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Clinical Trial Results:
A Phase 2/3, Randomized, Observer-Blind, Placebo-Controlled Study to Evaluate the Safety, Reactogenicity, and Effectiveness of mRNA-1273 SARS-CoV-2 Vaccine in Healthy Adolescents 12 to <18 Years of Age

Summary
EudraCT number	2023-000382-14
Trial protocol	Outside EU/EEA
Global end of trial date	12 Jul 2024

Results information
Results version number	v1(current)
This version publication date	26 Jan 2025
First version publication date	26 Jan 2025
Other versions

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

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Trial information

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Sponsor protocol code

mRNA-1273-P203

ISRCTN number

US NCT number

NCT04649151

WHO universal trial number (UTN)

Sponsor organisation name

ModernaTX, Inc.

Sponsor organisation address

325 Binney Street, Cambridge, MA, United States, 02142

Public contact

Moderna Clinical Trials Support Center, ModernaTX, Inc., +1 877-777-7187, clinicaltrials@modernatx.com

Scientific contact

Moderna Clinical Trials Support Center, ModernaTX, Inc., +1 877-777-7187, clinicaltrials@modernatx.com

Is trial part of an agreed paediatric investigation plan (PIP)

Yes

EMA paediatric investigation plan number(s)

EMEA-002893-PIP01-20

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Yes

Analysis stage

Final

Date of interim/final analysis

23 Jul 2024

Is this the analysis of the primary completion data?

Yes

Primary completion date

14 Jun 2024

Global end of trial reached?

Yes

Global end of trial date

12 Jul 2024

Was the trial ended prematurely?

Main objective of the trial

The study was designed to primarily evaluate the safety, reactogenicity, and effectiveness of mRNA-1273 vaccine administered as primary series and a booster dose (BD) to an adolescent population. The study also evaluated the safety and immunogenicity of an mRNA-1273.222 vaccine against the SARS-CoV- 2 omicron variant.

Protection of trial subjects

This study was conducted in accordance with the protocol and consensus ethical principles derived from international guidelines including the Declaration of Helsinki, and Council for International Organizations of Medical Sciences (CIOMS) International Ethical Guidelines, applicable International Council for Harmonisation (ICH) Good Clinical Practice (GCP) guidelines, and other applicable laws and regulatory requirements.

Background therapy

Evidence for comparator

Actual start date of recruitment

09 Dec 2020

Long term follow-up planned

Yes

Long term follow-up rationale

Safety

Long term follow-up duration

12 Months

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

United States: 3994

Country: Number of subjects enrolled

Dominican Republic: 334

Worldwide total number of subjects

4328

EEA total number of subjects

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

4328

Adults (18-64 years)

From 65 to 84 years

85 years and over

Subject disposition

Top of page

Recruitment details

Screening details

The study included Part 1A as the Blinded Phase with participants remaining blinded until the initiation of Part 1B (open-label cross-over phase), and Parts 1C-1, 1C-2, 2, and 3 as open-label. A comparison to the mRNA-1273-P301 (P301) (NCT04470427) study's efficacy data was performed on a subgroup of P301 study participants aged 18-25 (N=296).

Period 1 title

Parts 1, 2, and 3

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Carer, Monitor

Blinding implementation details

Part 1A was observer-blind. Participants remained blinded until the initiation of Part 1B (open-label cross-over phase). Parts 1C-1, 1C-2, 2, and 3 were open-label.

Are arms mutually exclusive

Yes

Part 1A: mRNA-1273 100 μg

Arm description

Participants received 2 doses of 100 micrograms (μg) mRNA-1273 by intramuscular (IM) injection (Day 1 and Day 29).

Arm type

Experimental

Investigational medicinal product name

mRNA-1273

Investigational medicinal product code

Other name

Pharmaceutical forms

Sterile concentrate

Routes of administration

Intramuscular use

Dosage and administration details

mRNA-1273 was administered per dose and schedule specified in the arm description.

Part 1A: Placebo

Arm description

Participants received 2 doses of placebo matched to mRNA-1273 100 μg by IM injection (Day 1 and Day 29).

Arm type

Placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Sterile concentrate

Routes of administration

Intramuscular use

Dosage and administration details

Placebo matched to mRNA-1273 was administered per schedule specified in the arm description.

Part 1C-2: mRNA-1273 50 μg BD

Arm description

Participants who completed primary COVID-19 vaccination series with a non-Moderna vaccine under emergency use authorization (EUA), received a single BD of 50 μg mRNA-1273 IM injection on BD Day 1.

Arm type

Experimental

Investigational medicinal product name

mRNA-1273

Investigational medicinal product code

Other name

Pharmaceutical forms

Sterile concentrate

Routes of administration

Intramuscular use

Dosage and administration details

mRNA-1273 was administered per dose and schedule specified in the arm description.

Part 2: mRNA-1273 50 μg

Arm description

Participants received 2 doses of 50 μg mRNA-1273 by IM injection (Day 1 and Day 29).

Arm type

Experimental

Investigational medicinal product name

mRNA-1273

Investigational medicinal product code

Other name

Pharmaceutical forms

Sterile concentrate

Routes of administration

Intramuscular use

Dosage and administration details

mRNA-1273 was administered per dose and schedule specified in the arm description.

Part 3: mRNA-1273.222 50 µg

Arm description

Participants received 1 dose of mRNA-1273.222 50 µg by IM injection (Day 1). Some participants may have received a second dose of mRNA-1273.222 50 µg at approximately 6 months after the first dose (Day 181).

Arm type

Experimental

Investigational medicinal product name

mRNA-1273.222

Investigational medicinal product code

Other name

Pharmaceutical forms

Sterile concentrate

Routes of administration

Intramuscular use

Dosage and administration details

mRNA-1273.222 was administered per dose and schedule specified in the arm description.

Number of subjects in period 1	Part 1A: mRNA-1273 100 μg	Part 1A: Placebo	Part 1C-2: mRNA-1273 50 μg BD	Part 2: mRNA-1273 50 μg	Part 3: mRNA-1273.222 50 µg
Started	2490	1243	155	52	388
Part 1: 1st Injection	2486	1240	0 ^[1]	0 ^[2]	0 ^[3]
Part 2: 1st Injection	0 ^[4]	0 ^[5]	0 ^[6]	52	0 ^[7]
Part 1: 2nd Injection	2480	1222	0 ^[8]	0 ^[9]	0 ^[10]
Part 2: 2nd Injection	0 ^[11]	0 ^[12]	0 ^[13]	50	0 ^[14]
Part 1C-2: BD	0 ^[15]	0 ^[16]	155	0 ^[17]	0 ^[18]
Part 3: 1 Dose	0 ^[19]	0 ^[20]	0 ^[21]	0 ^[22]	388
Part 3: 2 Doses	0 ^[23]	0 ^[24]	0 ^[25]	0 ^[26]	335 ^[27]
Safety Analysis Set	2486	1240	155	52	388
Solicited Safety Set	2485	1240	125 ^[28]	52	387
Per-Protocol (PP) Immunogenicity Subset	340 ^[29]	0 ^[30]	136 ^[31]	46	373
PP Set for Efficacy	2142 ^[32]	1044	0 ^[33]	0 ^[34]	0 ^[35]
Part 2 BD	0 ^[36]	0 ^[37]	0 ^[38]	19 ^[39]	0 ^[40]
PP Immunogenicity SARS-CoV-2 Positive	0 ^[41]	0 ^[42]	0 ^[43]	44	372
Completed	2246	279	143	41	358
Not completed	244	964	12	11	30
Physician decision	2	-	-	1	1
Consent withdrawn by subject	112	88	2	7	15
Protocol Deviation	2	2	-	-	-
Adverse event, non-fatal	1	-	-	-	-
Death	-	-	-	-	1
Pregnancy	-	-	-	-	3
Other than specified	21	229	-	-	4
Received another COVID-19 vaccine under EUA	39	630	-	-	-
Lost to follow-up	67	15	10	3	6

Notes
[1] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Value indicates the number of applicable participants for the milestone and dose group.
[2] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Value indicates the number of applicable participants for the milestone and dose group.
[3] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Value indicates the number of applicable participants for the milestone and dose group.
[4] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Value indicates the number of applicable participants for the milestone and dose group.
[5] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Value indicates the number of applicable participants for the milestone and dose group.
[6] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Value indicates the number of applicable participants for the milestone and dose group.
[7] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Value indicates the number of applicable participants for the milestone and dose group.
[8] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Value indicates the number of applicable participants for the milestone and dose group.
[9] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Value indicates the number of applicable participants for the milestone and dose group.
[10] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Value indicates the number of applicable participants for the milestone and dose group.
[11] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Value indicates the number of applicable participants for the milestone and dose group.
[12] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Value indicates the number of applicable participants for the milestone and dose group.
[13] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Value indicates the number of applicable participants for the milestone and dose group.
[14] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Value indicates the number of applicable participants for the milestone and dose group.
[15] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Value indicates the number of applicable participants for the milestone and dose group.
[16] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Value indicates the number of applicable participants for the milestone and dose group.
[17] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Value indicates the number of applicable participants for the milestone and dose group.
[18] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Value indicates the number of applicable participants for the milestone and dose group.
[19] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Value indicates the number of applicable participants for the milestone and dose group.
[20] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Value indicates the number of applicable participants for the milestone and dose group.
[21] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Value indicates the number of applicable participants for the milestone and dose group.
[22] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Value indicates the number of applicable participants for the milestone and dose group.
[23] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Value indicates the number of applicable participants for the milestone and dose group.
[24] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Value indicates the number of applicable participants for the milestone and dose group.
[25] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Value indicates the number of applicable participants for the milestone and dose group.
[26] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Value indicates the number of applicable participants for the milestone and dose group.
[27] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Value indicates the number of applicable participants for the milestone and dose group.
[28] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Value indicates the number of applicable participants for the milestone and dose group.
[29] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Value indicates the number of applicable participants for the milestone and dose group.
[30] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Value indicates the number of applicable participants for the milestone and dose group.
[31] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Value indicates the number of applicable participants for the milestone and dose group.
[32] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Value indicates the number of applicable participants for the milestone and dose group.
[33] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Value indicates the number of applicable participants for the milestone and dose group.
[34] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Value indicates the number of applicable participants for the milestone and dose group.
[35] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Value indicates the number of applicable participants for the milestone and dose group.
[36] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Value indicates the number of applicable participants for the milestone and dose group.
[37] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Value indicates the number of applicable participants for the milestone and dose group.
[38] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Value indicates the number of applicable participants for the milestone and dose group.
[39] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Value indicates the number of applicable participants for the milestone and dose group.
[40] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Value indicates the number of applicable participants for the milestone and dose group.
[41] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Value indicates the number of applicable participants for the milestone and dose group.
[42] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Value indicates the number of applicable participants for the milestone and dose group.
[43] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Value indicates the number of applicable participants for the milestone and dose group.

Period 2 title

Part 1C-1 BD

Is this the baseline period?

Allocation method

Not applicable

Blinding used

Not blinded

Part 1C-1: mRNA-1273 50 µg BD

Arm description

Participants received mRNA-1273 100 µg in blinded or cross-over phase (Parts 1A or 1B) and then a single BD of 50 μg mRNA-1273 IM injection on BD Day 1 in Part 1 C-1.

Arm type

Experimental

Investigational medicinal product name

mRNA-1273

Investigational medicinal product code

Other name

Pharmaceutical forms

Sterile concentrate

Routes of administration

Intramuscular use

Dosage and administration details

mRNA-1273 was administered per dose and schedule specified in the arm description.

Number of subjects in period 2 ^[44]	Part 1C-1: mRNA-1273 50 µg BD
Started	1408
Safety Set	1408
Solicited Safety Set	1351
PPIS	331 ^[45]
PP Immunogenicity SARS-CoV-2 Negative	267 ^[46]
Completed	1136
Not completed	272
Physician decision	3
Consent withdrawn by subject	123
Protocol Deviation	2
Other than specified	4
Received another COVID-19 vaccine under EUA	17
Lost to follow-up	123

Notes
[44] - The number of subjects starting the period is not consistent with the number completing the preceding period. It is expected the number of subjects starting the subsequent period will be the same as the number completing the preceding period.
Justification: Not all participants who started in Part 1 received BD in Part 1C-1.
[45] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Value indicates the number of applicable participants for the milestone and dose group.
[46] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Value indicates the number of applicable participants for the milestone and dose group.

Period 3 title

Part 1B Crossover Phase

Is this the baseline period?

Allocation method

Not applicable

Blinding used

Not blinded

Part 1 B: mRNA-1273 100 µg

Arm description

Participants previously received 2 doses of placebo in the blinded phase and then received crossover vaccination with 100 μg of mRNA-1273.

Arm type

Experimental

Investigational medicinal product name

mRNA-1273

Investigational medicinal product code

Other name

Pharmaceutical forms

Sterile concentrate

Routes of administration

Intramuscular use

Dosage and administration details

mRNA-1273 was administered per dose and schedule specified in the arm description.

Number of subjects in period 3 ^[47]	Part 1 B: mRNA-1273 100 µg
Started	96
Received First Injection on Day 1	96
Received Second Injection on Day 29	93
Safety Set	96
Completed	93
Not completed	3
Adverse event, non-fatal	1
Other than specified	1
Lost to follow-up	1

Notes
[47] - The number of subjects starting the period is not consistent with the number completing the preceding period. It is expected the number of subjects starting the subsequent period will be the same as the number completing the preceding period.
Justification: Not all participants who received placebo in Part 1 crossed over to Part 1B

Baseline characteristics

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Reporting group title

Part 1A: mRNA-1273 100 μg

Reporting group description

Participants received 2 doses of 100 micrograms (μg) mRNA-1273 by intramuscular (IM) injection (Day 1 and Day 29).

Reporting group title

Part 1A: Placebo

Reporting group description

Participants received 2 doses of placebo matched to mRNA-1273 100 μg by IM injection (Day 1 and Day 29).

Reporting group title

Part 1C-2: mRNA-1273 50 μg BD

Reporting group description

Participants who completed primary COVID-19 vaccination series with a non-Moderna vaccine under emergency use authorization (EUA), received a single BD of 50 μg mRNA-1273 IM injection on BD Day 1.

Reporting group title

Part 2: mRNA-1273 50 μg

Reporting group description

Participants received 2 doses of 50 μg mRNA-1273 by IM injection (Day 1 and Day 29).

Reporting group title

Part 3: mRNA-1273.222 50 µg

Reporting group description

Reporting group values	Part 1A: mRNA-1273 100 μg	Part 1A: Placebo	Part 1C-2: mRNA-1273 50 μg BD	Part 2: mRNA-1273 50 μg	Part 3: mRNA-1273.222 50 µg	Total
Number of subjects	2490	1243	155	52	388	4328
Age Categorical
Units: Subjects
In utero	0	0	0	0	0	0
Preterm newborn infants (gestational age < 37 wks)	0	0	0	0	0	0
Newborns (0-27 days)	0	0	0	0	0	0
Infants and toddlers (28 days-23 months)	0	0	0	0	0	0
Children (2-11 years)	0	0	0	0	0	0
Adolescents (12-17 years)	2490	1243	155	52	388	4328
Adults (18-64 years)	0	0	0	0	0	0
From 65-84 years	0	0	0	0	0	0
85 years and over	0	0	0	0	0	0
Gender Categorical
Units: Subjects
Female	1206	607	78	26	185	2102
Male	1284	636	77	26	203	2226

Subject analysis set title

Study mRNA-1273-P301 (NCT04470427) mRNA-1273 100 μg

Subject analysis set type

Per protocol

Subject analysis set description

Participants (young adults; 18-25 years of age) received 100 μg mRNA-1273 on a 2 injection schedule in Study mRNA-1273-P301 (P301).

Subject analysis set title

Part 2: mRNA-1273 50 μg First Injection

Subject analysis set type

Safety analysis

Subject analysis set description

Participants received 1 dose of 50 μg mRNA-1273 by IM injection (Day 1).

Subject analysis set title

Part 2: mRNA-1273 50 μg Second Injection

Subject analysis set type

Safety analysis

Subject analysis set description

Participants received 2nd dose of 50 μg mRNA-1273 by IM injection (Day 29).

Subject analysis set title

Part 2: mRNA-1273 50 μg BD

Subject analysis set type

Safety analysis

Subject analysis set description

Participants received open-label mRNA-1273 50 µg in Part 2 and then a single BD of 50 μg mRNA-1273 IM injection on BD Day 1 in Part 2.

Subject analysis set title

Part 3: mRNA-1273.222 50 µg 1 Dose

Subject analysis set type

Safety analysis

Subject analysis set description

Participants received 1 dose of mRNA-1273.222 50 µg by IM injection (Day 1).

Subject analysis set title

Part 1A: mRNA-1273 100 μg

Subject analysis set type

Safety analysis

Subject analysis set description

Participants received at least 1 dose of the 2-dose series of 100 μg mRNA-1273 by IM injection (Day 1 and Day 29).

Subject analysis set title

Part 1A: Placebo

Subject analysis set type

Safety analysis

Subject analysis set description

Participants received at least 1 dose of the 2-dose series of placebo matched to mRNA-1273 100 μg by IM injection (Day 1 and Day 29).

Subject analysis set title

Part 1B: mRNA-1273 100 μg

Subject analysis set type

Safety analysis

Subject analysis set description

Participants previously received 2 doses of placebo in the blinded phase and then received crossover vaccination with 100 μg of mRNA-1273.

Subject analysis set title

Part 1C-1: mRNA-1273 50 µg BD

Subject analysis set type

Safety analysis

Subject analysis set description

Participants received mRNA-1273 100 µg in blinded or cross-over phase (Parts 1A or 1B) and then a single BD of 50 μg mRNA-1273 IM injection on BD Day 1 in Part 1 C-1.

Subject analysis set title

Part 1C-2: mRNA-1273 50 μg BD

Subject analysis set type

Safety analysis

Subject analysis set description

Participants who completed primary COVID-19 vaccination series with a non-Moderna vaccine under EUA, received a single BD of 50 μg mRNA-1273 IM injection on BD Day 1

Subject analysis set title

Part 2: mRNA-1273 50 μg

Subject analysis set type

Safety analysis

Subject analysis set description

Participants received at least 1 dose of the 2-dose series of 50 μg mRNA-1273 by IM injection (Day 1 and Day 29).

Subject analysis sets values	Study mRNA-1273-P301 (NCT04470427) mRNA-1273 100 μg	Part 2: mRNA-1273 50 μg First Injection	Part 2: mRNA-1273 50 μg Second Injection	Part 2: mRNA-1273 50 μg BD	Part 3: mRNA-1273.222 50 µg 1 Dose	Part 1A: mRNA-1273 100 μg	Part 1A: Placebo	Part 1B: mRNA-1273 100 μg	Part 1C-1: mRNA-1273 50 µg BD	Part 1C-2: mRNA-1273 50 μg BD	Part 2: mRNA-1273 50 μg
Number of subjects	296	52	50	19	388	2486	1240	96	1408	155	52
Age Categorical
Units: Subjects
In utero	0
Preterm newborn infants (gestational age < 37 wks)	0
Newborns (0-27 days)	0
Infants and toddlers (28 days-23 months)	0
Children (2-11 years)	0
Adolescents (12-17 years)	0
Adults (18-64 years)	296
From 65-84 years	0
85 years and over	0
Age Continuous
Units: years
arithmetic mean (standard deviation)	( )	( )	( )	( )	( )	( )	( )	( )	( )	( )	( )
Gender Categorical
Units: Subjects
Female	153
Male	143

End points

Top of page

Reporting group title

Part 1A: mRNA-1273 100 μg

Reporting group description

Participants received 2 doses of 100 micrograms (μg) mRNA-1273 by intramuscular (IM) injection (Day 1 and Day 29).

Reporting group title

Part 1A: Placebo

Reporting group description

Participants received 2 doses of placebo matched to mRNA-1273 100 μg by IM injection (Day 1 and Day 29).

Reporting group title

Part 1C-2: mRNA-1273 50 μg BD

Reporting group description

Participants who completed primary COVID-19 vaccination series with a non-Moderna vaccine under emergency use authorization (EUA), received a single BD of 50 μg mRNA-1273 IM injection on BD Day 1.

Reporting group title

Part 2: mRNA-1273 50 μg

Reporting group description

Participants received 2 doses of 50 μg mRNA-1273 by IM injection (Day 1 and Day 29).

Reporting group title

Part 3: mRNA-1273.222 50 µg

Reporting group description

Reporting group title

Part 1C-1: mRNA-1273 50 µg BD

Reporting group description

Participants received mRNA-1273 100 µg in blinded or cross-over phase (Parts 1A or 1B) and then a single BD of 50 μg mRNA-1273 IM injection on BD Day 1 in Part 1 C-1.

Reporting group title

Part 1 B: mRNA-1273 100 µg

Reporting group description

Participants previously received 2 doses of placebo in the blinded phase and then received crossover vaccination with 100 μg of mRNA-1273.

Subject analysis set title

Study mRNA-1273-P301 (NCT04470427) mRNA-1273 100 μg

Subject analysis set type

Per protocol

Subject analysis set description

Participants (young adults; 18-25 years of age) received 100 μg mRNA-1273 on a 2 injection schedule in Study mRNA-1273-P301 (P301).

Subject analysis set title

Part 2: mRNA-1273 50 μg First Injection

Subject analysis set type

Safety analysis

Subject analysis set description

Participants received 1 dose of 50 μg mRNA-1273 by IM injection (Day 1).

Subject analysis set title

Part 2: mRNA-1273 50 μg Second Injection

Subject analysis set type

Safety analysis

Subject analysis set description

Participants received 2nd dose of 50 μg mRNA-1273 by IM injection (Day 29).

Subject analysis set title

Part 2: mRNA-1273 50 μg BD

Subject analysis set type

Safety analysis

Subject analysis set description

Participants received open-label mRNA-1273 50 µg in Part 2 and then a single BD of 50 μg mRNA-1273 IM injection on BD Day 1 in Part 2.

Subject analysis set title

Part 3: mRNA-1273.222 50 µg 1 Dose

Subject analysis set type

Safety analysis

Subject analysis set description

Participants received 1 dose of mRNA-1273.222 50 µg by IM injection (Day 1).

Subject analysis set title

Part 1A: mRNA-1273 100 μg

Subject analysis set type

Safety analysis

Subject analysis set description

Participants received at least 1 dose of the 2-dose series of 100 μg mRNA-1273 by IM injection (Day 1 and Day 29).

Subject analysis set title

Part 1A: Placebo

Subject analysis set type

Safety analysis

Subject analysis set description

Participants received at least 1 dose of the 2-dose series of placebo matched to mRNA-1273 100 μg by IM injection (Day 1 and Day 29).

Subject analysis set title

Part 1B: mRNA-1273 100 μg

Subject analysis set type

Safety analysis

Subject analysis set description

Participants previously received 2 doses of placebo in the blinded phase and then received crossover vaccination with 100 μg of mRNA-1273.

Subject analysis set title

Part 1C-1: mRNA-1273 50 µg BD

Subject analysis set type

Safety analysis

Subject analysis set description

Participants received mRNA-1273 100 µg in blinded or cross-over phase (Parts 1A or 1B) and then a single BD of 50 μg mRNA-1273 IM injection on BD Day 1 in Part 1 C-1.

Subject analysis set title

Part 1C-2: mRNA-1273 50 μg BD

Subject analysis set type

Safety analysis

Subject analysis set description

Participants who completed primary COVID-19 vaccination series with a non-Moderna vaccine under EUA, received a single BD of 50 μg mRNA-1273 IM injection on BD Day 1

Subject analysis set title

Part 2: mRNA-1273 50 μg

Subject analysis set type

Safety analysis

Subject analysis set description

Participants received at least 1 dose of the 2-dose series of 50 μg mRNA-1273 by IM injection (Day 1 and Day 29).

Primary: Number of Participants With Solicited Local and Systemic Adverse Reactions (ARs)

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End point title

Number of Participants With Solicited Local and Systemic Adverse Reactions (ARs) ^[1] ^[2]

End point description

Solicited ARs (local and systemic) were collected in an electronic diary (eDiary). Local ARs included injection site pain, injection site erythema (redness), injection site swelling/induration (hardness), and axillary (underarm) swelling or tenderness ipsilateral to the side of injection. Systemic ARs included fever, headache, fatigue, myalgia, arthralgia, nausea/vomiting, and chills. Solicited ARs considered causally related to injection were graded 1-4 (per Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials); lower score indicated lower severity, and higher score indicated greater severity. Solicited Safety Set included participants who received at least 1 dose of study drug and contributed any solicited AR data. Investigator reviewed if the solicited AR was recorded as an adverse event (AE). A Summary of serious AEs (SAEs) and nonserious AEs ("Other"), regardless of causality, is located in the AE section.

End point type

Primary

End point timeframe

7 days post-vaccination

Notes
[1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: As prespecified in the protocol, no statistical analysis was conducted for this endpoint.
[2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: As prespecified in the protocol, no statistical analysis was conducted for this endpoint.

End point values	Part 1A: mRNA-1273 100 μg	Part 1C-1: mRNA-1273 50 µg BD	Part 1A: Placebo	Part 1C-2: mRNA-1273 50 μg BD	Part 2: mRNA-1273 50 μg First Injection	Part 2: mRNA-1273 50 μg Second Injection	Part 2: mRNA-1273 50 μg BD	Part 3: mRNA-1273.222 50 µg 1 Dose
Number of subjects analysed	2485	1351	1240	125	52	46	19	387
Units: participants
Grade 1	586	627	585	42	25	18	7	145
Grade 2	1250	501	293	48	16	9	0	62
Grade 3	627	150	59	9	1	3	1	25
Grade 4	3	0	1	0	0	0	0	1
Any Solicited AR	2466	1278	938	99	42	30	8	233

No statistical analyses for this end point

Primary: Number of Participants With Unsolicited AEs

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End point title

Number of Participants With Unsolicited AEs ^[3] ^[4]

End point description

An AE was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. Any abnormal laboratory test result or other safety assessment, including one that worsened from baseline and was considered clinically significant by the Investigator was recorded as an AE. Non-serious SARs persisting beyond 7 days, leading to discontinuation, or medically attended were defined as AEs in Part 1/2 but not in Part 3. COVID-19/SARS-CoV-2 infections were AEs in Part1/2 but were considered clinical events for efficacy in Part 3 and not AEs. A Summary of SAEs and nonserious AEs ("Other"), regardless of causality, is located in the AE section. Safety Set: participants who received at least 1 dose of study drug.

End point type

Primary

End point timeframe

Up to 28 days post-vaccination

Notes
[3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: As prespecified in the protocol, no statistical analysis was conducted for this endpoint.
[4] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: As prespecified in the protocol, no statistical analysis was conducted for this endpoint.

End point values	Part 1A: mRNA-1273 100 μg	Part 1C-1: mRNA-1273 50 µg BD	Part 1A: Placebo	Part 1C-2: mRNA-1273 50 μg BD	Part 2: mRNA-1273 50 μg	Part 2: mRNA-1273 50 μg BD	Part 3: mRNA-1273.222 50 µg 1 Dose
Number of subjects analysed	2486	1405	1240	155	52	19	388
Units: participants	582	209	237	19	10	2	52

No statistical analyses for this end point

Primary: Part 1A Geometric Mean Value of Serum Pseudovirus Neutralizing Antibody (nAb) ID50 Titers From Study P203 Vaccine Recipients at Day 57 Compared With Those From Young Adult (18 to 25 Years of Age) Vaccine Recipients (Day 57) in Study P301

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End point title

Part 1A Geometric Mean Value of Serum Pseudovirus Neutralizing Antibody (nAb) ID50 Titers From Study P203 Vaccine Recipients at Day 57 Compared With Those From Young Adult (18 to 25 Years of Age) Vaccine Recipients (Day 57) in Study P301 ^[5]

End point description

Pseudovirus nAb ID50 titers were measured using pseudovirus neutralization assay (PsVNA) assay. Antibody values reported as below the lower limit of quantification (LLOQ) were replaced by 0.5*LLOQ. Values greater than the upper limit of quantification (ULOQ) were replaced by the ULOQ if actual values were not available (LLOQ: 18.5, ULOQ: 45118). Antibody levels were analyzed using an analysis of covariance (ANCOVA) model with the group variable (adolescents in P203 and young adults in P301) as fixed effect. The geometric least squares means are presented. PP Immunogenicity Set (PPIS): all randomized participants who received planned doses of study drug per schedule, complied with immunogenicity testing schedule, and had no major protocol deviations that impacted key or critical data.

End point type

Primary

End point timeframe

Day 57 Study P203/Day 57 Study P301

Notes
[5] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: As prespecified in the protocol, no statistical analysis was conducted for this endpoint.

End point values	Part 1A: mRNA-1273 100 μg	Study mRNA-1273-P301 (NCT04470427) mRNA-1273 100 μg
Number of subjects analysed	340	295
Units: titer
geometric mean (confidence interval 95%)	1401.670 (1276.218 to 1539.453)	1299.855 (1175.380 to 1437.511)

Statistical Analysis 1

Statistical analysis description

Geometric mean ratio (GMR) of P203 vs P301

Comparison groups

Part 1A: mRNA-1273 100 μg v Study mRNA-1273-P301 (NCT04470427) mRNA-1273 100 μg

Number of subjects included in analysis

635

Analysis specification

Pre-specified

Analysis type

non-inferiority

Method

Parameter type

GMR

Point estimate

1.078

Confidence interval

level

95%

sides

2-sided

lower limit

0.94

upper limit

1.237

Primary: Part 1A Seroresponse Rate (SRR) for Serum Pseudovirus nAb ID50 in Study P203 Vaccine Recipients at Day 57 Compared With Those From Young Adult (18 to 25 Years of Age) Vaccine Recipients (Day 57) in Study P301

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End point title

Part 1A Seroresponse Rate (SRR) for Serum Pseudovirus nAb ID50 in Study P203 Vaccine Recipients at Day 57 Compared With Those From Young Adult (18 to 25 Years of Age) Vaccine Recipients (Day 57) in Study P301 ^[6]

End point description

Percentage of participants with seroresponse for pseudovirus nAb ID50 measured using PsVNA assay are reported. Seroresponse was defined as a change from below the LLOQ to equal above 4*LLOQ, or at least a 4-fold rise if baseline is equal to or above the LLOQ. P301 mRNA-1273 group included young adults (≥18 and ≤25 years) who received 2 doses of mRNA-1273 in P301 Part A and who were baseline SARS-CoV-2 negative in P301 Part A. PPIS: all randomized participants who received planned doses of study drug per schedule, complied with immunogenicity testing schedule, and had no major protocol deviations that impacted key or critical data.

End point type

Primary

End point timeframe

Day 57 Study P203/Day 57 Study P301

Notes
[6] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: As prespecified in the protocol, no statistical analysis was conducted for this endpoint.

End point values	Part 1A: mRNA-1273 100 μg	Study mRNA-1273-P301 (NCT04470427) mRNA-1273 100 μg
Number of subjects analysed	340	295
Units: percentage of participants
number (confidence interval 95%)	98.8 (97.0 to 99.7)	99.0 (97.1 to 99.8)

Statistical Analysis 1

Statistical analysis description

SRR difference of P203 vs P301

Comparison groups

Part 1A: mRNA-1273 100 μg v Study mRNA-1273-P301 (NCT04470427) mRNA-1273 100 μg

Number of subjects included in analysis

635

Analysis specification

Pre-specified

Analysis type

non-inferiority

Method

Parameter type

percentage difference

Point estimate

-0.2

Confidence interval

level

95%

sides

2-sided

lower limit

-2.1

upper limit

1.9

Primary: Part 1C-1 Geometric Mean Concentration (GMC) of Serum Pseudovirus nAb Against the Original Strain After the BD in Study P203 at BD Day 29 Compared With Those From Young Adult (18 to 25 Years of Age) Vaccine Recipients (Day 57) in Study P301

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End point title

Part 1C-1 Geometric Mean Concentration (GMC) of Serum Pseudovirus nAb Against the Original Strain After the BD in Study P203 at BD Day 29 Compared With Those From Young Adult (18 to 25 Years of Age) Vaccine Recipients (Day 57) in Study P301

End point description

Pseudovirus nAb were measured using PsVNA assay. Antibody values reported as below the LLOQ were replaced by 0.5*LLOQ. Values greater than the ULOQ were replaced by the ULOQ if actual values were not available (LLOQ: 10, ULOQ: 281600). PPIS-Neg: All participants who received mRNA-1273 in the Blinded Phase per schedule, received BD, had a negative SARS-CoV-2 status at baseline (pre-Dose 1 of the Blinded Phase), had BD-Day 1 and BD-Day 29 Ab assessment for the analysis endpoint, had no major protocol deviations that impacted key or critical data, and were pre-booster SARS-CoV-2 negative, defined as no virologic or serologic evidence of SARSCoV-2 infection on or before BD-Day 1 (pre-booster). P301 mRNA-1273 group included young adults (≥18 and ≤25 years) who received 2 doses of mRNA-1273 in P301 Part A and who were baseline SARS-CoV-2 negative in P301 Part A. 'Overall number of participants analyzed' = participants evaluable for this endpoint.

End point type

Primary

End point timeframe

BD Day 29 Study P203/Day 57 Study P301

End point values	Part 1C-1: mRNA-1273 50 µg BD	Study mRNA-1273-P301 (NCT04470427) mRNA-1273 100 μg
Number of subjects analysed	264	294
Units: arbitrary units (AU)/mL
geometric mean (confidence interval 95%)	7102.0 (6553.2 to 7696.8)	1400.4 (1272.7 to 1541.0)

Statistical Analysis 1

Statistical analysis description

GMC Comparison of BD-Day 29 P203 vs Day 57 P301

Comparison groups

Part 1C-1: mRNA-1273 50 µg BD v Study mRNA-1273-P301 (NCT04470427) mRNA-1273 100 μg

Number of subjects included in analysis

558

Analysis specification

Pre-specified

Analysis type

non-inferiority

Method

Parameter type

GMR

Point estimate

5.071

Confidence interval

level

95%

sides

2-sided

lower limit

4.477

upper limit

5.745

Primary: Part 1C-1 SRR of Serum Pseudovirus nAb Against the Original Strain After the BD in Study P203 at BD Day 29 Compared With Those From Young Adult (18 to 25 Years of Age) Vaccine Recipients (Day 57) in Study P301

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End point title

Part 1C-1 SRR of Serum Pseudovirus nAb Against the Original Strain After the BD in Study P203 at BD Day 29 Compared With Those From Young Adult (18 to 25 Years of Age) Vaccine Recipients (Day 57) in Study P301

End point description

Percentage of participants with seroresponse for pseudovirus nAb measured using PsVNA assay are reported. Seroresponse relative to pre-Dose 1 (baseline) at a participant level was defined as a change from below the LLOQ to equal or above 4 * LLOQ, or at least a 4-fold-rise if baseline was equal to or above LLOQ. PPIS-Neg: all participants who received mRNA-1273 in the Blinded Phase per schedule, received BD, had a negative SARS-CoV-2 status at baseline (pre-Dose 1 of the Blinded Phase), had BD-Day 1 and BD-Day 29 Ab assessment, had no major protocol deviations that impacted key or critical data, and were pre-booster SARS-CoV-2 negative, defined as no virologic or serologic evidence of SARSCoV-2 infection on or before BD-Day 1. P301 mRNA-1273 group included young adults (≥18 and ≤25 years) who received 2 doses of mRNA-1273 in P301 Part A and who were baseline SARS-CoV-2 negative in P301 Part A.

End point type

Primary

End point timeframe

BD Day 29 Study P203/Day 57 Study P301

End point values	Part 1C-1: mRNA-1273 50 µg BD	Study mRNA-1273-P301 (NCT04470427) mRNA-1273 100 μg
Number of subjects analysed	264	294
Units: percentage of participants
number (confidence interval 95%)	100.0 (98.6 to 100.0)	99.3 (97.6 to 99.9)

Statistical Analysis 1

Statistical analysis description

SRR difference of P203 BD-Day 29 vs P301 Day 57

Comparison groups

Part 1C-1: mRNA-1273 50 µg BD v Study mRNA-1273-P301 (NCT04470427) mRNA-1273 100 μg

Number of subjects included in analysis

558

Analysis specification

Pre-specified

Analysis type

non-inferiority

Method

Parameter type

SRR Difference

Point estimate

0.7

Confidence interval

level

95%

sides

2-sided

lower limit

-0.8

upper limit

2.4

Primary: Part 3 GMC of nAb post Dose 1 mRNA 1273.222 Against Omicron BA.4/BA.5 Compared With Those From Young Adult (18 to 25 Years of Age) Vaccine Recipients (Day 57) in Study P301

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End point title

Part 3 GMC of nAb post Dose 1 mRNA 1273.222 Against Omicron BA.4/BA.5 Compared With Those From Young Adult (18 to 25 Years of Age) Vaccine Recipients (Day 57) in Study P301 ^[7]

End point description

Antibody values reported as below the LLOQ were replaced by 0.5*LLOQ. Values greater than the ULOQ were replaced by the ULOQ if actual values were not available (LLOQ: 103 AU/mL, ULOQ: 28571 AU/mL). ANCOVA model with the group variable (adolescents in P203 and young adults in P301) as fixed effect. The geometric least squares means are presented. P301 mRNA-1273 group included young adults (≥18 and ≤25 years) who received 2 doses of mRNA 1273 and were baseline SARS-CoV-2 negative. PPIS-Baseline SARS-CoV-2 Positive (PPIS-POS): all participants who received Dose 1 of mRNA-1273.222, had both Baseline (pre Dose 1) and Day 29 antibody assessment, had no major protocol deviations that impacted key or critical data, had not received off-study COVID-19 vaccination prior to Day 29, and were SARS-CoV-2 positive (serologic and/or virologic evidence of prior SARS-CoV-2 infection) at baseline. "Overall number of participants analyzed' = participants evaluable for this endpoint.

End point type

Primary

End point timeframe

Day 29 Study P203/Day 57 Study P301

Notes
[7] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: As prespecified in the protocol, no statistical analysis was conducted for this endpoint.

End point values	Part 3: mRNA-1273.222 50 µg	Study mRNA-1273-P301 (NCT04470427) mRNA-1273 100 μg
Number of subjects analysed	372	294
Units: AU/mL
geometric mean (confidence interval 95%)	2727.8 (2558.7 to 2908.1)	56.6 (52.7 to 60.8)

Statistical Analysis 1

Statistical analysis description

GMR of P203 vs P301

Comparison groups

Part 3: mRNA-1273.222 50 µg v Study mRNA-1273-P301 (NCT04470427) mRNA-1273 100 μg

Number of subjects included in analysis

666

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

GMR

Point estimate

48.191

Confidence interval

level

95%

sides

2-sided

lower limit

43.765

upper limit

53.065

Primary: Part 1C-2 GMC of Post-booster Pseudovirus nAb Against Ancestral Strain at BD Day 29

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End point title

Part 1C-2 GMC of Post-booster Pseudovirus nAb Against Ancestral Strain at BD Day 29 ^[8] ^[9]

End point description

Antibody values reported as below the LLOQ were replaced by 0.5 * LLOQ. Values greater than the ULOQ were replaced by the ULOQ if actual values were not available (LLOQ: 10 AU/mL, ULOQ: 111433 AU/mL). PPIS: all randomized participants who received BD in Part 1C-2, had BD-Day 29 Ab assessment for the analysis endpoint, and had no major protocol deviations that impacted key or critical data. 'Overall number of participants analyzed' = participants evaluable for this endpoint.

End point type

Primary

End point timeframe

BD Day 29

Notes
[8] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Part 1C-2 enrollment discontinued before planned number of participants were met for prespecified statistical analysis to be conducted.
[9] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Part 1C-2 enrollment discontinued before planned number of participants were met for prespecified statistical analysis to be conducted.

End point values	Part 1C-2: mRNA-1273 50 μg BD
Number of subjects analysed	134
Units: AU/mL
geometric mean (confidence interval 95%)	9433.4 (8496.8 to 10473.3)

No statistical analyses for this end point

Primary: Part 2 GMC of the Pseudovirus nAb Against Ancestral Strain at Day 57

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End point title

Part 2 GMC of the Pseudovirus nAb Against Ancestral Strain at Day 57 ^[10] ^[11]

End point description

Antibody values reported as below the LLOQ were replaced by 0.5 * LLOQ. Values greater than the ULOQ were replaced by the ULOQ if actual values were not available (LLOQ: 10 AU/mL, ULOQ: 111433 AU/mL). PPIS: all randomized participants who received at least 1 dose of the planned study drug, had Ab assessment for the analysis endpoint, and had no major protocol deviations that could impact key or critical data.

End point type

Primary

End point timeframe

Day 57

Notes
[10] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Part 2, due to the smaller number of participants enrolled, hypothesis testing was not conducted. Descriptive analysis included.
[11] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Part 2, due to the smaller number of participants enrolled, hypothesis testing was not conducted. Descriptive analysis included.

End point values	Part 2: mRNA-1273 50 μg
Number of subjects analysed	46
Units: AU/mL
geometric mean (confidence interval 95%)	7351.5 (5621.7 to 9613.7)

No statistical analyses for this end point

Primary: Part 3 GMC of nAb post Dose 1 mRNA 1273.222 Against SARS-CoV-2 Ancestral Strain Compared With Those From Young Adult (18 to 25 Years of Age) Vaccine Recipients (Day 57) in Study P301

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End point title

Part 3 GMC of nAb post Dose 1 mRNA 1273.222 Against SARS-CoV-2 Ancestral Strain Compared With Those From Young Adult (18 to 25 Years of Age) Vaccine Recipients (Day 57) in Study P301 ^[12]

End point description

Antibody values reported as below the LLOQ were replaced by 0.5*LLOQ. Values greater than the ULOQ were replaced by the ULOQ if actual values were not available (LLOQ: 10 AU/mL, ULOQ: 111433 AU/mL). ANCOVA model with the group variable (adolescents in P203 and young adults in P301) as fixed effect. The geometric least squares means are presented. P301 mRNA-1273 group included young adults (≥18 and ≤25 years) who received 2 doses of mRNA-1273 and were baseline SARS-CoV-2 negative. PPIS-POS: all participants who received Dose 1 of mRNA-1273.222, had both Baseline (pre Dose 1) and Day 29 antibody assessment, had no major protocol deviations that impacted key or critical data, had not received off-study COVID-19 vaccination prior to Day 29, and were SARS-CoV-2 positive (serologic and/or virologic evidence of prior SARS-CoV-2 infection) at baseline. 'Overall number of participants analyzed' = participants evaluable for this endpoint.

End point type

Primary

End point timeframe

Day 29 Study P203/Day 57 Study P301

Notes
[12] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: As prespecified in the protocol, no statistical analysis was conducted for this endpoint.

End point values	Part 3: mRNA-1273.222 50 µg	Study mRNA-1273-P301 (NCT04470427) mRNA-1273 100 μg
Number of subjects analysed	371	295
Units: AU/mL
geometric mean (confidence interval 95%)	7603.9 (7004.6 to 8254.6)	1692.3 (1543.4 to 1855.5)

Statistical Analysis 1

Statistical analysis description

GMR of P203 vs P301

Comparison groups

Part 3: mRNA-1273.222 50 µg v Study mRNA-1273-P301 (NCT04470427) mRNA-1273 100 μg

Number of subjects included in analysis

666

Analysis specification

Pre-specified

Analysis type

non-inferiority

Method

Parameter type

GMR

Point estimate

4.493

Confidence interval

level

95%

sides

2-sided

lower limit

3.972

upper limit

5.083

Primary: Part 2 SRR of Pseudovirus nAb Against Ancestral Strain

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End point title

Part 2 SRR of Pseudovirus nAb Against Ancestral Strain ^[13] ^[14]

End point description

End point type

Primary

End point timeframe

Day 57

Notes
[13] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Part 2, due to the smaller number of participants enrolled, hypothesis testing was not conducted. Descriptive analysis included.
[14] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Part 2, due to the smaller number of participants enrolled, hypothesis testing was not conducted. Descriptive analysis included.

End point values	Part 2: mRNA-1273 50 μg
Number of subjects analysed	46
Units: percentage of participants
number (confidence interval 95%)	91.3 (79.2 to 97.6)

No statistical analyses for this end point

Primary: Number of Participants With SAEs, AEs of Special Interest (AESIs), Medically Attended AEs (MAAEs), and AEs leading to Study Discontinuation

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End point title

Number of Participants With SAEs, AEs of Special Interest (AESIs), Medically Attended AEs (MAAEs), and AEs leading to Study Discontinuation ^[15] ^[16]

End point description

SAE was defined as any AE that resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in disability/permanent damage, was a congenital anomaly/birth defect, or was an important medical event. AESIs included thrombocytopenia, new onset of or worsening of the protocol specified neurologic diseases, anaphylaxis, and myocarditis/pericarditis. MAAE was an AE that led to an unscheduled visit to a healthcare practitioner, included visits to a study site for unscheduled assessments (for example, abnormal laboratory follow-up, and visits to healthcare practitioners external to the study site [for example, urgent care, primary care physician]). Number of participants with SAEs, AESIs, MAAEs, and AEs leading to study discontinuation up to end of study (EOS) are reported in this endpoint. Participants who received at least 1 dose of mRNA-1273 were included in the analysis.

End point type

Primary

End point timeframe

Day 1 up to Day 751 (end of study [EOS])

Notes
[15] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: As prespecified in the protocol, no statistical analysis was conducted for this endpoint.
[16] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: As prespecified in the protocol, no statistical analysis was conducted for this endpoint.

End point values	Part 1A: mRNA-1273 100 μg	Part 1C-1: mRNA-1273 50 µg BD	Part 1C-2: mRNA-1273 50 μg BD	Part 2: mRNA-1273 50 μg	Part 3: mRNA-1273.222 50 µg	Part 2: mRNA-1273 50 μg BD	Part 1B: mRNA-1273 100 μg
Number of subjects analysed	2486	1408	155	52	388	19	96
Units: participants
SAEs	21	9	3	0	16	0	2
AESIs	17	9	1	0	3	0	0
MAAEs	1040	541	45	12	183	7	31
AEs Leading to Study Discontinuation	0	0	0	0	1	0	0

No statistical analyses for this end point

Secondary: Part 1A Number of Participants with a SARS-CoV-2 Infection (Symptomatic or Asymptomatic)

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End point title

Part 1A Number of Participants with a SARS-CoV-2 Infection (Symptomatic or Asymptomatic) ^[17]

End point description

SARS-CoV-2 infection was defined in participants with negative SARS-CoV-2 status at baseline: bAb level against SARS-CoV-2 nucleocapsid protein negative at Day 1, that became positive postbaseline; or positive postbaseline. PP Set for Efficacy: all randomized participants who received planned doses of study drug, had no immunologic or virologic evidence of prior COVID-19, and had no major protocol deviations that impact key or critical efficacy data.

End point type

Secondary

End point timeframe

Day 43 (14 days after second injection) up to a median follow up of 2.5 months after second injection

Notes
[17] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: As prespecified in the protocol, no statistical analysis was conducted for this endpoint.

End point values	Part 1A: mRNA-1273 100 μg	Part 1A: Placebo
Number of subjects analysed	2142	1044
Units: participants	22	25

Statistical Analysis 1

Statistical analysis description

Vaccine efficacy (VE, percent), was defined as 1 - ratio of incidence rate (mRNA-1273 vs. placebo).

Comparison groups

Part 1A: mRNA-1273 100 μg v Part 1A: Placebo

Number of subjects included in analysis

3186

Analysis specification

Pre-specified

Analysis type

other ^[18]

Method

Parameter type

Point estimate

60.3

Confidence interval

level

95%

sides

2-sided

lower limit

26.6

upper limit

78.6

Notes
[18] - The 95% confidence interval (CI) of the ratio was calculated using the exact method conditional upon the total number of cases, adjusting for person-years.

Secondary: Part 1A Number of Participants With Asymptomatic SARS-CoV-2 Infection

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End point title

Part 1A Number of Participants With Asymptomatic SARS-CoV-2 Infection ^[19]

End point description

Asymptomatic SARS-CoV-2 infection was defined as absence of symptoms and a positive RT-PCR or serology test (bAb levels against SARS-CoV-2 nucleocapsid protein) post dosing in participants who did not have an infection at baseline or pre-Dose 1. PP Set for Efficacy: all randomized participants who received planned doses of study drug, had no immunologic or virologic evidence of prior COVID-19, and had no major protocol deviations that impact key or critical efficacy data.

End point type

Secondary

End point timeframe

Day 43 (14 days after second injection) up to a median follow up of 2.5 months after second injection

Notes
[19] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: As prespecified in the protocol, no statistical analysis was conducted for this endpoint.

End point values	Part 1A: mRNA-1273 100 μg	Part 1A: Placebo
Number of subjects analysed	2142	1044
Units: participants	20	16

Statistical Analysis 1

Statistical analysis description

VE (percent), was defined as 1 - ratio of incidence rate (mRNA-1273 vs. placebo).

Comparison groups

Part 1A: mRNA-1273 100 μg v Part 1A: Placebo

Number of subjects included in analysis

3186

Analysis specification

Pre-specified

Analysis type

other ^[20]

Method

Parameter type

Point estimate

43.5

Confidence interval

level

95%

sides

2-sided

lower limit

-16.5

upper limit

72.2

Notes
[20] - The 95% CI of the ratio was calculated using the exact method conditional upon the total number of cases, adjusting for person-years.

Secondary: Part 1A Number of Participants with a First Occurrence of Symptomatic COVID-19

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End point title

Part 1A Number of Participants with a First Occurrence of Symptomatic COVID-19 ^[21]

End point description

COVID-19 was defined as symptomatic disease based on the following criteria: participants experienced at least 2 of the following systemic symptoms: fever (≥ 38ºC/≥ 100.4ºF), chills, myalgia, headache, sore throat, new olfactory and taste disorder(s); or experienced at least 1 of the following respiratory signs/symptoms: cough, shortness of breath or difficulty breathing, or clinical or radiographical evidence of pneumonia; and had at least 1 NP swab, nasal swab, or saliva sample (or respiratory sample, if hospitalized) positive for SARS-CoV-2. PP Set for Efficacy: all randomized participants who received planned doses of study drug, had no immunologic or virologic evidence of prior COVID-19, and had no major protocol deviations that impact key or critical efficacy data.

End point type

Secondary

End point timeframe

Day 43 (14 days after second injection) up to 2.5 months after second injection

Notes
[21] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: As prespecified in the protocol, no statistical analysis was conducted for this endpoint.

End point values	Part 1A: mRNA-1273 100 μg	Part 1A: Placebo
Number of subjects analysed	2142	1044
Units: participants	0	6

Statistical Analysis 1

Statistical analysis description

VE (percent), was defined as 1 - ratio of incidence rate (mRNA-1273 vs. placebo).

Comparison groups

Part 1A: mRNA-1273 100 μg v Part 1A: Placebo

Number of subjects included in analysis

3186

Analysis specification

Pre-specified

Analysis type

other ^[22]

Method

Parameter type

Point estimate

100

Confidence interval

level

95%

sides

2-sided

lower limit

61.2

upper limit

9999

Notes
[22] - The 95% CI of the ratio was calculated using the exact method conditional upon the total number of cases, adjusting for person-years. 9999= not estimable (NE, not reached).

Secondary: Part 1A Number of Participants with Secondary Case Definition of COVID-19 (Center for Disease Control and Prevention [CDC] Case Definition)

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End point title

Part 1A Number of Participants with Secondary Case Definition of COVID-19 (Center for Disease Control and Prevention [CDC] Case Definition) ^[23]

End point description

Secondary case definition of COVID-19 was defined by the following criteria: 1 systemic or respiratory symptoms: fever (temperature > 38ºC/≥ 100.4ºF), or chills, cough, shortness of breath or difficulty breathing, fatigue, muscle aches, or body aches, headache, new loss of taste or smell, sore throat, congestion or runny nose, nausea, or vomiting or diarrhea, and at least one positive test for SARS-CoV-2. PP Set for Efficacy: all randomized participants who received planned doses of study drug, had no immunologic or virologic evidence of prior COVID-19, and had no major protocol deviations that impact key or critical efficacy data.

End point type

Secondary

End point timeframe

Day 43 (14 days after second injection) up to a median follow up of 2.5 months after second injection

Notes
[23] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: As prespecified in the protocol, no statistical analysis was conducted for this endpoint.

End point values	Part 1A: mRNA-1273 100 μg	Part 1A: Placebo
Number of subjects analysed	2142	1044
Units: participants	2	9

Statistical Analysis 1

Statistical analysis description

VE (percent), was defined as 1 - ratio of incidence rate (mRNA-1273 vs. placebo).

Comparison groups

Part 1A: mRNA-1273 100 μg v Part 1A: Placebo

Number of subjects included in analysis

3186

Analysis specification

Pre-specified

Analysis type

other ^[24]

Method

Parameter type

Point estimate

89.9

Confidence interval

level

95%

sides

2-sided

lower limit

upper limit

98.9

Notes
[24] - The 95% CI of the ratio was calculated using the exact method conditional upon the total number of cases, adjusting for person-years.

Secondary: Part 1C-1 SRR of the Post-booster Serum bAb Against Variants of Interest (B.1.1.7, B.1.351, B.1.617.2, and P.1) as Measured by MSD

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End point title

Part 1C-1 SRR of the Post-booster Serum bAb Against Variants of Interest (B.1.1.7, B.1.351, B.1.617.2, and P.1) as Measured by MSD

End point description

Seroresponse from baseline (pre-Dose 1) at a participant level was defined as a change from below the LLOQ to equal or above 4 * LLOQ, or at least a 4-fold-rise if baseline (pre-Dose 1 is equal to or above the LLOQ. PPIS: all randomized participants who received planned doses of study drug per schedule, complied with immunogenicity testing schedule, and had no major protocol deviations that impacted key or critical data. 'Overall number of participants analyzed' = participants evaluable for this endpoint.

End point type

Secondary

End point timeframe

BD Day 29

End point values	Part 1C-1: mRNA-1273 50 µg BD
Number of subjects analysed	324
Units: Percentage of participants
number (confidence interval 95%)
B.1.1.7	100.0 (98.9 to 100.0)
B.1.351	100.0 (98.9 to 100.0)
B.1.617.2	100.0 (98.9 to 100.0)
P.1	100.0 (98.9 to 100.0)

No statistical analyses for this end point

Secondary: Part 1C-1 GMC of Post-booster Pseudovirus nAb Against Variant Strain (B.1.1.529)

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End point title

Part 1C-1 GMC of Post-booster Pseudovirus nAb Against Variant Strain (B.1.1.529)

End point description

Post-booster Pseudovirus nAb against B.1.1.529 (LLOQ: 8 AU/mL, ULOQ: 24503 AU/mL). Antibody values reported as below the LLOQ were replaced by 0.5 * LLOQ. Values greater than the ULOQ were replaced by the ULOQ if actual values were not available. PP IS: all randomized participants who received planned doses of study drug per schedule, complied with immunogenicity testing schedule, and had no major protocol deviations that impacted key or critical data. 'Overall number of participants analyzed' = participants evaluable for this endpoint.

End point type

Secondary

End point timeframe

BD Day 29

End point values	Part 1C-1: mRNA-1273 50 µg BD
Number of subjects analysed	331
Units: AU/mL
geometric mean (confidence interval 95%)	943.4 (853.5 to 1042.8)

No statistical analyses for this end point

Secondary: Part 3 SRR of Serum Pseudovirus nAb Post Dose 1 of mRNA-1273.222 Against Omicron BA.4/BA.5 Compared with Young Adults (Study P301)

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End point title

Part 3 SRR of Serum Pseudovirus nAb Post Dose 1 of mRNA-1273.222 Against Omicron BA.4/BA.5 Compared with Young Adults (Study P301) ^[25]

End point description

Seroresponse from pre Dose 1 Baseline at a participant level was defined as a change from below the LLOQ to equal or above 4 * LLOQ, or at least a 4-fold rise if Baseline was equal to or above the LLOQ. P301 mRNA-1273 group included young adults (≥18 and ≤25 years) who received 2 doses of mRNA-1273 in P301 Part A and who were baseline SARS-CoV-2 negative in P301 Part A. PPIS-POS: all participants who received Dose 1 of mRNA-1273.222, had both Baseline (pre Dose 1) and Day 29 antibody assessment, had no major protocol deviations that impacted key or critical data, had not received off-study COVID-19 vaccination prior to Day 29 Visit, and who were SARS-CoV-2 positive (serologic and/or virologic evidence of prior SARS-CoV-2 infection) at baseline. ‘Overall number of participants analyzed = participants evaluable for this endpoint.

End point type

Secondary

End point timeframe

Day 29 Study P203/Day 57 Study P301

Notes
[25] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: As prespecified in the protocol, no statistical analysis was conducted for this endpoint.

End point values	Part 3: mRNA-1273.222 50 µg	Study mRNA-1273-P301 (NCT04470427) mRNA-1273 100 μg
Number of subjects analysed	372	294
Units: percentage of participants
number (confidence interval 95%)	95.4 (92.8 to 97.3)	0.0 (0.0 to 1.2)

No statistical analyses for this end point

Secondary: Part 3 Pseudovirus nAb SRR of post Dose 1 of mRNA-1273.222 Against Ancestral Strain Compared to Study P301

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End point title

Part 3 Pseudovirus nAb SRR of post Dose 1 of mRNA-1273.222 Against Ancestral Strain Compared to Study P301 ^[26]

End point description

Seroresponse from pre Dose 1 Baseline at a participant level was defined as a change from below the LLOQ to equal or above 4 * LLOQ, or at least a 4-fold rise if Baseline was equal to or above the LLOQ. P301 mRNA-1273 group included young adults (≥18 and ≤25 years) who received 2 doses of mRNA-1273 in P301 Part A and who were baseline SARS-CoV-2 negative in P301 Part A. PPIS-POS: all participants who received Dose 1 of mRNA-1273.222, had both Baseline (pre Dose 1) and Day 29 antibody assessment, had no major protocol deviations that impacted key or critical data, had not received off-study COVID-19 vaccination prior to Day 29 Visit, and who were SARS-CoV-2 positive (serologic and/or virologic evidence of prior SARS-CoV-2 infection) at baseline. 'Overall number of participants analyzed' = participants evaluable for this endpoint.

End point type

Secondary

End point timeframe

Day 29 P203/Day 57 P301

Notes
[26] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: As prespecified in the protocol, no statistical analysis was conducted for this endpoint.

End point values	Part 3: mRNA-1273.222 50 µg	Study mRNA-1273-P301 (NCT04470427) mRNA-1273 100 μg
Number of subjects analysed	370	295
Units: percentage of participants
number (confidence interval 95%)	94.9 (92.1 to 96.9)	99.3 (97.6 to 99.9)

No statistical analyses for this end point

Secondary: Part 3 GM Value of Post Dose 1 (Day 29) of mRNA-1273.222 bAb Against Other Variants of Interest

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End point title

Part 3 GM Value of Post Dose 1 (Day 29) of mRNA-1273.222 bAb Against Other Variants of Interest ^[27]

End point description

mRNA-1273.222 bAb was measured using a S-binding IgG immunoassay. Antibody values reported as below the LLOQ were replaced by 0.5 * LLOQ. Values greater than the ULOQ are replaced by the ULOQ if actual values are not available (LLOQ: 397 AU/ml, ULOQ: 2200000 AU/mL). PPIS: all participants who received Dose 1 of mRNA-1273.222 and had both Baseline (pre Dose 1) and Day 29 antibody assessment, had no major protocol deviations that impacted key or critical data; and had not received off-study COVID-19 vaccination prior to Day 29 visit.

End point type

Secondary

End point timeframe

Day 29

Notes
[27] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: As prespecified in the protocol, no statistical analysis was conducted for this endpoint.

End point values	Part 3: mRNA-1273.222 50 µg
Number of subjects analysed	372
Units: AU/mL
geometric mean (confidence interval 95%)
BA.5 (n=372)	282734.2 (266581.0 to 299866.1)
AY.4 (n=372)	557963.4 (529270.6 to 588211.6)
B.1.1.7 (n=372)	434879.0 (412699.2 to 458250.8)
B.1.351 (n=372)	431476.5 (409656.1 to 454459.1)
B.1.1.529 (n=372)	189826.0 (178578.0 to 201782.5)
P.1 (n=372)	471868.9 (446431.3 to 498756.0)

No statistical analyses for this end point

Secondary: Part 1C-2 GM Value of mRNA-1273 booster Against Variants of Interest at Day 29

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End point title

Part 1C-2 GM Value of mRNA-1273 booster Against Variants of Interest at Day 29 ^[28]

End point description

End point type

Secondary

End point timeframe

Day 29

Notes
[28] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: As prespecified in the protocol, no statistical analysis was conducted for this endpoint.

End point values	Part 1C-2: mRNA-1273 50 μg BD
Number of subjects analysed	0 ^[29]
Units: AU/mL
geometric mean (confidence interval 95%)	( to )

Notes
[29] - Data not collected due to discontinuation of enrollment.

No statistical analyses for this end point

Secondary: Part 1 A GM Level of SARS-CoV-2 Spike Protein-specific bAb at Days 1, 57, 209, 394

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End point title

Part 1 A GM Level of SARS-CoV-2 Spike Protein-specific bAb at Days 1, 57, 209, 394 ^[30]

End point description

SARS-CoV-2 Spike Protein-specific binding antibody (bAb) were measured using MesoScale Discovery (MSD) electrochemiluminescence multiplex assay. Antibody values reported as below the LLOQ were replaced by 0.5*LLOQ. Values greater than the ULOQ are replaced by the ULOQ if actual values are not available (LLOQ: 69, ULOQ: 14400000). PPIS for long term analysis included all randomized participants who received planned doses of study drug per schedule, complied with immunogenicity testing schedule, and had no major protocol deviations that impacted key or critical data. 'Overall number of participants analyzed' = participants evaluable for this endpoint.

End point type

Secondary

End point timeframe

Days 1, 57, 209, 394

Notes
[30] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: As prespecified in the protocol, no statistical analysis was conducted for this endpoint.

End point values	Part 1A: mRNA-1273 100 μg
Number of subjects analysed	369
Units: AU/mL
geometric mean (confidence interval 95%)
Day 1 (n=369)	65.848 (60.348 to 71.850)
Day 57 (n=366)	346830.736 (330758.387 to 363684.079)
Day 209 (n=366	79624.290 (73959.321 to 85723.172)
Day 394 (n=356)	58647.246 (52309.921 to 65752.336)

No statistical analyses for this end point

Secondary: Part 1A GM Value of SARS-CoV-2-Specific nAb at Days 1, 57, 209, 394

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End point title

Part 1A GM Value of SARS-CoV-2-Specific nAb at Days 1, 57, 209, 394 ^[31]

End point description

SARS-CoV-2-Specific nAb were measured using PsVNA assay. Antibody values reported as below the LLOQ were replaced by 0.5*LLOQ. Values greater than the ULOQ are replaced by the ULOQ if actual values are not available (LLOQ: 10, ULOQ: 281600). PPIS for long term analysis included all randomized participants who received planned doses of study drug per schedule, complied with immunogenicity testing schedule, and had no major protocol deviations that impacted key or critical data. 'Overall number of participants analyzed' = participants evaluable for this endpoint.

End point type

Secondary

End point timeframe

Days 1, 57, 209, 394

Notes
[31] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: As prespecified in the protocol, no statistical analysis was conducted for this endpoint.

End point values	Part 1A: mRNA-1273 100 μg
Number of subjects analysed	369
Units: AU/mL
geometric mean (confidence interval 95%)
Day 1 (n=369)	11.249 (10.712 to 11.812)
Day 57 (n=366)	1868.363 (1758.809 to 1984.742)
Day 209 (n=366)	625.363 (583.319 to 670.437)
Day 394 (n=363)	550.262 (489.875 to 618.093)

No statistical analyses for this end point

Secondary: Part 1C-1 GM Value of Post-booster Dose Serum bAb Against Variants of Interest (B.1.1.7, B.1.351, B.1.617.2, and P.1) as Measured by MSD

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End point title

Part 1C-1 GM Value of Post-booster Dose Serum bAb Against Variants of Interest (B.1.1.7, B.1.351, B.1.617.2, and P.1) as Measured by MSD

End point description

Antibody values reported as below the LLOQ were replaced by 0.5*LLOQ. Values greater than the ULOQ were replaced by the ULOQ if actual values were not available. B.1.1.7 (LLOQ: 52, ULOQ: 8800000), B.1.351 (LLOQ: 111, ULOQ: 5000000), B.1.617.2 (LLOQ: 49, ULOQ: 7400000), P.1 (LLOQ: 143, ULOQ: 5800000). PPIS: all randomized participants who received planned doses of study drug per schedule, complied with immunogenicity testing schedule, and had no major protocol deviations that impacted key or critical data. 'Overall number of participants analyzed' = participants evaluable for this endpoint.

End point type

Secondary

End point timeframe

BD Day 29

End point values	Part 1C-1: mRNA-1273 50 µg BD
Number of subjects analysed	324
Units: AU/mL
geometric mean (confidence interval 95%)
B.1.1.7	581097.8 (543987.7 to 620739.5)
B.1.351	431569.2 (404983.2 to 459900.6)
B.1.617.2	456423.3 (429083.9 to 485504.8)
P.1	417277.2 (391682.5 to 444544.5)

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

Day 1 up to EOS (Day 751)

Adverse event reporting additional description

All-cause mortality: enrolled; AEs: participants received 1 dose of study drug. Non-serious SARs persisting beyond 7 days, leading to discontinuation, or medically attended were defined as AEs in Part 1/2 but not in Part 3. COVID-19/SARS-CoV-2 infections were AEs in Part 1/2 but were considered clinical events for efficacy in Part 3 and not AEs.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

23.0

Reporting group title

Part 1A: Placebo

Reporting group description

Participants received 2 doses of placebo by IM injection (Day 1 and Day 29).

Reporting group title

Part 1A: mRNA-1273 100 μg

Reporting group description

Participants received 2 doses of 100 μg mRNA-1273 by IM injection (Day 1 and Day 29).

Reporting group title

Part 1 B: mRNA-1273 100 µg

Reporting group description

Participants previously received 2 doses of placebo in the blinded phase and then received crossover vaccination with 100 μg of mRNA-1273.

Reporting group title

Part 2: mRNA-1273 50 ug BD

Reporting group description

Participants received open-label mRNA-1273 50 µg in Part 2 and then a single BD of 50 μg mRNA-1273 IM injection on BD Day 1 in Part 2.

Reporting group title

Part 3: mRNA-1273.222 50 ug Second Dose

Reporting group description

Participants received 1 dose of mRNA-1273.222 50 µg by IM injection (Day 1). and a second dose approximately 6 months after the first dose (Day 181).

Reporting group title

Part 2: mRNA-1273 50 μg

Reporting group description

Participants received 2 doses of 50 μg mRNA-1273 by IM injection (Day 1 and Day 29).

Reporting group title

Part 1C-2: mRNA-1273 50 μg BD‌

Reporting group description

Participants who completed primary COVID-19 vaccination series with a non-Moderna vaccine under EUA, received a single booster of 50 μg mRNA-1273 IM injection on BD Day 1.

Reporting group title

Part 1C-1: mRNA-1273 50 µg BD

Reporting group description

Participants received mRNA-1273 100 µg in blinded or cross-over phase and then a single booster of 50 μg mRNA-1273 IM injection on Booster Dose Day 1.

Reporting group title

Part 3: mRNA1273.222 50 µg 1 Dose

Reporting group description

Participants received 1 dose of mRNA-1273.222 50 µg by IM injection (Day 1).

Serious adverse events	Part 1A: Placebo	Part 1A: mRNA-1273 100 μg	Part 1 B: mRNA-1273 100 µg	Part 2: mRNA-1273 50 ug BD	Part 3: mRNA-1273.222 50 ug Second Dose	Part 2: mRNA-1273 50 μg	Part 1C-2: mRNA-1273 50 μg BD‌	Part 1C-1: mRNA-1273 50 µg BD	Part 3: mRNA1273.222 50 µg 1 Dose
Total subjects affected by serious adverse events
subjects affected / exposed	4 / 1240 (0.32%)	21 / 2486 (0.84%)	2 / 96 (2.08%)	0 / 19 (0.00%)	4 / 335 (1.19%)	0 / 52 (0.00%)	3 / 155 (1.94%)	9 / 1408 (0.64%)	12 / 388 (3.09%)
number of deaths (all causes)	0	0	0	0	1	0	0	0	0
number of deaths resulting from adverse events
Vascular disorders
Hypertension
subjects affected / exposed	0 / 1240 (0.00%)	0 / 2486 (0.00%)	0 / 96 (0.00%)	0 / 19 (0.00%)	1 / 335 (0.30%)	0 / 52 (0.00%)	0 / 155 (0.00%)	0 / 1408 (0.00%)	1 / 388 (0.26%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pregnancy, puerperium and perinatal conditions
Abortion
subjects affected / exposed	0 / 1240 (0.00%)	0 / 2486 (0.00%)	0 / 96 (0.00%)	0 / 19 (0.00%)	0 / 335 (0.00%)	0 / 52 (0.00%)	0 / 155 (0.00%)	0 / 1408 (0.00%)	1 / 388 (0.26%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Abortion spontaneous
subjects affected / exposed	0 / 1240 (0.00%)	0 / 2486 (0.00%)	0 / 96 (0.00%)	0 / 19 (0.00%)	2 / 335 (0.60%)	0 / 52 (0.00%)	0 / 155 (0.00%)	0 / 1408 (0.00%)	0 / 388 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 2	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Immune system disorders
Anaphylactic reaction
subjects affected / exposed	0 / 1240 (0.00%)	0 / 2486 (0.00%)	0 / 96 (0.00%)	0 / 19 (0.00%)	0 / 335 (0.00%)	0 / 52 (0.00%)	1 / 155 (0.65%)	0 / 1408 (0.00%)	0 / 388 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Reproductive system and breast disorders
Vaginal haematoma
subjects affected / exposed	0 / 1240 (0.00%)	0 / 2486 (0.00%)	0 / 96 (0.00%)	0 / 19 (0.00%)	0 / 335 (0.00%)	0 / 52 (0.00%)	0 / 155 (0.00%)	1 / 1408 (0.07%)	0 / 388 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Psychiatric disorders
Depression
subjects affected / exposed	0 / 1240 (0.00%)	1 / 2486 (0.04%)	0 / 96 (0.00%)	0 / 19 (0.00%)	0 / 335 (0.00%)	0 / 52 (0.00%)	0 / 155 (0.00%)	1 / 1408 (0.07%)	1 / 388 (0.26%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Depression suicidal
subjects affected / exposed	0 / 1240 (0.00%)	1 / 2486 (0.04%)	0 / 96 (0.00%)	0 / 19 (0.00%)	0 / 335 (0.00%)	0 / 52 (0.00%)	0 / 155 (0.00%)	0 / 1408 (0.00%)	0 / 388 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Emotional distress
subjects affected / exposed	0 / 1240 (0.00%)	0 / 2486 (0.00%)	0 / 96 (0.00%)	0 / 19 (0.00%)	0 / 335 (0.00%)	0 / 52 (0.00%)	0 / 155 (0.00%)	1 / 1408 (0.07%)	0 / 388 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Major depression
subjects affected / exposed	0 / 1240 (0.00%)	2 / 2486 (0.08%)	0 / 96 (0.00%)	0 / 19 (0.00%)	0 / 335 (0.00%)	0 / 52 (0.00%)	0 / 155 (0.00%)	0 / 1408 (0.00%)	0 / 388 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 2	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Suicidal ideation
subjects affected / exposed	0 / 1240 (0.00%)	5 / 2486 (0.20%)	1 / 96 (1.04%)	0 / 19 (0.00%)	0 / 335 (0.00%)	0 / 52 (0.00%)	0 / 155 (0.00%)	2 / 1408 (0.14%)	0 / 388 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 5	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Suicide attempt
subjects affected / exposed	1 / 1240 (0.08%)	3 / 2486 (0.12%)	0 / 96 (0.00%)	0 / 19 (0.00%)	0 / 335 (0.00%)	0 / 52 (0.00%)	0 / 155 (0.00%)	1 / 1408 (0.07%)	0 / 388 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 3	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Investigations
Hepatic enzyme increased
subjects affected / exposed	0 / 1240 (0.00%)	0 / 2486 (0.00%)	0 / 96 (0.00%)	0 / 19 (0.00%)	0 / 335 (0.00%)	0 / 52 (0.00%)	0 / 155 (0.00%)	1 / 1408 (0.07%)	0 / 388 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Injury, poisoning and procedural complications
Clavicle fracture
subjects affected / exposed	0 / 1240 (0.00%)	1 / 2486 (0.04%)	0 / 96 (0.00%)	0 / 19 (0.00%)	0 / 335 (0.00%)	0 / 52 (0.00%)	0 / 155 (0.00%)	0 / 1408 (0.00%)	0 / 388 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Concussion
subjects affected / exposed	0 / 1240 (0.00%)	1 / 2486 (0.04%)	0 / 96 (0.00%)	0 / 19 (0.00%)	0 / 335 (0.00%)	0 / 52 (0.00%)	0 / 155 (0.00%)	0 / 1408 (0.00%)	0 / 388 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cervical vertebral fracture
subjects affected / exposed	0 / 1240 (0.00%)	0 / 2486 (0.00%)	0 / 96 (0.00%)	0 / 19 (0.00%)	0 / 335 (0.00%)	0 / 52 (0.00%)	0 / 155 (0.00%)	1 / 1408 (0.07%)	0 / 388 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gun shot wound
subjects affected / exposed	0 / 1240 (0.00%)	0 / 2486 (0.00%)	0 / 96 (0.00%)	0 / 19 (0.00%)	1 / 335 (0.30%)	0 / 52 (0.00%)	0 / 155 (0.00%)	0 / 1408 (0.00%)	0 / 388 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
Post procedural fever
subjects affected / exposed	0 / 1240 (0.00%)	1 / 2486 (0.04%)	0 / 96 (0.00%)	0 / 19 (0.00%)	0 / 335 (0.00%)	0 / 52 (0.00%)	0 / 155 (0.00%)	0 / 1408 (0.00%)	0 / 388 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Road traffic accident
subjects affected / exposed	0 / 1240 (0.00%)	0 / 2486 (0.00%)	1 / 96 (1.04%)	0 / 19 (0.00%)	0 / 335 (0.00%)	0 / 52 (0.00%)	0 / 155 (0.00%)	0 / 1408 (0.00%)	0 / 388 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Facial bones fracture
subjects affected / exposed	0 / 1240 (0.00%)	1 / 2486 (0.04%)	0 / 96 (0.00%)	0 / 19 (0.00%)	0 / 335 (0.00%)	0 / 52 (0.00%)	0 / 155 (0.00%)	0 / 1408 (0.00%)	0 / 388 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Femur fracture
subjects affected / exposed	0 / 1240 (0.00%)	1 / 2486 (0.04%)	0 / 96 (0.00%)	0 / 19 (0.00%)	0 / 335 (0.00%)	0 / 52 (0.00%)	0 / 155 (0.00%)	0 / 1408 (0.00%)	0 / 388 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Sunburn
subjects affected / exposed	0 / 1240 (0.00%)	1 / 2486 (0.04%)	0 / 96 (0.00%)	0 / 19 (0.00%)	0 / 335 (0.00%)	0 / 52 (0.00%)	0 / 155 (0.00%)	0 / 1408 (0.00%)	0 / 388 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Splenic injury
subjects affected / exposed	0 / 1240 (0.00%)	1 / 2486 (0.04%)	0 / 96 (0.00%)	0 / 19 (0.00%)	0 / 335 (0.00%)	0 / 52 (0.00%)	0 / 155 (0.00%)	0 / 1408 (0.00%)	0 / 388 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Vulvovaginal injury
subjects affected / exposed	0 / 1240 (0.00%)	0 / 2486 (0.00%)	0 / 96 (0.00%)	0 / 19 (0.00%)	0 / 335 (0.00%)	0 / 52 (0.00%)	0 / 155 (0.00%)	1 / 1408 (0.07%)	0 / 388 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Congenital, familial and genetic disorders
Pectus excavatum
subjects affected / exposed	0 / 1240 (0.00%)	1 / 2486 (0.04%)	0 / 96 (0.00%)	0 / 19 (0.00%)	0 / 335 (0.00%)	0 / 52 (0.00%)	0 / 155 (0.00%)	0 / 1408 (0.00%)	0 / 388 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Syringomyelia
subjects affected / exposed	0 / 1240 (0.00%)	1 / 2486 (0.04%)	0 / 96 (0.00%)	0 / 19 (0.00%)	0 / 335 (0.00%)	0 / 52 (0.00%)	0 / 155 (0.00%)	0 / 1408 (0.00%)	0 / 388 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Arnold-Chiari malformation
subjects affected / exposed	0 / 1240 (0.00%)	1 / 2486 (0.04%)	0 / 96 (0.00%)	0 / 19 (0.00%)	0 / 335 (0.00%)	0 / 52 (0.00%)	0 / 155 (0.00%)	0 / 1408 (0.00%)	0 / 388 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cardiac disorders
Cardiogenic shock
Additional description: Sponsor assessment was Not related based on medical history, results of the heart biopsy, including findings of long-standing pre-existing heart failure and long time to onset (256 days).
subjects affected / exposed	0 / 1240 (0.00%)	0 / 2486 (0.00%)	0 / 96 (0.00%)	0 / 19 (0.00%)	0 / 335 (0.00%)	0 / 52 (0.00%)	0 / 155 (0.00%)	0 / 1408 (0.00%)	1 / 388 (0.26%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Nervous system disorders
Status migrainosus
subjects affected / exposed	0 / 1240 (0.00%)	0 / 2486 (0.00%)	0 / 96 (0.00%)	0 / 19 (0.00%)	0 / 335 (0.00%)	0 / 52 (0.00%)	0 / 155 (0.00%)	1 / 1408 (0.07%)	0 / 388 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Seizure
subjects affected / exposed	0 / 1240 (0.00%)	0 / 2486 (0.00%)	0 / 96 (0.00%)	0 / 19 (0.00%)	0 / 335 (0.00%)	0 / 52 (0.00%)	1 / 155 (0.65%)	0 / 1408 (0.00%)	0 / 388 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Idiopathic generalised epilepsy
subjects affected / exposed	0 / 1240 (0.00%)	1 / 2486 (0.04%)	0 / 96 (0.00%)	0 / 19 (0.00%)	0 / 335 (0.00%)	0 / 52 (0.00%)	0 / 155 (0.00%)	0 / 1408 (0.00%)	0 / 388 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Epilepsy
subjects affected / exposed	1 / 1240 (0.08%)	0 / 2486 (0.00%)	0 / 96 (0.00%)	0 / 19 (0.00%)	0 / 335 (0.00%)	0 / 52 (0.00%)	0 / 155 (0.00%)	0 / 1408 (0.00%)	0 / 388 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Blood and lymphatic system disorders
Normochromic normocytic anaemia
subjects affected / exposed	0 / 1240 (0.00%)	0 / 2486 (0.00%)	0 / 96 (0.00%)	0 / 19 (0.00%)	1 / 335 (0.30%)	0 / 52 (0.00%)	0 / 155 (0.00%)	0 / 1408 (0.00%)	0 / 388 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hypercoagulation
Additional description: Sponsor assessment was Not related based on medical history, results of the heart biopsy, including findings of long-standing pre-existing heart failure and long time to onset (256 days).
subjects affected / exposed	0 / 1240 (0.00%)	0 / 2486 (0.00%)	0 / 96 (0.00%)	0 / 19 (0.00%)	0 / 335 (0.00%)	0 / 52 (0.00%)	0 / 155 (0.00%)	0 / 1408 (0.00%)	1 / 388 (0.26%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
Vomiting
subjects affected / exposed	0 / 1240 (0.00%)	1 / 2486 (0.04%)	0 / 96 (0.00%)	0 / 19 (0.00%)	0 / 335 (0.00%)	0 / 52 (0.00%)	0 / 155 (0.00%)	0 / 1408 (0.00%)	0 / 388 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Diarrhoea
subjects affected / exposed	0 / 1240 (0.00%)	1 / 2486 (0.04%)	0 / 96 (0.00%)	0 / 19 (0.00%)	0 / 335 (0.00%)	0 / 52 (0.00%)	0 / 155 (0.00%)	0 / 1408 (0.00%)	0 / 388 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hepatobiliary disorders
Hyperbilirubinaemia neonatal
subjects affected / exposed	0 / 1240 (0.00%)	0 / 2486 (0.00%)	0 / 96 (0.00%)	0 / 19 (0.00%)	0 / 335 (0.00%)	0 / 52 (0.00%)	0 / 155 (0.00%)	0 / 1408 (0.00%)	1 / 388 (0.26%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Drug-induced liver injury
subjects affected / exposed	0 / 1240 (0.00%)	1 / 2486 (0.04%)	0 / 96 (0.00%)	0 / 19 (0.00%)	0 / 335 (0.00%)	0 / 52 (0.00%)	0 / 155 (0.00%)	0 / 1408 (0.00%)	0 / 388 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Renal and urinary disorders
Nephrolithiasis
subjects affected / exposed	0 / 1240 (0.00%)	0 / 2486 (0.00%)	0 / 96 (0.00%)	0 / 19 (0.00%)	0 / 335 (0.00%)	0 / 52 (0.00%)	1 / 155 (0.65%)	0 / 1408 (0.00%)	0 / 388 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Nephrotic syndrome
subjects affected / exposed	0 / 1240 (0.00%)	0 / 2486 (0.00%)	0 / 96 (0.00%)	0 / 19 (0.00%)	1 / 335 (0.30%)	0 / 52 (0.00%)	0 / 155 (0.00%)	0 / 1408 (0.00%)	0 / 388 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Chronic kidney disease
subjects affected / exposed	0 / 1240 (0.00%)	0 / 2486 (0.00%)	0 / 96 (0.00%)	0 / 19 (0.00%)	1 / 335 (0.30%)	0 / 52 (0.00%)	0 / 155 (0.00%)	0 / 1408 (0.00%)	0 / 388 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Obstructive nephropathy
subjects affected / exposed	1 / 1240 (0.08%)	0 / 2486 (0.00%)	0 / 96 (0.00%)	0 / 19 (0.00%)	0 / 335 (0.00%)	0 / 52 (0.00%)	0 / 155 (0.00%)	0 / 1408 (0.00%)	0 / 388 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Infections and infestations
Amoebic dysentery
subjects affected / exposed	0 / 1240 (0.00%)	0 / 2486 (0.00%)	0 / 96 (0.00%)	0 / 19 (0.00%)	0 / 335 (0.00%)	0 / 52 (0.00%)	0 / 155 (0.00%)	0 / 1408 (0.00%)	1 / 388 (0.26%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Murine typhus
subjects affected / exposed	0 / 1240 (0.00%)	1 / 2486 (0.04%)	0 / 96 (0.00%)	0 / 19 (0.00%)	0 / 335 (0.00%)	0 / 52 (0.00%)	0 / 155 (0.00%)	0 / 1408 (0.00%)	0 / 388 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Dengue fever
subjects affected / exposed	0 / 1240 (0.00%)	0 / 2486 (0.00%)	0 / 96 (0.00%)	0 / 19 (0.00%)	0 / 335 (0.00%)	0 / 52 (0.00%)	0 / 155 (0.00%)	0 / 1408 (0.00%)	5 / 388 (1.29%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 5
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cellulitis
subjects affected / exposed	0 / 1240 (0.00%)	0 / 2486 (0.00%)	0 / 96 (0.00%)	0 / 19 (0.00%)	0 / 335 (0.00%)	0 / 52 (0.00%)	0 / 155 (0.00%)	0 / 1408 (0.00%)	1 / 388 (0.26%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pneumonia
subjects affected / exposed	0 / 1240 (0.00%)	0 / 2486 (0.00%)	0 / 96 (0.00%)	0 / 19 (0.00%)	0 / 335 (0.00%)	0 / 52 (0.00%)	0 / 155 (0.00%)	0 / 1408 (0.00%)	1 / 388 (0.26%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Appendicitis
subjects affected / exposed	1 / 1240 (0.08%)	2 / 2486 (0.08%)	0 / 96 (0.00%)	0 / 19 (0.00%)	0 / 335 (0.00%)	0 / 52 (0.00%)	0 / 155 (0.00%)	1 / 1408 (0.07%)	0 / 388 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 2	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Peritonitis
subjects affected / exposed	0 / 1240 (0.00%)	0 / 2486 (0.00%)	0 / 96 (0.00%)	0 / 19 (0.00%)	1 / 335 (0.30%)	0 / 52 (0.00%)	0 / 155 (0.00%)	0 / 1408 (0.00%)	0 / 388 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Metabolism and nutrition disorders
Decreased appetite
subjects affected / exposed	0 / 1240 (0.00%)	0 / 2486 (0.00%)	0 / 96 (0.00%)	0 / 19 (0.00%)	0 / 335 (0.00%)	0 / 52 (0.00%)	0 / 155 (0.00%)	1 / 1408 (0.07%)	0 / 388 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Dehydration
subjects affected / exposed	0 / 1240 (0.00%)	0 / 2486 (0.00%)	0 / 96 (0.00%)	0 / 19 (0.00%)	0 / 335 (0.00%)	0 / 52 (0.00%)	0 / 155 (0.00%)	1 / 1408 (0.07%)	1 / 388 (0.26%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Metabolic acidosis
subjects affected / exposed	0 / 1240 (0.00%)	0 / 2486 (0.00%)	0 / 96 (0.00%)	0 / 19 (0.00%)	1 / 335 (0.30%)	0 / 52 (0.00%)	0 / 155 (0.00%)	0 / 1408 (0.00%)	0 / 388 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hyperkalaemia
subjects affected / exposed	0 / 1240 (0.00%)	0 / 2486 (0.00%)	0 / 96 (0.00%)	0 / 19 (0.00%)	1 / 335 (0.30%)	0 / 52 (0.00%)	0 / 155 (0.00%)	0 / 1408 (0.00%)	0 / 388 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hypocalcaemia
subjects affected / exposed	0 / 1240 (0.00%)	0 / 2486 (0.00%)	0 / 96 (0.00%)	0 / 19 (0.00%)	1 / 335 (0.30%)	0 / 52 (0.00%)	0 / 155 (0.00%)	0 / 1408 (0.00%)	0 / 388 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 5%

Non-serious adverse events	Part 1A: Placebo	Part 1A: mRNA-1273 100 μg	Part 1 B: mRNA-1273 100 µg	Part 2: mRNA-1273 50 ug BD	Part 3: mRNA-1273.222 50 ug Second Dose	Part 2: mRNA-1273 50 μg	Part 1C-2: mRNA-1273 50 μg BD‌	Part 1C-1: mRNA-1273 50 µg BD	Part 3: mRNA1273.222 50 µg 1 Dose
Total subjects affected by non serious adverse events
subjects affected / exposed	155 / 1240 (12.50%)	943 / 2486 (37.93%)	22 / 96 (22.92%)	7 / 19 (36.84%)	51 / 335 (15.22%)	12 / 52 (23.08%)	28 / 155 (18.06%)	429 / 1408 (30.47%)	77 / 388 (19.85%)
Nervous system disorders
Headache
subjects affected / exposed	51 / 1240 (4.11%)	117 / 2486 (4.71%)	1 / 96 (1.04%)	0 / 19 (0.00%)	5 / 335 (1.49%)	1 / 52 (1.92%)	1 / 155 (0.65%)	28 / 1408 (1.99%)	20 / 388 (5.15%)
occurrences all number	57	129	1	0	5	1	1	29	27
General disorders and administration site conditions
Injection site lymphadenopathy
subjects affected / exposed	6 / 1240 (0.48%)	137 / 2486 (5.51%)	0 / 96 (0.00%)	0 / 19 (0.00%)	0 / 335 (0.00%)	1 / 52 (1.92%)	0 / 155 (0.00%)	5 / 1408 (0.36%)	0 / 388 (0.00%)
occurrences all number	6	146	0	0	0	1	0	5	0
Gastrointestinal disorders
Abdominal pain
subjects affected / exposed	3 / 1240 (0.24%)	8 / 2486 (0.32%)	0 / 96 (0.00%)	1 / 19 (5.26%)	1 / 335 (0.30%)	0 / 52 (0.00%)	0 / 155 (0.00%)	6 / 1408 (0.43%)	1 / 388 (0.26%)
occurrences all number	3	9	0	1	1	0	0	6	1
Skin and subcutaneous tissue disorders
Mechanical urticaria
subjects affected / exposed	0 / 1240 (0.00%)	0 / 2486 (0.00%)	0 / 96 (0.00%)	1 / 19 (5.26%)	0 / 335 (0.00%)	0 / 52 (0.00%)	0 / 155 (0.00%)	0 / 1408 (0.00%)	0 / 388 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0
Parapsoriasis
subjects affected / exposed	0 / 1240 (0.00%)	0 / 2486 (0.00%)	0 / 96 (0.00%)	1 / 19 (5.26%)	0 / 335 (0.00%)	0 / 52 (0.00%)	0 / 155 (0.00%)	0 / 1408 (0.00%)	0 / 388 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0
Psychiatric disorders
Anxiety
subjects affected / exposed	3 / 1240 (0.24%)	58 / 2486 (2.33%)	1 / 96 (1.04%)	1 / 19 (5.26%)	1 / 335 (0.30%)	0 / 52 (0.00%)	1 / 155 (0.65%)	26 / 1408 (1.85%)	0 / 388 (0.00%)
occurrences all number	3	60	1	1	1	0	1	27	0
Attention deficit hyperactivity disorder
subjects affected / exposed	6 / 1240 (0.48%)	41 / 2486 (1.65%)	0 / 96 (0.00%)	0 / 19 (0.00%)	0 / 335 (0.00%)	3 / 52 (5.77%)	2 / 155 (1.29%)	14 / 1408 (0.99%)	0 / 388 (0.00%)
occurrences all number	6	41	0	0	0	3	2	14	0
Infections and infestations
Respiratory tract infection
subjects affected / exposed	4 / 1240 (0.32%)	11 / 2486 (0.44%)	0 / 96 (0.00%)	0 / 19 (0.00%)	22 / 335 (6.57%)	0 / 52 (0.00%)	1 / 155 (0.65%)	2 / 1408 (0.14%)	26 / 388 (6.70%)
occurrences all number	4	12	0	0	30	0	1	2	34
Parainfluenzae virus infection
subjects affected / exposed	0 / 1240 (0.00%)	3 / 2486 (0.12%)	1 / 96 (1.04%)	1 / 19 (5.26%)	0 / 335 (0.00%)	0 / 52 (0.00%)	1 / 155 (0.65%)	2 / 1408 (0.14%)	1 / 388 (0.26%)
occurrences all number	0	3	1	1	0	0	1	2	1
COVID-19
subjects affected / exposed	34 / 1240 (2.74%)	382 / 2486 (15.37%)	11 / 96 (11.46%)	3 / 19 (15.79%)	0 / 335 (0.00%)	3 / 52 (5.77%)	10 / 155 (6.45%)	257 / 1408 (18.25%)	0 / 388 (0.00%)
occurrences all number	35	383	11	3	0	3	10	267	0
Influenza
subjects affected / exposed	0 / 1240 (0.00%)	19 / 2486 (0.76%)	1 / 96 (1.04%)	2 / 19 (10.53%)	0 / 335 (0.00%)	1 / 52 (1.92%)	7 / 155 (4.52%)	30 / 1408 (2.13%)	5 / 388 (1.29%)
occurrences all number	0	20	1	2	0	1	8	30	6
Nasopharyngitis
subjects affected / exposed	6 / 1240 (0.48%)	60 / 2486 (2.41%)	4 / 96 (4.17%)	0 / 19 (0.00%)	23 / 335 (6.87%)	0 / 52 (0.00%)	0 / 155 (0.00%)	16 / 1408 (1.14%)	30 / 388 (7.73%)
occurrences all number	6	64	4	0	26	0	0	17	34
Asymptomatic COVID-19
subjects affected / exposed	25 / 1240 (2.02%)	81 / 2486 (3.26%)	6 / 96 (6.25%)	0 / 19 (0.00%)	0 / 335 (0.00%)	2 / 52 (3.85%)	2 / 155 (1.29%)	39 / 1408 (2.77%)	0 / 388 (0.00%)
occurrences all number	25	82	6	0	0	2	2	39	0
Tooth abscess
subjects affected / exposed	0 / 1240 (0.00%)	2 / 2486 (0.08%)	0 / 96 (0.00%)	1 / 19 (5.26%)	1 / 335 (0.30%)	0 / 52 (0.00%)	0 / 155 (0.00%)	1 / 1408 (0.07%)	0 / 388 (0.00%)
occurrences all number	0	2	0	1	1	0	0	1	0
Upper respiratory tract infection
subjects affected / exposed	28 / 1240 (2.26%)	257 / 2486 (10.34%)	3 / 96 (3.13%)	1 / 19 (5.26%)	0 / 335 (0.00%)	2 / 52 (3.85%)	6 / 155 (3.87%)	81 / 1408 (5.75%)	4 / 388 (1.03%)
occurrences all number	32	293	3	1	0	2	8	101	4

More information

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Were there any global substantial amendments to the protocol? Yes

23 Mar 2021

- Addition of the crossover design - Study design was updated to describe the updated crossover design of the study, including Part A (the Blinded Phase) and Part B (the Open-label Observational Phase).

27 Jul 2021

- Added CDC case definitions for myocarditis and pericarditis. - Added assessment of risk of myocarditis and pericarditis.

04 Nov 2021

- Added Part C to the study. - Updated long-term analysis and Booster Phase analysis. - Addition of booster interim analyses. - Added nasal swab for samples for SARS-CoV-2. - Clarified that only Part A and Part C will have primary immunogenicity analyses.

25 Jan 2022

- Added Part 1C-2 and Part 2.

11 Oct 2022

- Modifications to primary objectives and endpoints, secondary endpoints, statistical hypothesis, power and sample size, analysis, and procedures in Part 2 of the study. - Clarified that immunogenicity hypothesis testing will not be performed for Part 2. - Discontinuation of enrollment in Part 1C-2 and Part 2 of the study. - Clarified that Convalescent Visits are applicable to Part 1A and 1B only. - Removed BD from Part 2 and convalescent visits from Part 1C-1, Part 1C-2, and Part 2 of the study. - Added an open-label Part 3 of the study. - Updated exclusion criteria. - Updated study assessments and procedures.

22 Jun 2023

-Modifications to primary and (key) secondary immunogenicity objectives and endpoints, statistical hypothesis, power and sample size, and analysis in Part 3 of the study. - Updated inclusion/exclusion criteria - Clarifying the definition of the SARS-CoV-2 status at baseline.

19 Oct 2023

- Updated Part 3 study design and objective to single dosing. - Updated to single dosing in Part 3. - Reduced safety follow-up duration for Part 3 participants who receive Dose 2. - Updated timepoints for collection of blood samples and nasopharyngeal or nasal swab samples. -Clarification of the end-of-study definition. - Clarification added on the time period for recording all concomitant medications and nonstudy vaccinations in the electronic case report form. - Updated safety assessments related to single dosing in Part 3. -Updated PP Immunogenicity Subset for Part 3. - Addition of schedule of assessments for Part 3 participants who receive only 1 dose. - Addition of schedule of assessments for Part 2 participants who receive the booster dose.

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

Part 1C-2 enrollment discontinued before planned number of participants. Part 2 discontinued early due to availability of updated variant vaccine (mRNA-1273.222); no hypothesis testing done for primary endpoint/other endpoints not assessed.

http://www.ncbi.nlm.nih.gov/pubmed/34379915
http://www.ncbi.nlm.nih.gov/pubmed/39091673
http://www.ncbi.nlm.nih.gov/pubmed/39332418

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Clinical trials

Clinical Trial Results: A Phase 2/3, Randomized, Observer-Blind, Placebo-Controlled Study to Evaluate the Safety, Reactogenicity, and Effectiveness of mRNA-1273 SARS-CoV-2 Vaccine in Healthy Adolescents 12 to <18 Years of Age

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Number of Participants With Solicited Local and Systemic Adverse Reactions (ARs)

Primary: Number of Participants With Solicited Local and Systemic Adverse Reactions (ARs)

Primary: Number of Participants With Unsolicited AEs

Primary: Number of Participants With Unsolicited AEs

Primary: Part 1A Geometric Mean Value of Serum Pseudovirus Neutralizing Antibody (nAb) ID50 Titers From Study P203 Vaccine Recipients at Day 57 Compared With Those From Young Adult (18 to 25 Years of Age) Vaccine Recipients (Day 57) in Study P301

Primary: Part 1A Geometric Mean Value of Serum Pseudovirus Neutralizing Antibody (nAb) ID50 Titers From Study P203 Vaccine Recipients at Day 57 Compared With Those From Young Adult (18 to 25 Years of Age) Vaccine Recipients (Day 57) in Study P301

Primary: Part 1A Seroresponse Rate (SRR) for Serum Pseudovirus nAb ID50 in Study P203 Vaccine Recipients at Day 57 Compared With Those From Young Adult (18 to 25 Years of Age) Vaccine Recipients (Day 57) in Study P301

Primary: Part 1A Seroresponse Rate (SRR) for Serum Pseudovirus nAb ID50 in Study P203 Vaccine Recipients at Day 57 Compared With Those From Young Adult (18 to 25 Years of Age) Vaccine Recipients (Day 57) in Study P301

Primary: Part 1C-1 Geometric Mean Concentration (GMC) of Serum Pseudovirus nAb Against the Original Strain After the BD in Study P203 at BD Day 29 Compared With Those From Young Adult (18 to 25 Years of Age) Vaccine Recipients (Day 57) in Study P301

Primary: Part 1C-1 Geometric Mean Concentration (GMC) of Serum Pseudovirus nAb Against the Original Strain After the BD in Study P203 at BD Day 29 Compared With Those From Young Adult (18 to 25 Years of Age) Vaccine Recipients (Day 57) in Study P301

Primary: Part 1C-1 SRR of Serum Pseudovirus nAb Against the Original Strain After the BD in Study P203 at BD Day 29 Compared With Those From Young Adult (18 to 25 Years of Age) Vaccine Recipients (Day 57) in Study P301

Primary: Part 1C-1 SRR of Serum Pseudovirus nAb Against the Original Strain After the BD in Study P203 at BD Day 29 Compared With Those From Young Adult (18 to 25 Years of Age) Vaccine Recipients (Day 57) in Study P301

Primary: Part 3 GMC of nAb post Dose 1 mRNA 1273.222 Against Omicron BA.4/BA.5 Compared With Those From Young Adult (18 to 25 Years of Age) Vaccine Recipients (Day 57) in Study P301

Primary: Part 3 GMC of nAb post Dose 1 mRNA 1273.222 Against Omicron BA.4/BA.5 Compared With Those From Young Adult (18 to 25 Years of Age) Vaccine Recipients (Day 57) in Study P301

Primary: Part 1C-2 GMC of Post-booster Pseudovirus nAb Against Ancestral Strain at BD Day 29

Primary: Part 1C-2 GMC of Post-booster Pseudovirus nAb Against Ancestral Strain at BD Day 29

Primary: Part 2 GMC of the Pseudovirus nAb Against Ancestral Strain at Day 57

Primary: Part 2 GMC of the Pseudovirus nAb Against Ancestral Strain at Day 57

Primary: Part 3 GMC of nAb post Dose 1 mRNA 1273.222 Against SARS-CoV-2 Ancestral Strain Compared With Those From Young Adult (18 to 25 Years of Age) Vaccine Recipients (Day 57) in Study P301

Primary: Part 3 GMC of nAb post Dose 1 mRNA 1273.222 Against SARS-CoV-2 Ancestral Strain Compared With Those From Young Adult (18 to 25 Years of Age) Vaccine Recipients (Day 57) in Study P301

Primary: Part 2 SRR of Pseudovirus nAb Against Ancestral Strain

Primary: Part 2 SRR of Pseudovirus nAb Against Ancestral Strain

Primary: Number of Participants With SAEs, AEs of Special Interest (AESIs), Medically Attended AEs (MAAEs), and AEs leading to Study Discontinuation

Primary: Number of Participants With SAEs, AEs of Special Interest (AESIs), Medically Attended AEs (MAAEs), and AEs leading to Study Discontinuation

Secondary: Part 1A Number of Participants with a SARS-CoV-2 Infection (Symptomatic or Asymptomatic)

Secondary: Part 1A Number of Participants with a SARS-CoV-2 Infection (Symptomatic or Asymptomatic)

Secondary: Part 1A Number of Participants With Asymptomatic SARS-CoV-2 Infection

Secondary: Part 1A Number of Participants With Asymptomatic SARS-CoV-2 Infection

Secondary: Part 1A Number of Participants with a First Occurrence of Symptomatic COVID-19

Secondary: Part 1A Number of Participants with a First Occurrence of Symptomatic COVID-19

Secondary: Part 1A Number of Participants with Secondary Case Definition of COVID-19 (Center for Disease Control and Prevention [CDC] Case Definition)

Secondary: Part 1A Number of Participants with Secondary Case Definition of COVID-19 (Center for Disease Control and Prevention [CDC] Case Definition)

Secondary: Part 1C-1 SRR of the Post-booster Serum bAb Against Variants of Interest (B.1.1.7, B.1.351, B.1.617.2, and P.1) as Measured by MSD

Secondary: Part 1C-1 SRR of the Post-booster Serum bAb Against Variants of Interest (B.1.1.7, B.1.351, B.1.617.2, and P.1) as Measured by MSD

Secondary: Part 1C-1 GMC of Post-booster Pseudovirus nAb Against Variant Strain (B.1.1.529)

Secondary: Part 1C-1 GMC of Post-booster Pseudovirus nAb Against Variant Strain (B.1.1.529)

Secondary: Part 3 SRR of Serum Pseudovirus nAb Post Dose 1 of mRNA-1273.222 Against Omicron BA.4/BA.5 Compared with Young Adults (Study P301)

Secondary: Part 3 SRR of Serum Pseudovirus nAb Post Dose 1 of mRNA-1273.222 Against Omicron BA.4/BA.5 Compared with Young Adults (Study P301)

Secondary: Part 3 Pseudovirus nAb SRR of post Dose 1 of mRNA-1273.222 Against Ancestral Strain Compared to Study P301

Secondary: Part 3 Pseudovirus nAb SRR of post Dose 1 of mRNA-1273.222 Against Ancestral Strain Compared to Study P301

Secondary: Part 3 GM Value of Post Dose 1 (Day 29) of mRNA-1273.222 bAb Against Other Variants of Interest

Secondary: Part 3 GM Value of Post Dose 1 (Day 29) of mRNA-1273.222 bAb Against Other Variants of Interest

Secondary: Part 1C-2 GM Value of mRNA-1273 booster Against Variants of Interest at Day 29

Secondary: Part 1C-2 GM Value of mRNA-1273 booster Against Variants of Interest at Day 29

Secondary: Part 1 A GM Level of SARS-CoV-2 Spike Protein-specific bAb at Days 1, 57, 209, 394

Secondary: Part 1 A GM Level of SARS-CoV-2 Spike Protein-specific bAb at Days 1, 57, 209, 394

Secondary: Part 1A GM Value of SARS-CoV-2-Specific nAb at Days 1, 57, 209, 394

Secondary: Part 1A GM Value of SARS-CoV-2-Specific nAb at Days 1, 57, 209, 394

Secondary: Part 1C-1 GM Value of Post-booster Dose Serum bAb Against Variants of Interest (B.1.1.7, B.1.351, B.1.617.2, and P.1) as Measured by MSD

Secondary: Part 1C-1 GM Value of Post-booster Dose Serum bAb Against Variants of Interest (B.1.1.7, B.1.351, B.1.617.2, and P.1) as Measured by MSD

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

Online references

More information

Clinical Trial Results:
A Phase 2/3, Randomized, Observer-Blind, Placebo-Controlled Study to Evaluate the Safety, Reactogenicity, and Effectiveness of mRNA-1273 SARS-CoV-2 Vaccine in Healthy Adolescents 12 to <18 Years of Age