Clinical trial NCT04649151: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: SARS-CoV-2
Keywords: 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
Omicron
Variant
Coronavirus
Virus Diseases
Messenger RNA
COVID-19
COVID-19 Vaccine
Moderna
Lead sponsor: ModernaTX, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Biomedical Advanced Research and Development Authority
First posted: 2020-12-02
Enrollment: 4331
Sex: ALL
Minimum age (years): 12
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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, 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: 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 and may receive a booster dose of mRNA-1273 SARS-CoV-2 vaccine. Part 3 is an open-label design. Participants will receive up to 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Number of Participants with Solicited Local and Systemic Adverse Reactions (ARs)
timeFrame: Up to Day 187 (7 days after injection/each injection)
measure: Number of Participants with Unsolicited Adverse Events (AEs)
timeFrame: Up to Day 208 (28 days after dose/each dose)
measure: Number of Participants with Serious Adverse Events (SAEs), Medically Attended AEs (MAAEs), or Adverse Events of Special Interest (AESI)
timeFrame: Up to Day 751
measure: Number of Participants With Serum Antibody (Ab) Levels that Meet or Exceed the Threshold of Protection From COVID-19
timeFrame: Day 57
measure: Geometric Mean (GM) Value of the Serum Ab Level
timeFrame: Day 57
measure: Seroresponse Rate (SRR) of Vaccine Recipients
timeFrame: Day 57
measure: Number of Participants with AEs Leading to Discontinuation From Study Post BD
timeFrame: Up to Day 751
measure: GM Value of the Serum Ab Level Against Ancestral Strain Post BD
timeFrame: BD-Day 29
measure: SRR of Vaccine Recipients Against Ancestral Strain Post BD at BD-Day 29
timeFrame: BD-Day 29
measure: GM Value of the Serum Ab Level Against Ancestral Strain Post Dose 2
timeFrame: Day 57
measure: SRR of Vaccine Recipients Against Ancestral Strain Post Dose 2
timeFrame: Day 57
measure: Number of Participants with AEs Leading to Discontinuation from Study from Dose 1
timeFrame: Up to Day 361
measure: GM Value of the Serum Ab Level After mRNA-1273.222 Vaccine Administration Against SARS-CoV-2 Omicron Variant
timeFrame: Day 29
measure: GM Value of the Serum Ab Level After mRNA-1273.222 Vaccine Administration Against Ancestral Strain
timeFrame: Day 29
Secondary outcomes:
measure: GM Value of SARS-CoV-2 Spike Protein (S2P)-Specific Binding Antibody (bAb)
timeFrame: Day 1, Day 57 (1 month after Dose 2), Day 209 (6 months after Dose 2), and Day 394 (1 year after Dose 2)
measure: GM Value of SARS-CoV-2-Specific Neutralizing Antibody (nAb)
timeFrame: Day 1, Day 57 (1 month after Dose 2), Day 209 (6 months after Dose 2), and Day 394 (1 year after Dose 2)
measure: Number of Participants with a SARS-CoV-2 Infection (Symptomatic or Asymptomatic) Starting 14 Days after the Second Dose of mRNA-1273 or Placebo
timeFrame: Day 43 up to Day 394
measure: 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
timeFrame: Day 43 up to Day 394
measure: Number of Participants with a First Occurrence of Symptomatic COVID-19 Starting 14 days After Second Dose of mRNA-1273 or Placebo
timeFrame: Day 43 up to Day 394
measure: GM Value of the Serum Ab Level After mRNA-1273 Vaccine Administration Against Circulating Strain
timeFrame: Day 29
measure: SRR After mRNA-1273 Vaccine Administration Against Circulating Strain
timeFrame: Day 29
measure: SRR After mRNA-1273.222 Vaccine Administration Against Omicron Variant
timeFrame: Day 29
measure: SRR After mRNA-1273.222 Vaccine Administration Against Ancestral Strain
timeFrame: Day 29
measure: GM Value of the Serum Ab Level After mRNA-1273.222 Vaccine Administration Against Other Variants of Interest
timeFrame: Day 29
Other outcomes:
Locations:
city: Banning
country: United States
facility: Velocity Clinical Research - Banning
state: California
city: La Mesa
country: United States
facility: Paradigm Clinical Research
state: California
city: Lake Worth
country: United States
facility: Altus Research - Hunt - PPDS
state: Florida
city: Orlando
country: United States
facility: Accel Research Sites - Nona Pediatric Center - ERN - PPDS
state: Florida
city: Chamblee
country: United States
facility: Tekton Research - Georgia - PPDS
state: Georgia
city: Columbus
country: United States
facility: IACT Health - Roswell - IACT - HyperCore - PPDS
state: Georgia
city: Macon
country: United States
facility: Meridian Clinical Research - (Macon Georgia) - Platinum - PPDS
state: Georgia
city: Stockbridge
country: United States
facility: Clinical Research Atlanta
state: Georgia
city: Meridian
country: United States
facility: Velocity Clinical Research - Boise - PPDS
state: Idaho
city: Chicago
country: United States
facility: Olivo Medical and Wellness Center
state: Illinois
city: Valparaiso
country: United States
facility: Velocity Clinical Research - Valparaiso
state: Indiana
city: Sioux City
country: United States
facility: Meridian Clinical Research (Sioux City - Iowa)
state: Iowa
city: El Dorado
country: United States
facility: Alliance for Multispecialty Research -El Dorado
state: Kansas
city: Lenexa
country: United States
facility: Johnson County Clin-Trials
state: Kansas
city: Metairie
country: United States
facility: Velocity Clinical Research - Metairie - PPDS
state: Louisiana
city: Worcester
country: United States
facility: University of Massachusetts Medical School, Molecu
state: Massachusetts
city: Minneapolis
country: United States
facility: Clinical Research Institute, Inc - CRN - PPDS
state: Minnesota
city: Gulfport
country: United States
facility: Velocity Clinical Research - Gulfport - PPDS
state: Mississippi
city: Saint Louis
country: United States
facility: Sundance Clinical Research - Platinum - PPDS
state: Missouri
city: Hastings
country: United States
facility: Meridian Clinical Research (Hastings-Nebraska) - Platinum - PPDS
state: Nebraska
city: Omaha
country: United States
facility: Quality Clinical Research - HyperCore - PPDS
state: Nebraska
city: Omaha
country: United States
facility: Meridian Clinical Research (Omaha-Nebraska) - Platinum - PPDS
state: Nebraska
city: Albuquerque
country: United States
facility: Velocity Clinical Research - Albuquerque - PPDS
state: New Mexico
city: East Syracuse
country: United States
facility: Child Healthcare Associates - East Syracuse
state: New York
city: Endwell
country: United States
facility: Meridian Clinical Research (Endwell-New York) - Platinum - PPDS
state: New York
city: Cincinnati
country: United States
facility: Velocity Clinical Research - Cincinnati - PPDS
state: Ohio
city: Oklahoma City
country: United States
facility: Lynn Health Science Institute
state: Oklahoma
city: Tulsa
country: United States
facility: Vital Prospects Clinical Research Institute PC - CRN - PPDS
state: Oklahoma
city: Gresham
country: United States
facility: Cyn3rgy Research - ClinEdge - PPDS
state: Oregon
city: East Greenwich
country: United States
facility: Velocity Clinical Research - Providence - PPDS
state: Rhode Island
city: Charleston
country: United States
facility: Coastal Pediatric Associates
state: South Carolina
city: Charleston
country: United States
facility: Meridian Clinical Research - Charleston, SC
state: South Carolina
city: North Charleston
country: United States
facility: Coastal Carolina Research Center
state: South Carolina
city: Austin
country: United States
facility: Benchmark Research
state: Texas
city: Corpus Christi
country: United States
facility: Coastal Bend Research Center
state: Texas
city: Frisco
country: United States
facility: ACRC Trials
state: Texas
city: Houston
country: United States
facility: DM Clinical Research - Kool Kids Pediatrics - ERN - PPDS
state: Texas
city: San Antonio
country: United States
facility: Clinical Trials of Texas, Inc. - PPDS
state: Texas
city: San Antonio
country: United States
facility: Tekton Research
state: Texas
city: San Antonio
country: United States
facility: Tekton Research
state: Texas
city: Bountiful
country: United States
facility: Cope Family Medicine - Ogden Clinic - CCT
state: Utah
city: Kaysville
country: United States
facility: Wee Care Pediatrics - Kaysville
state: Utah
city: Murray
country: United States
facility: Cottonwood Pediatrics
state: Utah
city: South Ogden
country: United States
facility: South Ogden Family Medicine/Ogden Clinic - CCT Research
state: Utah
city: Syracuse
country: United States
facility: Alliance for Multispecialty Research
state: Utah
city: West Jordan
country: United States
facility: Advanced Clinical Research - Jordan Valley - ERN - PPDS
state: Utah
city: Norfolk
country: United States
facility: Meridian Clinical Research (Norfolk, Virginia)
state: Virginia
city: Portsmouth
country: United States
facility: Meridian Clinical Research - Family Practice Ports - Portsmouth - Platinum - PPDS
state: Virginia
city: Santo Domingo
country: Dominican Republic
facility: Caimed Dominicana S.A.S
state: Distrito Nacional
city: Santo Domingo
country: Dominican Republic
facility: Hospital General Regional Dr. Marcelino Velez Santana
state: Distrito Nacional
city: Santo Domingo
country: Dominican Republic
facility: Hospital Materno Infantil San Lorenzo de Los Mina
state: Distrito Nacional
city: Santo Domingo
country: Dominican Republic
facility: Instituto Dermatologico y Cirugia de la Piel Dr. H Sede San Cristóbal
state: Distrito Nacional
city: Santo Domingo
country: Dominican Republic
facility: Instituto Dominicano de Estudios Virologicos IDEV
state: Distrito Nacional
Study officials:
References:
citation: 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.