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

• ClinicalTrials.gov Identifier: NCT04796896
• Recruitment Status: Active, not recruiting
• First Posted: March 15, 2021
• Last Update Posted: February 21, 2023
• Sponsor: ModernaTX, Inc.
• Information provided by (Responsible Party): ModernaTX, Inc.

Tracking Information

• First Submitted Date: March 11, 2021
• First Posted Date: March 15, 2021
• Last Update Posted Date: February 21, 2023
• Actual Study Start Date: March 15, 2021
• Estimated Primary Completion Date: November 12, 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 14, 2022)

• Number of Participants with Solicited Local and Systemic Adverse Reactions (ARs) [ Time Frame: Up to Day 156 (7 days after each injection) ]
• Number of Participants with Unsolicited Adverse Events (AEs) [ Time Frame: Up to Day 177 (28 days after each injection) ]
• Number of Participants with Medically-Attended AEs (MAAEs) [ Time Frame: Up to Day 514 (1 year after booster dose) ]
• Number of Participants with Serious Adverse Events (SAEs) [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: Day 57 (1 month after second injection) ]
  Threshold of protection as predefined for study.
• Geometric Mean (GM) Value of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Specific Serum Antibody [ Time Frame: Day 57 (1 month after second injection) ]
• Seroresponse Rate of Vaccine Recipients [ Time Frame: Day 57 (1 month after second injection) ]
• GM Value of Post-Booster Dose SARS-CoV-2 Specific Serum Antibody [ Time Frame: Day 149 (post third dose) ]
• Seroresponse Rate of Post-Booster Dose of Vaccine Recipients [ Time Frame: Day 149 (post third dose) ]

Original Primary Outcome Measures (submitted: March 11, 2021)

• Number of Participants with Solicited Local and Systemic Adverse Reactions (ARs) [ Time Frame: Up to Day 36 (7 days after second dose) ]
• Number of Participants with Unsolicited Adverse Events (AEs) [ Time Frame: Up to Day 57 (1 month after second dose) ]
• Number of Participants with Medically-Attended AEs (MAAEs) [ Time Frame: Up to Day 394 (1 year after second dose) ]
• Number of Participants with Serious Adverse Events (SAEs) [ Time Frame: Up to Day 394 (1 year after second dose) ]
• Number of Participants with Adverse Events of Special Interest (AESIs), including Multisystem Inflammatory Syndrome in Children (MIS-C) [ Time Frame: Up to Day 394 (1 year after second dose) ]
• Number of Participants with Serum Antibody (Ab) Levels that Meet or Exceed the Threshold of Protection from COVID-19 [ Time Frame: Day 57 (1 month after second dose) ]
  Threshold of protection as predefined for study.
• Geometric Mean (GM) of SARS-CoV-2 Specific Neutralizing Antibody (nAb) [ Time Frame: Day 57 (1 month after second dose) ]
• Seroresponse Rate of Vaccine Recipients [ Time Frame: Day 57 (1 month after second dose) ]

Current Secondary Outcome Measures (submitted: April 14, 2022)

• GM Value of SARS-CoV-2 S-Protein-Specific Binding Antibody (bAb) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: Up to Day 394 ]
  Clinical signs indicative of SARS-CoV-2 infection as predefined for the study.
• 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 [ Time Frame: Up to Day 394 ]
• Number of Participants with a First Occurrence of COVID-19 [ Time Frame: Up to Day 394 ]
  Clinical signs indicative of COVID-19 as predefined for the study.

Original Secondary Outcome Measures (submitted: March 11, 2021)

• GM of SARS-CoV-2 S-Protein Specific Binding Antibody (bAb) [ Time Frame: Day 1, Day 57, Day 209, and Day 394 ]
• GM of SARS-CoV-2 Specific nAb [ Time Frame: Day 1, Day 57, Day 209, and Day 394 ]
• Number of Participants with SARS-CoV-2 Infections Regardless of Symptomatology Starting 14 Days After the Second Dose [ Time Frame: Day 43 to Day 394 ]
  Clinical signs indicative of SARS-CoV-2 infection as predefined for the study.
• Number of Participants with Asymptomatic SARS-CoV-2 Infections [ Time Frame: Up to Day 394 ]
• Number of Participants with a First Occurrence of COVID-19 Starting 14 Days after Second Dose [ Time Frame: Day 43 to Day 394 ]
  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 Safety and Effectiveness of mRNA-1273 COVID-19 Vaccine in Healthy Children Between 6 Months of Age and Less Than 12 Years of Age
• Official Title: 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
• Brief Summary: 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

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.

• 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:

Parts 1 and 3 are Open-label; Part 2 Randomized and Observer-blind

Primary Purpose: Prevention

• Condition: SARS-CoV-2

Intervention

• Biological: mRNA-1273
  Sterile liquid for injection
• Biological: Placebo
  0.9% sodium chloride (normal saline) injection
• Biological: mRNA-1273.214
  Sterile liquid for injection

Study Arms

• Experimental: mRNA-1273

  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.

  Interventions:

  • Biological: mRNA-1273
  • Biological: mRNA-1273.214
• Placebo Comparator: Placebo
  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.
  Interventions:

  • Biological: mRNA-1273
  • Biological: Placebo
  • Biological: mRNA-1273.214

Publications *

• Anderson EJ, Creech CB, Berthaud V, Piramzadian A, Johnson KA, Zervos M, Garner F, Griffin C, Palanpurwala K, Turner M, Gerber J, Bennett RL, Ali K, Ampajwala M, Berman G, Nayak J, Chronis C, Rizzardi B, Muller WJ, Smith CA, Fuchs G, Hsia D, Tomassini JE, DeLucia D, Reuter C, Kuter B, Zhao X, Deng W, Zhou H, Ramirez Schrempp D, Hautzinger K, Girard B, Slobod K, McPhee R, Pajon R, Aunins A, Das R, Miller JM, Schnyder Ghamloush S; KidCOVE Study Group. Evaluation of mRNA-1273 Vaccine in Children 6 Months to 5 Years of Age. N Engl J Med. 2022 Nov 3;387(18):1673-1687. doi: 10.1056/NEJMoa2209367. Epub 2022 Oct 19.
• Creech CB, Anderson E, Berthaud V, Yildirim I, Atz AM, Melendez Baez I, Finkelstein D, Pickrell P, Kirstein J, Yut C, Blair R, Clifford RA, Dunn M, Campbell JD, Montefiori DC, Tomassini JE, Zhao X, Deng W, Zhou H, Ramirez Schrempp D, Hautzinger K, Girard B, Slobod K, McPhee R, Pajon R, Das R, Miller JM, Schnyder Ghamloush S; KidCOVE Study Group. Evaluation of mRNA-1273 Covid-19 Vaccine in Children 6 to 11 Years of Age. N Engl J Med. 2022 May 26;386(21):2011-2023. doi: 10.1056/NEJMoa2203315. Epub 2022 May 11.
• Lynch LR, Clifford H, Ko R, Hache M, Sun W. Primer of COVID-19 Vaccines for the Perioperative Physician. J Neurosurg Anesthesiol. 2022 Jan 1;34(1):101-106. doi: 10.1097/ANA.0000000000000802.

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: February 17, 2023): 11950
• Original Estimated Enrollment (submitted: March 11, 2021): 750
• Estimated Study Completion Date: November 12, 2023
• Estimated Primary Completion Date: November 12, 2023 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 6 Months to 11 Years (Child)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Canada, United States

Administrative Information

• NCT Number: NCT04796896
• Other Study ID Numbers: mRNA-1273-P204
• 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: Not Provided
• Investigators: Not Provided
• PRS Account: ModernaTX, Inc.
• Verification Date: February 2023