A Study to Evaluate the Safety, Reactogenicity, and Effectiveness of mRNA-1273 Vaccine in Adolescents 12 to <18 Years Old to Prevent COVID-19

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

Status

Completed

Phases

Phase 2Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT04649151

Acronym

TeenCove

Enrollment

4328

Registered

2020-12-02

Start date

2020-12-09

Completion date

2024-06-14

Last updated

2025-09-15

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

SARS-CoV-2

Keywords

mRNA-1273, mRNA-1273 vaccine, SARS-CoV-2, SARS-CoV-2 Vaccine, mRNA-1273.222 vaccine, SARS-CoV-2 VOC, SARS-CoV-2 VOC vaccine, Omicron, Variant, Coronavirus, Virus Diseases, Messenger RNA, COVID-19, COVID-19 Vaccine, Moderna

Brief summary

The mRNA-1273 vaccine is being developed to prevent COVID-19, the disease resulting from Severe Acute Respiratory Syndrome coronavirus (SARS-CoV-2) infection. The study is 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 will also evaluate the safety and immunogenicity of an mRNA-1273.222 vaccine against the SARS-CoV- 2 omicron variant as a primary series.

Detailed description

This is a Phase 2/3 study, with Part 1A (Blinded Phase), Part 1B (Open-label Observational Phase), Part 1C (Booster Dose \[BD\] Phase), which consists of Part 1C-1 and Part 1C-2, Part 2 (Open-Label), and Part 3 (Open-label). Participants in Part 1A are blinded to their treatment assignment, with participants receiving either 2 active mRNA-1273 vaccine doses or placebo. Part 1B of the study is designed to offer participants whose age group becomes Emergency Use Authorization (EUA) eligible to be unblinded so that participants who received placebo in Part 1A can request 2 doses of open-label mRNA-1273 vaccine. Part 1C-1 of the study will offer participants in Part 1A and Part 1B who are at least 5 months from the last dose, the option to request a homologous BD of mRNA-1273. Part 1C-2 is designed to provide a heterologous BD of mRNA-1273 to eligible participants who completed primary COVID-19 vaccination series with a non-Moderna vaccine under EUA and are at least 3 months from the last dose. Part 2 is an open-label design. Participants will receive 2 doses and may receive a booster dose of mRNA-1273 SARS-CoV-2 vaccine. Part 3 is an open-label design. Participants will receive up to 2 doses of mRNA-1273.222 vaccine. Please access http://TeenCoveStudy.com for additional information, such as Study Overview, Participation, Site Locations along with contact numbers for each location for the study.

Interventions

BIOLOGICALmRNA-1273

Sterile liquid for injection

BIOLOGICALPlacebo

0.9% sodium chloride (normal saline) injection

BIOLOGICALmRNA-1273.222

Sterile solution for injection

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

PREVENTION

Masking

QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)

Masking description

Part 1A is observer-blind. Participants will remain blinded until the initiation of Part 1B.

Eligibility

Sex/Gender

ALL

Age

12 Years to 18 Years

Healthy volunteers

Yes

Inclusion criteria

For Part 1A, Part 2 and Part 3: * Participants 12 to \<18 years of age at the time of consent (Screening Visit, Day 0) who, in the opinion of the Investigator, are in good general health based on review of medical history and screening physical examination. * Investigator assessment that the participant, in the case of an emancipated minor, or parent(s)/legally acceptable representative(s) (LAR\[s\]) understand and is willing and physically able to comply with protocol-mandated follow up, including all procedures and provides written informed consent/assent. * Body mass index (BMI) at or above the third percentile according to World Health Organization (WHO) Child Growth Standards at the Screening Visit (Day 0) * Female participants of nonchildbearing potential may be enrolled in the study. Nonchildbearing potential is defined as premenarche or surgically sterile (history of bilateral tubal ligation, bilateral oophorectomy, hysterectomy). * Female participants of childbearing potential may be enrolled in the study if the participant has a negative pregnancy test at Screening (Day 0), on the day of the first injection (Day 1), on the day of the second injection (Day 29 in Parts 1A and Part 2, and Day 181 in Part 3); has practiced adequate contraception or has abstained from all activities that could result in pregnancy for at least 28 days prior to the first injection (Day 1); and has agreed to continue adequate contraception or abstinence through 3 months following the second injection (Day 29 in Part 1A and Part 2, and Day 181 in Part 3). For Part 1B: * Participants must have been previously enrolled in mRNA-1273-P203 study. * Female participants of childbearing potential may be enrolled in the study if the participant has a negative pregnancy test on the day of the first injection (Open-Label-Day 1) and on the day of the second injection (Open-Label-Day 29). For Part 1C-1 Homologous Booster Dose: * Participants must have been previously enrolled in the mRNA-1273-P203 study, are actively participating in Part 1A or Part 1B and are least 5 months from the last dose. * Female participants of childbearing potential may be enrolled in the study if the participant has a negative pregnancy test on the day of the first injection (BD-Day 1). Part 1C-2 Heterologous Booster Dose: * Male or female, 12 to \< 18 years of age at the time of consent who, in the opinion of the investigator, is in good general health based on review of medical history and screening physical examination AND has completed non-Moderna primary COVID-19 vaccination series under EUA (for example, Pfizer) at least 3 months from consent.

Exclusion criteria

For Part 1A, Part 2, and Part 3: * Has a known history of SARS-CoV-2 infection within 2 weeks prior to administration of investigational product (IP) or known close contact with anyone with laboratory-confirmed SARS-CoV-2 infection of COVID-19 within 2 weeks prior to administration of IP (Part 2 participants only). For Part 3 participants, known history of SARS-CoV-2 infection within 90 days prior to administration of IP or known close contact with anyone with laboratory-confirmed SARS-CoV-2 infection or COVID-19 within 90 days prior to administration of IP. * Travel outside of the United States or home country (Part 2 and Part 3 only) in the 28 days prior to the Screening Visit (Day 0). * Pregnant or breastfeeding * Is acutely ill or febrile 24 hours prior to or at the Screening Visit (Day 0). Fever is defined as a body temperature ≥38.0°Celsius (C)/≥100.4°Farenheit (F). Participants who meet this criterion may have visits rescheduled within the relevant study visit windows. Afebrile participants with minor illnesses can be enrolled at the discretion of the Investigator. * Prior administration of an investigational coronavirus (for example, SARS-CoV-2, SARS-CoV, Middle East Respiratory Syndrome \[MERS-CoV\]) vaccine * Current treatment with investigational agents for prophylaxis against COVID-19 * Has a medical, psychiatric, or occupational condition that may pose additional risk as a result of participation, or that could interfere with safety assessments or interpretation of results according to the Investigator's judgment * Current use of any inhaled substance (for example, tobacco or cannabis smoke, nicotine vapors) * History of chronic smoking (≥1 cigarette a day) within 1 year of the Screening Visit (Day 0) * History of illegal substance use or alcohol abuse within the past 2 years. This exclusion does not apply to historical cannabis use that was formerly illegal in the participant's state but is legal at the time of screening. * History of a diagnosis or condition that, in the judgment of the Investigator, may affect study endpoint assessment or compromise participant safety, specifically: * Congenital or acquired immunodeficiency, including human immunodeficiency virus (HIV) infection * Suspected active hepatitis * Has a bleeding disorder that is considered a contraindication to IM injection or phlebotomy * Dermatologic conditions that could affect local solicited AR assessments * History of anaphylaxis, urticaria, or other significant AR requiring medical intervention after receipt of a vaccine * Diagnosis of malignancy within the previous 10 years (excluding nonmelanoma skin cancer) * Febrile seizures * Receipt of: * Any licensed vaccine within 28 days before the first dose of IP or plans for receipt of any licensed vaccine within 28 days before and/or after each dose of IP. * Systemic immunosuppressants or immune-modifying drugs for \>14 days in total within 6 months prior to the day of enrollment (for corticosteroids, ≥20 mg/day prednisone equivalent). Topical tacrolimus is allowed if not used within 14 days prior to the day of enrollment. Participants may have visits rescheduled for enrollment if they no longer meet this criterion within the Screening Visit window. Inhaled, nasal, and topical steroids are allowed. * Intravenous blood products (red cells, platelets, immunoglobulins) within 3 months prior to enrollment * Has donated ≥450 milliliters (mL) of blood products within 28 days prior to the Screening Visit (Day 0) or plans to donate blood products during the study * Participated in an interventional clinical study within 28 days prior to the Screening Visit (Day 0) or plans to do so while participating in this study * Is an immediate family member or has a household contact who is an employee of the research center or otherwise involved with the conduct of the study For Part 1C-1 and Part 1C-2: * Pregnant or breastfeeding. * Is acutely ill or febrile 24 hours prior to or at the Screening Visit (Day 0). Fever is defined as a body temperature ≥ 38.0°C/≥ 100.4°F. Participants who meet this criterion may have visits rescheduled within the relevant study visit windows. Afebrile participants with minor illnesses can be enrolled at the discretion of the investigator. * Has a medical, psychiatric, or occupational condition that may pose additional risk as a result of participation, or that could interfere with safety assessments or interpretation of results according to the investigator's judgment. * History of a diagnosis or condition (after enrolment in Part 1A) that, in the judgment of the investigator, may affect study endpoint assessment or compromise participant safety: * Suspected active hepatitis * Has a bleeding disorder that is considered a contraindication to IM injection or phlebotomy * Dermatologic conditions that could affect local solicited AR assessments * History of anaphylaxis, urticaria, or other significant AR requiring medical intervention after receipt of a vaccine * Diagnosis of malignancy (excluding nonmelanoma skin cancer) * Receipt of: • Any authorized or licensed vaccine within 28 days before the first dose of IP or plans for receipt of any licensed vaccine through 28 days following the last dose of IP or any seasonal influenza vaccine within 14 days before the first dose of IP or plans for receipt of any seasonal influenza vaccine 14 days following the last dose of IP. * Participated in an interventional clinical study, other than mRNA-1273-P203 study, within 28 days prior to the Screening Visit (Day 0 \[for Part 1C-1\], BD-Day 0 \[for Part 1C-2\]) or plans to do so while participating in this study. Part 1C-2 Heterologous Booster Dose: * Has a known history of SARS-CoV-2 infection within 2 weeks prior to administration of IP or known close contact with anyone with laboratory-confirmed SARS-CoV-2 infection or COVID 19 within 2 weeks prior to administration of IP.

Design outcomes

Primary

Measure	Time frame	Description
Number of Participants With SAEs, AEs of Special Interest (AESIs), Medically Attended AEs (MAAEs), and AEs Leading to Study Discontinuation	Day 1 up to Day 751	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 were identified based upon medical concepts that may be related to COVID-19 or were of interest in COVID-19 vaccine safety surveillance. 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 \[for example, urgent care, primary care physician\]). 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.
Number of Participants With Solicited Local and Systemic Adverse Reactions (ARs)	7 days post-vaccination	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. Investigator reviewed if the solicited AR was recorded as an adverse event (AE) as detailed in the AE section. A Summary of serious AEs (SAEs) and nonserious AEs (Other), regardless of causality, is located in the AE section.
Number of Participants With Unsolicited AEs	Up to 28 days post-vaccination	An unsolicited AE was any AE reported by the participant that was not specified as a solicited AR in the protocol or was specified as a solicited AR but started outside the protocol-defined period for reporting solicited ARs (onset after Day 7 of dosing). 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 classified 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.
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	Day 57 Study P203/Day 57 Study P301	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 arbitrary units (AU)/milliliter (mL), ULOQ: 45118 AU/mL). 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. PPIS P301: randomly selected participants from Study P301 aged 18-25 meeting pre-specified criteria were used for comparison assessments of immune response.
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	Day 57 Study P203/Day 57 Study P301	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 (LLOQ: 18.5 AU/mL), ULOQ: 45118 AU/mL). PPIS P301: randomly selected participants from Study P301 aged 18-25 meeting pre-specified criteria were used for comparison assessments of immune response.
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	BD Day 29 Study P203/Day 57 Study P301	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 P301: randomly selected participants from study P301 aged 18-25 meeting pre-specified criteria and SARS-CoV-2 negative were used for comparison assessments of immune response.
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	BD Day 29 Study P203/Day 57 Study P301	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 (LLOQ: 10 AU/mL, ULOQ: 281600 AU/mL). PPIS P301: randomly selected participants from Study P301 aged 18-25 meeting pre-specified criteria and SARS-CoV-2 negative were used for comparison assessments of immune response.
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	Day 29 Study P203/Day 57 Study P301	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. PPIS P301: randomly selected participants from Study P301 aged 18-25 meeting pre-specified criteria and SARS-CoV-2 negative were used for comparison of immune response.
Part 1C-2 GMC of Post-booster Pseudovirus nAb Against Ancestral Strain at BD Day 29	BD Day 29	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).
Part 2 GMC of the Pseudovirus nAb Against Ancestral Strain at Day 57	Day 57	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).
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	Day 29 Study P203/Day 57 Study P301	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. PPIS P301: randomly selected participants from Study P301 aged 18-25 meeting pre-specified criteria and SARS-CoV-2 negative were used for comparison of immune response.
Part 2 SRR of Pseudovirus nAb Against Ancestral Strain	Day 57	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 the LLOQ (LLOQ: 10 AU/mL, ULOQ: 111433 AU/mL).

Secondary

Measure	Time frame	Description
Part 1A GM Value of SARS-CoV-2-Specific nAb at Days 1, 57, 209, 394	Days 1, 57, 209, 394	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 AU/mL, ULOQ: 281600 AU/mL).
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	BD Day 29	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).
Part 1A Number of Participants With a SARS-CoV-2 Infection (Symptomatic or Asymptomatic)	Day 43 (14 days after second injection) up to a median follow up of 2.5 months after second injection	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.
Part 1A Number of Participants With Asymptomatic SARS-CoV-2 Infection	Day 43 (14 days after second injection) up to a median follow up of 2.5 months after second injection	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.
Part 1A Number of Participants With a First Occurrence of Symptomatic COVID-19	Day 43 (14 days after second injection) up to 2.5 months after second injection	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 nasopharyngeal swab, nasal swab, or saliva sample (or respiratory sample, if hospitalized) positive for SARS-CoV-2.
Part 1A Number of Participants With Secondary Case Definition of COVID-19 (Center for Disease Control and Prevention [CDC] Case Definition)	Day 43 (14 days after second injection) up to a median follow up of 2.5 months after second injection	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.
Part 1C-1 SRR of the Post-booster Serum Binding Antibody (bAb) Against Variants of Interest (B.1.1.7, B.1.351, B.1.617.2, and P.1) as Measured by MSD	BD Day 29	Percentage of participants with seroresponse for bAb measured using (MesoScale Discovery) MSD are reported. 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.
Part 1C-1 GMC of Post-booster Pseudovirus nAb Against Variant Strain (B.1.1.529)	BD Day 29	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.
Part 3 SRR of Serum Pseudovirus nAb Post Dose 1 of 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	Day 29 Study P203/Day 57 Study P301	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 (LLOQ: 103 AU/mL, ULOQ: 28571 AU/mL). PPIS P301: randomly selected participants from Study P301 aged 18-25 meeting pre-specified criteria and SARS-CoV-2 negative were used for comparison of immune response.
Part 3 Pseudovirus nAb SRR of Post Dose 1 of mRNA-1273.222 Against Ancestral Strain Compared With Those From Young Adult (18 to 25 Years of Age) Vaccine Recipients (Day 57) in Study P301	Day 29 P203/Day 57 P301	Percentage of participants with seroresponse for pseudovirus nAb measured using PsVNA assay are reported. 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. PPIS P301: randomly selected participants from Study P301 aged 18-25 meeting pre-specified criteria and SARS-CoV-2 negative were used for comparison assessments of immune response.
Part 3 GM Value of Post Dose 1 (Day 29) of mRNA-1273.222 bAb Against Other Variants of Interest	Day 29	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).
Part 1C-2 GM Value of mRNA-1273 Booster Against Variants of Interest at Day 29	Day 29	—
Part 1A GM Level of SARS-CoV-2 Spike Protein-specific bAb at Days 1, 57, 209, 394	Days 1, 57, 209, 394	SARS-CoV-2 Spike Protein-specific bAb were measured using 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 AU/mL, ULOQ: 14400000 AU/mL).

Other

Measure	Time frame	Description
Number of Deaths Related to Study Drug	Day 1 up to Day 751	A death that occurred during the study or that came to the attention of the investigator during the study was reported to the Sponsor, whether or not it was considered related to study drug. The investigator assessed causality (that is, whether there is a reasonable possibility that the study drug caused the death). The relationship was characterized using the following classifications: Not related: There was not a reasonable possibility of a relationship to the study drug. The temporal sequence of the death relative to administration of the study drug was not reasonable and/or the death was more likely explained by a cause other than the study drug. Related: There was a reasonable possibility of a relationship to the study drug. There was evidence of exposure to the study drug. The temporal sequence of the death relative to the administration of the study drug was reasonable. The death was more likely explained by the study drug than by another cause.

Countries

Dominican Republic, United States

Participant flow

Recruitment details

The study included Part 1A as the Blinded Phase with participants remaining blinded until the initiation of Part 1B (open-label cross-over vaccination phase), and Parts 1C-1, 1C-2, 2, and 3 as open-label.

Pre-assignment details

A per-protocol immunogenicity subset (PPIS) of randomly selected participants from study mRNA-1273-P301 (P301) (NCT04470427) aged 18-25 meeting pre-specified criteria (N=296) was used for comparison assessments of immune response. Study Completed and Not Completed data reported in the Participant Flow were collected from Overall Study (that is, as 1 period regardless if a booster dose was received).

Participants by arm

Arm	Count
Part 1A: mRNA-1273 100 μg Participants were randomized to receive 2 doses of 100 μg mRNA-1273 by IM injection (Day 1 and Day 29).	2,490
Part 1A: Placebo Participants were randomized to receive 2 doses of placebo by IM injection (Day 1 and Day 29). Participants had the option to receive crossover vaccination with 100 μg mRNA-1273 in Part 1B.	1,243
Part 1C-2: mRNA-1273 50 μg BD 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.	155
Part 2: mRNA-1273 50 μg Participants received at least 1 of 2 doses of 50 μg mRNA-1273 by IM injection (Day 1 and Day 29).	52
Part 3: mRNA-1273.222 50 µg Participants received 1 dose of mRNA-1273.222 50 µg by IM injection (Day 1). Participants may have received a second dose of mRNA-1273.222 50 µg at approximately month 6 after the first dose (Day 181).	388
Study mRNA-1273-P301 (NCT04470427) mRNA-1273 100 μg Participants (young adults; 18-25 years of age) received 100 μg mRNA-1273 on a 2 injection schedule in Study mRNA-1273-P301 (P301).	296
Total	4,624

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG002	FG003	FG004
Overall Study	Adverse Event	1	0	0	0	0
Overall Study	Death	0	0	0	0	1
Overall Study	Lost to Follow-up	256	29	10	3	6
Overall Study	Other than specified	59	294	0	0	4
Overall Study	Physician Decision	10	0	0	1	1
Overall Study	Pregnancy	0	0	0	0	3
Overall Study	Protocol Deviation	25	3	0	0	0
Overall Study	Received another COVID-19 vaccine under EUA	495	730	0	0	0
Overall Study	Withdrawal by Subject	370	113	2	7	15

Baseline characteristics

Characteristic	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	Study mRNA-1273-P301 (NCT04470427) mRNA-1273 100 μg	Total
Age, Customized Age Categorical Data for Participants Enrolled in Study mRNA-1273-P203 Adolescents (12-17 years)	2490 Participants	1243 Participants	155 Participants	52 Participants	388 Participants	0 Participants	4328 Participants
Age, Customized Age Categorical Data for Participants Enrolled in Study mRNA-1273-P203 Adults (18-64 years)	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Age, Customized Age Categorical Data for Participants Enrolled in Study mRNA-1273-P301 Adolescents (12-17 years)	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Age, Customized Age Categorical Data for Participants Enrolled in Study mRNA-1273-P301 Adults (18-64 years)	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	296 Participants	296 Participants
Ethnicity (NIH/OMB) Ethnicity Data for Participants Enrolled in Study mRNA-1273-P203 Hispanic or Latino	280 Participants	152 Participants	37 Participants	14 Participants	367 Participants	0 Participants	850 Participants
Ethnicity (NIH/OMB) Ethnicity Data for Participants Enrolled in Study mRNA-1273-P203 Not Hispanic or Latino	2190 Participants	1079 Participants	116 Participants	36 Participants	21 Participants	0 Participants	3442 Participants
Ethnicity (NIH/OMB) Ethnicity Data for Participants Enrolled in Study mRNA-1273-P203 Unknown or Not Reported	20 Participants	12 Participants	2 Participants	2 Participants	0 Participants	0 Participants	36 Participants
Ethnicity (NIH/OMB) Ethnicity Data for Participants Enrolled in Study mRNA-1273-P301 Hispanic or Latino	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	78 Participants	78 Participants
Ethnicity (NIH/OMB) Ethnicity Data for Participants Enrolled in Study mRNA-1273-P301 Not Hispanic or Latino	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	216 Participants	216 Participants
Ethnicity (NIH/OMB) Ethnicity Data for Participants Enrolled in Study mRNA-1273-P301 Unknown or Not Reported	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	2 Participants	2 Participants
Race/Ethnicity, Customized Race Data for Participants Enrolled in Study mRNA-1273-P203 American Indian or Alaska Native	12 Participants	7 Participants	1 Participants	0 Participants	1 Participants	0 Participants	21 Participants
Race/Ethnicity, Customized Race Data for Participants Enrolled in Study mRNA-1273-P203 Asian	143 Participants	80 Participants	3 Participants	3 Participants	0 Participants	0 Participants	229 Participants
Race/Ethnicity, Customized Race Data for Participants Enrolled in Study mRNA-1273-P203 Black or African American	83 Participants	42 Participants	23 Participants	18 Participants	126 Participants	0 Participants	292 Participants
Race/Ethnicity, Customized Race Data for Participants Enrolled in Study mRNA-1273-P203 Multiple	118 Participants	50 Participants	9 Participants	0 Participants	3 Participants	0 Participants	180 Participants
Race/Ethnicity, Customized Race Data for Participants Enrolled in Study mRNA-1273-P203 Native Hawaiian or Other Pacific Islander	3 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	3 Participants
Race/Ethnicity, Customized Race Data for Participants Enrolled in Study mRNA-1273-P203 Not Reported	11 Participants	11 Participants	0 Participants	0 Participants	0 Participants	0 Participants	22 Participants
Race/Ethnicity, Customized Race Data for Participants Enrolled in Study mRNA-1273-P203 Other	27 Participants	9 Participants	4 Participants	0 Participants	219 Participants	0 Participants	259 Participants
Race/Ethnicity, Customized Race Data for Participants Enrolled in Study mRNA-1273-P203 Unknown	6 Participants	1 Participants	0 Participants	1 Participants	0 Participants	0 Participants	8 Participants
Race/Ethnicity, Customized Race Data for Participants Enrolled in Study mRNA-1273-P203 White	2087 Participants	1043 Participants	115 Participants	30 Participants	39 Participants	0 Participants	3314 Participants
Race/Ethnicity, Customized Race Data for Participants Enrolled in Study mRNA-1273-P301 American Indian or Alaska Native	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	3 Participants	3 Participants
Race/Ethnicity, Customized Race Data for Participants Enrolled in Study mRNA-1273-P301 Asian	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	30 Participants	30 Participants
Race/Ethnicity, Customized Race Data for Participants Enrolled in Study mRNA-1273-P301 Black or African American	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	29 Participants	29 Participants
Race/Ethnicity, Customized Race Data for Participants Enrolled in Study mRNA-1273-P301 Multiple	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	14 Participants	14 Participants
Race/Ethnicity, Customized Race Data for Participants Enrolled in Study mRNA-1273-P301 Native Hawaiian or Other Pacific Islander	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	2 Participants	2 Participants
Race/Ethnicity, Customized Race Data for Participants Enrolled in Study mRNA-1273-P301 Not Reported	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	3 Participants	3 Participants
Race/Ethnicity, Customized Race Data for Participants Enrolled in Study mRNA-1273-P301 Other	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	8 Participants	8 Participants
Race/Ethnicity, Customized Race Data for Participants Enrolled in Study mRNA-1273-P301 Unknown	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Race/Ethnicity, Customized Race Data for Participants Enrolled in Study mRNA-1273-P301 White	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	207 Participants	207 Participants
Sex: Female, Male Sex Data for Participants Enrolled in Study mRNA-1273-P203 Female	1206 Participants	607 Participants	78 Participants	26 Participants	185 Participants	0 Participants	2102 Participants
Sex: Female, Male Sex Data for Participants Enrolled in Study mRNA-1273-P203 Male	1284 Participants	636 Participants	77 Participants	26 Participants	203 Participants	0 Participants	2226 Participants
Sex: Female, Male Sex Data for Participants Enrolled in Study mRNA-1273-P301 Female	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	153 Participants	153 Participants
Sex: Female, Male Sex Data for Participants Enrolled in Study mRNA-1273-P301 Male	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	143 Participants	143 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk	EG003 affected / at risk	EG004 affected / at risk	EG005 affected / at risk	EG006 affected / at risk	EG007 affected / at risk	EG008 affected / at risk
deaths Total, all-cause mortality	0 / 2,486	0 / 1,240	0 / 96	0 / 1,408	0 / 155	0 / 52	0 / 19	0 / 388	1 / 335
other Total, other adverse events	943 / 2,486	155 / 1,240	22 / 96	429 / 1,408	28 / 155	12 / 52	7 / 19	77 / 388	51 / 335
serious Total, serious adverse events	21 / 2,486	4 / 1,240	2 / 96	9 / 1,408	3 / 155	0 / 52	0 / 19	12 / 388	4 / 335

Outcome results

Primary

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

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 were identified based upon medical concepts that may be related to COVID-19 or were of interest in COVID-19 vaccine safety surveillance. 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 \[for example, urgent care, primary care physician\]). 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.

Time frame: Day 1 up to Day 751

Population: Participants who received at least 1 dose of mRNA-1273 were included in the analysis. 'Overall number of participants analyzed' = participants evaluable for this endpoint. Note: Part 3 is presented for overall study for this assessment (AE section presents AEs separately for 1 dose and second dose).

Arm	Measure	Group	Value (COUNT_OF_PARTICIPANTS)
Part 1A: mRNA-1273 100 μg	Number of Participants With SAEs, AEs of Special Interest (AESIs), Medically Attended AEs (MAAEs), and AEs Leading to Study Discontinuation	SAEs	21 Participants
Part 1A: mRNA-1273 100 μg	Number of Participants With SAEs, AEs of Special Interest (AESIs), Medically Attended AEs (MAAEs), and AEs Leading to Study Discontinuation	AESIs	17 Participants
Part 1A: mRNA-1273 100 μg	Number of Participants With SAEs, AEs of Special Interest (AESIs), Medically Attended AEs (MAAEs), and AEs Leading to Study Discontinuation	MAAEs	1040 Participants
Part 1A: mRNA-1273 100 μg	Number of Participants With SAEs, AEs of Special Interest (AESIs), Medically Attended AEs (MAAEs), and AEs Leading to Study Discontinuation	AEs Leading to Study Discontinuation	0 Participants
Part 1A: Placebo	Number of Participants With SAEs, AEs of Special Interest (AESIs), Medically Attended AEs (MAAEs), and AEs Leading to Study Discontinuation	AEs Leading to Study Discontinuation	0 Participants
Part 1A: Placebo	Number of Participants With SAEs, AEs of Special Interest (AESIs), Medically Attended AEs (MAAEs), and AEs Leading to Study Discontinuation	MAAEs	31 Participants
Part 1A: Placebo	Number of Participants With SAEs, AEs of Special Interest (AESIs), Medically Attended AEs (MAAEs), and AEs Leading to Study Discontinuation	SAEs	2 Participants
Part 1A: Placebo	Number of Participants With SAEs, AEs of Special Interest (AESIs), Medically Attended AEs (MAAEs), and AEs Leading to Study Discontinuation	AESIs	0 Participants
Part 1C-1: mRNA-1273 50 µg BD	Number of Participants With SAEs, AEs of Special Interest (AESIs), Medically Attended AEs (MAAEs), and AEs Leading to Study Discontinuation	MAAEs	541 Participants
Part 1C-1: mRNA-1273 50 µg BD	Number of Participants With SAEs, AEs of Special Interest (AESIs), Medically Attended AEs (MAAEs), and AEs Leading to Study Discontinuation	AESIs	9 Participants
Part 1C-1: mRNA-1273 50 µg BD	Number of Participants With SAEs, AEs of Special Interest (AESIs), Medically Attended AEs (MAAEs), and AEs Leading to Study Discontinuation	SAEs	9 Participants
Part 1C-1: mRNA-1273 50 µg BD	Number of Participants With SAEs, AEs of Special Interest (AESIs), Medically Attended AEs (MAAEs), and AEs Leading to Study Discontinuation	AEs Leading to Study Discontinuation	0 Participants
Part 1C-2: mRNA-1273 50 μg BD	Number of Participants With SAEs, AEs of Special Interest (AESIs), Medically Attended AEs (MAAEs), and AEs Leading to Study Discontinuation	SAEs	3 Participants
Part 1C-2: mRNA-1273 50 μg BD	Number of Participants With SAEs, AEs of Special Interest (AESIs), Medically Attended AEs (MAAEs), and AEs Leading to Study Discontinuation	AESIs	1 Participants
Part 1C-2: mRNA-1273 50 μg BD	Number of Participants With SAEs, AEs of Special Interest (AESIs), Medically Attended AEs (MAAEs), and AEs Leading to Study Discontinuation	MAAEs	45 Participants
Part 1C-2: mRNA-1273 50 μg BD	Number of Participants With SAEs, AEs of Special Interest (AESIs), Medically Attended AEs (MAAEs), and AEs Leading to Study Discontinuation	AEs Leading to Study Discontinuation	0 Participants
Part 2: mRNA-1273 50 μg First Injection	Number of Participants With SAEs, AEs of Special Interest (AESIs), Medically Attended AEs (MAAEs), and AEs Leading to Study Discontinuation	SAEs	0 Participants
Part 2: mRNA-1273 50 μg First Injection	Number of Participants With SAEs, AEs of Special Interest (AESIs), Medically Attended AEs (MAAEs), and AEs Leading to Study Discontinuation	AEs Leading to Study Discontinuation	0 Participants
Part 2: mRNA-1273 50 μg First Injection	Number of Participants With SAEs, AEs of Special Interest (AESIs), Medically Attended AEs (MAAEs), and AEs Leading to Study Discontinuation	AESIs	0 Participants
Part 2: mRNA-1273 50 μg First Injection	Number of Participants With SAEs, AEs of Special Interest (AESIs), Medically Attended AEs (MAAEs), and AEs Leading to Study Discontinuation	MAAEs	12 Participants
Part 2: mRNA-1273 50 μg Second Injection	Number of Participants With SAEs, AEs of Special Interest (AESIs), Medically Attended AEs (MAAEs), and AEs Leading to Study Discontinuation	AESIs	0 Participants
Part 2: mRNA-1273 50 μg Second Injection	Number of Participants With SAEs, AEs of Special Interest (AESIs), Medically Attended AEs (MAAEs), and AEs Leading to Study Discontinuation	SAEs	0 Participants
Part 2: mRNA-1273 50 μg Second Injection	Number of Participants With SAEs, AEs of Special Interest (AESIs), Medically Attended AEs (MAAEs), and AEs Leading to Study Discontinuation	MAAEs	7 Participants
Part 2: mRNA-1273 50 μg Second Injection	Number of Participants With SAEs, AEs of Special Interest (AESIs), Medically Attended AEs (MAAEs), and AEs Leading to Study Discontinuation	AEs Leading to Study Discontinuation	0 Participants
Part 2: mRNA-1273 50 μg BD	Number of Participants With SAEs, AEs of Special Interest (AESIs), Medically Attended AEs (MAAEs), and AEs Leading to Study Discontinuation	MAAEs	183 Participants
Part 2: mRNA-1273 50 μg BD	Number of Participants With SAEs, AEs of Special Interest (AESIs), Medically Attended AEs (MAAEs), and AEs Leading to Study Discontinuation	SAEs	16 Participants
Part 2: mRNA-1273 50 μg BD	Number of Participants With SAEs, AEs of Special Interest (AESIs), Medically Attended AEs (MAAEs), and AEs Leading to Study Discontinuation	AESIs	3 Participants
Part 2: mRNA-1273 50 μg BD	Number of Participants With SAEs, AEs of Special Interest (AESIs), Medically Attended AEs (MAAEs), and AEs Leading to Study Discontinuation	AEs Leading to Study Discontinuation	1 Participants

Primary

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

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. Investigator reviewed if the solicited AR was recorded as an adverse event (AE) as detailed in the AE section. A Summary of serious AEs (SAEs) and nonserious AEs (Other), regardless of causality, is located in the AE section.

Time frame: 7 days post-vaccination

Population: Solicited Safety Set included participants who received at least 1 dose of study drug and contributed any solicited AR data.

Arm	Measure	Group	Value (COUNT_OF_PARTICIPANTS)
Part 1A: mRNA-1273 100 μg	Number of Participants With Solicited Local and Systemic Adverse Reactions (ARs)	Grade 1	586 Participants
Part 1A: mRNA-1273 100 μg	Number of Participants With Solicited Local and Systemic Adverse Reactions (ARs)	Any Solicited (Grade 1-4)	2466 Participants
Part 1A: mRNA-1273 100 μg	Number of Participants With Solicited Local and Systemic Adverse Reactions (ARs)	Grade 4	3 Participants
Part 1A: mRNA-1273 100 μg	Number of Participants With Solicited Local and Systemic Adverse Reactions (ARs)	Grade 3	627 Participants
Part 1A: mRNA-1273 100 μg	Number of Participants With Solicited Local and Systemic Adverse Reactions (ARs)	Grade 2	1250 Participants
Part 1A: Placebo	Number of Participants With Solicited Local and Systemic Adverse Reactions (ARs)	Grade 2	293 Participants
Part 1A: Placebo	Number of Participants With Solicited Local and Systemic Adverse Reactions (ARs)	Grade 4	1 Participants
Part 1A: Placebo	Number of Participants With Solicited Local and Systemic Adverse Reactions (ARs)	Any Solicited (Grade 1-4)	938 Participants
Part 1A: Placebo	Number of Participants With Solicited Local and Systemic Adverse Reactions (ARs)	Grade 3	59 Participants
Part 1A: Placebo	Number of Participants With Solicited Local and Systemic Adverse Reactions (ARs)	Grade 1	585 Participants
Part 1C-1: mRNA-1273 50 µg BD	Number of Participants With Solicited Local and Systemic Adverse Reactions (ARs)	Grade 2	501 Participants
Part 1C-1: mRNA-1273 50 µg BD	Number of Participants With Solicited Local and Systemic Adverse Reactions (ARs)	Any Solicited (Grade 1-4)	1278 Participants
Part 1C-1: mRNA-1273 50 µg BD	Number of Participants With Solicited Local and Systemic Adverse Reactions (ARs)	Grade 1	627 Participants
Part 1C-1: mRNA-1273 50 µg BD	Number of Participants With Solicited Local and Systemic Adverse Reactions (ARs)	Grade 4	0 Participants
Part 1C-1: mRNA-1273 50 µg BD	Number of Participants With Solicited Local and Systemic Adverse Reactions (ARs)	Grade 3	150 Participants
Part 1C-2: mRNA-1273 50 μg BD	Number of Participants With Solicited Local and Systemic Adverse Reactions (ARs)	Grade 3	9 Participants
Part 1C-2: mRNA-1273 50 μg BD	Number of Participants With Solicited Local and Systemic Adverse Reactions (ARs)	Any Solicited (Grade 1-4)	99 Participants
Part 1C-2: mRNA-1273 50 μg BD	Number of Participants With Solicited Local and Systemic Adverse Reactions (ARs)	Grade 1	42 Participants
Part 1C-2: mRNA-1273 50 μg BD	Number of Participants With Solicited Local and Systemic Adverse Reactions (ARs)	Grade 2	48 Participants
Part 1C-2: mRNA-1273 50 μg BD	Number of Participants With Solicited Local and Systemic Adverse Reactions (ARs)	Grade 4	0 Participants
Part 2: mRNA-1273 50 μg First Injection	Number of Participants With Solicited Local and Systemic Adverse Reactions (ARs)	Grade 3	1 Participants
Part 2: mRNA-1273 50 μg First Injection	Number of Participants With Solicited Local and Systemic Adverse Reactions (ARs)	Grade 1	25 Participants
Part 2: mRNA-1273 50 μg First Injection	Number of Participants With Solicited Local and Systemic Adverse Reactions (ARs)	Grade 2	16 Participants
Part 2: mRNA-1273 50 μg First Injection	Number of Participants With Solicited Local and Systemic Adverse Reactions (ARs)	Grade 4	0 Participants
Part 2: mRNA-1273 50 μg First Injection	Number of Participants With Solicited Local and Systemic Adverse Reactions (ARs)	Any Solicited (Grade 1-4)	42 Participants
Part 2: mRNA-1273 50 μg Second Injection	Number of Participants With Solicited Local and Systemic Adverse Reactions (ARs)	Grade 3	3 Participants
Part 2: mRNA-1273 50 μg Second Injection	Number of Participants With Solicited Local and Systemic Adverse Reactions (ARs)	Grade 4	0 Participants
Part 2: mRNA-1273 50 μg Second Injection	Number of Participants With Solicited Local and Systemic Adverse Reactions (ARs)	Grade 2	9 Participants
Part 2: mRNA-1273 50 μg Second Injection	Number of Participants With Solicited Local and Systemic Adverse Reactions (ARs)	Grade 1	18 Participants
Part 2: mRNA-1273 50 μg Second Injection	Number of Participants With Solicited Local and Systemic Adverse Reactions (ARs)	Any Solicited (Grade 1-4)	30 Participants
Part 2: mRNA-1273 50 μg BD	Number of Participants With Solicited Local and Systemic Adverse Reactions (ARs)	Grade 3	1 Participants
Part 2: mRNA-1273 50 μg BD	Number of Participants With Solicited Local and Systemic Adverse Reactions (ARs)	Grade 1	7 Participants
Part 2: mRNA-1273 50 μg BD	Number of Participants With Solicited Local and Systemic Adverse Reactions (ARs)	Grade 2	0 Participants
Part 2: mRNA-1273 50 μg BD	Number of Participants With Solicited Local and Systemic Adverse Reactions (ARs)	Any Solicited (Grade 1-4)	8 Participants
Part 2: mRNA-1273 50 μg BD	Number of Participants With Solicited Local and Systemic Adverse Reactions (ARs)	Grade 4	0 Participants
Part 3: mRNA-1273.222 50 μg 1 Dose	Number of Participants With Solicited Local and Systemic Adverse Reactions (ARs)	Any Solicited (Grade 1-4)	233 Participants
Part 3: mRNA-1273.222 50 μg 1 Dose	Number of Participants With Solicited Local and Systemic Adverse Reactions (ARs)	Grade 4	1 Participants
Part 3: mRNA-1273.222 50 μg 1 Dose	Number of Participants With Solicited Local and Systemic Adverse Reactions (ARs)	Grade 1	145 Participants
Part 3: mRNA-1273.222 50 μg 1 Dose	Number of Participants With Solicited Local and Systemic Adverse Reactions (ARs)	Grade 3	25 Participants
Part 3: mRNA-1273.222 50 μg 1 Dose	Number of Participants With Solicited Local and Systemic Adverse Reactions (ARs)	Grade 2	62 Participants

Primary

Number of Participants With Unsolicited AEs

An unsolicited AE was any AE reported by the participant that was not specified as a solicited AR in the protocol or was specified as a solicited AR but started outside the protocol-defined period for reporting solicited ARs (onset after Day 7 of dosing). 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 classified 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.

Time frame: Up to 28 days post-vaccination

Population: Safety Set: participants who received at least 1 dose of study drug. As prespecified in the protocol, Part 1B was not assessed for this outcome measure. 'Overall number of participants analyzed' = participants evaluable for this endpoint.

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
Part 1A: mRNA-1273 100 μg	Number of Participants With Unsolicited AEs	582 Participants
Part 1A: Placebo	Number of Participants With Unsolicited AEs	237 Participants
Part 1C-1: mRNA-1273 50 µg BD	Number of Participants With Unsolicited AEs	209 Participants
Part 1C-2: mRNA-1273 50 μg BD	Number of Participants With Unsolicited AEs	19 Participants
Part 2: mRNA-1273 50 μg First Injection	Number of Participants With Unsolicited AEs	10 Participants
Part 2: mRNA-1273 50 μg Second Injection	Number of Participants With Unsolicited AEs	2 Participants
Part 2: mRNA-1273 50 μg BD	Number of Participants With Unsolicited AEs	52 Participants

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

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 arbitrary units (AU)/milliliter (mL), ULOQ: 45118 AU/mL). 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. PPIS P301: randomly selected participants from Study P301 aged 18-25 meeting pre-specified criteria were used for comparison assessments of immune response.

Time frame: Day 57 Study P203/Day 57 Study P301

Population: Part 1A PPIS: randomized participants who were selected for the Immunogenicity Subset, 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. Participants who were seropositive at baseline were excluded from the PPIS. 'Overall number of participants analyzed' = participants evaluable for this endpoint.

Arm	Measure	Value (GEOMETRIC_MEAN)
Part 1A: mRNA-1273 100 μg	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	1401.670 titer
Part 1A: Placebo	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	1299.855 titer

95% CI: [0.94, 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

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 (LLOQ: 18.5 AU/mL), ULOQ: 45118 AU/mL). PPIS P301: randomly selected participants from Study P301 aged 18-25 meeting pre-specified criteria were used for comparison assessments of immune response.

Time frame: Day 57 Study P203/Day 57 Study P301

Arm	Measure	Value (NUMBER)
Part 1A: mRNA-1273 100 μg	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	98.8 percentage of participants
Part 1A: Placebo	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	99.0 percentage of participants

95% CI: [-2.1, 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

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 P301: randomly selected participants from study P301 aged 18-25 meeting pre-specified criteria and SARS-CoV-2 negative were used for comparison assessments of immune response.

Time frame: BD Day 29 Study P203/Day 57 Study P301

Population: Part 1C-1 PPIS-Neg: participants were baseline (pre-dose 1 of part 1A) SARS-CoV-2 negative, had BD-Day 1 and BD-Day 29 Ab assessment, had no major protocol deviations, did not receive off-study COVID-19 vaccination prior to BD-Day 29 visit, received 2 doses of mRNA-1273 in the Blinded Phase per schedule, received BD, and were pre-booster SARS-CoV2 negative. 'Overall number of participants analyzed' = participants evaluable for this endpoint.

Arm	Measure	Value (GEOMETRIC_MEAN)
Part 1A: mRNA-1273 100 μg	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	7102.0 arbitrary units (AU)/mL
Part 1A: Placebo	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	1400.4 arbitrary units (AU)/mL

95% CI: [4.477, 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

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 (LLOQ: 10 AU/mL, ULOQ: 281600 AU/mL). PPIS P301: randomly selected participants from Study P301 aged 18-25 meeting pre-specified criteria and SARS-CoV-2 negative were used for comparison assessments of immune response.

Time frame: BD Day 29 Study P203/Day 57 Study P301

Arm	Measure	Value (NUMBER)
Part 1A: mRNA-1273 100 μg	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	100.0 percentage of participants
Part 1A: Placebo	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	99.3 percentage of participants

95% CI: [-0.8, 2.4]

Primary

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

Time frame: BD Day 29

Population: Part 1C-2 PPIS: all randomized participants who received BD in Part 1C-2, had BD-Day 29 Ab assessment, had no major protocol deviations that impacted key or critical data, and did not receive off-study COVID-19 vaccination prior to BD-Day 29 visit. 'Overall number of participants analyzed' = participants evaluable for this endpoint.

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Part 1A: mRNA-1273 100 μg	Part 1C-2 GMC of Post-booster Pseudovirus nAb Against Ancestral Strain at BD Day 29	9433.4 AU/mL	95% Confidence Interval 8496.8

Primary

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

Time frame: Day 57

Population: Part 2 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.

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Part 1A: mRNA-1273 100 μg	Part 2 GMC of the Pseudovirus nAb Against Ancestral Strain at Day 57	7351.5 AU/mL	95% Confidence Interval 5621.7

Primary

Part 2 SRR of Pseudovirus nAb Against Ancestral Strain

Time frame: Day 57

Arm	Measure	Value (NUMBER)	Dispersion
Part 1A: mRNA-1273 100 μg	Part 2 SRR of Pseudovirus nAb Against Ancestral Strain	91.3 percentage of participants	95% Confidence Interval 79.2

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

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. PPIS P301: randomly selected participants from Study P301 aged 18-25 meeting pre-specified criteria and SARS-CoV-2 negative were used for comparison of immune response.

Time frame: Day 29 Study P203/Day 57 Study P301

Population: Part 3 PPIS-Pos: participants received Dose 1 of mRNA-1273.222, had Day 29 antibody assessments, no major protocol deviations, did not receive off-study COVID-19 vaccination prior to Day 29, SARS-CoV-2 positive at Baseline. 'Overall number of participants analyzed' = participants evaluable for the endpoint.

Arm	Measure	Value (GEOMETRIC_MEAN)
Part 1A: mRNA-1273 100 μg	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	2727.8 AU/mL
Part 1A: Placebo	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	56.6 AU/mL

95% CI: [43.765, 53.065]

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

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. PPIS P301: randomly selected participants from Study P301 aged 18-25 meeting pre-specified criteria and SARS-CoV-2 negative were used for comparison of immune response.

Time frame: Day 29 Study P203/Day 57 Study P301

Arm	Measure	Value (GEOMETRIC_MEAN)
Part 1A: mRNA-1273 100 μg	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	7603.9 AU/mL
Part 1A: Placebo	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	1692.3 AU/mL

95% CI: [3.972, 5.083]

Secondary

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

SARS-CoV-2 Spike Protein-specific bAb were measured using 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 AU/mL, ULOQ: 14400000 AU/mL).

Time frame: Days 1, 57, 209, 394

Population: Part 1A PPIS for long term analysis included all randomized participants who had a negative SARS-CoV-2 status at baseline (pre-Dose 1), 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.

Arm	Measure	Group	Value (GEOMETRIC_MEAN)
Part 1A: mRNA-1273 100 μg	Part 1A GM Level of SARS-CoV-2 Spike Protein-specific bAb at Days 1, 57, 209, 394	Day 1	65.848 AU/mL
Part 1A: mRNA-1273 100 μg	Part 1A GM Level of SARS-CoV-2 Spike Protein-specific bAb at Days 1, 57, 209, 394	Day 57	346830.736 AU/mL
Part 1A: mRNA-1273 100 μg	Part 1A GM Level of SARS-CoV-2 Spike Protein-specific bAb at Days 1, 57, 209, 394	Day 209	79624.290 AU/mL
Part 1A: mRNA-1273 100 μg	Part 1A GM Level of SARS-CoV-2 Spike Protein-specific bAb at Days 1, 57, 209, 394	Day 394	58647.246 AU/mL

Secondary

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

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 AU/mL, ULOQ: 281600 AU/mL).

Time frame: Days 1, 57, 209, 394

Arm	Measure	Group	Value (GEOMETRIC_MEAN)
Part 1A: mRNA-1273 100 μg	Part 1A GM Value of SARS-CoV-2-Specific nAb at Days 1, 57, 209, 394	Day 1	11.249 AU/mL
Part 1A: mRNA-1273 100 μg	Part 1A GM Value of SARS-CoV-2-Specific nAb at Days 1, 57, 209, 394	Day 57	1868.363 AU/mL
Part 1A: mRNA-1273 100 μg	Part 1A GM Value of SARS-CoV-2-Specific nAb at Days 1, 57, 209, 394	Day 209	625.363 AU/mL
Part 1A: mRNA-1273 100 μg	Part 1A GM Value of SARS-CoV-2-Specific nAb at Days 1, 57, 209, 394	Day 394	550.262 AU/mL

Secondary

Part 1A Number of Participants With a First Occurrence of Symptomatic COVID-19

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 nasopharyngeal swab, nasal swab, or saliva sample (or respiratory sample, if hospitalized) positive for SARS-CoV-2.

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

Population: Part 1A 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.

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
Part 1A: mRNA-1273 100 μg	Part 1A Number of Participants With a First Occurrence of Symptomatic COVID-19	0 Participants
Part 1A: Placebo	Part 1A Number of Participants With a First Occurrence of Symptomatic COVID-19	6 Participants

Secondary

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

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.

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

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
Part 1A: mRNA-1273 100 μg	Part 1A Number of Participants With a SARS-CoV-2 Infection (Symptomatic or Asymptomatic)	22 Participants
Part 1A: Placebo	Part 1A Number of Participants With a SARS-CoV-2 Infection (Symptomatic or Asymptomatic)	25 Participants

95% CI: [26.6, 78.6]VE

Secondary

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

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.

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

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
Part 1A: mRNA-1273 100 μg	Part 1A Number of Participants With Asymptomatic SARS-CoV-2 Infection	20 Participants
Part 1A: Placebo	Part 1A Number of Participants With Asymptomatic SARS-CoV-2 Infection	16 Participants

95% CI: [-16.5, 72.2]VE

Secondary

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

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.

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

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
Part 1A: mRNA-1273 100 μg	Part 1A Number of Participants With Secondary Case Definition of COVID-19 (Center for Disease Control and Prevention [CDC] Case Definition)	2 Participants
Part 1A: Placebo	Part 1A Number of Participants With Secondary Case Definition of COVID-19 (Center for Disease Control and Prevention [CDC] Case Definition)	9 Participants

95% CI: [51, 98.9]VE

Secondary

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

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.

Time frame: BD Day 29

Population: Part 1C-1 PPIS: participants were baseline (pre-dose 1 of Part 1A) SARS-CoV-2 negative, had BD-Day 1 and BD-Day 29 Ab assessment, had no major protocol deviations, did not receive off-study COVID-19 vaccination prior to BD-Day 29 visit, received 2 doses of mRNA-1273 in the Blinded Phase per schedule, and received BD. Overall number of participants analyzed' = participants evaluable for this endpoint.

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Part 1A: mRNA-1273 100 μg	Part 1C-1 GMC of Post-booster Pseudovirus nAb Against Variant Strain (B.1.1.529)	943.4 AU/mL	95% Confidence Interval 853.5

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

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).

Time frame: BD Day 29

Population: Part 1C-1 PPIS: participants were baseline (pre-dose 1 of Part 1A) SARS-CoV-2 negative, had BD-Day 1 and BD-Day 29 Ab assessment, had no major protocol deviations, did not receive off-study COVID-19 vaccination prior to BD-Day 29 visit, received 2 doses of mRNA-1273 in the Blinded Phase per schedule, and received BD. 'Overall number of participants analyzed' = participants evaluable for this endpoint.

Arm	Measure	Group	Value (GEOMETRIC_MEAN)	Dispersion
Part 1A: mRNA-1273 100 μg	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	B.1.1.7	581097.8 AU/mL	95% Confidence Interval 543987.7
Part 1A: mRNA-1273 100 μg	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	B.1.351	431569.2 AU/mL	95% Confidence Interval 404983.2
Part 1A: mRNA-1273 100 μg	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	B.1.617.2	456423.3 AU/mL	95% Confidence Interval 429083.9
Part 1A: mRNA-1273 100 μg	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	P.1	417277.2 AU/mL	95% Confidence Interval 391682.5

Secondary

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

Percentage of participants with seroresponse for bAb measured using (MesoScale Discovery) MSD are reported. 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.

Time frame: BD Day 29

Population: Part 1C-1 PPIS: participants were baseline (pre-dose 1 of Part 1A) SARS-CoV-2 negative, had BD-Day 1 and BD-Day 29 Ab assessment, had no major protocol deviations, did not receive off-study COVID-19 vaccination prior to BD-Day 29 visit, received 2 doses of mRNA-1273 in the Blinded Phase per schedule, and received BD. 'Overall number of participants analyzed' = participants evaluable for this endpoint.

Arm	Measure	Group	Value (NUMBER)	Dispersion
Part 1A: mRNA-1273 100 μg	Part 1C-1 SRR of the Post-booster Serum Binding Antibody (bAb) Against Variants of Interest (B.1.1.7, B.1.351, B.1.617.2, and P.1) as Measured by MSD	B.1.1.7	100.0 Percentage of participants	95% Confidence Interval 98.9
Part 1A: mRNA-1273 100 μg	Part 1C-1 SRR of the Post-booster Serum Binding Antibody (bAb) Against Variants of Interest (B.1.1.7, B.1.351, B.1.617.2, and P.1) as Measured by MSD	B.1.351	100.0 Percentage of participants	95% Confidence Interval 98.9
Part 1A: mRNA-1273 100 μg	Part 1C-1 SRR of the Post-booster Serum Binding Antibody (bAb) Against Variants of Interest (B.1.1.7, B.1.351, B.1.617.2, and P.1) as Measured by MSD	B.1.617.2	100.0 Percentage of participants	95% Confidence Interval 98.9
Part 1A: mRNA-1273 100 μg	Part 1C-1 SRR of the Post-booster Serum Binding Antibody (bAb) Against Variants of Interest (B.1.1.7, B.1.351, B.1.617.2, and P.1) as Measured by MSD	P.1	100.0 Percentage of participants	95% Confidence Interval 98.9

Secondary

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

Time frame: Day 29

Population: As a result of emergence of a more divergent variant of concern (Omicron), Part 1C-2 enrollment and booster dosing were discontinued. Therefore, data were collected for Part 1C-2 Primary Outcome Measure but after Part 1C-2 was discontinued, per Sponsor, it was decided that data would not be collected for this Part 1C-2 Secondary Outcome Measure and instead collect data for the more updated variant containing vaccine (Part 3: mRNA-1273.222).

Secondary

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

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).

Time frame: Day 29

Population: Part 3 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. 'Overall number of participants analyzed' = participants evaluable for the endpoint.

Arm	Measure	Group	Value (GEOMETRIC_MEAN)
Part 1A: mRNA-1273 100 μg	Part 3 GM Value of Post Dose 1 (Day 29) of mRNA-1273.222 bAb Against Other Variants of Interest	BA.5	282734.2 AU/mL
Part 1A: mRNA-1273 100 μg	Part 3 GM Value of Post Dose 1 (Day 29) of mRNA-1273.222 bAb Against Other Variants of Interest	AY.4	557963.4 AU/mL
Part 1A: mRNA-1273 100 μg	Part 3 GM Value of Post Dose 1 (Day 29) of mRNA-1273.222 bAb Against Other Variants of Interest	B.1.1.7	434879.0 AU/mL
Part 1A: mRNA-1273 100 μg	Part 3 GM Value of Post Dose 1 (Day 29) of mRNA-1273.222 bAb Against Other Variants of Interest	B.1.351	431476.5 AU/mL
Part 1A: mRNA-1273 100 μg	Part 3 GM Value of Post Dose 1 (Day 29) of mRNA-1273.222 bAb Against Other Variants of Interest	B.1.1.529	189826.0 AU/mL
Part 1A: mRNA-1273 100 μg	Part 3 GM Value of Post Dose 1 (Day 29) of mRNA-1273.222 bAb Against Other Variants of Interest	P.1	471868.9 AU/mL

Secondary

Part 3 Pseudovirus nAb SRR of Post Dose 1 of mRNA-1273.222 Against Ancestral Strain Compared With Those From Young Adult (18 to 25 Years of Age) Vaccine Recipients (Day 57) in Study P301

Percentage of participants with seroresponse for pseudovirus nAb measured using PsVNA assay are reported. 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. PPIS P301: randomly selected participants from Study P301 aged 18-25 meeting pre-specified criteria and SARS-CoV-2 negative were used for comparison assessments of immune response.

Time frame: Day 29 P203/Day 57 P301

Population: Part 3 PPIS-Pos: participants who received Dose 1 of mRNA-1273.222, had Day 29 antibody assessments, no major protocol deviations, did not receive off-study COVID-19 vaccination prior to Day 29, and were SARS-CoV-2 positive at baseline. 'Overall number of participants analyzed' = participants evaluable for the endpoint.

Arm	Measure	Value (NUMBER)
Part 1A: mRNA-1273 100 μg	Part 3 Pseudovirus nAb SRR of Post Dose 1 of mRNA-1273.222 Against Ancestral Strain Compared With Those From Young Adult (18 to 25 Years of Age) Vaccine Recipients (Day 57) in Study P301	94.9 percentage of participants
Part 1A: Placebo	Part 3 Pseudovirus nAb SRR of Post Dose 1 of mRNA-1273.222 Against Ancestral Strain Compared With Those From Young Adult (18 to 25 Years of Age) Vaccine Recipients (Day 57) in Study P301	99.3 percentage of participants

Secondary

Part 3 SRR of Serum Pseudovirus nAb Post Dose 1 of 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

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 (LLOQ: 103 AU/mL, ULOQ: 28571 AU/mL). PPIS P301: randomly selected participants from Study P301 aged 18-25 meeting pre-specified criteria and SARS-CoV-2 negative were used for comparison of immune response.

Time frame: Day 29 Study P203/Day 57 Study P301

Arm	Measure	Value (NUMBER)
Part 1A: mRNA-1273 100 μg	Part 3 SRR of Serum Pseudovirus nAb Post Dose 1 of 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	95.4 percentage of participants
Part 1A: Placebo	Part 3 SRR of Serum Pseudovirus nAb Post Dose 1 of 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	0.0 percentage of participants

Other Pre-specified

Number of Deaths Related to Study Drug

A death that occurred during the study or that came to the attention of the investigator during the study was reported to the Sponsor, whether or not it was considered related to study drug. The investigator assessed causality (that is, whether there is a reasonable possibility that the study drug caused the death). The relationship was characterized using the following classifications: Not related: There was not a reasonable possibility of a relationship to the study drug. The temporal sequence of the death relative to administration of the study drug was not reasonable and/or the death was more likely explained by a cause other than the study drug. Related: There was a reasonable possibility of a relationship to the study drug. There was evidence of exposure to the study drug. The temporal sequence of the death relative to the administration of the study drug was reasonable. The death was more likely explained by the study drug than by another cause.

Time frame: Day 1 up to Day 751

Population: Safety Set: participants who received at least 1 dose of study drug.

Arm	Measure	Group	Value (COUNT_OF_PARTICIPANTS)
Part 1A: mRNA-1273 100 μg	Number of Deaths Related to Study Drug	Deaths	0 Participants
Part 1A: mRNA-1273 100 μg	Number of Deaths Related to Study Drug	Deaths related to study drug	0 Participants
Part 1A: Placebo	Number of Deaths Related to Study Drug	Deaths	0 Participants
Part 1A: Placebo	Number of Deaths Related to Study Drug	Deaths related to study drug	0 Participants
Part 1C-1: mRNA-1273 50 µg BD	Number of Deaths Related to Study Drug	Deaths	0 Participants
Part 1C-1: mRNA-1273 50 µg BD	Number of Deaths Related to Study Drug	Deaths related to study drug	0 Participants
Part 1C-2: mRNA-1273 50 μg BD	Number of Deaths Related to Study Drug	Deaths	0 Participants
Part 1C-2: mRNA-1273 50 μg BD	Number of Deaths Related to Study Drug	Deaths related to study drug	0 Participants
Part 2: mRNA-1273 50 μg First Injection	Number of Deaths Related to Study Drug	Deaths	0 Participants
Part 2: mRNA-1273 50 μg First Injection	Number of Deaths Related to Study Drug	Deaths related to study drug	0 Participants
Part 2: mRNA-1273 50 μg Second Injection	Number of Deaths Related to Study Drug	Deaths related to study drug	0 Participants
Part 2: mRNA-1273 50 μg Second Injection	Number of Deaths Related to Study Drug	Deaths	0 Participants
Part 2: mRNA-1273 50 μg BD	Number of Deaths Related to Study Drug	Deaths related to study drug	0 Participants
Part 2: mRNA-1273 50 μg BD	Number of Deaths Related to Study Drug	Deaths	0 Participants
Part 3: mRNA-1273.222 50 μg 1 Dose	Number of Deaths Related to Study Drug	Deaths	0 Participants
Part 3: mRNA-1273.222 50 μg 1 Dose	Number of Deaths Related to Study Drug	Deaths related to study drug	0 Participants
Part 3: mRNA-1273.222 50 ug Second Dose	Number of Deaths Related to Study Drug	Deaths	1 Participants
Part 3: mRNA-1273.222 50 ug Second Dose	Number of Deaths Related to Study Drug	Deaths related to study drug	0 Participants

Source: ClinicalTrials.gov · Data processed: Feb 21, 2026

A Study to Evaluate the Safety, Reactogenicity, and Effectiveness of mRNA-1273 Vaccine in Adolescents 12 to <18 Years Old to Prevent COVID-19

Conditions

Keywords

Brief summary

Detailed description

Related papers

Interventions

Sponsors

Study design

Masking description

Eligibility

Inclusion criteria

Exclusion criteria

Design outcomes

Primary

Secondary

Other

Countries

Participant flow

Recruitment details

Pre-assignment details

Participants by arm

Withdrawals & dropouts

Baseline characteristics

Adverse events

Outcome results

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

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

Number of Participants With Unsolicited AEs

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

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

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

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

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

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

Part 2 SRR of Pseudovirus nAb Against Ancestral Strain

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

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

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

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

Part 1A Number of Participants With a First Occurrence of Symptomatic COVID-19

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

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

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

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

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

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

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

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

Part 3 Pseudovirus nAb SRR of Post Dose 1 of mRNA-1273.222 Against Ancestral Strain Compared With Those From Young Adult (18 to 25 Years of Age) Vaccine Recipients (Day 57) in Study P301

Part 3 SRR of Serum Pseudovirus nAb Post Dose 1 of 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

Number of Deaths Related to Study Drug