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

• ClinicalTrials.gov Identifier: NCT04649151
• Recruitment Status: Recruiting
• First Posted: December 2, 2020
• Last Update Posted: April 4, 2022
• Sponsor: ModernaTX, Inc.
• Collaborator: Biomedical Advanced Research and Development Authority
• Information provided by (Responsible Party): ModernaTX, Inc.

Tracking Information

• First Submitted Date: November 30, 2020
• First Posted Date: December 2, 2020
• Last Update Posted Date: April 4, 2022
• Actual Study Start Date: December 9, 2020
• Estimated Primary Completion Date: May 28, 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 22, 2022)

• Number of Participants with Solicited Local and Systemic Adverse Reactions (ARs) [ Time Frame: Up to Day 8 (7 days post-vaccination) ]
• Number of Participants with Unsolicited Adverse Events (AEs) [ Time Frame: Up to Day 29 (28 days post-vaccination) ]
• Number of Participants with Serious Adverse Events (SAEs), Medically Attended AEs (MAAEs), or Adverse Events of Special Interest (AESI) [ Time Frame: Up to Day 514 ]
• Number of Participants With Serum Antibody (Ab) Levels that Meet or Exceed the Threshold of Protection From COVID-19 [ Time Frame: Day 57 (28 days after second dose) ]
  Acceptable serum Ab threshold as predefined for the study.
• Geometric Mean (GM) of the Serum Ab Level [ Time Frame: Day 57 (28 days after second dose) ]
• Seroresponse Rate (SRR) of Vaccine Recipients [ Time Frame: Day 57 (28 days after second dose) ]
• Number of Participants with AEs Leading to the Discontinuation From Study Post BD [ Time Frame: Up to Day 514 ]
• GM of the Serum Ab Level of Original Strain Post BD [ Time Frame: BD-Day 29 ]
• SRR of Vaccine Recipients of Original Strain Post BD [ Time Frame: BD-Day 29 ]

Original Primary Outcome Measures (submitted: November 30, 2020)

• Number of Participants with Solicited Local and Systemic Adverse Reactions (ARs) [ Time Frame: Up to Day 8 (7 days after first dose) and up to Day 36 (7 days after second dose) ]
• Number of Participants with Unsolicited Adverse Events (AEs) [ Time Frame: Up to Day 57 (28 days after each dose) ]
• Number of Participants with Serious Adverse Events (SAEs), Medically Attended AEs (MAAEs), or Adverse Events of Special Interest (AESI) [ Time Frame: Up to Day 394 (1 year after second dose) ]
• Number of Participants Who have Reached the Acceptable Threshold for the Serum Ab Level at Day 57 [ Time Frame: Day 57 (28 days after second dose) ]
  Acceptable serum Ab threshold as predefined for the study.
• Comparison of the Geometric Mean of the Serum Neutralizing Antibody (nAb) level against the Geometric Mean of the Serum nAb level in Study mRNA-1273-P301 (NCT04470427) [ Time Frame: Day 57 (28 days after second dose) ]

Current Secondary Outcome Measures (submitted: March 22, 2022)

• GM of SARS-CoV-2 Spike Protein (S2P)-Specific Binding Antibody (bAb) [ Time Frame: 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 of SARS-CoV-2-Specific Neutralizing Antibody (nAb) [ Time Frame: 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 [ Time Frame: Day 43 up to Day 394 ]
  Clinical signs indicative of SARS-CoV-2 infection as predefined for the study.
• 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 [ Time Frame: 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 [ Time Frame: Day 43 up to Day 394 ]
  Clinical signs indicative of symptomatic COVID-19 as predefined for the study.
• GM of the Serum Ab Level of Circulating Strain [ Time Frame: BD-Day 29; Part 2: Day 57 ]
• SRR of Vaccine Recipients of Circulating Strain [ Time Frame: BD-Day 29; Part 2: Day 57 ]

Original Secondary Outcome Measures (submitted: November 30, 2020)

• Geometric Mean Value of SARS-CoV-2 Spike Protein (S2P)-specific binding antibody (bAb) [ Time Frame: Day 1, Day 57 (1 month after dose 2), Day 209 (6 months after dose 2), and Day 394 (1 year after dose 2) ]
• Geometric Mean Value of SARS-CoV-2-specific nAb [ Time Frame: 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 Starting on Day 57 [ Time Frame: Day 57 up to Day 394 ]
  Clinical signs indicative of SARS-CoV-2 infection as predefined for the study.
• Number of Participants with a First Occurrence of COVID-19 Starting 14 days after Second Dose of mRNA-1273 or Placebo [ Time Frame: Day 29 (second dose) up to Day 394 (1 year after second dose) ]
  Clinical signs indicative of COVID-19 as predefined for the study.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study to Evaluate the Safety, Reactogenicity, and Effectiveness of mRNA-1273 Vaccine in Adolescents 12 to <18 Years Old to Prevent COVID-19
• Official Title: 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
• 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 and reactogenicity of a single dose level of mRNA-1273 vaccine administered in 2 doses 28 days apart to an adolescent population. The study will also evaluate the safety of an optional mRNA-1273 single dose level booster dose (BD).

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 and Part 2 (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 and a BD.

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.

• Study Type: Interventional
• Study Phase: Phase 2; Phase 3

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:

Part 1A is observer-blind. Participants will remain blinded until the initiation of Part 1B or Part 1C or Part 2.

Primary Purpose: Prevention

• Condition: SARS-CoV-2

Intervention

• Biological: mRNA-1273
  Sterile liquid for injection
• Biological: Placebo
  0.9% sodium chloride (normal saline) injection

Study Arms

• Experimental: mRNA-1273

  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.

  Intervention: Biological: mRNA-1273
• Placebo Comparator: Placebo
  Part 1A (Blinded Phase): Participants will receive 2 IM injections of mRNA-1273 matching placebo, 28 days apart, on Day 1 and Day 29.
  Intervention: Biological: Placebo
• Experimental: mRNA-1273 BD

  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.

  Part 2 (Open-Label): Participants will receive 1 IM injection as a BD of mRNA-1273 (50 ug) on Day 149, at least 3 months post-Dose 2.

  Intervention: Biological: mRNA-1273

• Publications *: Ali K, Berman G, Zhou H, Deng W, Faughnan V, Coronado-Voges M, Ding B, Dooley J, Girard B, Hillebrand W, Pajon R, Miller JM, Leav B, McPhee R. Evaluation of mRNA-1273 SARS-CoV-2 Vaccine in Adolescents. N Engl J Med. 2021 Dec 9;385(24):2241-2251. doi: 10.1056/NEJMoa2109522. Epub 2021 Aug 11.

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: March 22, 2022): 3724
• Original Estimated Enrollment (submitted: November 30, 2020): 3000
• Estimated Study Completion Date: May 28, 2024
• Estimated Primary Completion Date: May 28, 2024 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

For Part 1A and Part 2:

• 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), and on the day of the BD (Day 149) in Part 2; 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 through 3 months following the second injection (Day 29) and BD (Day 149) in Part 2.

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 and Part 2:

• 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).
• Travel outside of the United States or home country (Part 2 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, 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 (Day 1) or plans for receipt of any licensed vaccine through 28 days following any study injection
  • 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 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

• 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 immunodeficiencyvirus (HIV) infection.
  • Suspected active hepatitis
  • Has a bleeding disorder that is considered a contraindication to IM injection orphlebotomy
  • Dermatologic conditions that could affect local solicited AR assessments
  • History of anaphylaxis, urticaria, or other significant AR requiring medicalintervention after receipt of a vaccine
  • Diagnosis of malignancy within the previous 10 years (excluding nonmelanomaskin cancer)
  • Febrile seizures

For Part 1B:

• Participants who were previously enrolled in the mRNA-1273 P203 study and chose to be unblinded.
• 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 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 for potential participants in Part 1C-1) 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 investigational product (IP) or plans (COVID-19 vaccines are not exclusionary) 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 (BD-Day 0) or plans to do so while participating in this study.

• 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 immunodeficiencyvirus (HIV) infection.
  • Suspected active hepatitis
  • Has a bleeding disorder that is considered a contraindication to IM injection orphlebotomy
  • Dermatologic conditions that could affect local solicited AR assessments
  • History of anaphylaxis, urticaria, or other significant AR requiring medicalintervention after receipt of a vaccine
  • Diagnosis of malignancy within the previous 10 years (excluding nonmelanomaskin cancer)
  • Febrile seizures

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 12 Years to 18 Years (Child, Adult)
• Accepts Healthy Volunteers: Yes

Contacts

Contact: Moderna Clinical Trials Support Center; 1-877-777-7187; clinicaltrials@modernatx.com

Contact: See "Additional Information" below to access study website

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT04649151
• Other Study ID Numbers: mRNA-1273-P203
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: ModernaTX, Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: ModernaTX, Inc.
• Original Study Sponsor: Same as current
• Collaborators: Biomedical Advanced Research and Development Authority
• Investigators: Not Provided
• PRS Account: ModernaTX, Inc.
• Verification Date: March 2022