A Study to Evaluate the Safety and Immunogenicity of the mRNA-1273.214 COVID-19 Vaccine in Healthy Children Between 6 Months to Less Than 6 Years of Age

Study Overview
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Brief Summary
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This study will evaluate the safety and immunogenicity of the mRNA-1273.214 vaccine for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant of concerns (VOCs) in participants aged 6 months to <6 years, when administered as a primary series in SARS-CoV-2 vaccine-naïve participants (Part 1) and a single booster dose given to participants who previously received 2 doses of the mRNA-1273 vaccine as a primary series (Part 2).

Detailed Description
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Part 1 will enroll participants aged 6 months to <6 years who have not been previously vaccinated against SARS-CoV-2. Participants will receive 2 doses of the mRNA-1273.214 vaccine and will be followed for approximately 12 months after the second dose for safety and additional immunogenicity follow-up. Part 2 will enroll participants aged 6 months to <6 years who have previously been vaccinated with a mRNA-1273 primary series in Study mRNA-1273-P204. Participants will receive a single booster dose of the mRNA-1273.214 vaccine, at least 4 months after completion of the mRNA-1273 primary series and will be followed for approximately 6 months after the booster dose for safety and immunogenicity.

Official Title
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An Open-Label, Phase 3 Study to Evaluate the Safety and Immunogenicity of the mRNA-1273.214 Vaccine for SARS-CoV-2 Variants of Concern in Participants Aged 6 Months to < 6 Years

Conditions
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SARS-CoV-2

Intervention / Treatment
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* Biological: mRNA-1273.214


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: If the participant has a chronic disease (that is, asthma, diabetes mellitus, cystic fibrosis, human immunodeficiency virus [HIV] infection), the disease should be stable, per investigator assessment, so that the participant can be considered eligible for inclusion. Stable diseases are those which have had no change in their status or in the medications required to control them in the 6 months prior to Screening Visit. Note: a change in medication for dose optimization (that is, insulin dose changes, adjustments for age-related weight gain), change within class of medication, or reduction in dose are not considered signs of instability. In the investigator's opinion, the parent(s)/legally authorized representative(s) (LAR[s]) understand and are willing and physically able to comply with protocol-mandated follow-up, including all procedures and provide written informed consent. This includes inability to draw baseline blood samples (minimum amount needed). The participant is 2 years or older and has a body mass index (BMI) at or above the 2nd percentile according to World Health Organization (WHO) Child Growth Standards at the Screening Visit. OR The participant is less than 2 years of age and the participant's height and weight are both at or above the 2nd percentile according to WHO Child Growth Standards at the Screening Visit. Special inclusion criteria for participants aged 6 months to < 12 months: The participant was born at full-term (≥ 37 weeks gestation) with a minimum birth weight of 2.5 kilograms (kg). Inclusion criteria for Part 2: The participant must have received 2 doses of mRNA-1273, approximately 28 to 35 days apart, as 25-μg primary series, and 2nd dose was given at least 4 months prior to enrollment. Exclusion Criteria: Has a known history of SARS-CoV-2 infection (that is, reported AE of coronavirus disease 2019 [COVID-19] or asymptomatic SARS-CoV-2 infection during Study mRNA-1273-P204) in the 90 days prior to dosing in this study. Is acutely ill or febrile 24 hours prior to or at the Screening Visit. 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 previously been administered an investigational or approved CoV (that is, SARS-CoV-2, SARS-CoV, Middle East respiratory syndrome coronavirus [MERS-CoV]) vaccine. For Part 2, this applies to vaccines other than the mRNA-1273 (prototype) vaccine. Has undergone treatment with investigational or approved agents for prophylaxis against COVID-19 (including receipt of SARS-CoV-2 monoclonal antibodies for prophylaxis or treatment) within 90 days prior to enrollment. Has a known hypersensitivity to a component of the vaccine or its excipients. Hypersensitivity includes, but is not limited to, anaphylaxis or immediate allergic reaction of any severity to a previous dose of an mRNA COVID-19 vaccine or any of its components (including polyethylene glycol [PEG] or immediate allergic reaction of any severity to polysorbate). Has a medical or psychiatric condition that, according to the investigator's judgment, may pose additional risk as a result of participation, interfere with safety assessments, or interfere with interpretation of results. Has a history of diagnosis or condition that, in the judgment of the investigator, may affect study endpoint assessment or compromise participant safety, specifically the following: Congenital or acquired immunodeficiency, other than well-controlled HIV infection. Chronic hepatitis or suspected active hepatitis A bleeding disorder that is considered a contraindication to IM injection or phlebotomy Dermatologic conditions that could affect local solicited AR assessments Any prior diagnosis of malignancy (excluding nonmelanoma skin cancer) Has received the following: Any routine vaccination with inactivated or live vaccine(s) within 14 days prior to study vaccination or plans to receive such a vaccine through 14 days following study vaccination. Note: This excludes influenza vaccine that may be given anytime, but ideally at least 7 days before study dose. If a participant receives an influenza vaccine, this should be captured within the concomitant medication electronic case report form (eCRF). Systemic immunosuppressants or immune-modifying drugs for >14 days in total within 6 months prior to the day of enrollment (for corticosteroids, ≥1 milligrams (mg)/kg/day or ≥ 10 mg/day prednisone equivalent, if participant weighs >10 kg). Participants may have visits rescheduled for enrollment if they no longer meet this criterion within the Screening Visit window. Inhaled, nasal, and topical steroids, and palivizumab are allowed. Intravenous (IV) or subcutaneous (SC) blood products (red cells, platelets, immunoglobulins) within 3 months prior to enrollment.

Ages Eligible for Study
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Minimum Age: 6 Months
Maximum Age: 5 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: mRNA-1273.214<br>Part 1: Participants who have not been previously vaccinated against SARS-CoV-2, will receive 2 intramuscular (IM) injections of 25 microgram (μg) mRNA-1273.214 on Day 1 and Day 29. Part 2: Participants who have previously been vaccinated with a mRNA-1273 primary series, will receive a single IM booster dose (BD) of 10 μg mRNA-1273.214 at least 4 months after the last dose on BD Day 1. | Biological: mRNA-1273.214<br>* Sterile liquid for injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants with Solicited Local and Systemic Adverse Reactions (ARs) |  | Up to Day 8 (7 days post-vaccination) | 
| Number of Participants with Unsolicited Adverse Events (AEs) |  | Up to Day 29 (28 days after each injection) | 
| Number of Participants with Medically-Attended AEs (MAAEs) |  | Up to Day 575 | 
| Number of Participants with Serious AEs (SAEs) |  | Up to Day 575 | 
| Number of Participants with Adverse Events of Special Interest (AESI) |  | Up to Day 575 | 
| Number of Participants with AEs Leading to Withdrawal |  | Up to Day 575 | 
| Geometric Mean (GM) of the Serum Antibody (Ab) Level Against SARS-CoV-2 (Omicron BA.1 and Ancestral SARS-CoV-2) |  | Day 57 (28 days after second dose) | 
| GM of the Serum Ab Level Against SARS-CoV-2 (Omicron BA.1 and Ancestral SARS-CoV-2) |  | Day 29 (28 days after booster dose) | 
| SRR of Vaccine Recipients of SARS-CoV-2 VOC (Omicron BA.1 and Ancestral SARS-CoV-2) |  | Day 29 (28 days after booster dose) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Seroresponse Rate (SRR) of Vaccine Recipients of SARS-CoV-2 VOC (Omicron BA.1 and Ancestral SARS-CoV-2) |  | Day 57 (28 days after second dose) |