A Phase 2, Randomized, Active-Controlled, Observer-Blind, Dose-Ranging Study to Evaluate the Safety, Reactogenicity, and Immunogenicity of mRNA Vaccine Candidate Variations in Healthy Adults 18 to 49 Years of Age
Phase: PHASE2
Conditions: Influenza
Sponsor: ModernaTX, Inc.

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.
CLINICAL STUDY PROTOCOL 
Protocol Title: 
A Phase 2, randomized, active‑controlled, observer-blind, dose-ranging study to evaluate the 
safety, reactogenicity, and immunogenicity of mRNA vaccine candidate variations in healthy 
adults 18 to 49 years of age. 
Protocol Number: mRNA-CRID-004 
Date: 12 Apr 2023 
Compound: mRNA-1010 variations 
Brief Title: 
Study to evaluate the safety, reactogenicity, and immunogenicity of mRNA vaccine candidate 
variations in healthy adults 18 to 49 years of age. 
Study Phase: Phase 2 
Sponsor Name: 
ModernaTX, Inc. 
Legal Registered Address: 
200 Technology Square 
Cambridge, MA 02139 
Regulatory Agency Identifier Number(s): 
Registry 
ID 
FDA 
IND 028259 
Approval Date: 12-Apr-2023 
Sponsor Signatory: 
See e-Signature and date signed on last page the document. 
 
 
 
Date 
Sponsor Signatory and Contact Information will be provided separately. 
NCT #: NCT05868382
PPD

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DECLARATION OF INVESTIGATOR 
I have read and understood all sections of the protocol entitled “A Phase 2, randomized, 
active-controlled, observer-blind, dose-ranging study to evaluate the safety, reactogenicity, and 
immunogenicity of mRNA vaccine candidate variations in healthy adults 18 to 49 years of age” 
dated 12 Apr 2023 and the most recent version of the mRNA-1010 IB. 
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 local and country regulations. I will not 
make changes to the protocol before consulting with ModernaTX, Inc. or implement protocol 
changes without IRB/IEC approval except to eliminate an immediate risk to participants. 
I agree to administer study treatment only to participants under my personal supervision or the 
supervision of a Subinvestigator. I will not supply study treatment 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 staff and members of the IRB/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, regulations, and ICH E6(R2) GCP 
guidelines. 
 
Signature of Principal Investigator 
 
 
Date 
 
 
 
 
Printed Name of Principal Investigator  
 
 
 
 
 

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TABLE OF CONTENTS 
CLINICAL STUDY PROTOCOL ..................................................................................................1 
DECLARATION OF INVESTIGATOR .........................................................................................2 
LIST OF ABBREVIATIONS ..........................................................................................................8 
1. 
PROTOCOL SUMMARY ..........................................................................................10 
1.1. 
Protocol Synopsis .......................................................................................................10 
1.2. 
Schema ........................................................................................................................12 
1.3. 
Schedule of Activities .................................................................................................13 
2. 
INTRODUCTION ......................................................................................................17 
2.1. 
Study Rationale ...........................................................................................................17 
2.2. 
Background .................................................................................................................17 
2.3. 
Benefit/Risk Assessment ............................................................................................17 
2.3.1. 
Risk Assessment .........................................................................................................17 
2.3.2. 
Benefit Assessment .....................................................................................................18 
2.3.3. 
Overall Benefit/Risk Conclusion ................................................................................18 
3. 
OBJECTIVES AND ENDPOINTS ............................................................................19 
4. 
STUDY DESIGN .......................................................................................................20 
4.1. 
Overall Design ............................................................................................................20 
4.2. 
Scientific Rationale for Study Design ........................................................................21 
4.3. 
Justification for Dose ..................................................................................................21 
4.4. 
End-of-Study Definition .............................................................................................21 
5. 
STUDY POPULATION .............................................................................................22 
5.1. 
Inclusion Criteria ........................................................................................................22 
5.2. 
Exclusion Criteria .......................................................................................................23 
5.3. 
Screen Failures ............................................................................................................25 
5.4. 
Criteria for Temporarily Delaying Administration of Study Intervention .................25 
6. 
STUDY INTERVENTIONS AND CONCOMITANT THERAPY...........................26 
6.1. 
Study Interventions Administered ..............................................................................26 
6.2. 
Preparation, Handling, Storage, and Accountability ..................................................27 
6.3. 
Assignment to Study Intervention ..............................................................................28 
6.4. 
Blinding ......................................................................................................................28 
6.5. 
Study Intervention Compliance ..................................................................................28 

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6.6. 
Dose Modification ......................................................................................................29 
6.7. 
Continued Access to Study Intervention after End-of-Study .....................................29 
6.8. 
Treatment of Overdose ...............................................................................................29 
6.9. 
Prior and Concomitant Therapy ..................................................................................29 
6.9.1. 
Concomitant Medications and Therapies ...................................................................29 
6.9.2. 
Concomitant Medications and Vaccines that May Lead to the Elimination of 
a Participant from Per Protocol Analyses ....................................................................30 
7. 
DISCONTINUATION OF STUDY INTERVENTION AND 
PARTICIPANT DISCONTINUATION/WITHDRAWAL .......................................32 
7.1. 
Discontinuation of Study Intervention........................................................................32 
7.2. 
Participant Discontinuation/Withdrawal from the Study ...........................................32 
7.3. 
Lost to Follow-up .......................................................................................................33 
7.4. 
Pause Rules .................................................................................................................34 
8. 
STUDY ASSESSMENTS AND PROCEDURES ......................................................35 
8.1. 
Demography ...............................................................................................................35 
8.2. 
Immunogenicity Assessments ....................................................................................36 
8.3. 
Safety Assessments .....................................................................................................36 
8.3.1. 
Physical Examinations ................................................................................................36 
8.3.2. 
Vital Signs ..................................................................................................................37 
8.3.3. 
Pregnancy Testing ......................................................................................................37 
8.3.4. 
Assessments for Respiratory Viral Infections ............................................................38 
8.3.5. 
Safety Calls .................................................................................................................38 
8.3.6. 
Use of Electronic Diaries ............................................................................................38 
8.4. 
Adverse Events, Serious Adverse Events, and Other Safety Reporting .....................39 
8.4.1. 
Time Period and Frequency for Collecting AE and SAE Information .......................39 
8.4.2. 
Method of Detecting AEs and SAEs ..........................................................................40 
8.4.3. 
Follow-up of AEs and SAEs .......................................................................................40 
8.4.4. 
Regulatory Reporting Requirements for SAEs ...........................................................40 
8.4.5. 
Pregnancy ...................................................................................................................41 
8.4.6. 
Solicited Adverse Reactions .......................................................................................41 
8.4.7. 
Medically Attended Adverse Events ..........................................................................42 
8.4.8. 
Adverse Events of Special Interest .............................................................................42 
8.4.8.1. 
Anaphylaxis ................................................................................................................43 

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8.4.8.2. 
Myocarditis and/or Pericarditis ...................................................................................43 
8.5. 
Pharmacokinetics ........................................................................................................44 
8.6. 
Pharmacodynamics .....................................................................................................44 
8.7. 
Genetics ......................................................................................................................44 
8.8. 
Biomarkers ..................................................................................................................44 
8.9. 
Health Economics OR Medical Resource Utilization and Health Economics ...........44 
9. 
STATISTICAL CONSIDERATIONS .......................................................................45 
9.1. 
Blinding and Responsibility for Analyses ..................................................................45 
9.2. 
Statistical Hypotheses .................................................................................................45 
9.3. 
Sample Size Determination ........................................................................................46 
9.4. 
Analysis Sets ...............................................................................................................46 
9.5. 
Statistical Analyses .....................................................................................................46 
9.5.1. 
Baseline Characteristics and Demographics ...............................................................47 
9.5.2. 
Immunogenicity Analyses ..........................................................................................47 
9.5.3. 
Safety Analyses ..........................................................................................................47 
9.5.4. 
Exploratory Analyses ..................................................................................................48 
9.6. 
Planned Analyses ........................................................................................................48 
9.6.1. 
Interim Analysis ..........................................................................................................48 
9.6.2. 
Final Clinical Study Report ........................................................................................48 
10. 
SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS ..................................................................................................49 
10.1. 
Appendix 1: Regulatory, Ethical, and Study Oversight Considerations ....................49 
10.1.1. 
Regulatory and Ethical Considerations ......................................................................49 
10.1.2. 
Financial Disclosure ...................................................................................................49 
10.1.3. 
Informed Consent Process ..........................................................................................50 
10.1.4. 
Recruitment Strategy ..................................................................................................50 
10.1.5. 
Data Protection ...........................................................................................................50 
10.1.6. 
Committees Structure .................................................................................................51 
10.1.6.1. 
Internal Safety team ....................................................................................................51 
10.1.6.2. 
Cardiac Event Adjudication Committee .....................................................................51 
10.1.7. 
Dissemination of Clinical Study Data ........................................................................51 
10.1.8. 
Data Quality Assurance ..............................................................................................52 
10.1.9. 
Source Documents ......................................................................................................52 

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10.1.10. 
Study and Site Start and Closure ................................................................................53 
10.1.11. 
Publication Policy .......................................................................................................53 
10.2. 
Appendix 2: Clinical Laboratory Tests .......................................................................55 
10.3. 
Appendix 3: AEs and SAEs: Definitions and Procedures for Recording, 
Evaluating, Follow-up, and Reporting ........................................................................56 
10.3.1. 
Definition of AE .........................................................................................................56 
10.3.2. 
Definition of SAE .......................................................................................................57 
10.3.3. 
Definition of MAAE ...................................................................................................58 
10.3.4. 
Definition of AESI ......................................................................................................58 
10.3.5. 
Recording and Follow-Up of AE and/or SAE ............................................................58 
10.3.6. 
Reporting of SAEs/AESI ............................................................................................61 
10.4. 
Appendix 4: Contraceptive and Barrier Guidance ......................................................63 
10.4.1. 
Definitions ..................................................................................................................63 
10.4.2. 
Contraception Guidance .............................................................................................64 
10.5. 
Appendix 5: Adverse Event of Special Interest ..........................................................66 
10.6. 
Appendix 6: CDC Working Case Definitions of Pericarditis, Myocarditis, 
and Myopericarditis Occurring After Receipt of COVID-19 mRNA 
Vaccines ......................................................................................................................67 
11. 
REFERENCES ...........................................................................................................69 
 

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LIST OF TABLES 
Table 1: 
Schedule of Activities .................................................................................................13 
Table 2: 
Objectives and Endpoints ...........................................................................................19 
Table 3: 
Study Interventions Administered ..............................................................................26 
Table 4: 
Study Arms and Dosing Regimens .............................................................................27 
Table 5: 
Analysis Sets ...............................................................................................................46 
Table 6: 
Protocol-required Safety Laboratory Tests .................................................................55 
Table 7: 
Adult and Adolescent Solicited Adverse Reactions and Grades ................................59 
Table 8: 
Adverse Events of Special Interest .............................................................................66 
Table 9: 
Case Definitions of Probably and Confirmed Myocarditis, Pericarditis, and 
Myopericarditis ...........................................................................................................67 
 

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LIST OF ABBREVIATIONS 
Abbreviation or Specialist Term 
Definition 
AE 
adverse event 
AESI 
adverse events of special interest 
AFAB 
assigned female at birth 
AR 
adverse reaction 
AxMP 
auxiliary medicinal products 
BMI 
body mass index 
C 
clinic 
CDC 
Centers for Disease Control and Prevention 
CEAC 
Cardiac Event Adjudication Committee 
CFR 
Code of Federal Regulations 
COVID-19 
coronavirus disease 2019 
CRF 
case report form 
CRO 
contract research organization 
CSR 
clinical study report 
D 
day 
ECG 
electrocardiogram 
eCRF 
electronic case report form 
EDC 
electronic data capture 
eDiary 
electronic diary 
EKG 
electrocardiogram 
EoS 
end-of-study 
FAS 
full analysis set 
FDA 
Food and Drug Administration 
FSH 
follicle-stimulating hormone 
GCP 
Good Clinical Practice 
GM 
geometric mean 
GMFR 
geometric mean fold rise 
GMT 
geometric mean titer 
HA 
hemagglutinin 
HAI 
hemagglutination inhibition 
HIV 
human immunodeficiency virus 
IA 
interim analysis 
IB 
Investigator’s Brochure 

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Abbreviation or Specialist Term 
Definition 
ICF 
informed consent form 
ICH 
International Council for Harmonisation 
IEC 
independent ethics committee 
IM 
intramuscular(ly) 
IMP 
investigational medicinal product 
IRB 
institutional review board 
IST 
internal safety team 
IVRS 
interactive voice response system 
IWRS 
interactive web response system 
LLOQ 
lower limit of quantification 
LNP 
lipid nanoparticle 
LTFU 
lost to follow-up 
M 
month 
MAAE 
medically attended adverse event 
MedDRA 
Medical Dictionary for Regulatory Activities 
mRNA 
messenger ribonucleic acid 
NH 
Northern Hemisphere 
NIMP 
noninvestigational medicinal product 
NP 
nasopharyngeal 
POCBP 
person of childbearing potential 
PONCBP 
person of nonchildbearing potential 
PP 
per protocol 
RSV 
respiratory syncytial virus 
SAE 
serious adverse event 
SAP 
statistical analysis plan 
SARS-CoV-2 
severe acute respiratory syndrome coronavirus 2 
SC 
safety call 
SoA 
Schedule of Assessments 
ULOQ 
upper limit of quantification 
USV 
unscheduled visit 
UTR 
untranslated region 
WHO 
World Health Organization 
 

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1. 
PROTOCOL SUMMARY 
1.1. 
Protocol Synopsis 
Protocol Title: 
A Phase 2, randomized, active-controlled, observer-blind, dose-ranging study to evaluate the 
safety, reactogenicity, and immunogenicity of mRNA vaccine candidate variations in healthy 
adults 18 to 49 years of age. 
Brief Title: 
Study to evaluate the safety, reactogenicity, and immunogenicity of mRNA vaccine candidate 
variations in healthy adults 18 to 49 years of age. 
Regulatory Agency Identifier Number: 
Registry 
ID 
FDA 
IND 028259 
Rationale: 
The aim of this Phase 2 study is to identify common or unique adaptive and innate immune 
signals or inflammatory biomarkers with predictive value for mRNA vaccine-induced 
immunogenicity and/or reactogenicity to support the Sponsor’s mRNA-based vaccine platform 
and mRNA-1010 vaccine development. This study will be performed in an exploratory manner 
 
 
 
 
 
 
Objectives and Endpoints: 
Objectives 
Endpoints 
Primary 
• To evaluate the safety and 
reactogenicity of mRNA-1010 vaccine 
candidate variations. 
• Solicited local and systemic ARs through 7 days after 
study intervention. 
• Unsolicited AEs through 28 days after study 
intervention. 
• Medically attended AEs from Day 1 to EoS. 
• AESIs from Day 1 to EoS. 
• SAEs from Day 1 to EoS. 
• AEs leading to study or treatment discontinuation from 
Day 1 to EoS. 
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Objectives 
Endpoints 
Secondary 
• To evaluate the humoral 
immunogenicity of mRNA-1010 
vaccine candidate variations at 
evaluable humoral immunogenicity 
timepoints. 
• GMT at indicated timepoints as measured by HAI assay. 
• GMFR, comparing each timepoint with D1 (Baseline) as 
measured by HAI assay. 
• Percentage of participants with seroresponsea for 
mRNA-1010 at indicated timepoints, as measured by 
HAI assay. 
 
 
Abbreviations: AE=adverse event; AESI=adverse events of special interest; AR=adverse reaction; D=day; 
EoS=end-of-study; GMFR=geometric mean fold rise; GMT=geometric mean titer; HAI=hemagglutination 
inhibition; LLOQ=lower limit of quantification; SAE=serious adverse event. 
a. 
Vaccine seroresponse is defined as an increase of antibody titers and concentrations from predose below the 
LLOQ to ≥4 × LLOQ, or at least a 4-fold rise if predose is ≥LLOQ. 
Overall Design Synopsis: 
This will be a randomized, observer-blind, Phase 2 study to evaluate the safety, reactogenicity 
and immunogenicity of mRNA-1010 vaccine candidate variations using a systems biology 
approach in healthy adults 18 to 49 years of age. 
Approximately 270 participants will be randomly assigned in a ratio of 2:1:2:1:1:2 to one of 
6 study arms to receive one of the following treatments: 
• mRNA-1010 at 1 dose level 
 administered as a single dose. 
• mRNA-1010.4 at 1 of 2 dose levels 
 administered as a single dose. 
• mRNA-1010.6 at 1 of 3 dose levels 
 administered as a single dose. 
 
 
 
Enrollment in the study arms will proceed in parallel. 
Except for appropriately delegated unblinded pharmacists, vaccine administrators, and monitors, 
all personnel involved in the conduct of the study will remain blinded to individual treatment 
assignment until planned study unblinding or EoS. 
Safety monitoring for this study will include the blinded study team members, including, at least, 
the Sponsor Medical Monitor, a CRO Medical Monitor, and an unblinded IST. The unblinded 
IST will comprise 3 members who are not directly involved in the conduct of this study. The 
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study team will conduct ongoing blinded safety reviews during the study and will be responsible 
for notifying the unblinded IST in case of potential safety signal events. Details regarding 
composition, responsibilities, and procedures of the IST will be presented in the IST charter. 
An independent CEAC of medically qualified personnel, including cardiologists, will review all 
suspected cases of myocarditis and pericarditis to determine if they meet CDC criteria of 
“probable” or “confirmed” events which are reported in ongoing interventional clinical trials per 
the CEAC charter. 
Brief Summary: 
The study aims to identify common or unique adaptive and innate immune signals or 
inflammatory biomarkers with predictive value for immunogenicity and/or reactogenicity of 
mRNA-1010, mRNA-1010.4 and mRNA-1010.6 in healthy adult participants 18 to 49 years of 
age. 
Study details include: 
• Study visits for all participants will consist of a Screening Visit (up to 28 days before 
the D1 visit), a Study Intervention Visit at D1, and Clinic Visits 
 
 
 
• All participants will be asked to complete an eDiary for solicited ARs for 7 days (ie, 
the day of study intervention dosing and 6 subsequent days). 
• Frequent blood samples will be collected for the first 7 days to support the 
exploratory objective of the study. 
• Collection of all AEs will be through 28 days after study intervention dosing (ie, the 
day of study intervention dosing and 27 subsequent days). Collection of MAAEs, 
AESI, SAEs, and AEs leading to discontinuation from study participation will 
continue through 
/EoS. 
Number of Participants: 
Approximately 270 participants will be enrolled. 
Note: Enrolled means participants’ or their legally acceptable representatives’, agreement to 
participate in a clinical study following completion of the informed consent process and 
screening. Potential participants who are screened for the purpose of determining eligibility for 
the study, but do not participate in the study, are not considered enrolled, unless otherwise 
specified by the protocol. A participant will be considered enrolled if the informed consent is not 
withdrawn prior to participating in any study activity after screening. 
Study Arms and Duration: 
• The study will comprise 6 study arms. 
• The total duration of study participation is up to 7 months from the Screening Visit. 
1.2. 
Schema 
Not Applicable.
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1.3. 
Schedule of Activities 
The SoA is listed in Table 1. 
Table 1: 
Schedule of Activities 
Visit Number 
 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
USVa 
Type of Visit 
C 
C 
C 
C 
C 
C 
C 
SC 
C 
SC 
SC 
C 
C 
Month Timepoint 
 
 
Study Visit Day 
Screeningb 
Window 
Allowance (Days) 
-28 
NA 
NA 
0 
±1 
-1 to 
+3 
-7 to 
+3 
±5 
±5 
±5 
±5 
±14 
NA 
Days from Last 
Study 
Intervention 
 
ICF, 
demographics, 
concomitant 
medications, 
medical history 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
Inclusion/exclusion 
criteria 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
Physical 
examinationd 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
Vital signse 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
Pregnancy testingf 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
Blood for humoral 
immunogenicityg 
 
X 
 
 
 
X 
X 
 
X 
 
 
X 
 
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Visit Number 
 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
USVa 
Type of Visit 
C 
C 
C 
C 
C 
C 
C 
SC 
C 
SC 
SC 
C 
C 
Month Timepoint 
 
 
Study Visit Day 
Screeningb 
Window 
Allowance (Days) 
-28 
NA 
NA 
0 
±1 
-1 to 
+3 
-7 to 
+3 
±5 
±5 
±5 
±5 
±14 
NA 
Days from Last 
Study 
Intervention 
 
NP swab for virus 
detectionh 
 
X 
 
 
 
 
 
 
 
 
 
 
X 
Randomization 
 
X 
 
 
 
 
 
 
 
 
 
 
 
Study intervention 
(including 30-
minute postdosing 
observation period) 
 
X 
 
 
 
 
 
 
 
 
 
 
 
eDiary activation 
for recording 
solicited ARs 
(7 days)i 
 
X 
 
 
 
 
 
 
 
 
 
 
 
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Visit Number 
 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
USVa 
Type of Visit 
C 
C 
C 
C 
C 
C 
C 
SC 
C 
SC 
SC 
C 
C 
Month Timepoint 
 
 
Study Visit Day 
Screeningb 
Window 
Allowance (Days) 
-28 
NA 
NA 
0 
±1 
-1 to 
+3 
-7 to 
+3 
±5 
±5 
±5 
±5 
±14 
NA 
Days from Last 
Study 
Intervention 
 
Review of eDiary 
ARsj 
 
 
 
 
 
X 
 
 
 
 
 
 
 
Follow-up safety 
callsk 
 
 
 
 
 
 
 
X 
 
X 
X 
 
 
Unsolicited AEsl 
 
X 
X 
X 
X 
X 
X 
 
 
 
 
 
 
SAEs 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
AESIs, MAAEs, 
and AEs leading to 
withdrawal from 
the studym 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Concomitant 
medications and 
nonstudy 
vaccinationsm 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Abbreviations: AE=adverse event; AESI=adverse event of special interest; AR=adverse reaction; BMI=body mass index; C=clinic; COVID-19=coronavirus 
disease 2019; D=Day; EoS=end-of-study; eDiary=electronic diary; FDA=Food and Drug Administration; FSH=follicle-stimulating hormone; ICF=informed 
consent form; M=month; MAAE=medically attended AE; NA=not applicable; NP=nasopharyngeal; SAE=serious adverse event; SC=safety call; 
USV=unscheduled visit. 
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Note: In accordance with “FDA Guidance on Conduct of Clinical Trials of Medical Products during COVID-19 Public Health Emergency”(DHHS 2020), 
Investigators may convert study site visits to telemedicine visits with the approval of the Sponsor. 
a. 
Participants may experience AEs that necessitate a USV. Additional examinations may be conducted at these visits as necessary to ensure the safety and 
well-being of participants during the study. 
b. 
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. If a participant returns for the D1 visit more than 28 days after their Screening Visit for any reason and 
continues to provide consent to participate in the study, the participant may be rescreened, for study eligibility. All assessments for eligibility must be 
repeated. 
c. 
A blood draw will be collected at 6 hours post vaccine injection on D1. 
d. 
A full physical examination, including height, weight, and BMI will be performed at Screening. Symptom-directed physical examinations may be performed 
at other timepoints at discretion of the Investigator. On each dosing day before injection, 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 study visits should be reported as an MAAE. 
e. 
Vital signs measurements: Systolic and diastolic blood pressures, pulse 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 at least 30 minutes after vaccination. Vital signs 
may be collected at other clinic visits in conjunction with a symptom-directed physical examination. 
f. 
A pregnancy test either via blood or point-of-care urine 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. If a urine test cannot be confirmed as negative (eg, an ambiguous result), a serum pregnancy test is required. The participant’s FSH level may be 
measured at the Screening Visit, as necessary, and at the discretion of the Investigator, to confirm postmenopausal status. 
g. 
D1 (Baseline) blood samples for 
 
 
h. 
An NP swab specimen for viral respiratory pathogens will be collected prior to the study intervention administration on Day 1. At USVs participants with 
symptoms of respiratory tract infection may be tested by NP swab for respiratory viruses at the Investigator’s discretion to include influenza, RSV and 
SARS-CoV-2, which may impact analyses of reactogenicity and immunogenicity. 
i. 
eDiary entries will be recorded by the participant at approximately 30 minutes after vaccination while at the clinic with instruction provided by study staff. 
Study participants will continue to record in the eDiary each day, preferably in the evening and at the same time each day, on the day of vaccination and for 
6 days following vaccination. Any solicited AR that is ongoing beyond Day 7 will be reported until resolution. 
j. 
Solicited ARs recorded in the eDiaries that is ongoing beyond 7 days after injection will be followed up by the study site staff at the next scheduled 
telephone call or at the next study site visit. Any medication recorded in eDiaries that is taken to prevent or treat pain or fever will also be reviewed at this 
time. 
k. 
Trained study personnel will call all participants to collect information relating to any MAAEs, AESIs, AEs leading to withdrawal from the study, SAEs, 
information on concomitant medications associated with those events; receipt of any nonstudy vaccinations; and receipt of any systemic steroids, 
immunosuppressive therapies (drugs or biologics), immunoglobulins, and/or blood products. 
l. 
All unsolicited AEs will be recorded starting the day of each study intervention, and through 28 days following each study intervention. 
m. 
All concomitant medications will be recorded through 28 days after vaccination. All concomitant medications relevant to or for the treatment of the SAE, 
AESI, MAAE, or AE leading to study withdrawal will be recorded from D1 through EoS. Any nonstudy vaccinations will be recorded from D1 through EoS. 
 
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2. 
INTRODUCTION 
2.1. 
Study Rationale 
The aim of this Phase 2 study is to identify common or unique adaptive and innate immune 
signals or inflammatory biomarkers with predictive value for mRNA vaccine-induced 
immunogenicity and/or reactogenicity to support the Sponsor’s mRNA-based vaccine platform 
and mRNA-1010 vaccine development. 
 
 
 
 
 
 
2.2. 
Background 
ModernaTX, Inc. (the Sponsor) has developed a proprietary vaccine platform based on mRNA 
delivered through LNPs. The platform is based on the principle and observations that cells in 
vivo can take up LNP-encapsulated mRNA, translate it, and then express protein antigen(s) on 
the cell surface or secrete the antigens. The intracellularly delivered mRNA does not enter the 
cellular nucleus or interact with the genome, is nonreplicating, and is expressed transiently. 
Strongly encouraged by the successful development of its mRNA-based SARS-CoV-2 vaccine 
(mRNA-1273; Spikevax®), the Sponsor is currently using the mRNA/LNP-based vaccine 
delivery platform to develop vaccines against multiple viruses, including influenza 
(mRNA-1010), RSV (mRNA-1345), and cytomegalovirus (mRNA-1647). 
mRNA-1010 is an LNP-encapsulated, mRNA-based, prophylactic vaccine containing 4 mRNAs 
in an equivalent mRNA mass ratio that encode membrane-bound HA of the 4 different influenza 
strains, recommended by the WHO for 2022-2023 NH cell or recombinant based vaccines. The 
Sponsor has completed a Phase 1/2 study of mRNA-1010 (NCT04956575) at dose levels up to 
 and is now conducting several Phase 3 studies at a 
 dose level (NCT05415462 and 
NCT05566639). 
This study will evaluate several versions of the Sponsor’s seasonal influenza mRNA vaccine 
candidate (mRNA-1010) that are currently being evaluated in separate clinical Phase 1/2 
(mRNA-1083-P101) and Phase 3 development studies (mRNA-1010-P303) for their ability to 
further optimize the immunogenicity and tolerability of the mRNA-1010 vaccine. 
 
 
 
 
Additional details of mRNA-1010 are provided in the IB. 
2.3. 
Benefit/Risk Assessment 
2.3.1. 
Risk Assessment 
There have been very rare (<1 in 10,000 recipients) reports of myocarditis and pericarditis 
occurring after vaccination with COVID-19 vaccines, including mRNA vaccines. The majority 
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of the cases have been reported in adolescents and young males shortly after the second or 
subsequent doses of the vaccine. These are typically mild cases, and individuals tend to recover 
within a short time following conservative treatment (including rest, NSAIDs, and/or colchicine). 
Healthcare professionals and study participants should be alert to the signs and symptoms of 
myocarditis and pericarditis (Gargano et al 2021). It is not known whether the risk of myocarditis 
or pericarditis is increased following additional doses of other non-COVID mRNA vaccines. 
Safety and reactogenicity data from multiple studies with mRNA-1010 (NCT04956575, 
NCT05415462, and NCT05566639) have revealed no safety concerns to date. Additional details 
are provided in the IB. 
2.3.2. 
Benefit Assessment 
Participants will obtain information about their general health status through the medical 
evaluations/assessments associated with this study (eg, physical examination, vital signs 
measurement, and symptom-directed physical examination). 
Participants will be contributing to the process of developing a new potentially prophylactic 
measure for infection with influenza or other pathogens. 
2.3.3. 
Overall Benefit/Risk Conclusion 
Considering the safety data for mRNA-1010 to date, the Sponsor considers the potential benefits 
of participation to exceed the risks. 

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3. 
OBJECTIVES AND ENDPOINTS 
Table 2: 
Objectives and Endpoints 
Objectives 
Endpoints 
Primary 
• To evaluate the safety and 
reactogenicity of mRNA-1010 vaccine 
candidate variations. 
• Solicited local and systemic ARs through 7 days after 
study intervention. 
• Unsolicited AEs through 28 days after study 
intervention. 
• Medically attended AEs from Day 1 to EoS. 
• AESIs from Day 1 to EoS. 
• SAEs from Day 1 to EoS. 
• AEs leading to study or treatment discontinuation from 
Day 1 to EoS. 
Secondary 
• To evaluate the humoral 
immunogenicity of mRNA-1010 
vaccine candidate variations at 
evaluable humoral immunogenicity 
timepoints. 
• GMT at indicated timepoints as measured by HAI assay. 
• GMFR, comparing each timepoint with D1 (Baseline) as 
measured by HAI assay. 
• Percentage of participants with seroresponsea for 
mRNA-1010 at indicated timepoints, as measured by 
HAI assay. 
Abbreviations: AE=adverse event; AESI=adverse events of special interest; AR=adverse reaction; D=day; 
EoS=end-of-study; GMFR=geometric mean fold rise; GMT=geometric mean titer; HAI=hemagglutination 
inhibition; LLOQ=lower limit of quantification; SAE=serious adverse event. 
a. 
Vaccine seroresponse is defined as an increase of antibody titers and concentrations from predose below the 
LLOQ to ≥4 × LLOQ, or at least a 4-fold rise if predose is ≥LLOQ. 
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4. 
STUDY DESIGN 
4.1. 
Overall Design 
This will be a randomized, observer-blind, Phase 2 study to evaluate the safety, reactogenicity 
and immunogenicity of mRNA-1010 vaccine candidate variations using a systems biology 
approach in healthy adults 18 to 49 years of age. 
Three mRNA-1010 vaccine candidate versions will be evaluated (Table 3): 
• mRNA-1010:
 
 
 
 
• mRNA-1010.4: 
 
 
• mRNA-1010.6: 
 
 
 
 
 
This study will initially enroll approximately 270 participants 18 to 49 years of age. Participants 
will be randomly assigned to study arms 1, 2, 3, 4, 5, and 6 in a ratio of 2:1:2:1:1:2 to receive a 
single dose of 1 of the 3 mRNA-1010 vaccine candidate variations (ie, mRNA-1010, 
mRNA-1010.4, or mRNA-1010.6). Randomization will be stratified by receipt of a 2022-2023 
NH influenza vaccine (Yes/No). The different arms will include different dose levels for 
mRNA-1010.4 and mRNA-1010.6. See Table 4 for study arms and number of participants per 
study arm. 
Except for appropriately delegated unblinded pharmacists, vaccine administrators, and monitors, 
all personnel involved in the conduct of the study will remain blinded to individual treatment 
assignment until planned study unblinding. 
Study visits for all participants will consist of a Screening Visit (up to 28 days before the D1 
visit), a Study Intervention Visit at D1, and Clinic Visits 
 
 
 The duration of study participation for all participants is up to 7 months 
from the Screening Visit. Refer to the SoA (Table 1), for more details. 
Safety Oversight 
Safety monitoring for this study will include the blinded study team members, including, at least, 
the Sponsor Medical Monitor, a CRO Medical Monitor, a Clinical Safety Physician, and an 
unblinded IST. The unblinded IST will comprise 3 members who are not directly involved in the 
conduct of this study. The study team will conduct ongoing blinded safety reviews during the 
study and will be responsible for notifying the unblinded IST in case of potential safety signal 
events. Details regarding composition, responsibilities, and procedures of the IST will be 
presented in the IST charter. 
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An independent CEAC of medically qualified personnel, including cardiologists, will review all 
suspected cases of myocarditis and pericarditis to determine if they meet CDC criteria of 
“probable” or “confirmed” events which are reported in ongoing interventional clinical trials per 
the CEAC charter (Gargano et al 2021). 
4.2. 
Scientific Rationale for Study Design 
The study is designed as a randomized, observer-blind dose-ranging study to evaluate the safety, 
reactogenicity, and immunogenicity of mRNA vaccine candidate variations in healthy adults 
18 to 49 years of age. The randomized and observer-blind design will ensure unbiased collection 
of safety and immunogenicity data. 
This study will evaluate several versions of the Sponsor’s seasonal influenza mRNA vaccine 
candidate (mRNA-1010). 
 
 
 
 
 
 
This study will be performed in an exploratory manner 
 
 
 
 
 
 
4.3. 
Justification for Dose 
Participants will receive either 1 dose level of mRNA-1010 
 1 of 2 dose levels of 
mRNA-1010.4 
); or 1 of 3 dose levels of mRNA-1010.6 
 
administered on Day 1 (refer to Table 3). 
The selected dose levels in this study are based on the observed reactogenicity and 
immunogenicity profiles in clinical Phase 1/2 and Phase 3 studies conducted with mRNA-1010 
At least 15,000 adults have been dosed with mRNA-1010. No safety concerns were identified 
with mRNA-1010 dose levels up to 
 
4.4. 
End-of-Study Definition 
The EoS is defined as the date of the last visit of the last participant in the study or last scheduled 
procedure as shown in the SoA (Table 1) for the last participant in the study. 
A participant is considered to have completed the study if he or she has completed all parts of the 
study, including the last visit or scheduled procedure as shown in the SoA (Table 1). 
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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 
Participants are eligible to be included in the study only if all of the following criteria apply: 
Age 
1. Adults 18 to 49 years of age at the time of consent (Screening Visit) who, in the opinion 
of the Investigator, are in good health based on review of medical history and physical 
examination performed at screening. 
Sex and Contraceptive/Barrier Requirements 
2. A participant AFAB is eligible to participate if not pregnant or breastfeeding, and one of 
the following conditions applies: 
• Is a PONCBP as defined in Clinical Study Protocol, Appendix 4. 
OR 
• Is a POCBP and using an acceptable contraceptive method as described in 
Appendix 4 at least 28 days before the dose of study intervention and for at least 
3 months after the dose of study intervention. The Investigator should evaluate the 
potential for contraceptive method failure (eg, noncompliance, recently initiated) in 
relationship to the dose of study intervention. 
A POCBP must have a negative highly sensitive pregnancy test (urine or serum as 
required by local regulations) at the Screening Visit and again before the dose of 
study intervention if Day 1 is not on the same day as the Screening Visit (see 
Section 8.3.3). 
o If a urine test cannot be confirmed as negative (eg, an ambiguous result), a serum 
pregnancy test is required. If the serum pregnancy result is positive, the 
participant must be excluded from participation. 
The Investigator is responsible for review of medical history, menstrual history, and 
recent sexual activity to decrease the risk for inclusion of a participant with an early 
undetected pregnancy. 
Informed Consent 
3. Capable of giving signed informed consent as described in Section 10.1.3, which includes 
compliance with the requirements and restrictions listed in the ICF and in this protocol. 
4. Participant has provided written informed consent for participation in this study, 
including all evaluations and procedures as specified in this protocol. 

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5.2. 
Exclusion Criteria 
Participants are excluded from the study if any of the following criteria apply: 
Medical Conditions 
5. Participant has had close contact with someone with laboratory-confirmed influenza 
infection or with someone who has been treated with antiviral therapies for influenza (eg, 
Tamiflu®) within the past 5 days prior to D1. 
6. Participant has tested positive for influenza by local health authority-approved testing 
methods within 150 days prior to D1. 
7. Is acutely ill or febrile (temperature ≥38.0°C/100.4°F) within 72 hours prior to or at the 
Screening Visit or D1. Participants meeting this criterion may be rescheduled within the 
28-day Screening window and will retain their initially assigned participant number. 
8. 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 60 days prior to Screening and includes ongoing workup of an undiagnosed illness 
that could lead to a new diagnosis or condition. 
9. 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, because of immunosuppressive therapies (drugs or biologics) 
used to treat them, at the discretion of the Investigator. 
• Participants who have undergone surgical procedures within 7 days prior to Day 1 or 
are scheduled to undergo a surgical procedure within 28 days after study injection are 
also excluded. However, minor surgical procedures under local anesthesia 
(eg, excision of skin lesion) or diagnostic procedures (eg, colonoscopy) are allowed. 
10. Any medical, psychiatric, or occupational condition, including reported history of 
substance abuse, that may pose additional risk as a result of participation, or that 
could interfere with safety assessments or interpretation of results according to the 
Investigator’s judgment. 
11. Has a current or previous diagnosis of congenital or acquired immunodeficiency, to 
include HIV, immunosuppressive condition or immune-mediated (autoimmune) 
disease, asplenia, or recurrent severe infections, that requires treatment with systemic 
immunosuppressive drugs or biologics. Participants who use topical corticosteroids or 
other immunosuppressive agents (eg, topical calcineurin inhibitor) may be eligible for 
participation at the discretion of the Investigator. 
12. History of anaphylaxis, urticaria, or other significant AR requiring medical 
intervention after receipt of mRNA vaccines or any components of the mRNA-1010 
or influenza vaccines, including egg protein. 

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13. Any history of myocarditis or pericarditis. 
14. Reported history of coagulopathy or bleeding disorder considered a contraindication 
to IM injection or phlebotomy. 
15. Dermatologic conditions that could affect local solicited AR assessments (eg, tattoos, 
psoriasis patches affecting skin over the deltoid areas). 
16. Diagnosis of malignancy within the previous 2 years (excluding nonmelanoma skin 
cancer). 
17. History of Guillain-Barre syndrome. 
Prior/Concomitant Therapy 
18. Has received systemic immunosuppressive therapy (drugs or biologics) for more than 
14 days within 180 days prior to Screening (for corticosteroids ≥10 mg/day of 
prednisone equivalent) or is anticipating the need for systemic immunosuppressive 
treatment at any time during participation in the study. Inhaled, nasal, and topical 
steroids are allowed. Intra-articular and epidural steroid injections are not allowed 
within 28 days before and/or after study intervention dosing. 
19. Has received or plans to receive any licensed/authorized vaccine (to include 
SARS-CoV-2 vaccine) ≤28 days prior to or within 28 days after study intervention. 
20. Has received a licensed seasonal influenza vaccine within 5 months (150 days) prior 
to D1. 
21. Has participated in any investigational seasonal influenza vaccine study within 
12 months prior to D1. 
22. Is not aware of having received a seasonal influenza vaccine in the most recent 
influenza season (in the prior 12 months). 
23. Has been treated with antiviral therapies for influenza (eg, Tamiflu®) within 150 days 
prior to D1. 
24. Has received systemic immunoglobulins or blood products within 90 days prior to the 
Screening Visit or plans to receive the treatment during the study. In addition, 
participants who have received long-acting biological therapies that affect immune 
responses (eg, infliximab) within 90 days prior to the Screening Visit/Day 1, or plan 
to receive them, are also excluded. 
Prior/Concurrent Clinical Study Experience 
25. Has donated ≥450 mL of blood products within 28 days prior to the Screening Visit 
or plans to donate blood products during the study. 
26. Participated in an interventional clinical study within 28 days prior to the Screening 
Visit based on the medical history interview or plans to participate in an 
interventional clinical trial of an investigational vaccine or drug while participating in 
this study. 

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Other Exclusion Criteria 
27. Is working or has worked as study personnel or is an immediate family member or 
household member of study personnel, study site staff, or Sponsor personnel. 
5.3. 
Screen Failures 
A screen failure occurs when a participant who has consented to participate in the clinical study 
is not subsequently assigned to study intervention. A minimal set of screen failure information is 
required to ensure transparent reporting of screen failure participants to meet the CONSORT 
publishing requirements and to respond to queries from regulatory authorities. Minimal 
information includes demography, screen failure details, eligibility criteria, and any SAE. 
Individuals who do not meet the criteria for participation in this study (screen failure) may be 
rescreened once if they will be eligible upon rescreening. 
5.4. 
Criteria for Temporarily Delaying Administration of Study 
Intervention 
Body temperature (oral temperature preferred) must be measured on dosing visits before vaccine 
administration. The following events constitute criteria for delay of injection, and if any of these 
events occur at the time scheduled for dosing, the participant may receive the study intervention 
at a later date, or the participant may be discontinued from dosing at the discretion of the 
Investigator (Section 7.1): 
• Acute moderate or severe infection with or without fever at the time of dosing. 
• Fever, defined as body temperature ≥38.0°C/≥100.4°F at the time of dosing. 
Participants with a minor illness without fever, as assessed by the Investigator, can be 
vaccinated. 
Participants with a fever of ≥38.0°C/≥100.4°F will be contacted within the time window 
acceptable for participation and re-evaluated for eligibility. If the Investigator determines that the 
participant’s health on the day of dosing temporarily precludes injection, the visit should be 
rescheduled within the allowed interval for that visit. 

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6. 
STUDY INTERVENTIONS AND CONCOMITANT THERAPY 
Study interventions are all prespecified investigational and NIMPs, medical devices, and other 
interventions (eg, surgical and behavioral) intended to be administered to the study participants 
during the study conduct. 
6.1. 
Study Interventions Administered 
The study interventions administered are listed in Table 3. 
Table 3: 
Study Interventions Administered 
Intervention 
Label 
mRNA-1010 
mRNA-1010.4 
mRNA-1010.6 
Intervention 
Description 
LNP dispersion encoding 4 seasonal influenza vaccine antigens, HAs, from the 
influenza strains recommended by the WHO for 2022-2023 NH cell- or 
recombinant-based influenza vaccines. 
All mRNAs are formulated in LNPs composed of 4 lipids and provided as a sterile 
liquid for injection, white to off white dispersion in appearance, in Tris buffer with 
sucrose, and sodium acetate at pH 7.5. 
Type 
Vaccine 
Appearance 
White to off-white dispersion for injection 
Dosage 
Strengths 
 
Single Dose 
 
 
Single Dose 
 
 
 
Single Dose 
Route of 
Administration 
IM Injection 
Use 
Experimental 
IMP and 
NIMP/AxMP 
IMP 
Packaging and 
Labeling 
All study interventions will be prepared, packaged, and labeled in accordance with 
the standard operating procedures of ModernaTX, Inc. or those of its designee, CFR 
Title 21, GMP guidelines, ICH and GCP guidelines, guidelines for Quality System 
Regulations, and applicable regulations. 
Abbreviations: AxMP=auxiliary medicinal products; CFR=code of federal regulation; GCP=good clinical practice: 
GMP=good manufacturing practice; HA=hemagglutinin; ICH=International Council for Harmonisation; 
IM=intramuscular; IMP=investigational medicinal product; LNP=lipid nanoparticles; NH=Northern Hemisphere; 
NIMP=noninvestigational medicinal product. 
Study Arms and Dosing Regimens 
The study arms and dosing regimens are listed in Table 4. 
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Table 4: 
Study Arms and Dosing Regimens 
Study 
Arm 
Group Name 
Antigens 
Dose 
(Total) 
N 
(Total) 
Dose 
Schedule 
1 
mRNA-1010 
(Single dose) 
Influenza HA, quadrivalent for NH 
60 
D1 
2 
mRNA-1010.4 
(Single dose) 
30 
D1 
3 
mRNA-1010.4 
(Single dose) 
60 
D1 
4 
mRNA-1010.6 
(Single dose) 
30 
D1 
5 
mRNA-1010.6 
(Single dose) 
30 
D1 
6 
mRNA-1010.6 
(Single dose) 
60 
D1 
Abbreviations: D=day; HA=hemagglutinin; mRNA=messenger ribonucleic acid; N=number; NH=Northern 
Hemisphere. 
6.2. 
Preparation, Handling, Storage, and Accountability 
1. The Investigator or designee must confirm appropriate conditions (eg, temperature) 
have been maintained during transit for all study intervention received, and any 
discrepancies are reported and resolved before use of the study intervention. 
2. Only participants enrolled in the study may receive study intervention, and only 
authorized site staff may supply, prepare, or administer study intervention. 
Note: Enrolled means participants’, or their legally acceptable representatives’, 
agreement to participate in a clinical study following completion of the informed 
consent process and screening. Potential participants who are screened for the 
purpose of determining eligibility for the study, but do not participate in the study, are 
not considered enrolled, unless otherwise specified by the protocol. A participant will 
be considered enrolled if the informed consent is not withdrawn prior to participating 
in any study activity after screening. 
3. All study interventions must be stored in a secure, environmentally controlled, and 
monitored (manual or automated) area in accordance with the labeled storage 
conditions with access limited to the Investigator and authorized site staff. 
4. The Investigator, institution, the head of the medical institution (where applicable), or 
authorized site staff is responsible for study intervention accountability, 
reconciliation, and record maintenance (ie, receipt, reconciliation, and final 
disposition records). 
5. Further guidance and information for the final disposition of unused study 
interventions are provided in the pharmacy manual. 
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6.3. 
Assignment to Study Intervention 
All participants will be centrally assigned to randomized study intervention using an 
IVRS/IWRS. Before the study is initiated, the telephone number and call-in directions for the 
IVRS and/or the log-in information and directions for the IWRS will be provided to each site. 
Study intervention will be dispensed as summarized in the SoA (Table 1). 
Returned study intervention should not be redispensed to the participants. 
6.4. 
Blinding 
Refer to Section 9.1 for additional details on blinding. 
This is an observer-blinded study. Except for appropriately delegated unblinded pharmacists, 
vaccine administrators, and monitors, all personnel involved in the conduct of the study will 
remain blinded to individual treatment assignment until planned study unblinding or EoS. 
The IVRS/IWRS will be programmed with blind-breaking instructions. In case of an emergency, 
the Investigator has the sole responsibility for determining if unblinding of a participants’ 
intervention assignment is warranted. Participant safety must always be the first consideration in 
making such a determination. If the Investigator decides that unblinding is warranted, the 
Investigator may, at the Investigator’s discretion, contact the Sponsor to discuss the situation 
prior to unblinding a participant’s intervention assignment unless this could delay emergency 
treatment for the participant. If a participant’s intervention assignment is unblinded, the Sponsor 
must be notified within 24 hours of this occurrence. The date and reason for the unblinding must 
be recorded. 
Sponsor safety staff may unblind the intervention assignment for any participant with an SAE. If 
the SAE requires that an expedited regulatory report be sent to one or more regulatory agencies, 
a copy of the report identifying the participant’s intervention assignment may be sent to 
Investigators in accordance with local regulations and/or Sponsor policy. 
6.5. 
Study Intervention Compliance 
The study intervention will be administered at the study site under direct observation of 
medically qualified study staff, and study intervention administration will be appropriately 
recorded (date and time) in the eCRF. Qualified staff will confirm that the participant has 
received the entire dose of the study intervention. If a participant does not receive the study 
intervention, the reason for the missed dose will be recorded. Data will be reconciled with site 
accountability records to assess compliance. 
The study site staff are responsible for ensuring that participants comply with the allowed study 
visit windows. If a participant misses a visit, every effort should be made to contact the 
participant and complete a visit within the defined visit window specified in the SoA (Table 1). 
If a participant does not complete a visit within the time window, that visit will be classified as a 
missed visit, and the participant will continue with subsequent scheduled study visits. All safety 
requirements of the missed visit will be captured and included in the subsequent visit. 

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6.6. 
Dose Modification 
No dose modifications are allowed. 
6.7. 
Continued Access to Study Intervention after End-of-Study 
There will be no access to study intervention after EoS. 
6.8. 
Treatment of Overdose 
Because the study intervention is to be administered by a healthcare provider, it is unlikely that 
an overdose will occur. 
In the event of an overdose, the Investigator should: 
• Evaluate the participant to determine, in consultation with the Medical Monitor, if 
possible, whether study intervention should be interrupted or whether the dose should 
be reduced. 
• Closely monitor the participant for any AE/SAE and laboratory abnormalities until 
the last safety follow-up visit. 
• Report any signs or symptoms associated with the overdose as an AE and record 
details in the relevant AE/SAE sections in the eCRF. 
• Document the quantity of the excess dose in the eCRF. 
Dose deviations will be tracked as protocol deviations. 
6.9. 
Prior and Concomitant Therapy 
Prior Medications and Therapies 
The following prior medications and therapies must be recorded in the eCRF: 
• All 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. 
• Any licensed seasonal influenza vaccine administered in the prior 12 months. 
• Any licensed/authorized or investigational COVID-19 vaccine administered at any 
time before study intervention administration. 
• Any investigational influenza or RSV vaccine administered at any time before study 
intervention administration. 
6.9.1. 
Concomitant Medications and Therapies 
At each study visit (including SCs), study site staff must question the participant regarding any 
medications taken and nonstudy vaccinations received by the participant and record the 
following information in the eCRF along with the reason for use, dates of administration 
including start and end dates and dosage information including dose and frequency: 

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• All concomitant medications administered through 28 days (the day of study 
vaccination and the subsequent 27 days) after study vaccine administration. 
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 nonstudy vaccinations administered from Screening through EoS. 
• Systemic steroids, immunosuppressive therapy (drugs or biologics), 
immunoglobulins, and/or blood products administered from Screening through EoS. 
• Any concomitant medications or vaccines relevant to or for the treatment of an AESI, 
MAAE, or AE leading to study or treatment discontinuation will be recorded from the 
first dose at Day 1 through the EoS. 
• Any concomitant medications or vaccines relevant to or for the treatment of a SAE 
will be recorded from the signing of ICF through the EoS. 
The Medical Monitor should be contacted if there are any questions regarding concomitant or 
prior therapy. 
The participant will be asked in the eDiary if they have taken any antipyretic or analgesic 
medication to treat or prevent fever or pain within 7 days after the study vaccination, including 
the days of injection. Reported antipyretic or analgesic medications should be recorded in the 
source document by the study site staff during the study visits after vaccination or via other 
participant interactions (eg, telephone calls). 
Concomitant medications (including vaccinations) will be coded using WHODrug Global. 
It is the Investigator’s responsibility to ensure that details regarding the concomitant medications 
are adequately recorded in the eCRF. 
All medication and interventions necessary for the appropriate care of the study participant 
should be administered and appropriately documented along with the AE for which the treatment 
was initiated. 
6.9.2. 
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 PP analysis. 
Analysis sets are described in Section 9.4. 
• Any investigational or nonregistered product (drug or vaccine) other than the study 
vaccine used during the study period. 
• Systemic immunosuppressive therapy (drugs or biologics) administered chronically 
(ie, more than 14 days in total) during the study period. For glucocorticosteroids, this 
will mean that prednisone ≥10 mg/day or the equivalent is not permitted. Inhaled, 
nasal, and topical steroids are allowed. Intra-articular and epidural steroid injections 
within 28 days after study intervention dosing. 
• An authorized or licensed vaccine, including SARS-CoV-2 vaccine, administered 
28 days before and after study intervention. 

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• Long-acting immunosuppressive therapy (drugs or biologics) administered at any 
time during the study period (eg, infliximab). 
• Immunoglobulins and/or any blood products administered during the study period. 

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7. 
DISCONTINUATION OF STUDY INTERVENTION AND 
PARTICIPANT DISCONTINUATION/WITHDRAWAL 
Discontinuation of specific sites or of the study as a whole are detailed in Section 10.1.10. 
7.1. 
Discontinuation of Study Intervention 
Not applicable. 
7.2. 
Participant Discontinuation/Withdrawal from the Study 
• A participant may withdraw from the study at any time at the participant’s own 
request for any reason (or without providing any reason). 
• A participant may be withdrawn at any time at the discretion of the Investigator for 
safety, behavioral, or compliance reasons. 
• At the time of discontinuing from the study, if possible, an early discontinuation visit 
should be conducted, as shown in the SoA (Table 1). See the SoA (Table 1) for data 
to be collected at the time of study discontinuation and follow-up and for any further 
evaluations that need to be completed. 
• A participant who withdraws from the study will not be replaced. 
• 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. 
• If a participant withdraws from the study, the participant may request destruction of 
any samples taken and not tested, and the Investigator must document this in the site 
study records. 
• The Sponsor will continue to retain and use all research results that have already been 
collected for the study evaluation. All biological samples that have already been 
collected may be retained and analyzed at a later date (or as permitted by local 
regulations). 
From an analysis perspective, a “withdrawal” from the study refers to a situation wherein a 
participant does not return for the final visit foreseen in the protocol. All data collected until the 
date of withdrawal or last contact of the participant will be used for the analysis. A participant is 
considered a “withdrawal” from the study when no study procedure has occurred, no follow-up 
has been performed, and no further information has been collected for that participant from the 
date of withdrawal or last contact. 
Information relative to the withdrawal will be documented in the EDC. The Investigator will 
document whether the decision to withdraw a participant from the study was made by a 
participant or by the Investigator as well as which of the following possible reasons was 
responsible for withdrawal: 
• AE. 
• SAR/reactogenicity. 

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• Death. 
• LTFU. 
• Noncompliance with study procedures. 
• Physician decision. 
• Pregnancy. 
• Protocol deviation. 
• Screen failure. 
• Study terminated by Sponsor. 
• Withdrawal by participant. 
• Other. 
Participants who are withdrawn from the study because of an AE (including SAE, MAAE and 
AESI) or SAR/Reactogenicity event must be clearly distinguished from participants who are 
withdrawn for other reasons. Investigators will follow-up with participants who are withdrawn 
from the study because of an AE/SAE/AESI/MAAE or SAR/reactogenicity event until resolution 
of the event. 
7.3. 
Lost to Follow-up 
If a participant does not complete a visit within the time window specified in the SoA (Table 1), 
every effort should still be made to complete the assessments for that visit (even though outside 
of the defined visit window); the participant will continue with subsequent scheduled study visits 
per their original schedule (ie, relative to their Day 1 visit). If a participant still does not 
complete the visit after all these efforts, the visit will be classified as missed and all safety 
requirements of the missed visit will be captured and included in the subsequent visit. 
A participant will be considered LTFU if the participant repeatedly fails to return for scheduled 
visits and is unable to be contacted by the study site. 
The following actions must be taken if a participant fails to return to the clinic for a required 
study visit: 
• The site must attempt to contact the participant and reschedule the missed visit as 
soon as possible, counsel the participant on the importance of maintaining the 
assigned visit schedule and ascertain whether the participant wishes to and/or should 
continue in the study. 
• Before a participant is deemed 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 should be documented in the 
participant’s medical record. 
• Should the participant continue to be unreachable, the participant will be considered 
to have withdrawn from the study. 

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• A participant should be not considered LTFU until due diligence has been completed. 
7.4. 
Pause Rules 
Not applicable. 

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8. 
STUDY ASSESSMENTS AND PROCEDURES 
• Before performing any study procedures, all potential participants will sign an ICF 
(Section 10.1.3). 
• Study procedures and their timing are summarized in the SoA (Table 1). Protocol 
waivers or exemptions are not allowed. 
• Adherence to the study design requirements, including those specified in the SoA 
(Table 1), is essential and required for study conduct. 
• All screening evaluations must be completed and reviewed to confirm that potential 
participants meet all eligibility criteria. The Investigator will maintain a screening log 
to record details of all participants screened and to confirm eligibility or record 
reasons for screening failure, as applicable. 
• Procedures conducted as part of the participant’s routine clinical management (eg, 
blood count) and obtained before signing of the ICF may be utilized for screening or 
Baseline purposes provided the procedures met the protocol-specified criteria and 
were performed within the timeframe defined in the SoA (Table 1). 
• In the event of a significant study-continuity issue (eg, caused by a pandemic), 
alternate strategies for participant visits, assessments, medication distribution and 
monitoring may be implemented by the Sponsor or the Investigator, as per local 
health authority/ethics requirements. 
• Study results that could unblind the study will not be reported to investigative sites or 
other blinded personnel until the study has been unblinded. 
• The maximum amount of blood collected from each participant over the duration of 
the study, including any extra assessments that may be required, will not exceed 
blood limits specified by local regulations. 
• Repeat or unscheduled samples may be taken for safety reasons or for technical issues 
with the samples. Further details are provided in both the ICF and Laboratory 
Reference Manual. 
• If a visit cannot be scheduled within the indicated allowable window and/or the 
participant misses the visit, this is considered a protocol deviation. However, the visit 
should still be completed, if possible, to collect study data. Subsequent visits should 
be scheduled at the originally planned number of days after D1 defined in the SoA 
(Table 1). 
8.1. 
Demography 
Demographic information relating to the participant’s sex, age, and race will be recorded at 
Screening in the EDC. 
Medical history of each participant will be collected and recorded in the EDC. Significant 
findings that were present prior to the signing of the informed consent will also be included in 
the EDC. 

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8.2. 
Immunogenicity Assessments 
Planned timepoints for all humoral and cellular immunogenicity assessments are provided in the 
SoA (Table 1). The following analytes will be measured as appropriate: 
• Vaccine-specific humoral immune responses, including serum antibody levels as 
measured by the HAI assay. 
 
 
 
• 
 
 
 
 
8.3. 
Safety Assessments 
Safety assessments will include monitoring and recording of the following for each participant 
(see the SoA [Table 1] for details): 
• Solicited local and systemic ARs that occur during the 7 days following vaccine 
administration (ie, the day of study injection and 6 subsequent days). Solicited ARs 
will be recorded daily using eDiaries. 
• Unsolicited AEs observed or reported during the 28 days following each vaccine 
administration (ie, the day of study injection and 27 subsequent days). Unsolicited 
AEs are AEs that are not included in the protocol-defined solicited ARs. 
• AESIs, MAAEs, and AEs leading to discontinuation from study participation from 
D1 (poststudy intervention dosing) through EoS or discontinuation from the study. 
• SAEs from the signing of ICF through EoS or discontinuation from the study. 
• Vital sign measurements before and after study injection. 
• Physical examination findings. 
• Occurrences of pregnancy in participants will be collected after the start of study 
intervention and until the end of their participation in the study. All pregnancies must 
be followed to end of pregnancy. Pregnancy details and outcome data are to be 
collected beyond EoS, when required (ie, for pregnancies continuing beyond the EoS 
visit). 
• Concomitant medications and nonstudy vaccinations. 
8.3.1. 
Physical Examinations 
• Physical examination including height, weight, and BMI will be performed at the 
timepoints indicated in the SoA (Table 1). 
• A full examination will include assessment of skin, head, ears, eyes, nose, throat, 
neck, thyroid, lungs, heart, cardiovascular system, abdomen, lymph nodes, and 
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musculoskeletal system and extremities. Height and weight will also be measured and 
recorded as outlined in the SoA (Table 1). 
• Investigators should pay special attention to clinical signs related to previous serious 
illnesses. 
• On the day of study intervention administration, before administration, the arm 
receiving the injection should be examined, and the associated lymph node(s) should 
be evaluated. 
8.3.2. 
Vital Signs 
• Vital signs will be measured at the timepoints indicated in the SoA (Table 1). 
• Vital sign measurements include systolic and diastolic blood pressure, pulse rate, 
respiratory rate, and body temperature (oral being the preferred route). 
• The participant will be seated for at least 5 minutes before all measurements are 
taken. 
• On study intervention day, vital sign measurements will be collected once before 
study vaccine injection and at least 30 minutes after study vaccine injection (before 
participants are discharged from the study site). If vital signs are clinically 
concerning, participant should not be dosed. When applicable, vital sign 
measurements should be performed before blood collection. 
• Participants must not eat or drink anything hot or cold within 10 minutes before oral 
temperature is taken. 
• Participants who are febrile (fever is defined as a body temperature ≥38.0°C/100.4°F) 
before injection on dosing day must be rescheduled. Criteria for delay of study 
vaccine are provided in Section 5.4. Participants who are afebrile with minor illnesses 
may be injected at the discretion of the Investigator. If fever is clinically concerning, 
participant should not be dosed. 
• Abnormal vital sign measurements should be assessed by the Investigator to 
determine clinical significance and whether it should be reported as an AE. The 
Investigator will continue to monitor the participant with additional assessments until 
the vital sign value has reached the reference range, returns to the vital sign value at 
Baseline, is considered stable, or until the Investigator determines that follow-up is no 
longer medically necessary. 
8.3.3. 
Pregnancy Testing 
• Refer to Section 5.1 for pregnancy testing entry criteria. 
• Pregnancy testing (urine or serum as required by local regulations) should be 
conducted for all POCBP at the Screening Visit and before study intervention dosing 
on Day 1, if Day 1 is not at the same day as the Screening Visit (Table 1). 
• The FSH level may be measured at the Screening Visit as necessary, and at the 
discretion of the Investigator, to confirm postmenopausal status (Table 1). 

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• Additional serum or urine pregnancy tests may be performed, as determined 
necessary by the Investigator or required by local regulation, to establish the absence 
of pregnancy at any time during the participant’s participation in the study. 
8.3.4. 
Assessments for Respiratory Viral Infections 
NP swab specimen(s) for viral respiratory pathogens will be collected prior to study intervention 
dosing on Day 1. At USVs participants with symptoms of respiratory tract infection may be 
tested by NP swab for respiratory viruses at the Investigator’s discretion, to include influenza, 
RSV and SARS-CoV-2, which may impact analyses of reactogenicity and immunogenicity. 
8.3.5. 
Safety Calls 
An SC 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. SCs will follow a 
schedule for each participant, as shown in the SoA (Table 1). The participant will be interviewed 
according to the script about occurrence of MAAEs, SAEs, AESIs, AEs leading to withdrawal 
from the study, and concomitant medications associated with those events; receipt of any 
nonstudy vaccinations, and receipt of any systemic steroids, immunosuppressive therapy (drugs 
or biologics), immunoglobulins, and/or blood products. All safety information collected from the 
telephone call must be documented in the source documents as described by the participant and 
not documented on the script used for the telephone call. An unscheduled follow-up SC may be 
triggered if an eDiary record results in identification of a relevant safety event. An SC may 
trigger a USV. 
8.3.6. 
Use of Electronic Diaries 
At the time of consent, the participants must confirm they will be willing to complete an eDiary 
(for 7-day reactogenicity). The local and systemic ARs that will be solicited by the eDiary are 
described in Table 7. 
Solicited local and systemic reactogenicity ARs will be collected on the day of each study 
intervention and during the 7 days after study intervention (ie, the day of dosing and 
6 subsequent days). Details on the recording of local and systemic ARs are included in 
Section 8.4.6. 
At each dosing visit, participants will record data into the eDiary starting approximately 
30 minutes after dosing under supervision of the site staff to ensure successful entry of 
assessments. The 30-minute observation period is an opportunity for site staff to train the 
participant on eDiary completion requirements. The site staff will perform any retraining as 
necessary. 
At each dosing visit, participants will be instructed or reminded on thermometer usage to 
measure body temperature, ruler usage to measure injection site erythema (redness) and 
swelling/induration (hardness), and self-assessment for localized axillary (underarm) swelling or 
tenderness ipsilateral (on the same) side as the injection arm during the 7 days after study 
intervention. Daily oral temperature measurement should be performed at approximately the 
same time each day using the thermometer provided by the site staff. 

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The participant will be trained on how to complete the eDiary questions according to the SoA 
(Table 1) and also reminded to call the site immediately if they experience any new signs or 
symptoms. 
If a participant does not respond to the eDiary questions according to the SoA, site staff will 
follow-up with the participant. 
8.4. 
Adverse Events, Serious Adverse Events, and Other Safety 
Reporting 
The definitions of AEs and SAEs can be found in Section 10.3. 
The definitions of unsolicited and solicited AEs can be found in Section 10.3. 
The Investigator and any qualified designees are responsible for detecting, documenting, and 
recording events that meet the definition of an AE or SAE. The Investigator and any qualified 
designees shall be responsible for following up all AEs or SAEs or that caused the participant to 
discontinue the study intervention or study (see Section 7). This includes events reported by the 
participant (or, when appropriate, by a caregiver, surrogate, or the participant’s legally 
authorized representative). 
The method of recording, evaluating, and assessing causality of AEs and SAEs and the 
procedures for completing and transmitting SAE reports are provided in Section 10.3. 
8.4.1. 
Time Period and Frequency for Collecting AE and SAE Information 
All SAEs will be collected from the signing of ICF until the last day of study participation at the 
timepoints specified in the SoA (Table 1). 
All, AESIs, MAAEs, and AEs leading to withdrawal from the study will be collected from the 
start of study intervention until the last day of study participation at the timepoints specified in 
the SoA (Table 1). 
All other (unsolicited) AEs will be collected from the time of the administration of study 
vaccination through 28 days (the day of study vaccination and the subsequent 27 days) (see the 
SoA [Table 1]). 
Solicited ARs will be collected during the solicited period, for 7 days (the day of study 
vaccination and the subsequent 6 days). 
Non-serious medical occurrences that begin before the start of study intervention but after 
obtaining informed consent will be recorded as medical history/current medical conditions, not 
as AEs; however, if the condition worsens at any time during the study, it will be recorded and 
reported as an AE. 
All SAEs will be recorded and reported to the Sponsor or designee immediately and under no 
circumstance should this exceed 24 hours, as indicated in Section 10.3.5. 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 information on AEs or SAEs after conclusion of 
the study participation. However, if the Investigator learns of any SAE at any time after a 
participant has been discharged from the study, and the Investigator considers the event to be 

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reasonably related to the study intervention or study participation, the Investigator must promptly 
notify the Sponsor. 
8.4.2. 
Method of Detecting AEs and SAEs 
The Investigator is responsible for the documentation of AEs regardless of the 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, which requires 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. 
8.4.3. 
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. All SAEs and AESIs (as defined in Section 10.3.2 and 
Section 10.3.4, respectively) will be followed until resolution, stabilization, the event is 
otherwise explained, or the participant is LTFU (as defined in Section 7.3), even if the event 
continues beyond the participant’s EoS visit. Further information on follow-up procedures is 
provided in Section 10.3. 
8.4.4. 
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 toward 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, IRBs/IECs, and Investigators. 
• 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 IRB/IEC, if appropriate 
according to local requirements. 
• For expedited reporting purposes, the expectedness of SAEs will be assessed against 
the investigational treatment regimen the participant is receiving at the time of the 
event. AE terms not listed as expected events in the IB for investigational product 
will be considered unexpected. 
• Investigator safety reports must be prepared for SUSARs according to local 
regulatory requirements and Sponsor policy and forwarded to Investigators as 
necessary. 

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8.4.5. 
Pregnancy 
• The effects of the study intervention on the unborn child and/or newborn baby are not 
known. Therefore, is important that study participants are not pregnant and do not 
become pregnant during the study. 
• Pregnancy testing is scheduled to occur at the Screening Visit and Day 1, if Day 1 is 
not at the same day as the Screening Visit (Table 1). Participants who have a positive 
pregnancy test at the Screening Visit must not be enrolled and participants who have 
a positive pregnancy test at Day 1 must not receive the study intervention. Additional 
pregnancy testing may also be performed at any time during the study if required by 
local regulatory requirements, or at the discretion of the Investigator. 
• Details of all pregnancies in participants will be collected after the start of study 
intervention and until the end of their participation in the study. 
• If a pregnancy is reported, the Investigator will record pregnancy information on the 
appropriate form and submit it to the Sponsor within 24 hours of learning of the 
participant pregnancy. 
• Participants who have a positive pregnancy test after receiving study intervention 
should remain in the study and be followed-up for safety. 
• While pregnancy itself is not considered to be an AE or SAE, any pregnancy 
complication or elective termination of a pregnancy for medical reasons will be 
reported as an AE or SAE (refer to Section 10.3). 
• Abnormal pregnancy outcomes (eg, spontaneous abortion, fetal death, stillbirth, 
congenital anomalies, ectopic pregnancy) are considered SAEs and will be reported 
as such (refer to Section 10.3). 
• The participant will be followed to determine the outcome of the pregnancy. General 
pregnancy and outcome data may be collected beyond EoS (ie, for pregnancies 
continuing beyond EoS visit). 
8.4.6. 
Solicited Adverse Reactions 
Solicited ARs are a subset of AEs consisting of selected signs and symptoms that participants are 
asked to record/report. In this study, the solicited ARs are reactogenicity events. The term 
“reactogenicity” refers to the occurrence of transient adverse effects associated with vaccine 
administration. The eDiary will solicit daily participant reporting of ARs using a structured 
checklist. Participants will record such occurrences in the eDiary on the day of each study 
vaccine injection and 6 subsequent days. 
Severity grading of reactogenicity will occur automatically based on participant entry into the 
eDiary according to the grading scales presented in Appendix 3 (Section 10.3.5), which are 
modified from the Toxicity Grading Scales for Healthy Adult and Adolescent Volunteers 
Enrolled in Preventative Vaccine Clinical Trials (DHHS 2007). All solicited ARs (local and 
systemic) will be considered causally related to dosing. 

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Any solicited AR that meets any of the following criteria must be entered into the participant’s 
source document and must also be recorded by the study site staff in the EDC where 
reactogenicity is collected: 
• Solicited local or systemic ARs that were not recorded in the eDiary but reported to 
the study site/Investigator and is Grade 1 or greater. 
• Solicited local or systemic AR that results in a visit to a healthcare practitioner 
including USVs at the study site (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 
discontinuation). 
• Solicited local or systemic AR lasting beyond 7 days postinjection. 
• Solicited local or systemic AR that leads to participant discontinuation from study 
intervention. 
• Solicited local or systemic AR that otherwise meets the definition of an SAE 
(Section 10.3.2). 
If a participant reports a solicited AR with onset during the solicited period, but they did not 
record the event in the eDiary, then the event should be recorded by study staff in the EDC 
where reactogenicity is collected. 
If the event starts during the solicited period, but continues beyond 7 days after dosing, the 
participants should notify the site to provide an end date and close out the event in the EDC 
where reactogenicity is collected. 
If the participant reported an event that started after the solicited period (ie, beyond 7 days after 
dosing), it should be recorded as an unsolicited AE in the EDC. Causality for these events will be 
determined per assessment by the Investigator. 
8.4.7. 
Medically Attended Adverse Events 
A MAAE is an AE that leads to an unplanned visit to a healthcare practitioner. This would 
include visits to a study site for unscheduled assessments (eg, rash assessment, abnormal 
laboratory follow-up) and visits to healthcare practitioners external to the study site (eg, 
emergency room, urgent care, primary care physician). Investigators will review unsolicited AEs 
for the occurrence of any MAAEs. 
8.4.8. 
Adverse Events 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. 
AESI for this protocol are listed in Appendix 5. 
Investigators should report all events which fall into the following categories as an AESI per the 
reporting processes specified in Appendix 3. 

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8.4.8.1. 
Anaphylaxis 
All suspected cases of anaphylaxis associated with study intervention administration should be 
recorded as AESIs and reported as an SAE (Appendix 3), based on criteria for a medically 
important event, unless the event meets other serious criteria. For reporting purposes, a 
participant who displays signs/symptoms consistent with anaphylaxis as shown below should be 
reported as a potential case of anaphylaxis. This is provided as general guidance for Investigators 
and is based on the Brighton Collaboration case definition (Rüggeberg et al 2007). 
Anaphylaxis is an acute hypersensitivity 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. Anaphylaxis is a clinical syndrome characterized 
by: 
• Sudden onset AND 
• Rapid progression of signs and symptoms AND 
• Involving 2 or more organ systems, as follows: 
o Skin/mucosal: urticaria (hives), generalized erythema, angioedema, generalized 
pruritus with skin rash, generalized prickle sensation, red and itchy eyes. 
o Cardiovascular: measured hypotension, clinical diagnosis of uncompensated 
shock, loss of consciousness or decreased level of consciousness, evidence of 
reduced peripheral circulation. 
o Respiratory: bilateral wheeze (bronchospasm), difficulty breathing, stridor, upper 
airway swelling (lip, tongue, throat, uvula, or larynx), respiratory distress, 
persistent dry cough, hoarse voice, sensation of throat closure, sneezing, 
rhinorrhea. 
o Gastrointestinal: diarrhea, abdominal pain, nausea, vomiting. 
8.4.8.2. 
Myocarditis and/or Pericarditis 
A case of suspected, probable, or confirmed myocarditis, pericarditis, or myopericarditis should 
be reported as an AESI per Investigator’s medical assessment, even if it does not meet criteria 
per the CDC case definition below. The event should also be reported as an SAE if it meets 
seriousness criteria (Section 10.3.2). 
The Investigator’s medical judgment must be applied when assessing participants reporting 
symptoms concerning for myocarditis and/or pericarditis contained within the CDC case 
definition. Diagnostic evaluation (eg, EKG, echocardiogram) and laboratory testing 
(eg, troponin) included in the CDC definition (Table 9) should promptly be obtained if 
considered clinically indicated in any participant with concerning signs/symptoms. Referral to a 
cardiologist should be obtained in those with positive test results or clinically significant 
symptoms without other identifiable causes. Additional testing and evaluation may be indicated. 
The Investigator will submit any updated myocarditis, pericarditis or myopericarditis case data to 
the Sponsor within 24 hours of it being available. Cases of myocarditis and pericarditis will be 
followed until resolution of symptoms and abnormal test findings. Participants with events of 

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myocarditis and/or pericarditis will be discontinued from further vaccination but should continue 
to be followed in the study for safety as per the protocol. 
An independent CEAC will review all suspected cases of myocarditis, pericarditis, and 
myopericarditis which are reported in ongoing interventional clinical trials per the CEAC charter 
to determine if they meet CDC criteria for “probable” or “confirmed” events. (Section 10.1.6.2). 
The CDC Working Case Definitions are provided in Appendix 6 as guidance. 
8.5. 
Pharmacokinetics 
Pharmacokinetic parameters are not evaluated in this study. 
8.6. 
Pharmacodynamics 
Pharmacodynamic parameters are not evaluated in this study. 
8.7. 
Genetics 
 
 
 
 
8.8. 
Biomarkers 
 
 
 
 
 
 
 
 
 
8.9. 
Health Economics OR Medical Resource Utilization and Health 
Economics 
Health economics OR Medical resource utilization and health economics parameters are not 
evaluated in this study. 
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9. 
STATISTICAL CONSIDERATIONS 
This section summarizes the planned statistical analysis strategy and procedures for the study. 
The details of the statistical analyses will be provided in the SAP, which will be finalized before 
the clinical database lock for the study and treatment unblinding. Ad hoc exploratory analyses, if 
any, will be clearly identified in the CSR. 
9.1. 
Blinding and Responsibility for Analyses 
Blinding during the study will be conducted as described in Section 6.4, with the following 
exceptions: 
• Unblinded personnel (of limited number) will be assigned to vaccine accountability 
procedures and will prepare the study intervention for all participants. These 
personnel will have no study functions other than study intervention management, 
documentation, accountability, preparation, and administration. They will not be 
involved in participant evaluations and will not reveal the identity of the study 
intervention 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. 
• Unblinded study site staff will administer the study intervention. They will not be 
involved in assessments of any study endpoints. 
• Unblinded site monitors, not involved in other aspects of monitoring, will be assigned 
as the study intervention accountability monitors. They will have responsibilities to 
ensure that sites are following all proper study intervention accountability, 
preparation, and administration procedures. 
• An independent unblinded statistical and programming team will perform the 
preplanned primary analysis and the IA (Section 9.6.1). Sponsor team members will 
be unblinded for the primary analysis and the IA results and will not communicate the 
results to the blinded Investigators, study site staff, clinical monitors, or participants. 
• The IST may review unblinded data, as appropriate, to safeguard the interests of 
clinical study participants and to help ensure the integrity of the study. 
The dosing assignment will be concealed by having the unblinded pharmacy personnel prepare 
the study intervention in a secure location that is not accessible or visible to other study site staff. 
Only delegated unblinded study site staff will conduct the injection procedure. Once the injection 
is completed, only the blinded study site staff will perform further assessments and interact with 
the participants. Access to the randomization code will be strictly controlled at the pharmacy. 
The procedure for breaking the blind in the case of a medical emergency is provided in 
Section 6.4. 
9.2. 
Statistical Hypotheses 
No formal hypotheses will be tested in this study. 

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9.3. 
Sample Size Determination 
As there will be no hypothesis testing in this study, the number of proposed participants in 
Section 4.1 is considered sufficient to provide a descriptive summary of the safety, 
reactogenicity, and immunogenicity of the mRNA-1010 vaccine product variables. 
With 60 participants in the 
 study arms, there is an approximately 95% probability to 
observe at least 1 participant with an AE if the true incidence of the AE is 5%; if the true 
incidence rate is 3%, then the probability to observe an AE is approximately 84%. 
With 30 participants in the 
 study arms, there is an approximately 95% probability 
to observe at least 1 participant with an AE if the true incidence of the AE is 9.5%; if the true 
incidence rate is 7.5%, then the probability to observe an AE is approximately 90%. 
9.4. 
Analysis Sets 
Analysis sets are listed in Table 5. 
Table 5: 
Analysis Sets 
Participant Analysis Set 
Description 
Randomization Analysis Set 
The Randomization Analysis Set consists of all participants who are 
randomized. 
FAS 
The FAS consists of all randomized participants who receive the 
study intervention. Participants will be included in the study arm to 
which the participant is randomized. 
PPS for Immunogenicity 
The PPS consists of all participants in the FAS who comply with the 
injection schedule, comply with the timing of immunogenicity 
blood sampling to have a Baseline (D1) and at least 1 postinjection 
assessment, and have no major protocol deviations which impact the 
immune response. 
The PPS will be used as the primary analysis set for analyses of 
immunogenicity unless otherwise specified. 
Safety Set 
Safety Set consists of all participants who receive one dose of study 
intervention. The Safety Set will be used for all analyses of safety 
except for the solicited ARs. Participants will be included in the 
study arm corresponding to the study intervention that they actually 
received. 
Solicited Safety Set 
The Solicited Safety Set consists of all participants in the Safety Set 
who contribute any solicited AR data. 
The Solicited Safety Set will be used for the analyses of solicited 
ARs. Participants will be included in the treatment group 
corresponding to the study intervention that they actually received. 
Abbreviation: AR=adverse reaction; D=day; FAS=full analysis set; PPS=per protocol set. 
9.5. 
Statistical Analyses 
The SAP for the primary and secondary endpoints will be developed and finalized before 
database lock and will describe the preplanned statistical analysis details, data derivations, the 
CCI
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participant populations to be included in the analyses, and procedures for accounting for missing 
data. 
9.5.1. 
Baseline Characteristics and Demographics 
Demographic variables (eg, age, sex, race, ethnicity, height, weight, and BMI) and Baseline 
characteristics will be summarized by injection group and overall. 
Summary statistics (mean and standard deviation for continuous variables, and number and 
percentage for categorical variables) will be provided. 
9.5.2. 
Immunogenicity Analyses 
The analyses of immunogenicity will be based on the PPS. If the number of participants in the 
FAS and PPS differ (defined as the difference divided by the total number of participants in the 
PPS) by more than 10%, supportive analyses of immunogenicity may be conducted using the 
FAS. All immunogenicity analyses will be provided by study arm, at each timepoint unless 
otherwise specified. 
For the immunogenicity endpoints, the GM of antibody titers as measured by HAI assay with 
corresponding 95% CI at each timepoint will be provided by study arm. The GMFR of antibody 
titers as measured by HAI assay with corresponding 95% CI at each postdose timepoint over 
predose (D1) will be provided by study arm. The 95% CIs will be calculated based on the 
t-distribution of the log-transformed values and then back-transformed to the original scale. 
Descriptive summary statistics, including median, minimum, and maximum will also be 
provided. For calculation of GMTs reported as below the LLOQ will be replaced by 
0.5 × LLOQ. Values that are greater than the ULOQ will be converted to the ULOQ. 
Vaccine seroresponse rate will be provided with a 2-sided 95% CI using the Clopper-Pearson 
method by study arm. Vaccine seroresponse is defined as an increase of neutralizing antibody 
titers from predose below the LLOQ to ≥4 × LLOQ or at least a 4-fold rise if predose is ≥LLOQ. 
The number and percentage of participants with >2-, 3-fold increases from Baseline (if ≥LLOQ) 
or with >2-, 3-fold increases from LLOQ (if <LLOQ) will also be analyzed with 2-sided 95% CI 
using the Clopper-Pearson method by study arm, at each postdose timepoint. Further details will 
be described in the SAP. 
9.5.3. 
Safety Analyses 
All safety analyses will be based on the Safety Set, except summaries of solicited ARs, which 
will be based on the Solicited Safety Set. All safety analyses will be provided by vaccination 
group. Participants will be included in the study group corresponding to the study intervention 
that they actually received. 
Safety and reactogenicity will be assessed by clinical review of all relevant parameters including 
solicited ARs (local and systemic ARs), unsolicited AEs (including any clinically significant 
safety laboratory abnormalities), treatment-related AEs, severe AEs, SAEs, MAAEs, AESIs, and 
AEs leading to withdrawal from study participation. 
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 

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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 from study participation 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. 
The number of events of solicited ARs, unsolicited AEs, SAEs, MAAEs, and AESIs will be 
reported in summary tables accordingly. 
9.5.4. 
Exploratory Analyses 
 
 
 
 
 
 
 
9.6. 
Planned Analyses 
There will be at least one IA and a final CSR for this study. 
9.6.1. 
Interim Analysis 
 
 
 
9.6.2. 
Final Clinical Study Report 
The final CSR will include full unblinded analyses of all safety and immunogenicity with 
individual unblinded listings through EoS. 
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10. 
SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS 
10.1. 
Appendix 1: Regulatory, Ethical, and Study Oversight 
Considerations 
10.1.1. 
Regulatory and Ethical Considerations 
• This study will be conducted in accordance with the protocol and with the following: 
o Consensus ethical principles derived from international guidelines including the 
Declaration of Helsinki and Council for International Organizations of Medical 
Sciences international ethical guidelines. 
o Applicable ICH GCP guidelines. 
o Applicable laws and regulations. 
• The protocol, protocol amendments, ICF, IB, and other relevant documents (eg, 
advertisements) must be submitted to an IRB/IEC by the Investigator and reviewed 
and approved by the IRB/IEC before the study is initiated. 
• Any amendments to the protocol will require IRB/IEC approval before 
implementation of changes made to the study design, except for changes necessary to 
eliminate an immediate hazard to study participants. 
• Protocols and any substantial amendments to the protocol will require health 
authority approval prior to initiation except for changes necessary to eliminate an 
immediate hazard to study participants. 
• The Investigator will be responsible for the following, as applicable: 
o Providing written summaries of the status of the study to the IRB/IEC annually or 
more frequently in accordance with the requirements, policies, and procedures 
established by the IRB/IEC. 
o Notifying the IRB/IEC of SAEs or other significant safety findings as required by 
IRB/IEC procedures. 
o Providing oversight of the conduct of the study at the site and adherence to 
requirements of 21 CFR, ICH guidelines, the IRB/IEC, European regulation 
536/2014 for clinical studies, and all other applicable local regulations. 
10.1.2. 
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 required under 21 
CFR 54. 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 after completion of the study. 
The Sponsor, the CRO, and the study site are not financially responsible for further testing or 
treatment of any medical condition that may be detected during the screening process. In 

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addition, in the absence of specific arrangements, the Sponsor, the CRO, and the study site are 
not financially responsible for further treatment of the disease under study. 
10.1.3. 
Informed Consent Process 
• The Investigator or the Investigator’s representative will explain the nature of the 
study, including the risks and benefits, to the potential participant and answer all 
questions regarding the study. 
• Potential participants must be informed that their participation is voluntary. They will 
be required to sign a statement of informed consent that meets the requirements of 21 
CFR 50, local regulations, ICH guidelines, privacy and data protection requirements, 
where applicable, and the IRB/IEC or study center. 
• The medical record must include a statement that written informed consent was 
obtained before the participant was enrolled in the study and the date the written 
consent was obtained. The authorized person obtaining the informed consent must 
also sign the ICF. 
• Participants must be reconsented to the most current version of the ICF(s) during their 
participation in the study. 
• 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. 
The ICF will contain a separate section that addresses the use of remaining mandatory samples 
for optional exploratory research. The Investigator or authorized designee will explain to each 
participant the objectives of the exploratory research. Participants will be told that they are free 
to refuse to participate and may withdraw their consent at any time and for any reason during the 
storage period. The ICF will require the participant to clearly indicate whether or not the 
participant agrees to allow any remaining specimens to be used for exploratory research. 
10.1.4. 
Recruitment Strategy 
Enrollment targets will be established to ensure the participant population reflects those that are 
most at risk for the condition, or those that are most reflective of the general population, if 
appropriate. 
Participant recruitment and retention initiatives will be incorporated into the trial. These include, 
but are not limited to, services that provide a means to identify potential participants and direct 
them to participating clinical trial sites, participant support services such as concierge, and trial 
information and support collateral for both the participant and the site. 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 IRB/IEC. 
10.1.5. 
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; 

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participant names or any information which would make the participant identifiable 
will not be transferred. 
• The participant must be informed that their 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 who will be required to give consent for 
their data to be used as described in the informed consent. 
• The participant must be informed that their medical records may be examined by 
Clinical Quality Assurance auditors or other authorized personnel appointed by the 
Sponsor, by appropriate IRB/IEC members and by inspectors from regulatory 
authorities. 
• The contract between the Sponsor or designee and the study sites may specify 
responsibilities of the parties related to data protection, including handling of data 
security breaches and respective communication and cooperation of the parties. 
• Information technology systems used to collect, process, and store study-related data 
are secured by technical and organizational security measures designed to protect 
such data against accidental or unlawful loss, alteration, or unauthorized disclosure or 
access. 
10.1.6. 
Committees Structure 
10.1.6.1. Internal Safety team 
The Sponsor’s independent IST comprises 3 members, including clinical development 
physicians/clinicians and a safety physician, who are not involved in the study, and will oversee 
the safety of study participants in addition to the clinical development team in charge of the 
study. The IST may perform unblinded safety data reviews due to safety concerns that arise 
during the study, or as requested on ad hoc bases by the study team. Details regarding the 
composition, responsibilities, and procedures of the IST will be described in a charter. 
10.1.6.2. Cardiac Event Adjudication Committee 
An independent CEAC comprising medically qualified personnel, including cardiologists, will 
review all suspected cases of myocarditis and pericarditis, to determine if they meet CDC criteria 
for “probable” or “confirmed” events, which are reported in ongoing interventional clinical trials 
per the CEAC charter (Gargano et al 2021). Any cases that the CEAC assesses as representing 
probable or confirmed cases of myocarditis or pericarditis will be referred to the Sponsor, who 
will then determine if additional action is needed. The CEAC will operate under the rules of an 
approved charter that will be written and reviewed at the organizational meeting of the CEAC. 
Details regarding the CEAC composition, responsibilities, procedures, and frequency of data 
review will be defined in the charter. 
10.1.7. 
Dissemination of Clinical Study Data 
The Sponsor shares information about clinical studies and results on publicly accessible 
websites, based on international and local legal and regulatory requirements, and other clinical 
study disclosure commitments established by pharmaceutical industry associations. These 

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websites include clinicaltrials.gov, European Union clinical trial register, and some national 
registries. 
10.1.8. 
Data Quality Assurance 
• All participant data relating to the study will be recorded on printed or eCRFs 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 CRF. 
• Guidance on completion of CRFs will be provided in the CRF Completion 
Guidelines. 
• The Investigator must permit study-related monitoring, audits, IRB/IEC review, and 
regulatory agency inspections and provide direct access to source documents. 
• Monitoring details describing strategy, including definition of study critical data 
items and processes (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. 
• The Sponsor assumes accountability for actions delegated to other individuals 
(eg, CROs). 
• Records and documents, including signed ICFs, pertaining to the conduct of this 
study must be retained by the Investigator for 2 years after the last marketing 
application approval or, if not approved, 2 years following the discontinuance of the 
test article for investigation 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. 
10.1.9. 
Source Documents 
• 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 CRF 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. 
• Definition of what constitutes source data and its origin can be found in Source Data 
Agreement. 

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• The Investigator must maintain accurate documentation (source data) that supports 
the information entered in the CRF. 
• The Sponsor or designee will perform monitoring to confirm that data entered into the 
CRF 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. 
10.1.10. 
Study and Site Start and Closure 
First Act of Recruitment 
The study start date is the date on which the clinical study will be open for recruitment of 
participants. 
The first act of recruitment is the first site open and will be the study start date. 
Study/Site Termination 
The Sponsor or designee reserves the right to close the study site or terminate the study at any 
time for any reason at the sole discretion of the Sponsor. Study sites will be closed upon study 
completion. A study site is considered closed when all required documents and study supplies 
have been collected and a study site closure visit has been performed. 
The Investigator may initiate study site closure at any time, provided there is reasonable cause 
and sufficient notice is given in advance of the intended termination. 
Reasons for the early closure of a study site by the Sponsor or Investigator may include but are 
not limited to: 
For study termination: 
• Discontinuation of further study intervention development. 
For site termination: 
• Failure of the Investigator to comply with the protocol, the requirements of the 
IRB/IEC or local health authorities, the Sponsor’s procedures, or GCP guidelines. 
• Inadequate or no recruitment (evaluated after a reasonable amount of time) of 
participants by the Investigator. 
• Total number of participants included earlier than expected. 
If the study is prematurely terminated or suspended, the Sponsor shall promptly inform the 
Investigators, the IECs/IRBs, 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. 
10.1.11. 
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 

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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. 
 
 

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10.2. 
Appendix 2: Clinical Laboratory Tests 
• The tests detailed in Table 6 will be performed by the central laboratory. 
• Local laboratory results are only required in the event that the central laboratory 
results are not available in time for either study intervention administration and/or 
response evaluation. If a local sample is required, it is important that the sample for 
central analysis is obtained at the same time. Additionally, if the local laboratory 
results are used to make either a study intervention decision or response evaluation, 
the results must be recorded. 
• Protocol-specific requirements for inclusion or exclusion of participants are detailed 
in Section 5. 
• Additional tests may be performed at any time during the study as determined 
necessary by the Investigator or required by local regulations. 
• Investigators must document their review of each laboratory safety report. 
Table 6: 
Protocol-required Safety Laboratory Tests 
Laboratory Tests 
Parameters 
Pregnancy Testing 
• 
Highly sensitive serum or urine hCG pregnancy test (as needed for 
POCBP)1 
Other Screening Tests 
• 
FSH and estradiol (as needed in PONCBP only) 
Abbreviations: FSH=follicle-stimulating hormone; hCG=human chorionic gonadotropin; IEC=independent ethics 
committee; IRB=institutional review board; POCBP=person of childbearing potential; PONCBP=person of 
nonchildbearing potential. 
NOTES: 
1 
Local urine testing will be standard for the protocol unless serum testing is required by local regulation or 
IRB/IEC. 

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10.3. 
Appendix 3: AEs and SAEs: Definitions and Procedures for 
Recording, Evaluating, Follow-up, and Reporting 
10.3.1. 
Definition of AE 
AE Definition 
• An AE is any untoward medical occurrence in a clinical study participant, temporally 
associated with the use of study intervention, whether or not considered related to the 
study intervention. 
• NOTE: An AE can therefore be any unfavorable and unintended sign (including an 
abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally 
associated with the use of study intervention. 
Definition of Unsolicited and Solicited AE 
• An unsolicited AE is an AE that was not solicited using a participant diary and that is 
communicated by a participant who has signed the informed consent. Unsolicited 
AEs include serious and nonserious AEs. 
• Potential unsolicited AEs may be medically attended (ie, symptoms or illnesses 
requiring a hospitalization, emergency room visit, or visit to/by a healthcare 
provider). The participant will be instructed to contact the site as soon as possible to 
report medically attended event(s), as well as any events that, though not medically 
attended, are of participant concern. Detailed information about reported unsolicited 
AEs will be collected by qualified site personnel and documented in the participant’s 
records. 
• Unsolicited AEs that are not medically attended nor perceived as a concern by the 
participant will be collected during an interview with the participant and by review of 
available medical records at the next visit. 
• Solicited AEs are predefined local (at the injection site) and systemic events for 
which the participant is specifically questioned, and which are noted by the 
participant in their diary. 
Events Meeting the AE Definition 
• Any abnormal laboratory test results (hematology, clinical chemistry, or urinalysis) or 
other safety assessments (eg, ECG, radiological scans, vital signs measurements), 
including those that worsen from Baseline, considered clinically significant in the 
medical and scientific judgment of the Investigator (ie, not related to progression of 
underlying disease, or more severe than expected for the participant’s condition). 
• Exacerbation of a chronic or intermittent pre-existing condition including either an 
increase in frequency and/or intensity of the condition. 
• New condition detected or diagnosed after study intervention administration even 
though it may have been present before the start of the study. 
• Signs, symptoms, or the clinical sequelae of a suspected drug-drug interaction. 

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• Signs, symptoms, or the clinical sequelae of a suspected overdose of either study 
intervention or a concomitant medication. Overdose per se will not be reported as an 
AE/SAE unless it is an intentional overdose taken with possible suicidal/self-harming 
intent. Such overdoses should be reported regardless of sequelae. 
Events not Meeting the AE Definition 
• Medical or surgical procedure (eg, endoscopy, appendectomy): the condition that 
leads to the procedure is the AE. 
• Situations in which an untoward medical occurrence did not occur (social and/or 
convenience admission to a hospital). 
• Anticipated day-to-day fluctuations of pre-existing disease(s) or condition(s) present 
or detected at the start of the study that do not worsen. 
10.3.2. 
Definition of SAE 
An SAE is defined as any untoward medical occurrence that, at any dose, meets one or more of 
the criteria listed: 
a. Results in death. 
b. Is life-threatening. 
The term life-threatening in the definition of serious refers to an event in which the participant 
was at risk of death at the time of the event. It does not refer to an event, which hypothetically 
might have caused death, if it were more severe. 
c. Requires inpatient hospitalization or prolongation of existing hospitalization. 
• In general, hospitalization signifies that the participant has been admitted (usually 
involving at least an overnight stay) at the hospital or emergency ward for 
observation and/or treatment that would not have been appropriate in the physician’s 
office or outpatient setting. Complications that occur during hospitalization are AEs. 
If a complication prolongs hospitalization or fulfills any other serious criteria, the 
event is serious. When in doubt as to whether hospitalization occurred or was 
necessary, the AE should be considered serious. 
• Hospitalization for elective treatment of a pre-existing condition that did not worsen 
from Baseline is not considered an AE. 
d. Results in persistent or significant disability/incapacity. 
• The term disability means a substantial disruption of a person’s 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) that may interfere with or prevent 
everyday life functions but do not constitute a substantial disruption. 
e. Is a congenital anomaly/birth defect. 

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f. Other situations: 
• Medical or scientific judgment should be exercised by the Investigator in deciding 
whether SAE reporting is appropriate in other situations such as important medical 
events that that may not be immediately life-threatening or result in death or 
hospitalization but may jeopardize the participant or may require medical or surgical 
intervention to prevent one of the other outcomes listed in the above definition. These 
events should usually be considered serious. 
o Examples of such events include invasive or malignant cancers, intensive treatment in 
an emergency room or at home for allergic bronchospasm, blood dyscrasias, 
convulsions not resulting in hospitalization, or development of intervention 
dependency or intervention abuse. 
10.3.3. 
Definition of MAAE 
A MAAE is an AE that leads to a USV to a healthcare practitioner. This would include visits to a 
study site for unscheduled assessments not required per protocol (eg, rash assessment, abnormal 
laboratory follow-up) and visits to healthcare practitioners external to the study site (eg, 
emergency room, urgent care, primary care physician). 
10.3.4. 
Definition of AESI 
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. 
The AESIs defined for this protocol can be found in Section 10.5. 
10.3.5. 
Recording and Follow-Up of AE and/or SAE 
AE and SAE Recording 
• When an AE/SAE occurs, it is the responsibility of the Investigator to review all 
documentation (eg, hospital progress notes, laboratory reports, and diagnostics 
reports) related to the event. 
• The Investigator will then record all relevant AE/SAE information. 
• It is not acceptable for the Investigator to send photocopies of the participant’s 
medical records to the Sponsor or designee in lieu of the EDC entry. 
• There may be instances when copies of medical records for certain cases are 
requested by the Sponsor or designee. In this case, all participant identifiers, with the 
exception of the participant number, will be redacted on the copies of the medical 
records before submission to the Sponsor or designee. 
• The Investigator will attempt to establish a diagnosis of the event based on signs, 
symptoms, and/or other clinical information. Whenever possible, the diagnosis (not 
the individual signs/symptoms) will be documented as the AE/SAE. 

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Assessment of Intensity 
The Investigator will make an assessment of intensity for each AE and SAE reported during the 
study and assign it to one of the following categories: 
• Mild: 
A type of AE that is usually transient and may require only minimal treatment or 
therapeutic intervention. The event does not generally interfere with usual activities 
of daily living. 
• Moderate:  
A type of AE that is usually alleviated with additional specific therapeutic 
intervention. The event interferes with usual activities of daily living, causing 
discomfort but poses no significant or permanent risk of harm to the research 
participant. 
• Severe:  
A type of AE that interrupts usual activities of daily living, or significantly affects 
clinical status, or may require intensive therapeutic intervention. 
The Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in 
Preventative 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 trial. The intensity grading scale used in this trial is presented in Table 7. 
Table 7: 
Adult and Adolescent Solicited Adverse Reactions and Grades 
Reaction 
Grade 0 
(None) 
Grade 1 
(Mild) 
Grade 2 
(Moderate) 
Grade 3 
(Severe) 
Grade 4 
(Life-
threatening) 
Local 
Injection site pain 
None 
No interference 
with activity 
Some interference 
with activity 
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 

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Reaction 
Grade 0 
(None) 
Grade 1 
(Mild) 
Grade 2 
(Moderate) 
Grade 3 
(Severe) 
Grade 4 
(Life-
threatening) 
Axillary (underarm) 
swelling or 
tenderness 
ipsilateral to the 
side of injection 
None 
No interference 
with activity 
Some interference 
with activity 
Prevents daily 
activity 
Requires 
emergency 
room visit or 
hospitalization 
Systemic 
Headache 
None 
No interference 
with activity 
Some interference 
with activity 
Prevents daily 
activity 
Requires 
emergency 
room visit or 
hospitalization 
Fatigue 
None 
No interference 
with activity 
Some interference 
with activity 
Prevents daily 
activity 
Requires 
emergency 
room visit or 
hospitalization 
Myalgia 
(muscle aches all 
over body) 
None 
No interference 
with activity 
Some interference 
with activity 
Prevents daily 
activity 
Requires 
emergency 
room visit or 
hospitalization 
Arthralgia 
(joint aches in 
several joints) 
None 
No interference 
with activity 
Some interference 
with activity 
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 
Note: Events listed above but starting >7 days poststudy intervention will be recorded in EDC. Causality for each 
event will be determined per assessment by the Investigator. 
Source: Modified from the Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in 
Preventive Vaccine Clinical Trials (DHHS 2007). 

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Assessment of Causality 
• The Investigator is obligated to assess the relationship between study intervention and 
each occurrence of each AE/SAE. The Investigator will use clinical judgment to 
determine the relationship. 
• Not related: There is not a reasonable possibility of a relationship to the study 
intervention. Participant did not receive the study intervention OR temporal sequence 
of the AE onset relative to administration of the study intervention is not reasonable 
OR the AE is more likely explained by another cause than the study intervention. 
• Related: There is a reasonable possibility of a relationship to the study intervention. 
There is evidence of exposure to the study intervention. The temporal sequence of the 
AE onset relative to the administration of the study intervention is reasonable. The 
AE is more likely explained by the study intervention than by another cause. 
• For causality assessment, the Investigator will also consult the IB and/or product 
information, for marketed products. 
• The Investigator must review and provide an assessment of causality for each 
AE/SAE and document this in the medical notes. There may be situations in which an 
SAE has occurred and the Investigator has minimal information to include in the 
initial report to the Sponsor or designee. However, it is very important that the 
Investigator always make an assessment of causality for every event before the initial 
transmission of the SAE data to the Sponsor or designee. 
• The Investigator may change their opinion of causality in light of follow-up 
information and send an SAE follow-up report with the updated causality assessment. 
• The causality assessment is one of the criteria used when determining regulatory 
reporting requirements. 
Follow-up of AEs and SAEs 
• The Investigator is obligated to perform or arrange for the conduct of supplemental 
measurements and/or evaluations as medically indicated or as requested by the 
Sponsor or designee to elucidate the nature and/or causality of the AE or SAE as fully 
as possible. This may include additional laboratory tests or investigations, 
histopathological examinations, or consultation with other health care professionals. 
• If a participant dies during participation in the study or during a recognized follow-up 
period, the Investigator will provide the Sponsor or designee with a copy of any 
postmortem findings including histopathology. 
• New or updated information will be recorded in the originally submitted documents. 
• The Investigator will submit any updated SAE data to the Sponsor or designee within 
24 hours of receipt of the information. 
10.3.6. 
Reporting of SAEs/AESI 
NOTE: AESI will be reported in the same way as SAEs 

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SAE Reporting to the Sponsor or designee via an Electronic Data Collection Tool 
• The primary mechanism for reporting an SAE to the Sponsor or designee will be the 
electronic data collection tool (ie, EDC). 
• If the electronic system is unavailable, then the site will use the paper SAE data 
collection tool (see next section) to report the event within 24 hours. 
• The site will enter the SAE data into the electronic system as soon as it becomes 
available. 
• After the study is completed at a given site, the electronic data collection tool will be 
taken offline to prevent the entry of new data or changes to existing data. 
• If a site receives a report of a new SAE from a study participant or receives updated 
data on a previously reported SAE after the electronic data collection tool has been 
taken offline, then the site can report this information on a paper SAE form (see next 
section). 
SAE Reporting to the Sponsor or designee via Paper Data Collection Tool 
• Email transmission of the SAE paper data collection tool is the preferred method to 
transmit this information to the Sponsor. 
• Initial notification via email or fax does not replace the need for the Investigator to 
complete and sign the electronic SAE data collection tool within the designated 
reporting timeframes. 
• SAE reports should be emailed to drugsafety@modernatx.com. 

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10.4. 
Appendix 4: Contraceptive and Barrier Guidance 
10.4.1. 
Definitions 
Person of Childbearing Potential 
Persons AFAB are considered POCBP (fertile) following menarche: 
• From the time of menarche until becoming postmenopausal unless permanently sterile. 
• A postmenopausal state is defined as no menses for 12 months without an alternative 
medical cause. 
o A high FSH level in the postmenopausal range may be used to confirm a 
postmenopausal state in women not using hormonal contraception or hormonal 
replacement therapy. However, in the absence of 12 months of amenorrhea, 
confirmation with more than one FSH measurement is required. 
o Persons AFAB 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 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. 
Person of Nonchildbearing Potential 
Persons AFAB in the following categories are considered PONCBP: 
1. Premenopausal persons AFAB with permanent infertility due to one of the following: 
a. Documented hysterectomy. 
b. Documented bilateral salpingectomy. 
c. Documented bilateral oophorectomy. 
d. 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. 

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Note: Documentation can come from the site personnel’s review of the participant’s medical 
records, medical examination, or medical history interview. 
2. Postmenopausal persons AFAB: 
a. A postmenopausal state is defined as no menses for 12 months without an alternative 
medical cause. 
i. 
A high FSH level in the postmenopausal range may be used to confirm a 
postmenopausal state in women not using hormonal contraception or hormonal 
replacement therapy. However, in the absence of 12 months of amenorrhea, 
confirmation with more than one FSH measurement (>40 IU/L or mIU/mL) is 
required. 
ii. 
Persons AFAB on HRT and whose menopausal status is in doubt must 
discontinue HRT to allow confirmation of postmenopausal status before study 
enrollment. 
10.4.2. 
Contraception Guidance 
CONTRACEPTIVESa ALLOWED DURING THE STUDY INCLUDE: 
Highly Effective Methodsb That Have Low User Dependency Failure rate of <1% per year when 
used consistently and correctly. 
• 
Implantable progestogen-only hormone contraception associated with inhibition of ovulation. 
• 
IUD. 
• 
IUS. 
• 
Bilateral tubal occlusion. 
• 
Azoospermic partner (vasectomized or due to a medical cause). 
• 
Azoospermia is a highly effective contraceptive method provided that the partner is the sole 
sexual partner of the POCBP and the absence of sperm has been confirmed. If not, an 
additional highly effective method of contraception should be used. Spermatogenesis cycle is 
approximately 90 days. 
Note: documentation of azoospermia for a participant can come from the site personnel’s 
review of the participant’s medical records, medical examination, or medical history 
interview. 
Highly Effective Methodsb That Are User Dependent Failure rate of <1% per year when used 
consistently and correctly. 
Combined (estrogen- and progestogen-containing) hormonal contraception associated with inhibition 
of ovulation: 
Oral. 
Intravaginal. 
Transdermal. 
Injectable. 
Progestogen-only hormone contraception associated with inhibition of ovulation: 
Oral. 
Injectable. 

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CONTRACEPTIVESa ALLOWED DURING THE STUDY INCLUDE: 
Highly Effective Methodsb That Have Low User Dependency Failure rate of <1% per year when 
used consistently and correctly. 
Sexual abstinence. 
Sexual abstinence is considered a highly effective method only if defined as refraining from 
heterosexual intercourse during the entire period of risk associated with the study intervention. The 
reliability of sexual abstinence needs to be evaluated in relation to the duration of the study and the 
preferred and usual lifestyle of the participant. 
Effective Methods That Are Not Considered Highly Effective Failure rate of ≥1% per year when 
used consistently and correctly. 
• 
Progestogen-only oral hormonal contraception where inhibition of ovulation is not the 
primary mode of action. 
• 
External or internal condom with or without spermicide. 
• 
Cervical cap, diaphragm, or sponge with spermicide. 
• 
A combination of external condom with either cervical cap, diaphragm, or sponge with 
spermicide (double-barrier methods)c. 
a. Contraceptive use should be consistent with local regulations regarding the use of contraceptive 
methods for those participating in clinical studies. 
b. Failure rate of <1% per year when used consistently and correctly. Typical use failure rates differ 
from those when used consistently and correctly. 
c. Considered effective, but not highly effective - failure rate of ≥1% per year. 
Note: Periodic abstinence (calendar, symptothermal, postovulation methods), withdrawal (coitus 
interruptus), spermicides only, and LAM are not acceptable methods of contraception. External 
condom and internal condom should not be used together (due to risk of failure from friction). 
Abbreviations: IUD=intrauterine device; IUS=intrauterine hormone-releasing system; LAM=lactational amenorrhea 
method; POCBP=person of childbearing potential. 

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10.5. 
Appendix 5: Adverse Event of Special Interest 
Investigators should report all events that fall into the categories presented in Table 8 as an AESI 
per the reporting processes in Section 10.3.6. The following AESIs are medical concepts that are 
generally of interest in vaccine safety surveillance as per the Brighton Collaboration and Safety 
Platform for Emergency Vaccines or the vaccine platform. 
Table 8: 
Adverse Events of Special Interest 
Medical Concept 
Additional Notes 
Thrombocytopenia 
• 
Platelet counts <125 × 109. 
• 
Including but not limited to immune thrombocytopenia, platelet 
production decreased, thrombocytopenia, thrombocytopenic 
purpura, thrombotic thrombocytopenic purpura, or HELLP 
syndrome. 
New onset of or worsening 
of the following neurologic 
diseases: 
• 
Guillain-Barre Syndrome. 
• 
ADEM. 
• 
Idiopathic peripheral facial nerve palsy (Bell’s palsy). 
• 
Seizures including but not limited to febrile seizures and/or 
generalized seizures/convulsions. 
Anaphylaxis 
• 
Anaphylaxis associated with IP administration as defined per 
protocol in Section 8.4.8.1. 
• 
Follow reporting procedures in Section 10.3.6. 
Myocarditis/Pericarditis 
• 
Myocarditis. 
• 
Pericarditis. 
• 
Myopericarditis. 
Abbreviations: ADEM=acute disseminated encephalomyelitis; HELLP=hemolysis, elevated liver enzymes and low 
platelets; IP=investigational product. 
 
 

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10.6. 
Appendix 6: 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 9 as guidance. 
Table 9: 
Case Definitions of Probably and Confirmed Myocarditis, Pericarditis, and 
Myopericarditis 
Condition 
Definition 
Acute 
myocarditis 
Probable case 
Confirmed case 
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. 
• 
Tachypnea. 
• 
Lethargy. 
OR, infants and children aged <12 years 
might instead have ≥2 of the following 
symptoms: 
• 
Irritability. 
• 
Vomiting. 
• 
Poor feeding. 
• 
Tachypnea. 
• 
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. 
• 
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). 

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Condition 
Definition 
AND 
• 
No other identifiable cause of the 
symptoms and findings. 
AND 
• 
No other identifiable cause of the 
symptoms and findings. 
Acute 
pericarditis** 
Presence of ≥2 new or worsening of the following clinical features: 
• 
Acute chest pain††. 
• 
Pericardial rub on exam. 
• 
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: AV=atrioventricular; 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 comprising medically qualified personnel, including cardiologists, will review 
suspected cases of myocarditis, pericarditis, and myopericarditis to determine if they meet Center for Disease 
Control and Prevention 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 treatment. 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) AV 
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). 

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11. 
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;1:3-14. 
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 2022 Jun 23]. Available from: 
https://www.fda.gov/downloads/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInfor
mation/Guidances/Vaccines/ucm091977.pdf. 
Department of Health and Human Services. Conduct of Clinical Trials of Medical Products 
During the COVID-19 Public Health Emergency: Guidance for Industry, Investigators, and 
Institutional Review Boards. March 2020 [updated 2021 Jan 27; cited 2021 Mar 18] [38 screens]. 
Available from: https://www.fda.gov/media/136238/download. 2020. 
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;70(27):977-82. 
 
 
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 
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