A Study to Evaluate Safety and Effectiveness of mRNA-1273 COVID-19 Vaccine in Healthy Children Between 6 Months of Age and Less Than 12 Years of Age

Study Overview
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Brief Summary
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The primary goal for this study is to evaluate up to 3 dose levels of mRNA-1273 vaccine given to healthy children as intramuscular (IM) injection in 2 doses (in Parts 1 and 2) and 3 doses (in Part 3), and a third dose or an optional booster dose (BD) (in Parts 1 and 2).

Detailed Description
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This is a Phase 2/3, 3-part, open-label, dose-escalation, age de-escalation, randomized, observer-blind, placebo-controlled, expansion study intended to infer the effectiveness of mRNA-1273 in children aged 6 months to less than 12 years. Please access http://www.kidcovestudy.com for additional information, such as Study Overview, Participation, Site Locations along with contact numbers for each location for the study.

Official Title
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A Phase 2/3, Three-Part, Open-Label, Dose-Escalation, Age De-escalation and Randomized, Observer-Blind, Placebo-Controlled Expansion Study to Evaluate the Safety, Tolerability, Reactogenicity, and Effectiveness of mRNA-1273 SARS-CoV-2 Vaccine in Healthy Children 6 Months to Less Than 12 Years of Age

Conditions
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SARS-CoV-2

Intervention / Treatment
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* Biological: mRNA-1273
* Biological: Placebo
* Biological: mRNA-1273.214


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: For participants with chronic diseases (such as, asthma, diabetes mellitus, cystic fibrosis, human immunodeficiency virus [HIV] infection), the disease should be stable, per investigator assessment. Investigator assessment that the parent(s)/legally acceptable representatives understand and are willing and physically able to comply with protocol mandated follow-up, including all procedures, written informed consent is provided, and participants provide assent. For children 2 years of age or older has a body mass index at or above the third percentile according to World Health Organization (WHO) Child Growth Standards at the Screening Visit. For children 6 months to <12 months of age: born at full-term with a minimum birth weight of 2.5 kilograms (kg). For female participants of childbearing potential: negative pregnancy test, adequate contraception or has abstained from all activities that could result in pregnancy for at least 28 days prior to the first injection, agreement to continue adequate contraception or abstinence through 3 months following the second injection (Day 29) and the third dose in Part 3 (Day 149/booster dose Day 1), and not currently breastfeeding. Key Exclusion Criteria: Known history of SARS-CoV-2 infection within 2 weeks prior to administration of vaccine or known close contact with anyone with laboratory-confirmed SARS-CoV-2 infection or COVID-19 within 2 weeks prior to administration of vaccine. Prior administration of an investigational or approved CoV (such as, SARS-CoV-2, SARS CoV, Middle East Respiratory Syndrome CoV) vaccine. Treatment with investigational or approved agents for prophylaxis against COVID 19 (such as, receipt of SARS-CoV-2 monoclonal antibodies) within 6 months prior to enrollment. Known hypersensitivity to a component of the vaccine or its excipients. 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. History of a diagnosis or condition that, in the judgment of the investigator, may affect study endpoint assessment or compromise participant safety. Received any non-study vaccine within 14 days before or after any dose of vaccine (except for seasonal influenza vaccine, which is not permitted within 14 days before or after any dose of vaccine) Received intravenous or subcutaneous blood products (red blood cells, platelets, immunoglobulins) within 3 months prior to Day 1 Participated in an interventional clinical study within 28 days prior to Day 0 or plans to donate blood products while participating in this study.

Ages Eligible for Study
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Minimum Age: 6 Months
Maximum Age: 11 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: mRNA-1273<br>Part 1: Participants will receive 2 IM injections of mRNA-1273 at doses pre-specified for this study, on Days 1 and 29. Participants will be offered an optional BD of mRNA-1273 lower than the dose chosen for primary series, ≥6 months after Dose 2. After protocol amendment (PA) 9, participants who have not yet received a BD will be offered a BD with mRNA-1273.214. Part 2: Participants will receive 2 IM injections of mRNA-1273 at dose selected from Part 1 on Days 1 and 29. Participants (6 to <12 year) will be offered an optional BD of mRNA-1273 lower than the dose chosen for primary series, ≥6 months after Dose 2. After PA 9, participants who have not yet received a BD will be offered a BD with mRNA-1273.214. Part 3: Participants will receive 2 IM injections of mRNA-1273 on Days 1 and 29 as primary series then 1 IM injection as Dose 3, on Day 149 ≥3 months and ≤5 months after receipt of Dose 2 of primary series. All 3 injections will be administered at lower dose than that of Part 1. | Biological: mRNA-1273<br>* Sterile liquid for injection<br>Biological: mRNA-1273.214<br>* Sterile liquid for injection<br>|
| Placebo Comparator: Placebo<br>Part 2 only: Participants will receive 2 IM injections of mRNA-1273-matching placebo on Day 1 and Day 29. Participants (6 to <12 year old) will be offered an optional BD of mRNA-1273 at a dose lower than the dose that was chosen for the primary series for this age group, at least 6 months post-cross-over Dose 2. After PA 9, participants who have not yet received a BD will be offered a BD with mRNA-1273.214. | Biological: mRNA-1273<br>* Sterile liquid for injection<br>Biological: Placebo<br>* 0.9% sodium chloride (normal saline) injection<br>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 156 (7 days after each injection) | 
| Number of Participants with Unsolicited Adverse Events (AEs) |  | Up to Day 177 (28 days after each injection) | 
| Number of Participants with Medically-Attended AEs (MAAEs) |  | Up to Day 514 (1 year after booster dose) | 
| Number of Participants with Serious Adverse Events (SAEs) |  | Up to Day 514 (1 year after booster dose) | 
| Number of Participants with Adverse Events of Special Interest (AESIs), Including Multisystem Inflammatory Syndrome in Children (MIS-C), Myocarditis and/or Pericarditis |  | Up to Day 514 (1 year after booster dose) | 
| Number of Participants with AEs Leading to Discontinuation From Study Post-Booster Dose Through the Last Day of Study Participation |  | Day 149 (booster dose Day 1) through the last day of study participation (Day 514) | 
| Number of Participants with Serum Antibody Levels that Meet or Exceed the Threshold of Protection From COVID-19 | Threshold of protection as predefined for study. | Day 57 (1 month after second injection) | 
| Geometric Mean (GM) Value of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Specific Serum Antibody |  | Day 57 (1 month after second injection) | 
| Seroresponse Rate of Vaccine Recipients |  | Day 57 (1 month after second injection) | 
| GM Value of Post-Booster Dose SARS-CoV-2 Specific Serum Antibody |  | Day 149 (post third dose) | 
| Seroresponse Rate of Post-Booster Dose of Vaccine Recipients |  | Day 149 (post third dose) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| GM Value of SARS-CoV-2 S-Protein-Specific Binding Antibody (bAb) |  | Day 1, Day 57, Day 209, Day 394, booster dose Day 1, booster dose Day 29, booster dose Day 181, and booster dose Day 366 | 
| GM Value of SARS-CoV-2- Specific Neutralizing Antibody (nAb) |  | Day 1, Day 57, Day 209, Day 394, booster dose Day 1, booster dose Day 29, booster dose Day 181, and booster dose Day 366 | 
| Number of Participants with SARS-CoV-2 Infections Regardless of Symptomatology, as Assessed by Serology and/or Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) | Clinical signs indicative of SARS-CoV-2 infection as predefined for the study. | Up to Day 394 | 
| Number of Participants with SARS-CoV-2 Infection Measured by RT-PCR and/or bAb Levels Against SARS-CoV-2 Nucleocapsid Protein in Participants with Negative SARS-CoV-2 at Baseline, in the Absence of Any COVID-19 Symptoms |  | Up to Day 394 | 
| Number of Participants with a First Occurrence of COVID-19 | Clinical signs indicative of COVID-19 as predefined for the study. | Up to Day 394 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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mRNA-1273, mRNA-1273 vaccine, SARS-CoV-2, SARS-CoV-2 Vaccine, Coronavirus, Virus Diseases, Messenger RNA, COVID-19, COVID-19 Vaccine, Moderna