper or lower respiratory 
infection at the investigator’s discretion. Additionally, clinical information will be collected to 
evaluate the severity of the clinical case. 
Following authorization of the mRNA-1273.214 booster, the study was amended to allow a 
transition to Phase B, the open-label, observational phase. Transitioning the study to the open-
label, observational phase allows eligible participants in either treatment arm in Part 1 and Part 2 
to receive an additional booster outside of the study after completing the Month 6 and Month 3 
study visit, respectively. 
4.3. 
Justification for Dose and Control Product 
The Sponsor developed mRNA-1273, an mRNA-based vaccine against SARS-CoV-2. Having 
achieved the primary endpoint in a pivotal Phase 3 study conducted in persons at high risk for 
SARS-CoV-2 infection in December 2020, mRNA-1273 was granted EUA for the prevention of 
COVID-19 for individuals 18 years of age and older based on the demonstration of efficacy and 
safety in a pivotal Phase 3 study (Baden et al 2021). Given the potential for waning immunity, 
the emergence of highly transmissible SARS-CoV-2 variants, and the ability of some variants to 
partially escape immunity, the Sponsor assessed the immunogenicity and safety of a 50 μg 
booster immunization. Administration of a booster dose of 50 µg at least 6 months after 
administration of the second of 2 doses of the mRNA-1273 primary series greatly enhanced 
immune responses compared to pre-boost levels. Additionally, no new safety signals emerged 
upon administration of the 50 µg booster dose (Phase 2 mRNA-1273-P201; NCT04405076). 
Based on cumulative evidence, the benefit-risk profile of a 50 µg booster dose of mRNA-1273 is 

ModernaTX, Inc. 
mRNA-1273-P305 Protocol Amendment 2 
mRNA-1273 
Confidential 
Page 70 
favorable, particularly in light of increasing breakthrough disease with the emergence of the 
Delta/Omicron variants. The FDA has authorized the emergency use administration of a single 
booster dose (50 µg) of mRNA-1273 vaccine at least 5 months after completing the primary 
series of this vaccine in individuals 18 years of age and older. 
Based on the Sponsor’s prior studies as described above with mRNA-1273, a dose level of 50 µg 
for mRNA-1273.529 and mRNA-1273.214 was selected and is anticipated to be immunogenic 
and well tolerated. 
4.4. 
End of Study Definition 
The end of study (EoS) is defined as completion of the last visit of the last participant in each part 
of the study or last scheduled procedure as shown in the schedule of events (SoE) Table 1 for Part 1 
and Table 2 for Part 2) for the last participant in the study. 
A participant is considered to have completed the study only if they complete the final visit on 
Day 359 (Month 12) as shown in the SoE (Table 1 and Table 2). 

ModernaTX, Inc. 
mRNA-1273-P305 Protocol Amendment 2 
mRNA-1273 
Confidential 
Page 71 
5. 
STUDY POPULATION 
Prospective approval of protocol deviations to recruitment and enrollment criteria, also known as 
protocol waivers or exemptions, is not permitted. 
5.1. 
Inclusion Criteria 
Each participant must meet all of the following criteria during the screening period and at 
Day 1, unless noted otherwise, to be enrolled in this study:  
1. Is male or female, at least 16 years of age at the time of consent (Screening Visit). 
2. Investigator’s assessment that the participant understands and is willing and physically 
able to comply with protocol-mandated follow-up, including all procedures. 
3. Participant has provided written informed consent for participation in this study, 
including all evaluations and procedures as specified in this protocol. 
4. Female participants of nonchildbearing potential may be enrolled in the study. 
Nonchildbearing potential is defined as postmenopausal or permanently sterilized 
(Section 11.2). A Follicle stimulating hormone (FSH) level should be measured at the 
discretion of the investigator to confirm postmenopausal status, if necessary. 
5. 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 the Screening Visit and on the day of vaccination 
prior to vaccine dose being administered on 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 dose (Day 1). Adequate 
female contraception is defined as consistent and correct use of a local health 
authority approved contraceptive method in accordance with the product label. 
• Has agreed to continue adequate contraception through 90 days following vaccine 
administration. 
6. Has received 2 prior doses of one of the following approved/authorized COVID-19 
vaccines: Moderna, Pfizer/BioNTech, Oxford/AstraZeneca, Janssen. A heterologous 
vaccine regimen is acceptable.  
7. Participants who will receive the 4th dose as part of the study must have previously 
received a mRNA vaccine (Moderna or Pfizer/BioNTech) as the 3rd dose of a COVID-19 
vaccine. Participants who will receive the 3rd dose as part of the study may have 
previously received 2 doses of an approved/authorized mRNA or a non-mRNA 
COVID-19 vaccine (a heterologous vaccine regimen is acceptable). 

ModernaTX, Inc. 
mRNA-1273-P305 Protocol Amendment 2 
mRNA-1273 
Confidential 
Page 72 
5.2. 
Exclusion Criteria 
Participants meeting any of the following criteria, unless noted otherwise, will be excluded 
from the study: 
1. Had close contact (without personal protective equipment [PPE]) as defined by the CDC 
in the past 14 days to someone diagnosed with SARS-CoV-2 infection or COVID-19 
within 10 days of the close contact. Participants may be rescreened after 14 days 
provided that they remain asymptomatic. 
2. Participant is acutely ill or febrile (temperature ≥ 38.0°C/100.4°F) 72 hours prior to or at 
the Screening Visit or Day 1. Participants meeting this criterion may be rescheduled 
within the 28-day screening window and will retain their initially assigned participant 
number. 
3. Has tested positive for SARS-CoV-2 by an authorized/approved lateral flow/rapid 
antigen or PCR test within 90 days of Screening.  
4. Has received a COVID-19 vaccine within 90 days of the Screening Visit. 
5. Has received a total of 4 doses or more of COVID-19 vaccine. 
6. Has received a COVID-19 vaccine at a dose different from the authorized/approved dose. 
7. History of a diagnosis or condition that, in the judgment of the Investigator, is clinically 
unstable or may affect participant safety, assessment of safety endpoints, assessment of 
immune response, or adherence to study procedures. Clinically unstable is defined as a 
diagnosis or condition requiring significant changes in management or medication within 
the 2 months prior to screening and includes ongoing workup of an undiagnosed illness 
that could lead to a new diagnosis or condition.  
8. Reported history of congenital or acquired immunodeficiency, immunosuppressive 
condition, or immune-mediated disease requiring immunosuppressive treatment or other 
immunosuppressive condition. 
9. Dermatologic conditions that could affect local solicited AR assessments (eg, tattoos, 
psoriasis patches affecting skin over the deltoid areas). 
10. Reported history of anaphylaxis or severe hypersensitivity reaction after receipt of any 
components of mRNA vaccine. 
11. Reported history of bleeding disorder that is considered a contraindication to 
intramuscular (IM) injection or phlebotomy. 
12. Any medical, psychiatric, or occupational condition, including reported history of 
substance abuse, that, in the opinion of the Investigator, might pose additional risk due to 
participation in the study or could interfere with the interpretation of study results.  

ModernaTX, Inc. 
mRNA-1273-P305 Protocol Amendment 2 
mRNA-1273 
Confidential 
Page 73 
13. Has received systemic immunosuppressants or immune-modifying drugs for > 14 days in 
total within 181 days prior to screening (for corticosteroids ≥ 10 mg/day of prednisone or 
equivalent) or is anticipating the need for immunosuppressive treatment at any time 
during participation in the study. 
14. Has received or plans to receive any licensed vaccine ≤ 28 days prior to the study 
injection (Day 1) or plans to receive a licensed vaccine within 28 days after the study 
injection (with the exception that approved seasonal influenza vaccine may be received 
by at least 7 days and preferably 14 days apart from the study injection). 
15. Has received systemic immunoglobulins or blood products within 90 days prior to the 
Screening Visit or plans to receive during the study. 
16. Diagnosis of malignancy within the previous 10 years (excluding nonmelanoma skin 
cancer). 
17. Has donated ≥ 450 mL of blood products within 28 days prior to the Screening Visit or 
plans to donate blood products during the study. 
18. Has participated in an interventional clinical study within 28 days prior to the Screening 
Visit based on the medical history interview or plans to do so while participating in this 
study. 
19. Is an immediate family member or household member of study personnel, study site staff, 
or Sponsor personnel. 
5.3. 
Lifestyle Restrictions 
Participants must not eat or drink anything hot or cold within 10 minutes before oral temperature 
is taken.  
5.4. 
Screen Failures 
Screen failures are defined as participants who consent to participate in the clinical study but are 
not subsequently randomly assigned to treatment. 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 publishing requirements and to respond to queries from regulatory 
authorities. Minimal information includes date of informed consent, demography, screen failure 
details, eligibility criteria, and information on any SAE which may have occurred from the time 
informed consent was obtained to the time of withdrawal. 
Individuals who do not meet the criteria for participation in this study (screen failure) may be 
rescreened one time if they will be eligible upon rescreening. 

ModernaTX, Inc. 
mRNA-1273-P305 Protocol Amendment 2 
mRNA-1273 
Confidential 
Page 74 
6. 
STUDY TREATMENT 
6.1. 
Investigational Product and Active Comparator Administered 
The vaccines to be administered in this study are described in Table 7. 
Table 7: 
Investigational Product and Active Comparator Administered 
Study Arm: 
mRNA-1273 
mRNA-1273.529 
mRNA-1273.214 
Intervention 
Name: 
mRNA-1273 (aka, 
Moderna COVID-19 
Vaccine) 
mRNA-1273.529 
mRNA-1273.214 
Type: 
Vaccine 
Vaccine 
Vaccine 
Dosage Level(s): 
50 µg (mRNA) 
50 µg (mRNA) 
50 µg (mRNA) 
Route of 
Administration: 
IM injection 
IM injection 
IM injection 
Physical 
Description: 
Sterile liquid for 
injection, 
white-to-off-white 
dispersion 
Sterile liquid for 
injection, 
white-to-off-white 
dispersion 
Sterile liquid for 
injection, white-to-off-
white dispersion 
Source: 
Sourced locally by the 
sites  
Provided centrally by 
the Sponsor 
Provided centrally by 
the Sponsor 
Packaging and 
Labeling: 
mRNA-1273 will be 
provided in its 
commercial presentation  
mRNA-1273.529 will 
be provided in 
2R borosilicate glass 
vials. Vials will be 
labeled as required per 
local requirement. 
mRNA-1273.214 will 
be provided in 2R 
borosilicate glass vials. 
Vials will be labeled as 
required per local 
requirement.  
Abbreviations: IM = intramuscular; mRNA = messenger ribonucleic acid. 
mRNA-1273 is a LNP dispersion of an mRNA encoding the prefusion stabilized S protein of 
SARS-CoV-2.  
mRNA 1273.529 contains mRNA CX-031302 encoding for the S-2P of the SARS-CoV-2 
Omicron variant (B.1.1.529). mRNA 1273 contains mRNA CX-024414 encoding for the S-2P of 
Wuhan-Hu-1. mRNA-1273.214 is a bivalent vaccine containing mRNA-1273.529 and 
mRNA-1273 co-formulated at a 1:1 ratio. mRNA-1273.529, mRNA-1273, and mRNA-1273.214 
each consists of mRNAs formulated in a mixture of 4 lipids common to the Sponsor’s mRNA 
vaccine platform: SM-102, cholesterol, DSPC, and PEG 2000 DMG. 

ModernaTX, Inc. 
mRNA-1273-P305 Protocol Amendment 2 
mRNA-1273 
Confidential 
Page 75 
mRNA-1273.529, mRNA-1273, and mRNA-1273.214 will be administered at a 50 µg dose level 
as an IM injection into the deltoid muscle on Day 1.  
6.2. 
Randomization and Blinding 
Randomization during the blinded Phase (Phase A) will be performed using an interactive 
response technology (IRT). In Part 1, approximately 600-1000 participants will be randomized in 
a 1:1 ratio to receive a single dose of either 50 µg of mRNA-1273.529 or 50 μg of mRNA-1273 
(active control). In Part 2, approximately 2,924 participants will be randomized in a 1:1 ratio to 
receive a single dose of either 50 µg of mRNA-1273.214 or 50 μg of mRNA-1273 (active 
control). In both parts, randomization will be stratified by age groups (16 to < 65 years or ≥ 65 
years) and number of booster doses received (to receive study vaccine as the 4th dose or to 
receive study vaccine as the 3rd dose). At least ≥ 90% of participants will receive study vaccine 
as the 4th dose. 
As the appearance of the study vaccines differ, enrollment will be observer-blinded as to 
treatment assignment. 
Dose preparation, administration, and accountability will be performed by designated unblinded 
site personnel who will not participate in any of the clinical study evaluations. The unblinded site 
personnel will prepare the dose out of view of the participant and the blinded site personnel. 
These personnel will have no study functions other than investigational product (IP) 
management, documentation, accountability, preparation, and administration. They will not be 
involved in participant evaluations and will not reveal the identity of the IP to either the 
participant or the blinded clinic personnel involved in the conduct of the study unless this 
information is necessary in the case of an emergency. Once the injection is completed, only the 
blinded clinic staff will perform further assessments and interact with the participants. Access to 
the randomization code will be strictly controlled at the pharmacy. 
Unblinded site monitors, not involved in other aspects of monitoring, will be assigned as the IP 
accountability monitors. They will have responsibilities to ensure that sites are following all 
proper IP accountability, preparation, and administration procedures. 
The laboratory personnel in charge of immunogenicity testing will be blinded to the treatment 
assignment of the samples tested throughout the course of the study. 
Except in the case of medical necessity and optional unblinding (Section 6.3.7), a participant’s 
treatment should not be unblinded without the approval of the Sponsor. The treatment code 
should be broken only if the investigator in charge of the participant feels that the case cannot be 
treated without knowing the identity of the study vaccine. Instructions regarding emergency 
unblinding will be provided to the investigator and are discussed in Section 6.3.7. 

ModernaTX, Inc. 
mRNA-1273-P305 Protocol Amendment 2 
mRNA-1273 
Confidential 
Page 76 
The investigator, clinic staff, study participants, site monitors, and Sponsor personnel (or its 
designees) will be blinded to the IP administered until the unblinding occurs (Section 6.3.7) or 
until study database is locked and unblinded for the final analysis. At the planned analyses (see 
Section 9.7), pre-identified Sponsor team members and selected contract research organization 
(CRO) team members will be unblinded to conduct the analyses.  
6.3. 
Preparation/Handling/Storage/Accountability 
6.3.1. 
Clinical Study Material Preparation 
The IP will be prepared for each participant based on their vaccination group assignment. The 
mRNA-1273.529 vaccine injection will have a volume of 0.25 mL and will contain 
mRNA-1273.529 at a dose of 50 µg. The mRNA-1273.214 vaccine will have a volume of 
0.25 mL and will contain mRNA-1273.214 at the dose of 50 µg. The active comparator 
(mRNA-1273) will be administered at a volume of 0.25 mL and will contain mRNA-1273 at a 
dose of 50 µg. The mRNA-1273.529, mRNA-1273.214, and mRNA-1273 preparation 
instructions are detailed in the Pharmacy Manual. 
6.3.2. 
Clinical Study Material Administration 
The study vaccine will be administered as a single IM injection into the deltoid muscle on Day 1. 
Preferably, the IP should be administered into the nondominant arm. 
Participants will be monitored for a minimum of 15 minutes after administration of the study 
injection. Assessments will include vital sign measurements and monitoring for local or systemic 
reactions as shown in the SoE (Table 1 and Table 2). 
The clinic will be appropriately staffed with individuals with basic cardiopulmonary 
resuscitation training/certification. Either onsite resuscitation equipment and personnel or 
appropriate protocols for the rapid transport of a participant to a resuscitation area or facility are 
required. 
Further instructions for the preparation and administration of mRNA-1273.529, 
mRNA-1273.214, and active comparator (mRNA-1273) are described in the Pharmacy Manual. 
6.3.3. 
Clinical Study Material Packaging and Labeling 
The Sponsor will provide the investigator (via the clinic pharmacy) with adequate quantities of 
the IP. 
mRNA-1273.529 is provided as a sterile solution for injection at a concentration of 0.2 mg/mL in 
20 mM Tris buffer with sucrose, at pH 7.5 and presented in 2R United States Pharmacopeia 
(USP) Type I borosilicate glass vials with PLASCAP vial seal containing a 13 mm FluroTec 

ModernaTX, Inc. 
mRNA-1273-P305 Protocol Amendment 2 
mRNA-1273 
Confidential 
Page 77 
coated plug stopper with a 0.8 mL nominal fill volume. mRNA-1273.529 will have all required 
labeling per regulations and will be supplied to the pharmacy in an unblinded manner. 
mRNA-1273.214 is provided as a sterile solution for injection at a concentration of 0.1 mg/mL in 
20 mM Tris buffer with sucrose, at pH 7.5 and presented in 2R United States Pharmacopeia 
(USP) Type I borosilicate glass vials with PLASCAP vial seal containing a 13 mm FluroTec 
coated plug stopper with a 0.8 mL nominal fill volume. mRNA-1273.214 will have all required 
labeling per regulations and will be supplied to the pharmacy in an unblinded manner. 
mRNA-1273 injection will be sourced locally as commercial supply.  
All IPs used in this study will be prepared, packaged, and labeled in accordance with the 
standard operating procedures of the Sponsor or those of its designee, Code of Federal 
Regulations Title 21, Good Manufacturing Practice guidelines, International Council for 
Harmonisation (ICH) Good Clinical Practice (GCP) guidelines, guidelines for Quality System 
Regulations, and applicable regulations. 
Updates to this clinical study material packaging and labeling information may be provided in 
the Pharmacy Manual or associated Commercial Packaging and will supersede the information 
provided in the protocol. 
6.3.4. 
Clinical Study Material Storage 
mRNA-1273 must be stored in accordance with commercial packaging in a secure area with 
limited access until they are prepared for administration. mRNA-1273.529 and mRNA-1273.214 
must be stored at -90°C to -60°C (-130°F to -76°F) in a secure area with limited access and must 
be protected from moisture and light until they are prepared for administration. The designated 
freezer should have automated temperature recording and a 24- hour alert system in place that 
allows for rapid response in case of freezer malfunction. It is recommended that there should be 
an available backup freezer. It is also recommended that the freezer should be connected to a 
backup generator. In addition, for IP accountability, staff are required to keep a temperature log 
to establish a record of compliance with these storage conditions. The study site is responsible 
for reporting any IP that was not temperature controlled during shipment or storage. Such IP will 
be retained for inspection by the monitor and disposed of according to approved methods. 
Clinical study material storage requirements presented in the protocol may be superseded in 
accordance with requirements provided with the IP label. 
6.3.5. 
Clinical Study Material Accountability 
The investigator is responsible for ensuring the IP accountability staff maintain an accurate 
record of the shipment receipt, the inventory at the site, dispensing of study vaccines, and the 
return to the Sponsor or alternative disposition of used/unused product(s) in a drug accountability 

ModernaTX, Inc. 
mRNA-1273-P305 Protocol Amendment 2 
mRNA-1273 
Confidential 
Page 78 
log. Drug accountability will be noted by the site monitor during site visits and at the completion 
of the study. For further direction, refer to the Pharmacy Manual. 
6.3.6. 
Clinical Study Material Handling and Disposal 
A site monitor will reconcile the clinical study material during study conduct and at the end of 
the study for compliance. Once fully reconciled at the site, the clinical study material can be 
destroyed at the investigational site or Sponsor-selected third party, as appropriate. 
Study products may be destroyed at the clinic only if permitted by local regulations and 
authorized by the Sponsor. A Certificate of Destruction must be obtained and sent to the Sponsor 
or designee. For further direction, refer to the Pharmacy Manual. 
6.3.7. 
Unblinding 
Participants who report eligibility to receive an additional booster outside of the mRNA-1273-
P305 study have the option to be unblinded in Part 1 of the study after the completion of their 
scheduled Month 6 visit and in Part 2 after the completion of their scheduled Month 3 visit. 
Unblinding may be performed remotely over the phone prior to signing the updated informed 
consent form (ICF) based on participant preference. Both unblinded and blinded participants will 
continue to follow the Schedule of Events (Section 1.3). 
Except in the case of medical necessity and as part of the unblinding described above, a 
participant’s treatment assignment should not be unblinded without the approval of the Sponsor. 
If a participant becomes seriously ill or pregnant during the study, the blind will be broken only 
if knowledge of the treatment assignment will affect that participant’s clinical management. The 
investigator will be responsible for documenting the time, date, reason for unblinding, and the 
names of the personnel involved. The investigator (or designee) will have access to unblind 
participants within IRT. All unblindings will be tracked via an audit trail in IRT and documented 
in the final study report. 
6.4. 
Study Intervention Compliance 
All vaccinations will be administered by qualified and trained study personnel to ensure that all 
vaccine doses administered comply with those planned. Study vaccine doses administered will 
be recorded in the electronic case report form (eCRF). Administration data will be reconciled 
with site accountability records to determine compliance. 

ModernaTX, Inc. 
mRNA-1273-P305 Protocol Amendment 2 
mRNA-1273 
Confidential 
Page 79 
6.5. 
Prior and Concomitant Medications 
6.5.1. 
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. 
6.5.2. 
Concomitant Medications and Therapies 
At the study site, study staff must question the participant regarding any concomitant 
medications taken and non-study vaccinations received by the participant and record the 
following information in the eCRF: 
• Any vaccine (authorized or investigational) administered in the prior 28 days before the 
study injection. 
• Seasonal influenza vaccine administered for the current influenza season (typically 
October through April in the Northern Hemisphere). 
• All concomitant medications taken through 28 days after the study 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. 
• All non-study vaccines at any time during the study period after the IP injection, including 
any authorized or investigational COVID-19 vaccine.  
• Any concomitant medications used to prevent or treat COVID-19 or its symptoms. 
• Systemic steroids (≥ 10 mg/day prednisone or equivalent), immunosuppressants, 
immune-modifying drugs, immunoglobulins, and/or blood products administered at any 
time during the study period after the IP injection. 
• Any concomitant medications relevant to or for the treatment of a SAE, AESI, MAAE, or 
AE leading to withdrawal from Day 1 through EoS. 
• The participant will be asked in the electronic diary (eDiary) if they have taken any 
antipyretic or analgesic to treat or prevent fever or pain within 7 days after the IP injection, 
including the day of injection. Reported antipyretic or analgesic medications should be 
recorded in the source document by the clinic staff during the clinic visits after vaccination 
or via other participant interactions (eg, telephone calls). 
Concomitant medications (including vaccinations) will be coded using the WHO Drug Global. 

ModernaTX, Inc. 
mRNA-1273-P305 Protocol Amendment 2 
mRNA-1273 
Confidential 
Page 80 
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 the study vaccination 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. 
6.5.3. 
Concomitant Medications and Vaccines That May Lead to the Elimination of a 
Participant from Per-protocol Analyses 
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 evaluability in the per-protocol 
(PP) analysis (analysis sets are described in Section 9.5): 
• 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 ≥ 10 mg/day or the equivalent is not permitted. Inhaled and topical steroids are 
allowed. 
• Long -acting, immune-modifying drugs administered at any time during the study period 
(eg, infliximab). 
• An authorized or licensed vaccine administered during the period from 28 days before 
through 28 days after vaccination, except for any licensed influenza vaccine that was 
administered by at least 7 days and preferably 14 days before or after vaccination. 
• Any COVID-19 vaccine received outside of the study after the study vaccination. 
• Immunoglobulins and/or any blood products administered during the study period. 

ModernaTX, Inc. 
mRNA-1273-P305 Protocol Amendment 2 
mRNA-1273 
Confidential 
Page 81 
7. 
DELAY OR DISCONTINUATION OF STUDY INTERVENTION 
AND PARTICIPANT DISCONTINUATION/WITHDRAWAL 
7.1. 
Participant Discontinuation/Withdrawal from the Study 
Participants who withdraw or are withdrawn from the study will not be replaced. 
From an analysis perspective, a “withdrawal” from the study refers to a situation wherein a 
participant does not return for the final visit planned in the protocol. 
Participants can withdraw consent and withdraw from the study at any time, for any reason, 
without prejudice to further treatment the participant may need to receive. The investigator will 
request that the participant complete all study procedures pending at the time of withdrawal. 
If a participant desires to withdraw from the study because of an AE, the investigator will 
attempt to obtain agreement to follow-up with the participant until the event is considered 
resolved or stable and will then complete the end of study eCRF. 
All data collected until the date of withdrawal or last contact of the participant will be used for 
the analysis. 
Information related to the withdrawal will be documented in the eCRF. The investigator will 
document whether the decision to withdraw a participant from the study was made by the 
participant or by the investigator, as well as which of the following possible reasons was 
responsible for withdrawal: 
• AE (specify) 
• SAE (specify) 
• Solicited AR or reactogenicity event (specify) 
• Death 
• Lost to follow-up (LTFU) 
• Physician decision (specify) 
• Pregnancy 
• Protocol deviation 
• Study terminated by Sponsor 
• Withdrawal of consent by participant (specify) 
• Other (specify) 

ModernaTX, Inc. 
mRNA-1273-P305 Protocol Amendment 2 
mRNA-1273 
Confidential 
Page 82 
Participants who are withdrawn from the study because of AEs (including SAEs, solicited ARs, 
or reactogenicity events) must be clearly distinguished from participants who are withdrawn for 
other reasons. Investigators will follow-up with participants who are withdrawn from the study 
as result of an AE, SAE, solicited AR, or reactogenicity event until resolution of the event. 
A participant withdrawing from the study may request destruction of any samples taken and not 
tested, and the investigator must document this in the site study records. 
If the participant withdraws consent for disclosure of future information, the Sponsor may retain 
and continue to use any data collected before such a withdrawal of consent (see Section 11.1.6). 
The Sponsor will continue to retain and use all research results that have already been collected 
for the study evaluation, unless the participant has requested destruction of these samples. All 
biological samples that have already been collected may be retained and analyzed at a later date 
(or as permitted by local regulations). 
7.2. 
Lost to Follow-up 
A participant will be considered LTFU 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 clinic. The 
following actions must be taken if a participant fails to return to the clinic for a required clinic 
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 LTFU, 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 medical record. 
• Should the participant continue to be unreachable or noncompliant with clinic visits or 
procedures, he or she will be considered to have withdrawn from the study. 
• A participant should not be considered LTFU until due diligence has been completed. 

ModernaTX, Inc. 
mRNA-1273-P305 Protocol Amendment 2 
mRNA-1273 
Confidential 
Page 83 
8. 
STUDY ASSESSMENTS AND PROCEDURES 
The study SoE for Part 1 and Part 2 of the study can be found in Table 1 and Table 2. 
8.1. 
Screening 
Before performing any study procedures, all potential participants will sign an ICF 
(Section 11.1.6). 
At the Screening Visit (up to 28 days for the Day 1 visit), all screening requirements, including 
reason for screen failure if a participant is not randomized, must be completed. The Enrollment 
Page in the eCRF must also be completed. 
The Screening Visit and Day 1 may be performed on the same day or a different day. 
Additionally, the Screening Visit may be performed over multiple visits if within the 28-day 
screening window. 
8.2. 
Confirm Inclusion and Exclusion Criteria 
All inclusion and exclusion criteria described in Section 5.1 and Section 5.2 must be met before 
randomization (Day 1 visit). 
8.3. 
Demographic and Baseline Data 
Demographic information relating to the participant’s sex, age, race, ethnicity, height, weight, 
and body mass index will be recorded at the Screening Visit on the appropriate eCRF page. 
COVID-19 vaccine history will also be recorded at the Screening Visit on the appropriate eCRF 
page. 
8.4. 
Medical History 
Medical history will be collected and recorded from each participant on the appropriate eCRF 
page. Significant findings that were present prior to the signature of the informed consent must 
be included in the Medical History eCRF page. 
8.5. 
Randomization 
Vaccination group allocation will be performed at the Day 1 visit during Phase A (blinded) as 
described in Section 6.2. The confirmation for study vaccine administration must be recorded on 
the Exposure page of the eCRF. 
8.6. 
Physical Examination and Vital Signs 
A full physical examination, including height and weight, will be performed at the Screening 
Visit; symptom-directed physical examinations may be performed at other clinic visits. Interim 

ModernaTX, Inc. 
mRNA-1273-P305 Protocol Amendment 2 
mRNA-1273 
Confidential 
Page 84 
physical examinations will be performed at the discretion of the investigator. Any clinically 
significant finding identified by a healthcare professional during clinic visits should be reported 
as a MAAE (Section 8.10.4). 
Vital sign measurements include the assessment of systolic and diastolic blood pressures, heart 
rate, respiratory rate, and body temperature. The preferred route of temperature assessment is 
oral. On the day of vaccination, vital signs will be collected once prior to vaccination and once 
15 minutes after vaccination. Vital signs may be collected at other clinic visits in conjunction 
with a symptom-directed physical examination. 
The information collected will be recorded in the eCRF. 
8.7. 
Study Vaccine Administration 
A single dose vaccination (mRNA-1273.529, mRNA-1273.214, or mRNA-1273) will be 
administered to all participants. 
After completing all prerequisite procedures prior to vaccination, the study vaccine will be 
administered via IM injection into the deltoid muscle. Additional details regarding vaccine 
administration procedure are provided in Section 6.3.2. 
The participants will be observed closely (via clinical assessment including measurement of vital 
signs) for at least 15 minutes following the administration of the vaccine, with appropriate 
medical treatment readily available in case of anaphylaxis or other hypersensitivity reactions. 
8.8. 
Immunogenicity and Efficacy Assessments 
8.8.1. 
Immunogenicity Assessments 
Blood samples for immunogenicity assessments will be collected at the time points indicated in 
the SoE (Table 1 and Table 2) for the following parameters: 
• Serum binding antibody (bAb) level against SARS-CoV-2 as measured by ligand binding 
assay specific to the SARS-CoV-2 S protein and the S protein RBD. 
• Serum nAb level against SARS-CoV-2 as measured by pseudovirus neutralization assays. 
• Testing for serologic markers for SARS-CoV-2 infection as measured by anti-nucleocapsid 
antibodies detected by immunoassay. 
Measurements will be performed in a laboratory or laboratories designated by the Sponsor. 
According to the ICF (Section 11.1.6), 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 vaccines, additional assay development, and the immune 
response across SARS-CoV-2 viruses (Section 11.1.10). 

ModernaTX, Inc. 
mRNA-1273-P305 Protocol Amendment 2 
mRNA-1273 
Confidential 
Page 85 
8.8.2. 
Vaccine Efficacy and Surveillance for COVID-19 Symptoms 
Vaccine efficacy will be assessed as an exploratory endpoint in Part 1 and as a secondary endpoint 
in Part 2 of this study. Active surveillance for COVID-19 and SARS-CoV-2 infection will be 
performed in both parts of the study (see Table 1 and Table 2). 
8.9. 
Safety Assessments 
Safety assessment will include monitoring and recording of the following for each participant 
according to the SoE (Table 1 and Table 2): 
• Solicited local and systemic ARs that occur during the 7 days following vaccination (ie, 
the day of injection and 6 subsequent days). Solicited ARs will be recorded daily using 
eDiaries. 
• Unsolicited AEs observed or reported during the 28 days following vaccination. 
Unsolicited AEs are AEs that are not included in the protocol-defined solicited ARs. 
• AEs leading to withdrawal from the study. 
• MAAEs from vaccination on Day 1 through EoS or withdrawal from the study. 
• AESIs from vaccination on Day 1 through EoS or withdrawal from the study. 
• SAEs from vaccination on Day 1 through EoS or withdrawal from the study. 
• Vital sign measurements before and after vaccination. 
• Physical examination findings (if performed). 
• Assessments for SARS-CoV-2 infection from Day 1 through study completion. 
• Details of all pregnancies in female participants will be collected after the start of study 
vaccine and until the end of their participation in the study. All pregnancies must be 
followed to determine the outcome; however, pregnancy related data received after the end 
of the study may not be collected in the clinical database. 
8.9.1. 
Pregnancy Screen and Testing 
A point of- -care urine pregnancy test will be performed for all female participants of 
childbearing potential at the Screening Visit and before the vaccine dose on Day 1, if Day 1 is 
not on the same day as the Screening Visit. At the discretion of the investigator, a pregnancy test 
either via blood or point -of -care urine can be performed at any time. The participant’s FSH 
level should be measured at the Screening Visit, if necessary, and at the discretion of the 
investigator, to confirm postmenopausal status. 
Further details on reporting and follow-up of pregnancy are provided in Section 8.10.6. 

ModernaTX, Inc. 
mRNA-1273-P305 Protocol Amendment 2 
mRNA-1273 
Confidential 
Page 86 
8.9.2. 
Assessments for SARS-CoV-2 Infection 
Study participants will have NP swab samples collected for SARS-CoV-2 testing as specified in 
the SoE (Table 1 and Table 2). 
For the duration of the study, participants will be directed as soon as possible and within 24 
hours to obtain an approved/authorized PCR test for SARS-CoV-2 locally outside of the study 
according to prior National Health Service (NHS) guidance if they experience symptoms of 
COVID-19 as previously defined by the NHS: 
• High temperature (feel hot to touch on the chest or back) 
• A new, continuous cough (coughing a lot for more than an hour, or 3 or more coughing 
episodes in 24 hours, or worse than usual cough) 
• A loss or change to sense of smell or taste 
If a PCR test is unavailable locally, participants will be requested to come in for a study visit or 
take an approved/authorized lateral flow/rapid antigen test for SARS-CoV-2. 
Participants will be directed as soon as possible and within 24 hours to take an 
approved/authorized lateral flow/rapid antigen test for SARS-CoV-2 if they experience any of 
the following (but do not meet the symptoms of COVID-19 as previously defined by the NHS 
and described above): 
• Signs or symptoms of SARS-CoV-2 infection as defined by the CDC 
(https://www.cdc.gov/coronavirus/2019-ncov/symptoms-testing/symptoms.html) with 
modifications: 
o Chills 
o Cough (not meeting COVID-19 symptoms defined by the NHS) 
o Shortness of breath or difficulty breathing 
o Fatigue 
o Muscle or body aches 
o Headache 
o Sore throat 
o Congestion or runny nose 
o Nausea or vomiting 
o Diarrhea 

ModernaTX, Inc. 
mRNA-1273-P305 Protocol Amendment 2 
mRNA-1273 
Confidential 
Page 87 
Lateral flow/rapid antigen test for SARS-CoV-2 may be repeated every 24-48 hours if 
participants continue to have symptoms above. 
Participants will be directed to take an approved/authorized lateral flow/rapid antigen test for 
SARS-CoV-2 within 4 to 6 days after last exposure* (see definition of last exposure below) if a 
participant experiences the following: 
• Known close contact with someone who has known COVID-19 or SARS-CoV-2 
infection. Examples include: 
o Being within 2 meters (without PPE) for a total of 15 minutes or more 
o Providing care at home 
o Having direct physical contact (hugged or kissed them) 
o Sharing eating or drinking utensils 
o Being sneezed or coughed upon or getting respiratory droplets on the participant 
*Last exposure is defined as the last day a participant was in close contact with a symptomatic 
person in the household (if the participant was then isolated from that person) or the last day of 
the quarantine of the person the participant was exposed to, if that person was asymptomatic 
and/or the participant was unable to isolate from that person. 
A study illness visit (study site visit) will be arranged as soon as possible and within 72 hours for 
participants who test positive or equivocal for SARS-CoV-2 using an authorized/approved lateral 
flow/rapid antigen or local PCR testing. If a test for SARS-CoV-2 is unavailable or if there is 
uncertainty on the test result, a study site visit may be arranged as soon as possible and within 
72 hours.  
At this visit, an NP swab will be collected to evaluate for the presence of SARS-CoV-2 infection. 
Active surveillance for COVID-19 will be conducted throughout the study as described in the SoE 
(Table 1 and Table 2). 
All cases that have RT-PCR-confirmed COVID-19 as defined by the NHS or the CDC should be 
captured as MAAEs (unless the definition of an SAE is met) along with relevant concomitant 
medications, hospitalizations, outpatient medical care, and details about severity, seriousness, 
and outcome. Clinical information including but not limited to the following should be collected, 
if applicable: clinical assessment or imaging (including percentage of lung infiltrates), oxygen 
saturation (SpO2), respiratory rate, and hospital course including (but not limited to) PaO2/FiO2 
ratio, respiratory failure, oxygen support, shock, organ dysfunction, and life-sustaining treatment. 
In addition to SARS-CoV-2 assessment and testing outlined in this protocol, also follow local 
testing guidelines. 

ModernaTX, Inc. 
mRNA-1273-P305 Protocol Amendment 2 
mRNA-1273 
Confidential 
Page 88 
8.9.3. 
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. Safety 
telephone calls will follow a schedule for each participant, as shown in the SoE (Table 1 and 
Table 2). 
The participant will be interviewed according to the script about occurrence of AEs, MAAEs, 
SAEs, AESIs, AEs leading to withdrawal from study participation, concomitant medications 
associated with those events, and any non-study vaccinations (Section 8.10.13). 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. An unscheduled follow-up safety call may be triggered if an eDiary record results in 
identification of a relevant safety event. 
8.9.4. 
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 own device or using a device that is provided at 
the time of enrollment. Before enrollment on Day 1, the participants will be instructed to 
download the eDiary application or will be provided an eDiary device to record solicited ARs 
(Section 8.10.3). Participants will also use the eDiary to respond to questionnaires related to 
COVID-19 (as part of active surveillance) every 2 weeks from Day 43 through Day 359/EoS. 
Participants will be instructed on Day 1 on thermometer usage to measure body temperature, 
ruler usage to measure injection site erythema and swelling/induration (hardness), and 
self-assessment of localized axillary swelling or tenderness on the same side as the injection arm. 
Participants will record data into the eDiary starting approximately 15 minutes after injection 
under supervision of the study staff to ensure successful entry of assessments. The clinic staff 
will perform any retraining as necessary. Participants will continue to record data in the eDiary 
after they leave the clinic, preferably in the evening and at the same time each day, on the day of 
injection, and for 6 days following injection. 
Participants will record the following data in the eDiary: 
• Solicited local and systemic ARs, as defined in Section 8.10.3, that occur on the 
day of vaccination and during the 7 days after vaccination (ie, the day of 
injection and 6 subsequent days).  
• Daily oral body temperature measurement should be performed at 
approximately the same time each day using the thermometer provided by the 

ModernaTX, Inc. 
mRNA-1273-P305 Protocol Amendment 2 
mRNA-1273 
Confidential 
Page 89 
clinic. If body temperature is taken more than once in a given day, only the 
highest temperature reading should be recorded. 
• Measurements, as applicable, for solicited local ARs (injection site erythema 
and swelling/induration) will be performed using the ruler provided by the 
clinic. 
• Any medications taken to treat or prevent pain or fever on the day of injection 
or for the next 6 days. 
The eDiary should be the primary source document allowed for solicited systemic or local ARs 
(including body temperature measurements) up to Day 7 post vaccination. 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 the solicited ARs. 
Any new safety information reported during safety telephone calls or at clinic 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 in the SAR section of the eCRF. 
Clinic staff will review eDiary data with participants at a visit 7 days after the injection. 
8.9.5. 
Blood Sampling Volumes 
The maximum planned volumes of blood sampled per participant will not exceed 450 mL for 
each part of the study. 
8.9.6. 
Ancillary Supplies for Participant Use 
Clinics will distribute Sponsor provided oral thermometers and rulers for use by participants in 
assessing body temperature and injection site reactions, for recording solicited ARs in the 
eDiaries. Based on availability, smartphone devices may be provided to those participants who 
do not have their own device to use for eDiary activities. 
8.10. 
Safety Definitions 
8.10.1. 
Adverse Event 
An AE is defined as any untoward medical occurrence associated with the use of a drug/vaccine 
in humans, whether or not considered related to the drug/vaccine. 
A treatment-emergent AE (TEAE) is defined as any event not present before exposure to IP or 
any event already present that worsens in intensity or frequency after exposure. 

ModernaTX, Inc. 
mRNA-1273-P305 Protocol Amendment 2 
mRNA-1273 
Confidential 
Page 90 
Events Meeting the Adverse Event Definition 
• Exacerbation of a chronic or intermittent pre-existing condition, including 
either an increase in frequency and/or intensity of the condition, after the IP 
injection 
• New conditions detected or diagnosed after the first dose of IP even though they 
may have been present before the start of the study 
Events NOT Meeting the Adverse Event Definition 
• Procedures planned before study entry (eg, hospitalization for preplanned 
surgical procedure) 
• Medical or surgical procedure (eg, endoscopy, appendectomy): the condition 
that leads to the procedure should be the AE 
• Situations in which an untoward medical occurrence did not occur (social 
and/or convenience admission to a hospital) 
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 but starts outside the protocol-defined period for 
reporting solicited ARs (ie, 7 days after vaccination). 
8.10.2. 
Serious Adverse Events 
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 IP. 
• 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 

ModernaTX, Inc. 
mRNA-1273-P305 Protocol Amendment 2 
mRNA-1273 
Confidential 
Page 91 
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. 
• 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. 
8.10.3. 
Solicited Adverse Reactions 
The term “reactogenicity” refers to the occurrence and intensity of selected signs and symptoms 
(ARs) occurring after IP injection. The eDiary will solicit daily participant reporting of ARs 
using a structured checklist (Section 8.9.4). Participants will record such occurrences in an 
eDiary on the day of IP injection and for the 6 days after the day of dosing. 
Severity grading of reactogenicity will occur automatically based on participant entries into the 
eDiary according to the grading scales presented in Table 8, which are 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 starts more than 7 days after dosing, it should be captured on 
the AE page until resolution, not to exceed 28 days after vaccination. 
If a solicited local or systemic AR continues beyond 7 days after dosing, the participant should 
notify the site to provide an end date and close out the event.  
ARs beyond Day 7 should be reviewed by the clinic staff either during the next scheduled 
telephone call or at the next clinic visit, or during an unscheduled visit. 

ModernaTX, Inc. 
mRNA-1273-P305 Protocol Amendment 2 
mRNA-1273 
Confidential 
Page 92 
All solicited ARs (local and systemic) will be considered causally related to dosing. 
Table 8: 
Solicited Adverse Reactions and Grades 
Reaction 
Grade 0 
(None) 
Grade 1 
(Mild) 
Grade 2 
(Moderate) 
Grade 3 
(Severe) 
Grade 41 
(Life-threatening) 
Local 
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 pain 
reliever > 24 hours or 
some interference 
with activity 
Any use of 
prescription 
pain 
reliever or 
prevents 
daily 
activity 
Emergency room 
visit or 
hospitalization 
Systemic 
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 
Requires 
emergency room 
visit or 

ModernaTX, Inc. 
mRNA-1273-P305 Protocol Amendment 2 
mRNA-1273 
Confidential 
Page 93 
activity  
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 
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 
1. Grading of Grade 4 events will be determined per investigator and assessment is recorded on the reactogenicity 
event page in the electronic case report form. 
Any solicited AR that meets any of the following criteria must be entered into the 
participant’s source document and must also be recorded in the participant’s eCRF: 
• Solicited local or systemic AR that results in a visit to a healthcare practitioner (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 continuing beyond 7 days post injection 
• Solicited local or systemic AR that leads to participant withdrawal from IP 
• Solicited local or systemic AR that otherwise meets the definition of an SAE 
8.10.4. 
Medically Attended Adverse Events 
A MAAE is an AE that leads to an unscheduled visit to an HCP. This would include visits to a 
clinic for unscheduled assessments (eg, rash assessment, abnormal laboratory follow-up, 

ModernaTX, Inc. 
mRNA-1273-P305 Protocol Amendment 2 
mRNA-1273 
Confidential 
Page 94 
COVID-19) and visits to HCPs external to the clinic (eg, urgent care, primary care physician). 
Investigators will review unsolicited AEs for the occurrence of any MAAEs. Unsolicited AEs 
will be captured on the AE page of the eCRF. 
All PCR-confirmed COVID-19 cases will be recorded as MAAEs under the AE term of 
“COVID-19.” Cases of participants who test positive using an approved/authorized lateral 
flow/rapid antigen test and report symptoms of COVID-19 as defined by the NHS or the CDC 
(Section 8.9.2) but test negative by PCR or are unable to obtain PCR testing within 2 weeks of 
symptom onset will be recorded as an AE. 
8.10.5. 
Adverse Event of Special Interest 
An AESI is an AE (serious or nonserious) of scientific and medical concern specific to the 
Sponsor’s product or program, for which ongoing monitoring and immediate notification by the 
investigator to the Sponsor are required. Such events may require further investigation to 
characterize and understand them. 
A complete list of AESIs for this protocol are listed in Section 11.3. Additional information for 
anaphylaxis (Section 8.10.5.1) and myocarditis/pericarditis (Section 8.10.5.2) are provided 
below. 
All AESIs will be collected through the entire study period and must be reported to the Sponsor 
or designee immediately and in all circumstances within 24 hours of becoming aware of the 
event via the electronic data capture system. If a site received a report of a new AESI from a 
participant or receives updated information on a previously reported AESI at a time after the 
eCRF has been taken offline, then the site can report this information on a paper AESI form 
using the SAE Mailbox (see Section 8.10.11). 
8.10.5.1. Anaphylaxis 
All suspected cases of anaphylaxis should be recorded as MAAEs and AESIs and reported as an 
SAE, based on the criteria for a 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, per Section 8.10.11. 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 or symptoms consistent with anaphylaxis (as 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 (Rüggeberg et al 2007).  
Anaphylaxis is an acute hypersensitive reaction with multiorgan 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. 

ModernaTX, Inc. 
mRNA-1273-P305 Protocol Amendment 2 
mRNA-1273 
Confidential 
Page 95 
Anaphylaxis is a clinical syndrome characterized by the following: 
• Sudden onset AND 
• Rapid progression of signs and symptoms AND 
• Involves 2 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 
8.10.5.2. Myocarditis/Pericarditis 
A case of suspected, probable, or confirmed myocarditis, pericarditis, or myopericarditis should 
be reported as an AESI, even if it does not meet criteria per the CDC Working Case Definitions. 
The event should also be reported as an SAE if it meets seriousness criteria (see Section 8.10.2). 
An independent Cardiac Event Adjudication Committee (CEAC) will be utilized and is described 
in Section 8.11. 
The CDC Working Case Definitions are provided in Section 11.4 as guidance. These definitions 
are intended to serve as a guide to help reporting of suspected cases of myocarditis, pericarditis, 
or myopericarditis, but the diagnosis of suspected cases is left to the investigator's clinical 
judgment. 
8.10.6. 
Recording and Follow-up of Pregnancy 
Female individuals who have a positive pregnancy test at the Screening Visit should not be 
enrolled; participants who have a positive pregnancy test any time during the study should receive 
no further dosing with IP but should be asked to remain in the study and be followed-up for safety. 
Pregnancy testing is scheduled to occur at the Screening Visit and Day 1 (Table 1 and Table 2). 
Details of all pregnancies in female participants will be collected after the start of study vaccine 
and until EoS. 

ModernaTX, Inc. 
mRNA-1273-P305 Protocol Amendment 2 
mRNA-1273 
Confidential 
Page 96 
• If a pregnancy is reported, the investigator should inform the Sponsor within 24 hours of 
learning of the pregnancy and should follow the procedures outlined in this section. 
• Abnormal pregnancy outcomes (eg, spontaneous abortion, fetal death, stillbirth, 
congenital anomalies, ectopic pregnancy) are considered SAEs. 
Pregnancies occurring in participants after enrollment must be reported to the Sponsor or 
designee within 24 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 the intended duration of the safety follow-up for the study has 
ended. Pregnancy report forms will be distributed to the clinic to be used for this purpose. The 
investigator must immediately (within 24 hours of awareness) report to the Sponsor any 
pregnancy resulting in an abnormal outcome according to the procedures described for SAEs. 
8.10.7. 
Recording and Follow-up of an AE and/or SAE 
The investigator is responsible for ensuring that all AEs and SAEs are recorded in the eCRF and 
reported to the Sponsor. 
Solicited ARs will be collected from Day 1 through 7 days after the vaccine dose (ie, the day of 
injection and 6 subsequent days). Other (unsolicited) AEs will be collected from Day 1 through 
28 days after the vaccine dose (ie, the day of injection and 27 subsequent days). 
Medically attended AEs, SAEs, AESIs, and AEs leading to withdrawal will be collected from 
participants as specified in the SoE (Table 1 and Table 2) from Day 1 until the end of their 
participation in the study. Any AEs occurring before receipt of IP will be analyzed separately from 
TEAEs. 
At every clinic visit or telephone contact, participants will be asked a standard question to elicit 
any medically related changes in their well-being (including surveillance for respiratory viral 
infection symptoms) 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, physical examination findings and other documents 
relevant to participant safety classified as an AE will be documented on the AE page of the 
eCRF. 
After the initial AE/SAE report, the investigator is required to proactively follow each participant 
at subsequent visits/contacts. All AEs and SAEs will be treated as medically appropriate and 

ModernaTX, Inc. 
mRNA-1273-P305 Protocol Amendment 2 
mRNA-1273 
Confidential 
Page 97 
followed until resolution, stabilization, the event is otherwise explained, the participant is LTFU 
(Section 7.2), or the participant withdraws consent (Section 7.1). 
8.10.8. 
Assessment of Intensity 
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 8.10.2), 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. 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 reactogenicity events (solicited ARs), clinical laboratory test results, and vital sign 
measurements observed during this study. Specific criteria for local and systemic reactogenicity 
events are presented in Section 8.10.3. 
The determination of severity for all unsolicited AEs should be made by the investigator based 
upon medical judgment and the definitions of severity as follows: 
• Mild: These events do not interfere with the participant’s daily activities. 
• Moderate: These events cause some interference with the participant’s daily activities 
and require limited or no medical intervention. 
• Severe: These events prevent the participant’s daily activity and require intensive 
therapeutic intervention. 
Clinic staff should elicit from the participant the impact of AEs on the participant’s activities of 
daily living to assess severity and document appropriately in the participant’s source 
documentation. Changes in the severity of an AE should be documented in the participant’s 
source documentation 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. An AE that fluctuates in severity during the course of the event is 
reported once in the eCRF at the highest severity observed. 
8.10.9. 
Assessment of Causality 
The investigator’s assessment of an AE’s relationship to IP 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 IP 
caused the event) for all AEs and SAEs. The relationship will be characterized using the 
following classification: 

ModernaTX, Inc. 
mRNA-1273-P305 Protocol Amendment 2 
mRNA-1273 
Confidential 
Page 98 
Not related: There is not a reasonable possibility of a relationship to the IP. Participant did not 
receive the IP OR temporal sequence of the AE onset relative to administration of the IP is not 
reasonable OR the AE is more likely explained by another cause than the IP. 
Related: There is a reasonable possibility of a relationship to the IP. There is evidence of 
exposure to the IP. The temporal sequence of the AE onset relative to the administration of the IP 
is reasonable. The AE is more likely explained by the IP than by another cause. 
8.10.10. 
Reporting Adverse Events 
The investigator is responsible for reporting all AEs that are observed or reported during the 
study, regardless of their relationship to IP 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, type of event, time of onset, investigator-specified 
assessment of severity (impact on activities of daily living) and relationship to IP, 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. 
8.10.11. 
Reporting Serious Adverse Events 
Any AE considered serious by the investigator or that meets SAE criteria (Section 8.10.2) 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 IP caused the SAE. The 
Sponsor will be responsible for notifying the relevant regulatory authorities of any SAE. The 
investigator is responsible for notifying the independent ethics committee (IEC) 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: Safety_Moderna@iqvia.com 
• SAE Hotline: 08-009175406 
• SAE Fax line: 08-082340330 

ModernaTX, Inc. 
mRNA-1273-P305 Protocol Amendment 2 
mRNA-1273 
Confidential 
Page 99 
Regulatory reporting requirements for SAEs are described in Section 8.10.15. 
The investigator and any qualified designees are responsible for detecting, documenting, and 
recording events that meet the definition of an AE, including SAEs, and remain responsible for 
following up AEs that are serious, considered related to the IP or study procedures, or that 
caused the participant to discontinue the study. 
8.10.12. 
Time Period and Frequency for Collecting AE and SAE Information 
Medical occurrences that begin before the start of IP administration but after obtaining informed 
consent will be recorded in the Medical History/Current Medical Conditions section of the eCRF 
and not in the AE section; however, if the condition worsens at any time during the study, it will 
be recorded and reported as an AE. 

ModernaTX, Inc. 
mRNA-1273-P305 Protocol Amendment 2 
mRNA-1273 
Confidential 
Page 100 
AEs may be collected as follows: 
• Observing the participant 
• Receiving an unsolicited complaint from the participant 
• Questioning the participant in an unbiased and nonleading manner 
All SAEs will be recorded and reported to the Sponsor or designee immediately and under no 
circumstance should this exceed 24 hours of becoming aware of the event, as indicated in 
Section 8.10.2. The investigator will submit any updated SAE data to the Sponsor within 
24 hours of it being available. 
Investigators are not obligated to actively seek AEs or SAEs after conclusion of the study 
participation (EoS). However, if an investigator learns of any SAE, including a death, at any time 
after a participant has completed or withdrawn from the study and considers the event to be 
reasonably related to the study IP or study participation, the investigator must promptly notify 
the Sponsor. 
8.10.13. 
Method of Detecting AEs and SAEs 
Electronic diaries have specifically been designed for this study by the Sponsor. At the time of 
consent, the participants must confirm they will be willing to complete the eDiary via an 
application downloaded to their smartphone or via a device that is provided at the time of 
enrollment. Prior to 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. The diaries will 
include prelisted AEs (solicited ARs) and intensity scales; they will also include blank space for 
the recording of information on other AEs (unsolicited AEs) and concomitant 
medications/vaccinations. 
The investigator is responsible for the documentation of AEs regardless of vaccination group or 
suspected causal relationship to the IP. For all AEs, the investigator must pursue and obtain 
information adequate to determine the outcome of the AE and to assess whether the AE meets 
the criteria for classification as an SAE or AESI requiring immediate notification to the Sponsor 
or its designated representative. 
Care will be taken not to introduce bias when detecting AEs and/or SAEs. Open-ended and 
nonleading verbal questioning of the participant is the preferred method to inquire about 
AE occurrences. 
8.10.14. 
Follow-up of AEs and SAEs 
After the initial AE/SAE report, the investigator is required to proactively follow each participant 
at subsequent visits/contacts. 

ModernaTX, Inc. 
mRNA-1273-P305 Protocol Amendment 2 
mRNA-1273 
Confidential 
Page 101 
All AEs, SAEs, and AESIs will be treated as medically appropriate and followed until resolution, 
stabilization, the event is otherwise explained, the participant is LTFU (Section 7.2), or the 
participant withdraws consent (Section 7.1). 
8.10.15. 
Regulatory Reporting Requirements for SAEs 
Prompt notification by the investigator to the Sponsor of an SAE is essential so that legal 
obligations and ethical responsibilities towards the safety of participants and the safety of a study 
intervention under clinical investigation are met. 
The Sponsor has a legal responsibility to notify both the local regulatory authority and other 
regulatory agencies about the safety of a study intervention under clinical investigation. The 
Sponsor will comply with country-specific regulatory requirements relating to safety reporting to 
the regulatory authority, IECs, and investigators. 
Investigator safety reports must be prepared for suspected unexpected serious adverse reactions 
according to local regulatory requirements and Sponsor policy and forwarded to investigators as 
necessary. 
For the mRNA-1273-P305 study, events of anaphylaxis, myocarditis and pericarditis that are 
assessed as serious and related by the Investigator will be reported in an expedited manner to the 
local regulatory authority by the Sponsor, and mRNA-1273-P305 study IECs and Investigators 
will be notified, if appropriate according to local requirements.  
An investigator who receives an investigator safety report describing an SAE or other specific 
safety information (eg, summary or listing of SAEs) from the Sponsor, will review and then file 
it along with the IB and will notify the IEC, if appropriate according to local requirements. 
8.11. 
Safety Oversight 
Safety monitoring for this study will include the blinded study team members, inclusive of at a 
minimum, the Sponsor medical monitor and CRO medical monitor, as well as safety reviews by 
an unblinded Data and Safety Monitoring Board (DSMB). The study team will conduct ongoing 
blinded safety reviews during the study and will be responsible for notifying the DSMB of 
potential safety signal events. The DSMB, composed of external, independent subject matter 
experts, including an unblinded statistician, will conduct unblinded reviews of safety data on a 
periodic basis, as defined in a DSMB charter, or as otherwise requested by the study team. 
An independent CEAC comprised of medically qualified personnel, including cardiologists, will 
review suspected cases of myocarditis, pericarditis, and myopericarditis to determine if they 
meet CDC criteria for “probable” or “confirmed” events (Gargano et al 2021) and provide the 
assessment to the Sponsor. The CEAC members will be blinded to study vaccine assignment. 

ModernaTX, Inc. 
mRNA-1273-P305 Protocol Amendment 2 
mRNA-1273 
Confidential 
Page 102 
Details regarding the CEAC composition, responsibilities, procedures, and frequency of data 
review will be defined in the CEAC charter. 
8.12. 
Treatment of Overdose 
As the study treatment is to be administered by a healthcare professional, it is unlikely that an 
overdose will occur. Dose deviations will be tracked as protocol deviations (Section 11.1.8). 
8.13. 
Pharmacokinetics 
Pharmacokinetic parameters are not evaluated in this study. 
8.14. 
Pharmacodynamics 
Pharmacodynamic parameters are not evaluated in this study. 
8.15. 
Biomarkers 
Biomarker assessments (to be determined) will be evaluated as part of the study. 

ModernaTX, Inc. 
mRNA-1273-P305 Protocol Amendment 2 
mRNA-1273 
Confidential 
Page 103 
9. 
STATISTICAL ANALYSIS PLAN 
This section summarizes the planned statistical analysis strategy and procedures for the study 
focusing on the randomized, blinded phase (Phase A) of 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. If changes are made to primary and/or secondary objectives 
or the related statistical methods after the study has begun, 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 clinical study report (CSR) for the study. Ad hoc 
exploratory analyses, if any, will be clearly identified in the CSR. Statistical analyses of the 
open-label, observational phase (Phase B) will be provided in the SAP. 
9.1. 
Blinding and Responsibility for Analyses 
Phase A of this study is observer-blind. The study participants, investigators, site personnel, site 
monitors, and Sponsor personnel (or its designees) will be blinded to the IP administered until 
the unblinding occurs (Section 6.3.7) or until study database is locked and unblinded, with the 
following exceptions: 
• An independent unblinded statistical and programming team who are not involved in study 
design and conduct of the CRO will perform the planned primary analysis, (Section 9.7). 
Select Sponsor team members including biostatistician and statistical programmers will be 
prespecified to be unblinded to the primary analysis results and will not communicate the 
results to the blinded investigators, clinic staff, clinical monitors, or participants. The 
details will be included in the Data Blinding Plan. 
• The DSMB may review data, as appropriate, to safeguard the interests of clinical study 
participants and to help ensure the integrity of the study. 
Procedures for breaking the blind in the case of a medical necessity are provided in 
Section 6.3.7. 
9.2. 
Statistical Hypotheses 
Part 1: 
The primary objective on immune response in Part 1 of this study is based on the participants who 
will receive the 4th dose in Part 1 of the study.  
Primary Hypotheses:  
1) mRNA-1273.529, as a single booster dose, is non-inferior to mRNA-1273 based on 
GMT ratio against the B.1.1.529 strain with a non-inferiority margin of 1.5 at Day 29. 

ModernaTX, Inc. 
mRNA-1273-P305 Protocol Amendment 2 
mRNA-1273 
Confidential 
Page 104 
2) mRNA-1273.529, as a single booster dose, is non-inferior to mRNA-1273 based on 
GMT ratio against the B.1.1.529 strain with a non-inferiority margin of 1.5 at 
Month 3. 
Key Secondary Hypothesis:  
mRNA-1273.529, as a single booster dose, is superior to mRNA-1273 based on GMT ratio 
against the B.1.1.529 strain at Day 29 or Month 3. 
For the primary objective of immune response, hypotheses testing based on participants 
receiving the 4th dose, alpha of 0.05 (2-sided) will be allocated to the 2 time points: alpha of 0.01 
(2-sided) will be allocated to Day 29, alpha of 0.04 (2-sided) will be allocated to Month 3.  
The non-inferiority of mRNA-1273.529 as compared to mRNA-1273 against the B.1.1.529 strain 
at Day 29 will be assessed using a non-inferiority margin of 1.5 at 2-sided alpha of 0.01. The 
primary immunogenicity objective is considered met if non-inferiority against the B.1.1.529 
strain is demonstrated, ie, the lower bound of the 99% confidence interval (CI) of the GMT ratio 
of mRNA-1273.529 vs. mRNA-1273 against B.1.1.529 is ≥ 0.67 (1/1.5).  
The non-inferiority of mRNA-1273.529 as compared to mRNA-1273 against the B.1.1.529 strain 
at Month 3 will be assessed using a non-inferiority margin of 1.5 at 2-sided alpha of 0.04. The 
primary immunogenicity objective is considered met if non-inferiority against the B.1.1.529 strain 
is demonstrated, ie, the lower bound of the 96% confidence interval (CI) of the GMT ratio of 
mRNA-1273.529 vs. mRNA-1273 against B.1.1.529 is ≥ 0.67 (1/1.5). 
Part 2: 
The primary objective on immune response in Part 2 of this study is based on the participants who 
will receive the 4th dose in Part 2 of the study. There are 6 hypotheses on immune response of 
mRNA-1273.214 listed below. Part 2 of this study is considered to have met its primary objective 
if non-inferiority of mRNA-1273.214 against the B.1.1.529 strain, non-inferiority of mRNA-
1273.214 against the prototype strain, and superiority of mRNA-1273.214 against the B.1.1.529 
strain are demonstrated as compared to mRNA-1273 at Day 29 or Month 3. Figure 2 depicts the 
hypotheses testing strategy. 
Primary Hypotheses: 
1) mRNA-1273.214, as a single booster dose, is non-inferior to mRNA-1273 based on GMT 
ratio against the B.1.1.529 strain with a non-inferiority margin of 1.5 at Day 29. 
2) mRNA-1273.214, as a single booster dose, is non-inferior to mRNA-1273 based on GMT 
ratio against the prototype strain with a non-inferiority margin of 1.5 at Day 29. 

ModernaTX, Inc. 
mRNA-1273-P305 Protocol Amendment 2 
mRNA-1273 
Confidential 
Page 105 
3) mRNA-1273.214, as a single booster dose, is superior to mRNA-1273 based on GMT 
ratio against the B.1.1.529 strain at Day 29. 
4) mRNA-1273.214, as a single booster dose, is non-inferior to mRNA-1273 based on GMT 
ratio against the B.1.1.529 strain with a non-inferiority margin of 1.5 at Month 3. 
5) mRNA 1273.214, as a single booster dose, is non-inferior to mRNA -1273 based on GMT 
ratio against the prototype strain with a non-inferiority margin of 1.5 at Month 3. 
6) mRNA-1273.214, as a single booster dose, is superior to mRNA-1273 based on GMT ratio 
against the B.1.1.529 strain at Month 3. 
Figure 2: 
Statistical Hypothesis Testing Strategy of mRNA-1273 vs. mRNA-1273 
(Part 2) 
 
Abbreviations: M = month; mRNA = messenger ribonucleic acid. 
For the primary objective of immune response, hypothesis testing based on participants receiving 
the 4th dose, alpha of 0.05 (2-sided) will be allocated to the 2 timepoints: alpha of 0.01 (2-sided) 
will be allocated to Day 29, and alpha of 0.04 (2-sided) will be allocated to Month 3.  
For the primary immunogenicity objective, the non-inferiority of mRNA-1273.214 as compared 
to mRNA-1273 against the B.1.1.529 strain and the non-inferiority of mRNA-1273.214 as 
compared to mRNA-1273 against the prototype strain at Day 29 will be assessed using a non-

ModernaTX, Inc. 
mRNA-1273-P305 Protocol Amendment 2 
mRNA-1273 
Confidential 
Page 106 
inferiority margin of 1.5 at 2-sided alpha of 0.01. The primary immunogenicity objective is 
considered met if non-inferiority against the B.1.1.529 strain and the prototype strain are both 
demonstrated, ie, the lower bound of the 99% confidence interval (CI) of the GMT ratio of 
mRNA-1273.214 vs. mRNA-1273 against B.1.1.529 is ≥ 0.67 (1/1.5) and the lower bound of the 
99% CI of the GMR of mRNA-1273.214 vs mRNA-1273 against prototype is ≥ 0.67. 
Superiority of mRNA-1273.214 as compared to mRNA-1273 against the B.1.1.529 strain will be 
evaluated at Day 29. Once the non-inferiority of mRNA-1273.214 as compared to mRNA-1273 
against the B.1.1.529 strain and against the prototype strain is demonstrated, the 99% CI of GMT 
ratio (mRNA-1273.214 vs. mRNA-1273) will be used to assess superiority of mRNA-1273.214 
as compared to mRNA-1273. If the lower bound of the GMT ratio rules out (>) 1 at Day 29, 
superiority of mRNA-1273.214 compared to mRNA-1273 against B.1.1.529 will be considered 
demonstrated. 
Hypotheses testing at Month 3 will be performed in the same manner, first testing 2 non-
inferiority hypotheses (one against the B.1.1.529 strain and one against the prototype strain) at 
alpha of 0.04 level (2-sided). Once non-inferiority is demonstrated for both B.1.1529 and 
prototype strains, then superiority testing against the B.1.1.529 at alpha of 0.04 level (2-sided) 
will be performed. 
9.3. 
Sample Size and Power Calculation  
This study will include:  
1. Participants who received 2 doses of a COVID-19 vaccine as the primary series and the 3rd 
dose of a COVID-19 vaccine and will receive the 4th dose as part of the study. 
2. Participants who received 2 doses of a COVID-19 vaccine as the primary series and will 
receive the 3rd dose as part of the study. 
Part 1 (50 µg 1273.529 and 50 µg 1273 in 1:1 ratio) 
The primary immunogenicity objective is to assess immune response of mRNA-1273.529 against 
B.1.1.529 in participants who are receiving mRNA-1273.529 (or mRNA-1273) as the 4th dose in 
Part 1 of this study.  
The target enrollment is up to 500 participants (minimum 300 participants) for each treatment 
arm (1:1). The assumptions are: 1) at least 
 participants will be in 4th dose subgroup; and 2) 
 of participants will be excluded from the PP set for immunogenicity, SARS-CoV-2 negative 
(e.g., due to infection with the SARS-CoV-2 Omicron variant). 
The target enrollment is approximately 500 participants for each study arm (1:1). The 
assumptions are: 1) at least 
 participants will be in 4th dose subgroup; and 2) 
 of 
CCI
CCI
CCI
CCI

ModernaTX, Inc. 
mRNA-1273-P305 Protocol Amendment 2 
mRNA-1273 
Confidential 
Page 107 
participants will be excluded from the PP set for immunogenicity, SARS-CoV-2 negative (eg, 
due to infection with the SARS-CoV-2 Omicron variant).  
Statistical power for hypotheses testing at Day 29 (alpha=0.01, 2-sided): 
With approximately 
 evaluable participants per arm, there is 
 power to 
demonstrate non-inferiority of mRNA-1273.529 against the B.1.1.529 strain at 2-sided alpha of 
1.0% at Day 29. With this range of sample sizes, the power to demonstrate superiority of 
mRNA-1273.529 against the B.1.1.529 variant strain at a 2-sided alpha of 1% at Day 29 ranges 
from 
 The assumptions are: the true GMT ratio (mRNA-1273.529 vs mRNA-1273) 
ranges from 
, the standard deviation of the natural log-transformed titer is 
, with a 
non-inferiority margin of 1.5. 
Statistical power for hypotheses testing at Month 3 (alpha=0.04, 2-sided): 
With approximately 
 evaluable participants per arm, there is 
 power to 
demonstrate non-inferiority of mRNA-1273.529 against the B.1.1.529 strain at 2-sided alpha of 
4.0% at Month 3. With this range of sample sizes, the power to demonstrate superiority of 
mRNA-1273.529 against the B.1.1.529 variant strain at a 2-sided alpha of 4% at Month 3 ranges 
from 
. The assumptions are: the true GMT ratio (mRNA-1273.529 vs mRNA-1273) 
ranges from 
, the standard deviation of the natural log-transformed titer is 
, with a 
non-inferiority margin of 1.5. Specific operating characteristics for Part 1 are provided in 
Table 9. With approximately 
 participants receiving the 4th dose in each study arm, 
there is at least 90% probability to observe one participant reporting an AE in each study arm if 
the true incidence of AEs is 1%.  
CCI
CCI
CCI
CCI
CCI
CCI
CCI
CCI
CCI
CCI
CCI

ModernaTX, Inc. 
mRNA-1273-P305 Protocol Amendment 2 
mRNA-1273 
Confidential 
Page 108 
Table 9:  
Operating Characteristics and Power for the Primary and Key Secondary 
Objectives Under Various GMR and the Number of Evaluable Participants 
with Immunogenicity Data Who Receives the 4th Dose in this Study (Part 1) 
True GMR  
 
(mRNA-1273.529 
vs. mRNA-1273 
against B.1.1.529) 
Number 
evaluable 
patients 
per arm 
(4th dose) 
Minimum empirical 
GMR for the primary 
objective 
Power 
Two-sided Type I Error (α) = 0.01 (Day 29) 
Primary Objective: Non-inferiority (lower bound of the (1-α) *100% of GMR ≥ 0.67) 
Key Secondary Objective: Superiority (lower bound of the (1-α) *100% of GMR rules out 1) 
1.1 
3% 
Two-sided Type I Error (α) = 0.04 (Month 3) 
Primary Objective: Non-inferiority (lower bound of the (1-α) *100% of GMR ≥ 0.67) 
1.1 
90% 
Key Secondary Objective: Superiority (lower bound of the (1-α) *100% of GMR rules out 1) 
CCI
CCI
CCI
CCI

ModernaTX, Inc. 
mRNA-1273-P305 Protocol Amendment 2 
mRNA-1273 
Confidential 
Page 109 
Abbreviations: GMR = geometric mean ratio; mRNA = messenger ribonucleic acid. 
Part 2 (50 µg 1273.214 and 50 µg 1273 in 1:1 ratio) 
The primary immunogenicity objective is to assess immune response of mRNA-1273.214 against 
B.1.1.529 and prototype in participants who are receiving mRNA-1273.214 (or mRNA-1273) as 
the 4th dose in Part 2 of this study. The sample size is driven by this subgroup. 
Hypotheses testing on immunogenicity data will be performed at 2 timepoints of interest (Day 29 
and Month 3 post booster). To preserve family-wise alpha of 0.05 (2-sided), alpha will be 
allocated to Day 29 of 0.01 (2-sided), and Month 3 of 0.04 (2-sided). 
Statistical power for hypotheses testing at Day 29 (alpha=0.01, 2-sided): 
For the 4th dose subgroup, the target enrollment is approximately 1328 participants for each 
treatment arm (1:1). Assuming 
 of participants will be excluded from the PP Set for 
Immunogenicity, SARS-CoV-2 negative, with approximately 
 evaluable participants in each 
arm, there is 
 power to demonstrate non-inferiority of mRNA-1273.214 against 
the B.1.1.529 and against the prototype at 2-sided alpha of 1.0%. With this sample size, there is 
approximately 
 power to demonstrate superiority of mRNA-1273.214 against the 
B.1.1.529 variant strain at a 2-sided alpha of 1.0% at Day 29. The assumptions are: the true GMT 
ratio (mRNA-1273.214 vs. mRNA-1273) against the B.1.1.529 strain ranges from 
 
and the true GMT ratio (mRNA-1273.214 vs. mRNA-1273) against the prototype strain is , the 
standard deviation of the natural log-transformed titer is 
, with a non-inferiority margin of 1.5.  
Statistical power for hypotheses testing at Month 3 (alpha=0.04, 2-sided): 
With approximately 
 evaluable participants in each arm, there is 
 power to 
demonstrate non-inferiority of mRNA-1273.214 against the B.1.1.529 strain and against 
prototype at 2-sided alpha of 4.0% at Month 3. With this sample size, there is approximately 
 power to demonstrate superiority of mRNA-1273.214 against the B.1.1.529 
variant strain at a 2-sided alpha of 4.0% at Month 3. The assumptions are: the true GMT ratio 
(mRNA-1273.214 vs. mRNA-1273) against the B.1.1.529 strain ranges from 
 and the 
true GMT ratio (mRNA-1273.214 vs. mRNA-1273) against the prototype strain is , the standard 
deviation of the natural log-transformed titer is 
, with a non-inferiority margin of 1.5. 
CCI
CCI
CCI
CCI
CCI
CCI
CCI
CCI
CCI
CCI
CCI
CCI
CCI
CCI

ModernaTX, Inc. 
mRNA-1273-P305 Protocol Amendment 2 
mRNA-1273 
Confidential 
Page 110 
With approximately 1328 participants receiving the 4th dose in each study arm, there is at least 
90% probability to observe one participant reporting an AE in each study arm if the true 
incidence of AEs is 1%.  
The enrollment target of this study is approximately 1328 participants per arm to receive the 4th 
dose. The Omicron VOC has spread quickly throughout the world. There may be an urgency to 
perform Day 29 or Month 3 analysis as early as possible, and depending on the operational 
feasibility, particularly the testing capability of assays of antibodies against B.1.1.529, the 
Sponsor may decide to perform the analysis of immunogenicity after immunogenicity data from 
a subset of the participants receiving the 4th dose. Such a decision will be documented prior to 
the planned analysis at Day 29 or Month 3.  
Table 10 includes the power and operating characteristics under various GMT ratios and 
2 different scenarios for the number of evaluable participants with immunogenicity data. Based 
on 
 evaluable participants per arm (4th dose), under the same assumptions outlined above, 
there is 
 power to demonstrate non-inferiority of mRNA-1273.214 compared to 
mRNA-1273 against B.1.1.529 at Day 29 at α = 1% if true GMT ratio 
; and there is 
approximately 
 power to demonstrate superiority at α = 1% if the true ratio if 
. With this 
size, there is 
 power at Month 3 (primary objective) at α = 4% (2-sided) if the true 
GMR is 
; and 
 power to demonstrate superiority at α = 4% (2-sided) if the true 
GMR is 
. 
 
CCI
CCI
CCI
CCI
CCI
CCI
CCI
CCI
CCI

ModernaTX, Inc. 
mRNA-1273-P305 Protocol Amendment 2 
mRNA-1273 
Confidential 
Page 111 
Table 10: 
Operating Characteristics and Power for the Primary and Key Secondary 
Objectives Under Various GMR and the Number of Evaluable Participants 
with Immunogenicity Data Who Receives the 4th Dose in this Study (Part 2) 
True GMR  
 
(mRNA-1273.214 
vs. mRNA-1273 
against 
B.1.1.529) 
Number 
evaluable 
patients per 
arm (4th 
dose) 
Minimum empirical 
GMR for the primary 
objective 
Power 
Two-sided Type I Error (α) = 0.01 (Day 29) 
Primary Objective: Non-inferiority (lower bound of the (1-α) *100% of GMR ≥ 0.67) 
Primary Objective: Superiority (lower bound of the (1-α) *100% of GMR rules out 1) 
Two-sided Type I Error (α) = 0.04 (Month 3) 
CCI
CCI

ModernaTX, Inc. 
mRNA-1273-P305 Protocol Amendment 2 
mRNA-1273 
Confidential 
Page 112 
Primary Objective: Non-inferiority (lower bound of the (1-α) *100% of GMR ≥ 0.67) 
Primary Objective: Superiority (lower bound of the (1-α) *100% of GMR rules out 1) 
Abbreviations: GMR = geometric mean titer ratio; mRNA = messenger ribonucleic acid. 
9.4. 
Multiplicity 
Statistical testing in Part 1 is independent of testing in Part 2. In each Part, the family-wise alpha 
of 0.05 (2-sided) will be preserved by allocating alpha across 2 time points: 0.01 (2-sided) at 
Day 29 and 0.04 (2-sided) at Month 3. 
9.5. 
Analyses Populations 
The analysis populations for Part 1 and Part 2 are defined in Table 11. 
CCI
CCI

ModernaTX, Inc. 
mRNA-1273-P305 Protocol Amendment 2 
mRNA-1273 
Confidential 
Page 113 
Table 11: 
Populations for Analyses 
Set 
Description 
Full Analysis Set (FAS) 
The FAS consists of all randomized participants who receive the IP. 
Participants will be analyzed according to their randomized study arm. 
Modified Intent-to-Treat (mITT) 
Set 
The mITT Set consists of all participants in the FAS who have no serologic 
or virologic evidence of prior SARS-CoV-2 infection (both negative RT-
PCR test for SARS-CoV-2 and negative serology test based on bAb 
specific to SARS-CoV-2 nucleocapsid) prebooster, ie, all FAS participants 
with pre-booster/baseline SARS-CoV-2 negative status. Participants will be 
analyzed according to their randomized study arm. 
PP Set for Immunogenicity (PPSI) 
The PPSI consists of all participants in the FAS who receive the planned 
dose of study vaccination and have no major protocol deviations that 
impact key or critical data. Participants will be analyzed according to their 
randomized study arm. 
PP Set for Immunogenicity –
SARS-CoV-2 negative (PPSI-Neg) 
Participants in the PPSI who have no serologic or virologic evidence of 
SARS-CoV-2 infection up to day of visit analysis, ie, who are SARS-CoV-
2 negative, defined by both negative RT-PCR test for SARS-CoV-2 and 
negative serology test based on bAb specific to SARS-CoV-2 
nucleocapsid. 
PPSI-Neg will be the primary analysis set for analyses of immunogenicity 
unless otherwise specified.  
Solicited Safety Set 
The Solicited Safety Set consists of all randomized participants who 
receive IP and contribute any solicited AR data. 
The Solicited Safety Set will be used for the analyses of solicited ARs. 
Participants will be included in the study arm that they actually received. 
Safety Set 
The Safety Set consists of all randomized participants who receive IP. The 
Safety Set will be used for all analyses of safety except for the solicited 
ARs. Participants will be included in the study arm that they actually 
received. 
PP Set for Efficacy (PPSE) 
The PPSE consists of all participants in the mITT who receive the planned 
study vaccination and have no major protocol deviations that impact key or 
critical data. 
Abbreviations: AR = adverse reaction; FAS = full analysis set; IP = investigational product; mITT = modified intent-to-treat; 
PP = Per-protocol; RT-PCR = reverse transcription polymerase chain reaction; SARS-CoV-2 = severe acute respiratory 
syndrome coronavirus 2. 
9.6. 
Statistical Analyses 
This section provides a summary of the planned statistical analyses of the primary and secondary 
objectives in Phase A (randomized, blinded). The SAP will be developed and finalized before the 
first planned analysis (Section 9.7).  

ModernaTX, Inc. 
mRNA-1273-P305 Protocol Amendment 2 
mRNA-1273 
Confidential 
Page 114 
9.6.1. 
Immunogenicity Analyses 
Part 1:An analysis of covariance (ANCOVA) model will be performed to assess the difference 
in immune response between mRNA-1273.529 and mRNA-1273 as the 4th dose in the subgroup 
of participants who received the 4th dose. This analysis will be carried out for immune response 
against the B.1.1.529 strain and the prototype virus strain separately in the PPSI-Neg analysis 
population. 
Specifically, for immune response against the B.1.1.529 strain, in the ANCOVA model, antibody 
titers at Day 29 post-booster against the B.1.1.529 strain will be a dependent variable, and a 
group variable (mRNA-1273.529 and mRNA-1273) will be the fixed effect, adjusting for age 
groups (< 65, ≥ 65 years) and pre-booster antibody titer level, if applicable. The GMT will be 
estimated by the geometric least square mean (GLSM) from the model and its corresponding 
99% CIs will be provided for each group. The GMR (ratio of GMTs) for mRNA-1273.529 with 
respect to mRNA-1273 will be estimated by the ratio of GLSM from the model and the 
corresponding 99% CIs will be provided. The 99% CI for GMR will be used to assess the 
between group difference in immune response against the B.1.1.529 strain for mRNA-1273.529 
at Day 29 compared to the mRNA-1273 as a booster for non-inferiority testing.  
Against the B.1.1.529 strain, the non-inferiority of immune response of mRNA-1273.529 as 
compared to mRNA-1273 will be considered demonstrated if the lower bound of the 
corresponding 99% CI is ≥ 0.67 (Day 29) based on a non-inferiority margin of 1.5. 
Once non-inferiority against B.1.1.529 is demonstrated, superiority of mRNA-1273.529 as 
compared to mRNA-1273 against B.1.1529 will be tested; if the lower bound of the 99% CI of 
the GMT ratio is > 1 (Day 29), superiority is demonstrated.  
The same ANCOVA model will be used to assess immune response of mRNA-1273.529 against 
the B.1.1.529 strain at Month 3; the 96% CI for GMR will be used to assess the between group 
difference in immune response against the B.1.1.529 strain for non-inferiority and superiority. 
For the immune response against the prototype virus strain, the same analysis method will be 
used. 

ModernaTX, Inc. 
mRNA-1273-P305 Protocol Amendment 2 
mRNA-1273 
Confidential 
Page 115 
Part 2: 
An ANCOVA model will be carried out to assess the difference in immune response between 
mRNA-1273.214 and mRNA-1273 in the subgroup of participants who received the 4th dose. 
This analysis will be carried out for immune response against the B.1.1.529 strain and the 
prototype virus strain separately using the PPSI-Neg analysis population. 
Specifically, for immune response against the B.1.1.529 strain, in the ANCOVA model, antibody 
titers at Day 29 post-booster against the B.1.1.529 strain will be a dependent variable, and a 
group variable (mRNA-1273.214 and mRNA-1273) will be the fixed effect, adjusting for age 
groups (< 65, ≥ 65 years) and pre-booster antibody titer level, if applicable. The GMT will be 
estimated by the geometric least square mean (GLSM) from the model and its corresponding 
99% CIs will be provided for each group. The GMR (ratio of GMTs) for mRNA-1273.214 with 
respect to mRNA-1273 will be estimated by the ratio of GLSM from the model and the 
corresponding 99% CIs will be provided. The 99% CI for GMR will be used to assess the 
between group difference in immune response against the B.1.1.529 strain for mRNA-1273.214 
at Day 29 compared to the mRNA-1273 as a booster for non-inferiority testing.  
Against the B.1.1.529 strain, the non-inferiority of immune response of mRNA-1273.214 as 
compared to mRNA-1273 will be considered demonstrated if the lower bound of the 
corresponding 99% CI is ≥ 0.67 based on a non-inferiority margin of 1.5. 
Once non-inferiority against B.1.1.529 is demonstrated, superiority of mRNA-1273.214 as 
compared to mRNA-1273 against B.1.1529 will be tested (at Day 29); if the lower bound of the 
99% CI of the GMT ratio is > 1, superiority is demonstrated. 
The same ANCOVA model will be used to assess immune response of mRNA-1273.214 against 
the B.1.1.529 strain at Month 3. The 96% CI for GMR will be used to assess the between group 
difference in immune response against the B.1.1.529 strain for non-inferiority and superiority. 
For the immune response against the prototype virus strain, the same analysis method will be 
used. 
As part of the secondary analysis to assess for immune response against other variants, the same 
analysis method described above will be used. A 95% CI for GMR will be used to assess for 
non-inferiority and superiority. 
Following section is applicable for both Part 1 and Part 2: 
Immunogenicity, SARS-CoV-2-specific bAb and nAb, will be assessed at multiple time points in 
this study. Mixed effects models will be used to analyze all post-booster/baseline measures. The 
models will include treatment group, analysis visit, treatment by visit interaction, and adjustment 
for age groups and pre-booster titer levels. An unstructured covariance structure will be used to 

ModernaTX, Inc. 
mRNA-1273-P305 Protocol Amendment 2 
mRNA-1273 
Confidential 
Page 116 
model the within-participant errors. The GMT will be estimated from the model and its 
corresponding 95% CI will be provided for each group at each post-boost timepoint. The GMR 
(ratio of GMTs) for mRNA-1273.529 and for mRNA-1273.214 with respect to mRNA-1273 will 
be estimated from each model and the corresponding 95% CI will be provided at each post-boost 
time point. 
For each of the antibodies of interest (eg, levels of SARS-CoV-2–specific bAb and 
SARS-CoV-2-specific nAb), the GMT or level with corresponding 95% CI at each time point, 
and GMFR of post-booster/pre-booster titers or levels with corresponding 95% CI at each post 
baseline time point will be provided for each arm. The 95% CIs will be calculated based on the 
t-distribution of the log-transformed values then back-transformed to the original scale for 
presentation. The following descriptive statistics will also be provided at each time point: 
number of participants (n), median, minimum, and maximum. PPSI will be used as the analysis 
population to summarize the immune responses (antibodies of interest) and will the above 
summary statistics including GMT and GMFR will be provided by pre-booster/study baseline 
SARS-CoV-2 status. 
SRR definitions and analyses will be defined in the SAP. 
9.6.2. 
Efficacy Analyses 
Number and incidence rates of symptomatic COVID-19 disease, asymptomatic SARS-CoV-2 
infection, as well as COVID-19 regardless of symptoms will be provided for each study arm. 
Vaccine efficacy may be estimated if the number of cases accrued is deemed to be sufficient. 
Efficacy analyses will be performed using the mITT and PP Set for Efficacy analysis populations 
and the details will be provided in SAP. 
9.6.3. 
Safety Analyses 
All safety analyses will be based on the Safety Set, except analyses of solicited ARs, which will 
be based on the Solicited Safety Set.  
Safety and reactogenicity will be assessed by clinical review of all relevant parameters including 
solicited ARs (local and systemic ARs), unsolicited AEs, and physical examination findings.  
The number and percentage of participants with any solicited local AR, with any solicited 
systemic AR, with any solicited AR during the 7-day follow-up period after vaccination, and 
with Grade 3 or higher solicited AR will be provided. A 2-sided 95% exact CI using the Clopper 
Pearson method will be provided for the percentage of participants with any solicited AR. 
The number and percentage of participants with unsolicited AEs, treatment-related AEs, severe 
AEs, SAEs, MAAEs, AESIs, and AEs leading to withdrawal will be summarized. The follow-up 
windows for AEs are detailed in the SoE (Table 1 and Table 2). Unsolicited AEs will be presented 

ModernaTX, Inc. 
mRNA-1273-P305 Protocol Amendment 2 
mRNA-1273 
Confidential 
Page 117 
by MedDRA system organ class and preferred term. Unsolicited AEs will be coded according to 
the MedDRA Dictionary for Adverse Reaction Terminology. 
Pregnancy outcomes will also be summarized. 
Table 12 summarizes the analysis strategy for safety parameters. Further details will be described 
in the SAP. 
Table 12: 
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 AESI 
X 
__ 
Any unsolicited MAAE 
X 
— 
Any unsolicited treatment-related AE 
X 
— 
Any treatment-related SAE 
X 
— 
Discontinuation due to AE 
X 
— 
Any severe AE 
X 
— 
Any treatment-related severe AE 
X 
— 
Abbreviations: AE = adverse event; AESI = adverse event of special interest; AR = adverse reaction; CI = confidence interval; 
MAAE = medically attended adverse event; PT = preferred term; SAE = serious adverse event; SOC = system organ class. 
Notes: 95% CI using the Clopper-Pearson method, X = results will be provided. Unsolicited AEs will be summarized by SOC 
and PT coded by MedDRA. 
9.6.4. 
Exploratory Analyses 
For the exploratory analyses for mRNA-1273.529 or mRNA-1273.214 against other variants (eg, 
Alpha, Beta, Delta), the same analyses methods described in Section 9.6.1 will be employed to 
analyze immunogenicity data. 
9.7. 
Planned Analyses 
The planned analyses of immunogenicity and safety will be conducted after participants have 
completed Day 29 and Month 3 visit assessments. Analyses of the Month 6 and Month 12 visit 
including the Phase B (open-label, observational) part of the study will be exploratory. The final 
analysis of all endpoints will be performed after all participants have completed or discontinued 
from the study. Results of this analysis will be presented in a final CSR. 

ModernaTX, Inc. 
mRNA-1273-P305 Protocol Amendment 2 
mRNA-1273 
Confidential 
Page 118 
10. 
REFERENCES 
Aretz HT, Billingham ME, Edwards WD, Factor SM, Fallon JT, Fenoglio JJ Jr., et al. 
Myocarditis. A histopathologic definition and classification. Am J Cardiovasc Pathol. 
1987;1(1):3-14. 
Baden LR, El Sahly HM, Essink B, Kotloff K, Frey S, Novak R, et al. Efficacy and safety of the 
mRNA 1273 SARS-CoV-2 vaccine. N Engl J Med. 2021;384(5):403-16. 
Bruxvoort KJ, Sy LS, Qian L, Ackerson BK, Luo Y, and Lee GS, et al. Effectiveness of mRNA-
1273 against Delta, Mu, and other emerging variants. medRxiv 2021.09.29.21264199 [Preprint]. 
2021 September 29. https://doi.org/10.1101/2021.09.29.21264199  
Choi A, Koch M, Wu K, Dixon G, Oestreicher J, Legault H, et al. Serum neutralizing activity of 
mRNA-1273 against SARS-CoV-2 variants. bioRxiv [Preprint]. 2021 June 28 doi: 
https://doi.org/10.1101/2021.06.28.449914.  
Corbett KS, Edwards DK, Leist SR, Abiona OM, Boyoglu-Barnum S, Gillespie RA, et al. SARS 
CoV-2 mRNA vaccine development enabled by prototype pathogen preparedness. Nature. 2020. 
Oct;586(7830):567-71. . 
Department of Health and Human Services (DHHS), Food and Drug Administration, Center for 
Biologics Evaluation and Research (US). Guidance for industry: Toxicity grading scale for 
healthy adult and adolescent volunteers enrolled in preventive vaccine clinical trials. September 
2007 [cited 2021 Oct 18] [10 screens]. Available from: 
https://www.fda.gov/media/73679/download. 
Doria-Rose N, Suthar MS, Makowski M, O'Connell S, McDermott AB, Flach B, et al. Antibody 
persistence through 6 months after the second dose of mRNA-1273 vaccine for COVID-19. 
N Engl J Med. 2021 Jun 10;384(23):2259-61. 
FDA News Release. Coronovirus (COVID-19 update: FDA takes action by approving second 
COVID-19 vaccine. 31 Jan 2022. Available at: https://www.fda.gov/news-events/press-
announcements/coronavirus-covid-19-update-fda-takes-key-action-approving-second-covid-19-
vaccine. 
Gargano JW, Wallace M, Hadler SC, Langley G, Su JR, Oster ME, et al. Use of mRNA COVID 
19 vaccine after reports of myocarditis among vaccine recipients: update from the Advisory 
Committee on Immunization Practices – United States, June 2021. MMWR Morb Mortal Wkly 
Rep. 2021 Jul;70(27):977-82. 
Greaney AJ, Loes AN, Crawford KHD, Starr TN, Malone KD, Chu HY, et al. Comprehensive 
mapping of mutations to the SARS-CoV-2 receptor-binding domain that affect recognition by 
polyclonal human serum antibodies. BioRxiv doi: https://doi.org/10.1101/2020.12.31.425021. 

ModernaTX, Inc. 
mRNA-1273-P305 Protocol Amendment 2 
mRNA-1273 
Confidential 
Page 119 
Madhi SA, Baillie V, Cutland CL, Voysey M, Fairlie L, Koen AL, et al. for the NGS-SA Group 
Wits–VIDA COVID Group. Efficacy of the ChAdOx1 nCoV-19 Covid-19 vaccine against the 
B.1.351 variant. N Engl J Med. 2021 Mar;384(20):1885-98. 
Martin MA, VanInsberghe D, Koelle K. Insights from SARS-CoV-2 sequences. Science. 
2021;371(6528):466-67. 
Pegu A, O'Connell S, Schmidt SD, O'Dell S, Talana CA, Lai L, et al. Durability of mRNA-1273-
induced antibodies against SARS-CoV-2 variants. bioRxiv [Preprint]. 2021 May 16. 
Rüggeberg JU, Gold MS, Bayas JM, Blum MD, Bonhoeffer J, Friedlander S, et al; Brighton 
Collaboration Anaphylaxis Working Group. Anaphylaxis: case definition and guidelines for data 
collection, analysis, and presentation of immunization safety data. Vaccine. 2007 Aug 
1;25(31):5675-84. 
Sadoff J, Gray G, Vandebosch A, Cárdenas V, Shukarev G, Grinsztejn B, et al. Safety and 
efficacy of single-dose Ad26.COV2.S vaccine against Covid-19. N Engl J Med. 2021 Jun 
10;384(23)2187-2201. 
Wang Z, Schmidt F, Weisblum Y, Muecksch F, Barnes CO, Finkin S, et al. mRNA vaccine-
elicited antibodies to SARS-CoV-2 and circulating variants. bioRxiv. 2021 Jan 30; doi: 
10.1101/2021.01.15.426911. 
World Health Organization (WHO). Coronavirus disease 2019 (COVID-19) Weekly 
Epidemiological Update [Internet]. Geneva, Switzerland: WHO; 2021 [cited 2021 December 7]. 
Available from: https://www.who.int/publications/m/item/weekly-epidemiological-update-on-
covid-19-7-December-2021. 
Wu K, Werner AP, Moliva JI, Koch M, Choi A, Stewart-Jones GBE, et al. Serum neutralizing 
activity elicited by mRNA-1273 vaccine. NEJM. 2021a Apr 15. doi: 10.1056/NEJMc2102179. 
Wu K, Choi A, Koch M, Elbashir S, Ma L, Lee D, et al. Variant SARS-CoV-2 mRNA vaccines 
confer broad neutralization as primary or booster series in mice. bioRxiv. 2021b Apr 13. doi: 
0.1101/2021.04.13.439482. 
Wrapp D, Wang N, Corbett KS, Goldsmith JA, Hsieh CL, Abiona O, et al. Cryo-EM structure of 
the 2019-nCoV spike in the prefusion conformation. Science. 2020 Mar 13;367(6483):1260-63. 
 

ModernaTX, Inc. 
mRNA-1273-P305 Protocol Amendment 2 
mRNA-1273 
Confidential 
Page 120 
11. 
SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS 

ModernaTX, Inc. 
mRNA-1273-P305 Protocol Amendment 2 
mRNA-1273 
Confidential 
Page 121 
11.1. 
APPENDIX 1: Study Governance Considerations 
11.1.1. 
Regulatory and Ethical Considerations 
This study will be conducted in accordance with the protocol and with the following: 
• Consensus ethical principles derived from international guidelines including the 
Declaration of Helsinki and Council for International Organizations of Medical Sciences 
International Ethical Guidelines. 
• Applicable ICH GCP Guidelines. 
• Applicable laws and regulatory requirements. 
• The protocol, protocol amendments, ICF, IB, and other relevant documents 
(eg, advertisements) must be submitted to an IEC by the investigator and reviewed and 
approved by the IEC before the study is initiated. 
• Any amendments to the protocol will require IEC approval before implementation of 
changes made to the study design, except for changes necessary to eliminate an 
immediate hazard to study participants. 
• The investigator will be responsible for the following: 
− 
Providing written summaries of the status of the study to the IEC annually or more 
frequently in accordance with the requirements, policies, and procedures established 
by the IEC 
− 
Notifying the IEC of SAEs or other significant safety findings as required by IEC 
procedures 
− 
Providing oversight of the conduct of the study at the site and adherence to ICH 
guidelines, the IEC, European regulation 536/2014 for clinical studies (if applicable), 
and all other applicable local regulations. 
11.1.2. 
Study Monitoring 
Before an investigational site can enter a participant into the study, a representative of the 
Sponsor or its representatives may visit the investigational clinic to: 
• Determine the adequacy of the facilities. 

ModernaTX, Inc. 
mRNA-1273-P305 Protocol Amendment 2 
mRNA-1273 
Confidential 
Page 122 
• Discuss with the investigator(s) and other personnel their responsibilities with regard to 
protocol adherence, and the responsibilities of the Sponsor or its representatives. This 
will be documented in a Clinical Study Agreement between the Sponsor, designated 
CRO, and the investigator. 
According to ICH GCP guideline, the Sponsor of the study is responsible for ensuring the proper 
conduct of the study with regard to protocol adherence and validity of data recorded on the 
eCRFs. The study monitor’s duties are to aid the investigator and the Sponsor in the maintenance 
of complete, accurate, legible, well-organized, and easily retrievable data. The study monitor will 
advise the investigator of the regulatory necessity for study-related monitoring, audits, IEC 
review, and inspection by providing direct access to the source data/documents. In addition, the 
study monitor will explain to and interpret for the investigator all regulations applicable to the 
clinical evaluation of an IP as documented in ICH guidelines. 
It is the study monitor’s responsibility to inspect the eCRFs and source documentation 
throughout the study to protect the rights of the participants; to verify adherence to the protocol; 
to verify completeness, accuracy, and consistency of the data; and to confirm adherence of study 
conduct to any local regulations. Details will be outlined in the Clinical Monitoring Plan. During 
the study, a monitor from the Sponsor or a representative will have regular contacts with the 
investigational site, for the following: 
• Provide information and support to the investigator(s). 
• Confirm that facilities remain acceptable. 
• Confirm that the investigational team is adhering to the protocol, that the data are being 
accurately recorded in the eCRFs, and that IP accountability checks are being performed. 
• Perform source data verification. This includes a comparison of the data in the eCRFs 
with the participant’s medical records at the hospital or practice, and other records 
relevant to the study. This will require direct access to all original records for each 
participant (eg, clinical charts or electronic medical record system). 
• Record and report any protocol deviations not previously sent. 
• Confirm AEs and SAEs have been properly documented on eCRFs and confirm any 
SAEs have been forwarded to the SAE Hotline, and those SAEs that met criteria for 
reporting have been forwarded to the IEC. 
The monitor will be available between visits if the investigator(s) or other staff needs 
information or advice. 

ModernaTX, Inc. 
mRNA-1273-P305 Protocol Amendment 2 
mRNA-1273 
Confidential 
Page 123 
11.1.3. 
Audits and Inspections 
The Sponsor, their designee(s), the IEC, or regulatory authorities will be allowed to conduct site 
visits to the investigational facilities for the purpose of monitoring or inspecting any aspect of the 
study. The investigator agrees to allow the Sponsor, their designee(s), the IEC, or regulatory 
authorities to inspect the IP storage area, IP stocks, IP records, participant charts and study 
source documents, and other records relative to study conduct. 
Authorized representatives of the Sponsor, a regulatory authority, and any IEC may visit the site 
to perform audits or inspections, including source data verification. The purpose of a Sponsor 
audit or inspection is to systematically and independently examine all study-related activities and 
documents to determine whether these activities were conducted, and data were recorded, 
analyzed, and accurately reported according to the protocol, ICH GCP (R2), and any applicable 
regulatory requirements. The investigator should contact the Sponsor immediately if contacted 
by a regulatory agency about an inspection. 
The Principal Investigator must obtain IEC approval for the investigation. Initial IEC approval 
and all materials approved by the IEC for this study, including the participant consent form and 
recruitment materials, must be maintained by the investigator and made available for inspection. 
11.1.4. 
Financial Disclosure 
The investigator is required to provide financial disclosure information to allow the Sponsor to 
submit the complete and accurate certification or disclosure statements. In addition, the 
investigator must provide the Sponsor with 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. 
The Sponsor, the CRO, and the clinic are not 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, the Sponsor, the CRO, and the clinic are not financially 
responsible for further treatment of the disease under study. 
11.1.5. 
Recruitment Procedures 
Advertisements to be used for the recruitment of study participants, and any other written 
information regarding this study to be provided to the participant, should be submitted to the 
Sponsor for approval. All documents must be approved by the IEC. 
11.1.6. 
Informed Consent Process 
The informed consent document(s) must meet the requirements of local regulations, ICH 
guidelines, Health Insurance Portability and Accountability Act requirements, where applicable, 
and the IEC or study center. All consent documents will be approved by the appropriate IEC. 

ModernaTX, Inc. 
mRNA-1273-P305 Protocol Amendment 2 
mRNA-1273 
Confidential 
Page 124 
The actual ICF used at each center may differ, depending on local regulations and IEC 
requirements. However, all versions must contain the standard information found in the sample 
ICF provided by the Sponsor. Any change to the content of the ICF must be approved by the 
Sponsor and the IEC prior to the form being used. 
If new information becomes available that may be relevant to the participant’s willingness to 
continue participation in the study, this will be communicated to him or her in a timely manner. 
Such information will be provided via a revised ICF or an addendum to the original ICF. 
The investigator or his or her representative will explain the nature of the study to the participant 
and answer all questions regarding the study. 
The investigator is responsible for ensuring that the participant fully understands the nature and 
purpose of the study. Information should be given in both oral and written form whenever 
possible. 
No participant should be obliged to participate in the study. The participant must be informed 
that participation is voluntary. Participants, their relatives, guardians, or (if applicable) legal 
representatives must be given ample opportunity to inquire about details of the study. The 
information must make clear that refusal to participate in the study or withdrawal from the study 
at any stage is without any prejudice to the participant’s subsequent care. 
The participant must be allowed sufficient time to decide whether they wish to participate. 
The participant must be made aware of and give consent to direct access to his or her source 
medical records by study monitors, auditors, the IEC, and regulatory authorities. The participant 
should be informed that such access will not violate participant confidentiality or any applicable 
regulations. The participant should also be informed that he or she is authorizing such access by 
signing the ICF. 
A copy of the ICF(s) must be provided to the participant. 
A participant who is rescreened is not required to sign another ICF if the rescreening occurs 
within 28 days from the previous ICF signature date (within the initial screening period). 
The ICF will contain a separate consent form(s) that addresses the use of remaining optional 
samples for optional exploratory research. The investigator or authorized designee will explain to 
each participant the objectives of the exploratory research. A participant will be told that they are 
free to refuse participation and may withdraw their consent at any time and for any reason during 
the storage period. A separate signature will be required to document agreement to allow any 
remaining specimens to be used for exploratory research. A participant who declines to 
participate in this optional research will not provide this separate signature. 

ModernaTX, Inc. 
mRNA-1273-P305 Protocol Amendment 2 
mRNA-1273 
Confidential 
Page 125 
11.1.7. 
Protocol Amendments 
No change or amendment to this protocol may be made by the investigator or the Sponsor after 
the protocol has been agreed to and signed by all parties unless such change(s) or amendment(s) 
has (have) been agreed upon by the investigator or the Sponsor. Any change agreed upon will be 
recorded in writing, and the written amendment will be signed by the investigator and the 
Sponsor. Institutional review board approval is required prior to the implementation of an 
amendment, unless overriding safety reasons warrant immediate action, in which case the IEC(s) 
will be promptly notified. 
Any modifications to the protocol or the ICF, which may impact the conduct of the study, 
potential benefit of the study, or may affect participant safety, including changes of study 
objectives, study design, participant population, sample sizes, study procedures, or significant 
administrative aspects will require a formal amendment to the protocol. Such amendment will be 
released by the Sponsor, agreed to by the investigator(s), and approved by the relevant IEC(s) 
prior to implementation. A signed and dated statement that the protocol, any subsequent relevant 
amended documents, and the ICF have been approved by relevant IEC(s) must be provided to the 
Sponsor before the study is initiated. 
Administrative changes of the protocol are minor corrections and/or clarifications that have no 
effect on the way the study is to be conducted. These administrative changes will be released by 
the Sponsor, agreed by the investigator(s), and notified to the IEC(s). 
11.1.8. 
Protocol Deviations 
The noncompliance may be either on the part of the participant, the investigator, or the clinic 
staff. As a result of deviations, corrective actions are to be developed by the site and 
implemented promptly. 
It is the responsibility of the site investigator to use continuous vigilance to identify and report 
deviations within a timely manner of the scheduled protocol-required activity. All deviations 
must be addressed in study source documents and reported to the Sponsor and the study medical 
monitor. Protocol deviations must be sent to the reviewing IEC per their policies. The site 
investigator is responsible for knowing and adhering to the reviewing IEC requirements. 
11.1.9. 
Data Protection 
Participants will be assigned a unique identifier by the Sponsor. Any participant records or 
datasets that are transferred to the Sponsor will contain the identifier only; participant names or 
any information which would make the participant identifiable will not be transferred. 

ModernaTX, Inc. 
mRNA-1273-P305 Protocol Amendment 2 
mRNA-1273 
Confidential 
Page 126 
The participant must be informed that his or her personal study-related data will be used by the 
Sponsor in accordance with local data protection law. The level of disclosure must also be 
explained to the participant. 
The participant must be informed that his or her medical records may be examined by Clinical 
Quality Assurance (QA) auditors or other authorized personnel appointed by the Sponsor, by 
appropriate IEC members, and by inspectors from regulatory authorities. 
Individual participant medical information obtained as a result of this study is considered 
confidential, and disclosure to third parties is prohibited. Information will be accessible to 
authorized parties or personnel only. Medical information may be given to the participant’s 
physician or to other appropriate medical personnel responsible for the participant’s well-being. 
Each participant will be asked to complete a form allowing the investigator to notify the 
participant’s primary health care provider of his or her participation in this study. 
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 IEC. 
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 
confidential information to other parties. 
11.1.10. 
Sample Retention and Future Biomedical Research 
The retention period of laboratory samples will be 20 years, or as permitted by local regulations, 
to address further scientific questions related to mRNA-1273/mRNA-1273.529/mRNA-1273.214 
or anti-respiratory virus immune response. In addition, identifiable samples can be destroyed at 
any time at the request of the participant. During the study, or during the retention period, in 
addition to the analysis outlined in the study endpoints, exploratory analysis may be conducted 
using other measures of adaptive immunity to SARS-CoV-2 to include humoral and cellular 
immune assay methodologies on any remaining blood or serum samples, including samples from 
participants who are screened but are not subsequently enrolled. These analyses will extend the 
search for other potentially relevant biomarkers to investigate the effect of mRNA-1273/mRNA-
1273.529/mRNA-1273.214 as well as to determine how changes in biomarkers may relate to 
exposure and clinical outcomes. A decision to perform such exploratory research may arise from 

ModernaTX, Inc. 
mRNA-1273-P305 Protocol Amendment 2 
mRNA-1273 
Confidential 
Page 127 
new scientific findings related to the drug class or disease, as well as reagent and assay 
availability. 
11.1.11. 
Data and Safety Monitoring Board 
A DSMB will be used throughout the conduct of this study. The DSMB will be composed of 
independent members with relevant therapeutic and/or biostatistical expertise to allow for the 
ongoing review of safety data from this study population. The data to be reviewed will be 
unblinded. Safety data will be reviewed according to intervals defined in the DSMB charter and 
as needed if potential safety concerns are identified. 
11.1.12. 
Dissemination of Clinical Study Data 
The Sponsor shares information about clinical trials and results on publicly accessible websites, 
based on international and local legal and regulatory requirements, and other clinical trial 
disclosure commitments established by pharmaceutical industry associations. These websites 
include clinicaltrials.gov, EU clinical trial register (eu.ctr), etc., as well as some national 
registries. 
11.1.13. 
Data Quality Assurance and Quality Control 
Data collection is the responsibility of the clinical study staff at the site under the supervision of 
the site investigator. The investigator is responsible for ensuring the accuracy, completeness, 
legibility, and timeliness of the data reported. 
• All participant data relating to the study will be recorded in an eCRF unless 
transmitted to the Sponsor or designee electronically (eg, laboratory data). The 
investigator is responsible for verifying that data entries are accurate and correct by 
physically or electronically signing the eCRF. 
• The investigator must maintain accurate documentation (source data) that supports 
the information entered in the eCRF. 
• The investigator must permit study-related monitoring, audits, IEC review, and 
regulatory agency inspections and provide direct access to source data documents. 
• Monitoring details describing strategy (eg, risk-based initiatives in operations and 
quality such as Risk Management and Mitigation Strategies and Analytical -Risk 
Based Monitoring), methods, responsibilities and requirements, including handling of 
noncompliance issues and monitoring techniques (central, remote, or on-site 
monitoring) are provided in the Clinical Monitoring Plan. 
• The Sponsor or designee is responsible for the data management of this study 
including quality checking of the data. 

ModernaTX, Inc. 
mRNA-1273-P305 Protocol Amendment 2 
mRNA-1273 
Confidential 
Page 128 
• The Sponsor assumes accountability for actions delegated to other individuals 
(eg, CROs). 
• Study monitors will perform ongoing source data verification to confirm that data 
entered into the eCRF by authorized site personnel are accurate, complete, and 
verifiable from source documents; that the safety and rights of participants are being 
protected; and that the study is being conducted in accordance with the currently 
approved protocol and any other study agreements, ICH GCP, and all applicable 
regulatory requirements. 
• Records and documents, including signed ICFs, pertaining to the conduct of this 
study must be retained by the investigator for 2 years after study completion unless 
local regulations or institutional policies require a longer retention period. No records 
may be destroyed during the retention period without the written approval of the 
Sponsor. No records may be transferred to another location or party without written 
notification to the Sponsor. 
Quality assurance includes all the planned and systematic actions that are established to ensure 
that the clinical study is performed, and the data are generated, documented (recorded), and 
reported according to ICH GCP and local/regional regulatory standards. 
A QA representative from the Sponsor or qualified designee, who is independent of and 
separated from routine monitoring, may periodically arrange inspections/audits of the clinical 
study by reviewing the data obtained and procedural aspects. These inspections may include 
on-site inspections/audits and source data checks. Direct access to source documents is required 
for the purpose of these periodic inspections/audits. 
11.1.14. 
Data Collection and Management 
This study will be conducted in compliance with ICH CGP guidelines. This study will also be 
conducted in accordance with the most recent version of the Declaration of Helsinki. 
This study will use electronic data collection to collect data directly from the investigational site 
using eCRFs. The investigator is responsible for ensuring that all sections of each eCRF are 
completed promptly and correctly and that entries can be verified against any source data. 
Study monitors will perform source document verification to identify inconsistencies between 
the eCRFs and source documents. Discrepancies will be resolved in accordance with the 
principles of GCP. Detailed study monitoring procedures are provided in the Clinical Monitoring 
Plan. 
Adverse events will be coded with MedDRA. Concomitant medications will be coded using the 
WHO-drug reference list. 

ModernaTX, Inc. 
mRNA-1273-P305 Protocol Amendment 2 
mRNA-1273 
Confidential 
Page 129 
11.1.15. 
Source Documents 
Source documents are original documents or certified copies and include, but are not limited to, 
diary cards, medical and hospital records, screening logs, informed consent forms, telephone 
contact logs, and worksheets. Source documents provide evidence for the existence of the 
participant and substantiate the integrity of the data collected. Source documents are filed at the 
investigator’s site. 
Data reported on the case report form or entered in the eCRF that are transcribed from source 
documents must be consistent with the source documents or the discrepancies must be explained. 
The investigator may need to request previous medical records or transfer records, depending on 
the study. Also, current medical records must be available. 
The Sponsor or its designee requires that the investigator prepare and maintain adequate and 
accurate records for each participant treated with the IP. Source documents such as any hospital, 
clinic, or office charts and the signed ICFs forms are to be included in the investigator’s files 
with the participant’s study records. 
11.1.16. 
Retention of Records 
The Principal Investigator must maintain all documentation relating to the study for a period of 
at least 2 years after the last marketing application approval or, if not approved, 2 years 
following the discontinuance of the test article for investigation. If this requirement differs from 
any local regulations, the local regulations will take precedence unless the local retention policy 
is less than 2 years. 
If it becomes necessary for the Sponsor or the regulatory authority to review any documentation 
relating to the study, the investigator must permit access to such records. No records will be 
destroyed without the written consent of the Sponsor, if applicable. It is the responsibility of the 
Sponsor to inform the investigator when these documents no longer need to be retained. 
11.1.17. 
Study and Site Closure 
If the study is prematurely terminated or suspended, the Sponsor shall promptly inform the 
investigators, the IEC(s), the regulatory authorities, and any CRO(s) used in the study of the 
reason for termination or suspension, as specified by the applicable regulatory requirements. The 
investigator shall promptly inform the participant and should assure appropriate participant 
therapy and/or follow-up. 
The Sponsor or designee reserves the right to close the clinic or terminate the study at any time 
for any reason at the sole discretion of the Sponsor. 
The investigator may initiate clinic closure at any time, provided there is reasonable cause and 
sufficient notice is given in advance of the intended termination. 

ModernaTX, Inc. 
mRNA-1273-P305 Protocol Amendment 2 
mRNA-1273 
Confidential 
Page 130 
Reasons for the early closure of a clinic by the Sponsor or investigator may include but are not 
limited to: 
• Continuation of the study represents a significant medical risk to participants. 
• Failure of the investigator to comply with the protocol, the requirements of the IEC or 
local health authorities, the Sponsor's procedures, or GCP guidelines. 
• Inadequate recruitment of participants by the investigator. 
• Discontinuation of further mRNA-1273 development. 
Clinics will be closed upon study completion. A clinic is considered closed when all required 
documents and study supplies have been collected and a clinic closure visit has been performed. 
11.1.18. 
Publication Policy 
The results of this study may be published or presented at scientific meetings. If this is foreseen, 
the investigator agrees to submit all manuscripts or abstracts to the Sponsor before submission. 
This allows the Sponsor to protect proprietary information and to provide comments. 
The Sponsor will comply with the requirements for publication of study results. In accordance 
with standard editorial and ethical practice, the Sponsor will generally support publication of 
multicenter studies only in their entirety and not as individual site data. In this case, a 
Coordinating Investigator will be designated by mutual agreement. 
Authorship will be determined by mutual agreement and in line with International Committee of 
Medical Journal Editors authorship requirements. 
The clinical study plan and the results of the study will be published on www.ClinicalTrials.gov. 
The results of and data from this study belong to the Sponsor. 

ModernaTX, Inc. 
mRNA-1273-P305 Protocol Amendment 2 
mRNA-1273 
Confidential 
Page 131 
11.2. 
APPENDIX 2: Contraceptive Guidance 
Definitions: Woman of Childbearing Potential (WOCBP) 
Women in the following categories are considered WOCBP (fertile): 
1. Following menarche 
From the time of menarche until becoming postmenopausal unless permanently sterile (see 
below) 
A postmenopausal state is defined as no menses for 12 months without an alternative 
medical cause. 
o A high follicle-stimulating hormone (FSH) level in the postmenopausal range 
may be used to confirm a postmenopausal state in women not using hormonal 
contraception or hormonal replacement therapy (HRT). However, in the 
absence of 12 months of amenorrhea, confirmation with FSH measurement is 
required.  
o Females on HRT and whose menopausal status is in doubt will be required to 
use one of the nonestrogen hormonal highly effective contraception methods 
if they wish to continue their HRT during the study. Otherwise, they must 
discontinue HRT to allow confirmation of postmenopausal status before study 
enrollment. 
Permanent sterilization methods (for the purpose of this study) include: 
o Documented hysterectomy 
o Documented bilateral salpingectomy 
o Documented bilateral oophorectomy 
o Documented tubal ligation 
o For individuals with permanent infertility due to an alternate medical cause 
other than the above, (eg, Mullerian agenesis, androgen insensitivity, gonadal 
dysgenesis), investigator discretion should be applied to determining study 
entry. 
Note: Documentation can come from the site personnel’s review of the 
participant’s medical records, medical examination, or medical history interview. 
If fertility is unclear (eg, amenorrhea in adolescents or athletes) and a menstrual cycle 
cannot be confirmed before first dose of study intervention, additional evaluation 
should be considered. 
Contraception Guidance: 
Adequate female contraception is defined as consistent and correct use of a regulatory 
agency-approved contraceptive method in accordance with the product label. For example: 

ModernaTX, Inc. 
mRNA-1273-P305 Protocol Amendment 2 
mRNA-1273 
Confidential 
Page 132 
• Barrier method (such as condoms, diaphragm, or cervical cap) 
• 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. 

ModernaTX, Inc. 
mRNA-1273-P305 Protocol Amendment 2 
mRNA-1273 
Confidential 
Page 133 
11.3. 
APPENDIX 3: Adverse Events of Special Interest 
Investigators should report all events which fall into the categories presented in Table 13 as an 
AESI per the reporting processes specified in Section 8.10.5. The following AESIs are medical 
concepts that may be related to COVID-19 or are of interest in COVID-19 vaccine safety 
surveillance. Even if the events below occur in the setting of a COVID infection, the event 
should still be reported as an AESI if it is one of the medical concepts below. 
Table 13: 
Adverse Events of Special Interest 
Medical Concept 
Additional Notes 
Anosmia, Ageusia 
New onset coronavirus disease (COVID)-associated or idiopathic events 
without other etiology excluding congenital etiologies or trauma. 
Subacute thyroiditis 
Including but not limited to events of atrophic thyroiditis, autoimmune 
thyroiditis, immune-mediated thyroiditis, silent thyroiditis, thyrotoxicosis, 
and thyroiditis. 
Acute pancreatitis 
• 
Including but not limited to events of autoimmune pancreatitis, 
immune-mediated pancreatitis, ischemic pancreatitis, edematous 
pancreatitis, pancreatitis, acute pancreatitis, hemorrhagic pancreatitis, 
necrotizing pancreatitis, viral pancreatitis, and subacute pancreatitis. 
• 
Excluding known etiologic causes of pancreatitis (alcohol, gallstones, 
trauma, recent invasive procedures). 
Appendicitis 
Include any event of appendicitis. 
Rhabdomyolysis 
New onset rhabdomyolysis without known etiology such as excessive 
exercise or trauma. 
Acute respiratory distress 
syndrome  
Including but not limited to new events of acute respiratory distress 
syndrome and respiratory failure. 
Coagulation disorders 
Including but not limited to thromboembolic and bleeding disorders, 
disseminated intravascular coagulation, pulmonary embolism, and deep 
vein thrombosis. 
Acute cardiovascular 
injury 
Including but not limited to myocarditis, pericarditis, microangiopathy, 
coronary artery disease, arrhythmia, stress cardiomyopathy, heart failure, 
or acute myocardial infarction. 
Acute kidney injury 
• 
Include events with idiopathic or autoimmune etiologies 
• 
Exclude events with clear alternate etiology (trauma, infection, tumor, 
or iatrogenic causes such as medications or radiocontrast agents, etc) 
• 
Include all cases that meet the following criteria: 
o Increase in serum creatinine by ≥ 0.3 mg/dL (≥ 26.5 µmol/L) 
within 48 hours; OR 
o Increase in serum creatinine to ≥ 1.5 times baseline, known or 
presumed to have occurred within prior 7 days; OR 
o Urine volume ≤ 0.5 mL/kg/hour for 6 hours. 

ModernaTX, Inc. 
mRNA-1273-P305 Protocol Amendment 2 
mRNA-1273 
Confidential 
Page 134 
Medical Concept 
Additional Notes 
Acute liver injury 
• 
Include events with idiopathic or autoimmune etiologies 
• 
Exclude events with clear alternate etiology (trauma, infection, tumor, 
etc) 
• 
Include all cases that meet the following criteria: 
o > 3-fold elevation above the upper normal limit for alanine 
transaminase or aspartate aminotransferase OR 
o > 2-fold elevation above the upper normal limit for total serum 
bilirubin or gamma glutamyl transferase or alkaline phosphatase. 
Dermatologic findings 
• 
Chilblain-like lesions; 
• 
Single organ cutaneous vasculitis; 
• 
Erythema multiforme; 
• 
Bullous rashes; 
• 
Severe cutaneous adverse reactions including but not limited to: 
Stevens-Johnson syndrome, Toxic Epidermal Necrolysis, Drug 
Reaction with Eosinophilia and Systemic Symptoms, and fixed drug 
eruptions. 
Multisystem 
inflammatory disorders 
• 
Multisystem inflammatory syndrome in adults 
• 
Multisystem inflammatory syndrome in children 
• 
Kawasaki’s disease 
Thrombocytopenia 
• 
Platelet counts < 150 ×109 per mm3 
• 
Including but not limited to immune thrombocytopenia, platelet 
production decreased, thrombocytopenia, thrombocytopenic purpura, 
thrombotic thrombocytopenic purpura, or hemolysis, elevated liver 
enzymes, low platelet count (HELLP) syndrome. 
Acute aseptic arthritis 
• 
New onset aseptic arthritis without clear alternate etiology (eg, gout, 
osteoarthritis, and trauma). 
New onset of or 
worsening of neurologic 
disease 
• 
Including but not limited to  
o Guillain-Barre syndrome 
o Acute disseminated encephalomyelitis 
o Peripheral facial nerve palsy (Bell’s palsy)  
o Transverse myelitis 
o Encephalitis/Encephalomyelitis 
o Aseptic meningitis 
o Febrile seizures 
o Generalized seizures/convulsions 
o Stroke (Hemorrhagic and non-hemorrhagic)  
o Narcolepsy 
Anaphylaxis 
• 
Anaphylaxis as defined per Section 8.10.5. 
• 
Follow reporting procedures per Section 8.10.2 

ModernaTX, Inc. 
mRNA-1273-P305 Protocol Amendment 2 
mRNA-1273 
Confidential 
Page 135 
Medical Concept 
Additional Notes 
Other syndromes 
• 
Fibromyalgia 
• 
Postural Orthostatic Tachycardia Syndrome 
• 
Chronic Fatigue Syndrome (includes myalgic encephalomyelitis and 
postviral fatigue syndrome) 
• 
Myasthenia gravis 

ModernaTX, Inc. 
mRNA-1273-P305 Protocol Amendment 2 
mRNA-1273 
Confidential 
Page 136 
11.4. 
APPENDIX 4: CDC Working Case Definitions of Pericarditis, 
Myocarditis, and Myopericarditis Occurring After Receipt of 
COVID-19 mRNA Vaccines 
The CDC Working Case Definitions of probable and confirmed myocarditis, pericarditis, and 
myopericarditis (Gargano et al 2021) are provided in Table 14 as guidance. 
Table 14: 
Case Definitions of Probable and Confirmed Myocarditis, Pericarditis, and 
Myopericarditis 
Condition 
Definition 
Probable Case 
Confirmed Case 
Acute myocarditis 
Presence of ≥ 1 new or worsening of the 
following clinical symptoms:* 
• 
Chest pain, pressure, or 
discomfort 
• 
Dyspnea, shortness of breath, 
or pain with breathing 
• 
Palpitations 
• 
Syncope 
Presence of ≥ 1 new or worsening of the 
following clinical symptoms:* 
• 
Chest pain, pressure, or 
discomfort 
• 
Dyspnea, shortness of breath, 
or pain with breathing 
• 
Palpitations 
• 
Syncope 
OR infants and children aged < 12 years 
might instead have ≥ 2 of the following 
symptoms: 
• 
Irritability 
• 
Vomiting 
• 
Poor feeding 
• 
Tachycardia 
• 
Lethargy 
OR infants and children aged 
< 12 years might instead have ≥ 2 of the 
following symptoms: 
• 
Irritability 
• 
Vomiting 
• 
Poor feeding 
• 
Tachycardia 
• 
Lethargy 
AND ≥ 1 new finding of: 
• 
Troponin level above upper 
limit of normal (any type of 
troponin) 
• 
Abnormal electrocardiogram 
(ECG or EKG) or rhythm 
monitoring findings consistent 
with myocarditis§ 
• 
Abnormal cardiac function or 
wall motion abnormalities on 
echocardiogram 
• 
Cardiac magnetic resonance 
imaging (cMRI) findings 
consistent with myocarditis 
AND ≥ 1 new finding of: 
• 
Histopathologic confirmation 
of myocarditis† 
• 
cMRI findings consistent with 
myocarditis in the presence of 
troponin level above upper 
limit of normal (any type of 
troponin) 
AND 
AND 
• 
No other identifiable cause of 
the symptoms and findings 
• 
No other identifiable cause of 
the symptoms and findings 

ModernaTX, Inc. 
mRNA-1273-P305 Protocol Amendment 2 
mRNA-1273 
Confidential 
Page 137 
Condition 
Definition 
Probable Case 
Confirmed Case 
Acute pericarditis** 
Presence of ≥ 2 new or worsening of the following clinical features: 
• 
Acute chest pain†† 
• 
Pericardial rub on examination 
• 
New ST-elevation or PR-depression on EKG 
• 
New or worsening pericardial effusion on echocardiogram or MRI 
Myopericarditis 
This term may be used for patients who meet criteria for both myocarditis and 
pericarditis. 
Abbreviations: CDC = Centers for Disease Control and Prevention; CEAC = Cardiac Event Adjudication 
Committee; cMRI = cardiac magnetic resonance imaging; ECG or EKG = electrocardiogram; MRI = magnetic 
resonance imaging. 
Note: An independent CEAC comprised of medically qualified personnel, including cardiologists, will review 
suspected cases of myocarditis, pericarditis, and myopericarditis to determine if they meet CDC criteria for 
“probable” or “confirmed” events (Gargano et al 2021) and provide the assessment to the Sponsor. The CEAC 
members will be blinded to study vaccine assignment. Details regarding the CEAC composition, responsibilities, 
procedures, and frequency of data review will be defined in the CEAC charter. 
* Persons who lack the listed symptoms but who meet other criteria may be classified as subclinical myocarditis 
(probable or confirmed). 
† Using the Dallas criteria (Aretz et al 1987). Autopsy cases may be classified as confirmed clinical myocarditis on 
the basis of meeting histopathologic criteria if no other identifiable cause. 
§ To meet the ECG or rhythm monitoring criterion, a probable case must include at least one of: 1) ST-segment or T-
wave abnormalities; 2) paroxysmal or sustained atrial, supraventricular, or ventricular arrhythmias; or 3) 
atrioventricular nodal conduction delays or intraventricular conduction defects. 
¶ Using either the original or the revised Lake Louise criteria. 
https://www.sciencedirect.com/science/article/pii/S0735109718388430?via%3Dihubexternal icon 
** https://academic.oup.com/eurheartj/article/36/42/2921/2293375external icon 
†† Typically described as pain made worse by lying down, deep inspiration, or cough, and relieved by sitting up or 
leaning forward, although other types of chest pain might occur. 
Reference: Gargano et al 2021. 

ModernaTX, Inc. 
mRNA-1273-P305 Protocol Amendment 2 
mRNA-1273 
Confidential 
Page 138 
11.5. 
APPENDIX 5: Protocol Amendment History 
11.5.1. 
Amendment 1, 03 Mar 2022 
This amendment is considered to be substantial based on the criteria set forth in Article 10(a) of 
Directive 2001/20/EC of the European Parliament and the Council of the European Union. 
Main Rationale for the Amendment: 
The main rationale for this amendment is to modify the study design to include 2 parts: Part 1) 
mRNA 1273.529 with a reduced sample size, and Part 2) mRNA 1273.214 with a similar study 
design to Part 1.  
The summary of changes table provided below describes the major changes made in Amendment 
1 relative to the original protocol, including the sections modified and the corresponding rationales. 
The synopsis of Amendment 1 has been modified to correspond to changes in the body of the 
protocol. Minor grammar and formatting corrections were made throughout the document to 
enhance clarity and readability (which did not affect the conduct of the study). 
Summary of Major Changes in Protocol Amendment 1: 
Section # and Name 
Description of Change 
Brief Rationale 
Cover Page, Protocol 
Approval Page, and 1.1 
Protocol Synopsis 
Removed mRNA-1273.529 
(B.1.1.529) from the title  
Modified to make it 
inclusive of mRNA-
1273.214. 
Global 
Changed “within 3 months” to 
“within 90 days” 
To enhance clarity 
1.1 Protocol Synopsis and 
Section 5.2, Exclusion 
Criteria 
Removed from Exclusion Criteria 
#12: “Asymptomatic conditions and 
conditions with no evidence of end 
organ involvement (eg, mild 
hypertension, dyslipidemia) are not 
exclusionary, provided that they are 
being appropriately managed and are 
clinically stable (ie, unlikely to result 
in symptomatic illness within the 
time course of this study). Illnesses 
or conditions may be exclusionary, 
even if otherwise stable, due to 
therapies used to treat them (eg, 
immune-modifying treatments), at 
the discretion of the Investigator.” 
Removed due to 
redundancy 

ModernaTX, Inc. 
mRNA-1273-P305 Protocol Amendment 2 
mRNA-1273 
Confidential 
Page 139 
Section # and Name 
Description of Change 
Brief Rationale 
1.1 Protocol Synopsis and 
Section 3, Objectives and 
Endpoints 
Added an objective and endpoint 
table for the new Part 2 (mRNA-
1273.214 and mRNA-1273). 
To reflect the updated 
study design which 
will now have 2 parts. 
1.1 Protocol Synopsis and 
Section 3, Objectives and 
Endpoints:  
Primary Endpoint (Part 1) 
For the primary non-inferiority of the 
immune response of mRNA-
1273.529 compared to mRNA-1273 
booster administered as a 4th dose 
against the B.1.1.529 strain endpoint 
in Part 1, Month 3 was added as an 
assessment timepoint.  
Due to revisit of the 
primary objectives and 
endpoints. 
1.1 Protocol Synopsis and 
Section 3, Objectives and 
Endpoints: 
Other Secondary Endpoints 
(Part 1) 
For the other secondary endpoints of 
the evaluation of the 
immunogenicity of mRNA-1273.529 
booster compared to mRNA-1273 
booster administered at the 3rd or 4th 
dose in Part 1, immunogenicity will 
be evaluated at all measured 
timepoints. 
Due to revisit of the 
Other Secondary 
objectives and 
endpoints. 
1.1 Protocol Synopsis and 
Section 3, Objectives and 
Endpoints: 
Other Secondary Endpoints 
(Part 1) 
Changed the endpoint of evaluating 
the immunogenicity of 
mRNA-1273.529 and mRNA-1273 
booster at all evaluable endpoints 
against the B.1.1.529 strain (and 
prototype strain) rather than against 
other strains. 
To enhance clarity as 
the evaluation of the 
immunogenicity of 
mRNA-1273.529 
booster against other 
variant strains is 
already included as an 
exploratory objective.  
1.1 Protocol Synopsis and 
Section 3, Objectives and 
Endpoints: Other Secondary  
Removed the other secondary 
endpoint to evaluate the 
immunogenicity of mRNA-1273.529 
and mRNA-1273 booster at all 
evaluable time points after the 
vaccination administration. 
This other secondary 
endpoint was 
repetitive to the to the 
other secondary 
endpoints. 
1.1 Protocol Synopsis and 
Section 3, Objectives and 
Endpoints: 
Exploratory Endpoints 
(Part 1) 
Removed the exploratory 
endpoint/objective to evaluate 
cellular immunogenicity of a subset 
of participants in Part 1. 
Due to a revisit of the 
exploratory 
endpoint/objective. 

ModernaTX, Inc. 
mRNA-1273-P305 Protocol Amendment 2 
mRNA-1273 
Confidential 
Page 140 
Section # and Name 
Description of Change 
Brief Rationale 
1.1 Protocol Synopsis and 
Section 3, Objectives and 
Endpoints: 
Part 2 
Added Objectives and Endpoints for 
Part 2 of the study. 
New objects and 
endpoints added to 
address Part 2 of the 
study. 
1.1 Protocol Synopsis, 
Overall Study Design; 
Section 4.1, General Design 
Provided study design details for 
Part 1 and Part 2. 
To add study conduct 
details with the 
addition of mRNA-
1273.214. 
1.1 Protocol Synopsis, 
Number of Participants  
Updated the section to include the 
approximate number of participants 
in Part 1 and Part 2. 
Changes due to the 
addition of Part 2 
administration of the 
mRNA-1273.214. 
1.1 Protocol Synopsis and 
Section 5.1, Inclusion Criteria 
Update the definition of “women of 
nonchildbearing potential” 
To align with the 
updated protocol 
template language. 
1.1 Protocol Synopsis and 
Section 5.2, Exclusion 
Criteria #1 
Modified the definition of the 
exposure criteria for SARS-CoV-2 
infection or COVID-19 
Exclusion criteria 
updated to provide 
clarity. 
1.1 Protocol Synopsis and 
Section 5.2, Exclusion 
Criteria #3 
Modified timing of a positive PCR 
test from 08 November 2021 to 
within 90 days of Screening 
To enhance clarity and 
accommodate the 
addition of mRNA-
1273.214. 
1.1 Protocol Synopsis, Study 
Treatments and Section 6.1, 
Investigational Product 
Add Investigational product 
information for the mRNA-1273.214 
product. 
To provide additional 
details on the 
formulation of the 
mRNA-1273.214. 
Section 8.8.2, Vaccine 
Efficacy and Surveillance for 
COVID-19 Symptoms 
In Section 8.8.2, added “vaccine 
efficacy” to the heading. 
Updated to provide 
details of the new 
study design. 
1.1 Protocol Synopsis, 
Efficacy Assessments and 
Section 8.8.2, Vaccine 
Efficacy and Surveillance of 
COVID-19 Symptoms 
Added surveillance for COVID-19 
and SARS-CoV-2 infection to Part 2. 
Added for Part 2 of 
the study. No changes 
for Part 1 of the study. 
1.1 Protocol Synopsis and 
Section 9.2, Statistic 
Hypotheses  
Modified the statistical hypotheses 
for Part 1.  
Modified Part 1 and 
added Part 2 

ModernaTX, Inc. 
mRNA-1273-P305 Protocol Amendment 2 
mRNA-1273 
Confidential 
Page 141 
Section # and Name 
Description of Change 
Brief Rationale 
Added statistical hypotheses for 
Part 2.  
information due to 
study design changes. 
1.1 Protocol Synopsis, 
Figure 1 
Added Part 2 of the study to the title 
of Figure 1 to summarize statistical 
hypotheses testing strategy for 
mRNA-1273.214 and mRNA-1273. 
Added due to changes 
in study design. 
1.1 Protocol Synopsis, 
Sample Size and Section 9.3 
Sample Size and Power 
Calculation 
Modified (Part 1) and added (Part 2) 
details for targeted enrollment and 
other sample size assumptions. 
Changed Part 1 due to 
study design 
modifications and 
added information for 
Part 2. 
1.1 Protocol Synopsis and 
Section 9.5, Analysis 
Populations 
Clarified the analysis population 
definitions for the Full Analysis Set, 
Modified Intent-to-treat, and PP Set 
for Immunogenicity 
Minor wording 
clarification 
Section 9.4, Multiplicity 
Added this section to describe the 
statistical testing in Part 1 and Part 2.  
Other subsequent section headings 
within the protocol were renumbered 
due to this additional heading in 
Section 9.4: 
9.5 Analyses Populations 
9.6 Statistical Analyses 
9.7 Planned Analyses 
Added due to the 
study design change. 
1.1 Protocol Synopsis and 
Section 9.6.1, 
Immunogenicity Analysis 
(Part 1) 
Modified Part 1 immunogenicity 
analysis. 
Modified Part 1 
immunogenicity 
analysis due to study 
design change.  
1.1 Protocol Synopsis and 
Section 9.6.1, 
Immunogenicity Analysis 
(Part 2) 
Added details of the immunogenicity 
analysis in Part 2. 
Added due to the 
study design change. 
1.1 Protocol Synopsis and 
Section 9.7, Planned Analysis 
Removed the subheadings “primary” 
and “final” analysis.  
Changed “primary analyses” to 
“planned analyses” of the 
immunogenicity and safety. Added 
Modified to provide 
clarity. 

ModernaTX, Inc. 
mRNA-1273-P305 Protocol Amendment 2 
mRNA-1273 
Confidential 
Page 142 
Section # and Name 
Description of Change 
Brief Rationale 
Months 3 and 6 to the planned 
analyses 
Section 1.2, Figure 2 Study 
Schema 
Modified Part 1 and added new Part 
2 study information. 
Modified Part 1 and 
added Part 2 due to 
new study design. 
Section 1.3, SoE 
Deleted Screening from the SoE for 
Recording of SAEs and concomitant 
medications relevant to or for the 
treatment of the SAE. 
Added Table 2 for new Part 2 of the 
study 
To correct a minor 
error. 
Section 2.2, Background; 
Section 2.2.1, mRNA-1273 
and mRNA-1273.529; 
Section 2.3, Benefit/Risk 
Assessment; Section 4.2, 
Scientific Rationale for Study 
Design; Section 8.7, Study 
Vaccine Administration 
Added the mRNA-1273.214 vaccine, 
where applicable. 
To provide more 
details of the mRNA-
1273.214 product and 
formulation. 
Section 2.2, Background  
Added sentence to state FDA 
approval date of Spikevax. 
Updated clinical 
program. 
Section 2.2.3, Clinical 
Studies 
Added information regarding the 
preliminary data from the Phase 2 
trial. 
To provide 
information to support 
the testing of the 
bivalent mRNA-
1273.214 vaccine in 
Part 2.  
Section 10, References 
Added FDA New Release to the 
reference section to support FDA 
approval. 
Added due to new 
information on the 
marketing approval of 
mRNA-1273. 
Section 6.3, 
Preparation/Handling/Storage 
/Accountability 
Updated clinical study material 
information, administration, 
packaging, labeling, and storage for 
the mRNA-1273.214 product. 
Added due to study 
design changes. 
Section 6.3.7, Unblinding 
Removed statement regarding the 
instructions to the investigator 
Modified per 
regulatory feedback. 

ModernaTX, Inc. 
mRNA-1273-P305 Protocol Amendment 2 
mRNA-1273 
Confidential 
Page 143 
Section # and Name 
Description of Change 
Brief Rationale 
communicating the unblinding of a 
participant. 
Section 8.9.1, Pregnancy 
Screen and Testing 
Changed the participant’s FSH level 
from “may” to “should” be measured 
at the Screening Visit, if necessary. 
Modified to clarify. 
Section 8.10.15, Regulatory 
Reporting Requirements for 
SAEs 
Added information regarding the 
events of anaphylaxis, myocarditis, 
and pericarditis that are assessed as 
serious and related by the 
investigator to be reported in an 
expedited manner. 
Provided details 
specifying that events 
deemed as serious and 
related by the 
investigator will be 
reported appropriately 
according to local 
requirements. 
11.2 Appendix 2: 
Contraception Guidance 
Updated the definition of “women of 
childbearing potential” and the 
definition of “nonchildbearing 
potential”. 
To align with the 
updated protocol 
template language. 
11.2 Appendix 2: 
Contraception Guidance 
Deleted “used in conjunction with 
spermicide”. 
To clarify what 
constitutes adequate 
contraception for 
practical conduct of 
the study. 
 

Signature Page for VV-CLIN-004704 v3.0
Signature Page for VV-CLIN-004704 v3.0
2nd Approval
PPD