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

Study Overview
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Brief Summary
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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
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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 of mRNA-1273 SARS-CoV-2 vaccine. Part 3 is an open-label design. Participants will receive 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.

Official Title
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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

Conditions
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SARS-CoV-2

Intervention / Treatment
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* Biological: mRNA-1273
* Biological: Placebo
* Biological: mRNA-1273.222


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 12 Years
Maximum Age: 18 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 1A (Blinded Phase): Participants will receive 2 intramuscular (IM) injections of mRNA-1273 (100 microgram [ug] each), 28 days apart, on Day 1 and Day 29. Part 1B (Open-Label Phase): Participants who cross over from placebo in Part 1A to Part 1B will receive 2 IM injections of mRNA-1273 (100 ug each), 28 days apart on Open Label Day 1 and Open Label Day 29. Part 2 (Open-Label): Participants will receive 2 intramuscular (IM) injections of mRNA-1273 (50 ug each), 28 days apart, on Day 1 and Day 29. | Biological: mRNA-1273<br>* Sterile liquid for injection<br>|
| Placebo Comparator: Placebo<br>Part 1A (Blinded Phase): Participants will receive 2 IM injections of mRNA-1273 matching placebo, 28 days apart, on Day 1 and Day 29. | Biological: Placebo<br>* 0.9% sodium chloride (normal saline) injection<br>|
| Experimental: mRNA-1273 BD<br>Part 1C-1 (BD Phase): Participants will receive 1 IM injection of mRNA-1273 (50 ug) on BD-Day 1, 5 months after the last dose of Part 1A and 1B. Part 1C-2 (BD Phase): Participants will receive 1 IM injection of mRNA-1273 (50 ug) on BD-Day 1, at least 3 months post-last dose. | Biological: mRNA-1273<br>* Sterile liquid for injection<br>|
| Experimental: mRNA-1273.222<br>Part 3 (Open-Label): Participants will receive 2 IM injections of mRNA-1273.222 (50 ug each), 6 months apart, on Day 1 and Day 181. | Biological: mRNA-1273.222<br>* Sterile solution 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 187 (7 days after each injection) | 
| Number of Participants with Unsolicited Adverse Events (AEs) |  | Up to Day 208 (28 days after each dose) | 
| Number of Participants with Serious Adverse Events (SAEs), Medically Attended AEs (MAAEs), or Adverse Events of Special Interest (AESI) |  | Up to Day 751 | 
| Number of Participants With Serum Antibody (Ab) Levels that Meet or Exceed the Threshold of Protection From COVID-19 | Acceptable serum Ab threshold as predefined for the study. | Day 57 | 
| Geometric Mean (GM) Value of the Serum Ab Level |  | Day 57 | 
| Seroresponse Rate (SRR) of Vaccine Recipients |  | Day 57 | 
| Number of Participants with AEs Leading to Discontinuation From Study Post BD |  | Up to Day 751 | 
| GM Value of the Serum Ab Level Against Ancestral Strain Post BD |  | BD-Day 29 | 
| SRR of Vaccine Recipients Against Ancestral Strain Post BD at BD-Day 29 |  | BD-Day 29 | 
| GM Value of the Serum Ab Level Against Ancestral Strain Post Dose 2 |  | Day 57 | 
| SRR of Vaccine Recipients Against Ancestral Strain Post Dose 2 |  | Day 57 | 
| Number of Participants with AEs Leading to Discontinuation from Dosing from Dose 1 |  | Up to Day 361 | 
| GM Value of the Serum Ab Level After mRNA-1273.222 Vaccine Administration Against SARS-CoV-2 Omicron Variant |  | Day 29 | 
| GM Value of the Serum Ab Level After mRNA-1273.222 Vaccine Administration Against Ancestral Strain |  | Day 29 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| GM Value of SARS-CoV-2 Spike Protein (S2P)-Specific Binding Antibody (bAb) |  | Day 1, Day 57 (1 month after Dose 2), Day 209 (6 months after Dose 2), and Day 394 (1 year after Dose 2) | 
| GM Value of SARS-CoV-2-Specific Neutralizing Antibody (nAb) |  | Day 1, Day 57 (1 month after Dose 2), Day 209 (6 months after Dose 2), and Day 394 (1 year after Dose 2) | 
| Number of Participants with a SARS-CoV-2 Infection (Symptomatic or Asymptomatic) Starting 14 Days after the Second Dose of mRNA-1273 or Placebo | Clinical signs indicative of SARS-CoV-2 infection as predefined for the study. | Day 43 up to Day 394 | 
| Number of Participants With Asymptomatic SARS-CoV-2 Infection Measured by Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) and/or bAb Levels Against SARS-CoV-2 Nucleocapsid Protein |  | Day 43 up to Day 394 | 
| Number of Participants with a First Occurrence of Symptomatic COVID-19 Starting 14 days After Second Dose of mRNA-1273 or Placebo | Clinical signs indicative of symptomatic COVID-19 as predefined for the study. | Day 43 up to Day 394 | 
| GM Value of the Serum Ab Level After mRNA-1273 Vaccine Administration Against Circulating Strain |  | Day 29 | 
| SRR After mRNA-1273 Vaccine Administration Against Circulating Strain |  | Day 29 | 
| SRR After mRNA-1273.222 Vaccine Administration Against Omicron Variant |  | Days 29 and 209 | 
| SRR After mRNA-1273.222 Vaccine Administration Against Ancestral Strain |  | Days 29 and 209 | 
| GM Value of the Serum Ab Level After mRNA-1273.222 Vaccine Administration Against Omicron Variant |  | Day 209 | 
| GM Value of the Serum Ab Level After mRNA-1273.222 Vaccine Administration Against Ancestral Strain |  | Day 209 | 
| GM Value of the Serum Ab Level After mRNA-1273.222 Vaccine Administration Against Other Variants of Interest |  | Days 29 and 209 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Omicron, Variant, 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, Coronavirus, Virus Diseases, Messenger RNA, COVID-19, COVID-19 Vaccine, Moderna