A Study to Evaluate the Immunogenicity and Safety of mRNA Vaccine Boosters for SARS-CoV-2 (COVID-19) Variants

NCT ID: NCT04927065

Last Updated: 2025-02-28

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 5161 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-05-28
• Study Completion Date: 2023-11-17

Brief Summary

This is a study to evaluate the immunogenicity, safety, and reactogenicity of mRNA-1273.211, mRNA-1273, mRNA-1273.617.2, mRNA-1273.213, mRNA-1273.529, mRNA-1273.214, mRNA-1273.222, mRNA-1273.815, and mRNA-1273.231 administered as booster doses.

Detailed Description

This clinical study will consist of 9 parts: A (1 and 2), B, C, D, E, F, G, H, and J.

Part A.1 will evaluate 2 dose levels of the mRNA-1273.211 vaccine when administered as a single booster dose to adult participants of the mRNA-1273-P301 (COVE [NCT04470427]) study who have previously received 2 doses of mRNA-1273.

Part A.2 will evaluate the immunogenicity, safety, and reactogenicity of the mRNA-1273.214 vaccine candidate when administered as a second booster dose to adult participants of the mRNA-1273-P205 study who have previously received 2 doses of mRNA-1273 as a primary series and a first booster of (50 μg total mRNA content) of the mRNA-1273.211 in Part A.1 of this study.

Part B will evaluate the mRNA-1273 vaccine when administered as a single booster dose to adult participants of the mRNA-1273-P301 (COVE [NCT04470427]) study who have previously received 2 doses of mRNA-1273.

Part C will evaluate 2 dose levels of the mRNA-1273.617.2 vaccine when administered as a single booster dose to adult participants of the mRNA-1273-P301 (COVE [NCT04470427]) study who have previously received 2 doses of mRNA-1273.

Part D will evaluate 2 dose levels of the mRNA-1273.213 vaccine when administered as a single booster dose to adult participants of the mRNA-1273-P301 (COVE [NCT04470427]) study who have previously received 2 doses of mRNA-1273.

Part E will be enrolled at a single clinical study site. Part E will evaluate the mRNA-1273.213 vaccine when administered as a single booster dose to adult participants who have previously received 2 doses of any SARS-CoV-2 mRNA authorized vaccine, including mRNA-1273.

Part F will consist of 2 cohorts: Cohort 1 will consist of adults who have previously received 2 doses of mRNA-1273 as primary series. Cohort 1 will evaluate the mRNA-1273.529 vaccine as a single booster dose. Cohort 2 will consist of adults who have previously received 2 doses of mRNA-1273 as a primary series and a single booster dose of mRNA-1273 in study mRNA-1273-P301 (COVE [NCT04470427]) or under the emergency use authorization (EUA). Cohort 2 will evaluate the mRNA-1273.529 and mRNA-1273 vaccines as a single booster dose.

Part G will evaluate the mRNA1273.214 vaccine candidate when administered as a second booster dose to adults who have previously received 2 doses of mRNA-1273 as a primary series and a single booster dose of mRNA-1273.

Part H will evaluate the immunogenicity, safety, and reactogenicity of the mRNA- 1273.222 vaccine candidate when administered as a second booster dose to adults who have previously received 2 doses of mRNA-1273 as a primary series and a single booster dose of mRNA-1273.

Part J will evaluate mRNA-1273.815 and mRNA-1273.231 when administered as a booster dose to adults who previously received a primary series of mRNA vaccine, a first booster dose of a monovalent mRNA vaccine, and a second booster dose of a bivalent mRNA vaccine against SARS-COV-2.

Conditions

SARS-CoV-2

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

Part A.1: mRNA-1273.211 50 μg

Participants will receive 1 intramuscular booster dose of 50 micrograms (μg) of mRNA-1273.211 on Day 1.

Group Type: EXPERIMENTAL

mRNA-1273.211

Intervention Type: BIOLOGICAL

Sterile liquid for injection

Part A.1: mRNA-1273.211 100 μg

Participants will receive 1 intramuscular booster dose of 100 μg of mRNA-1273.211 on Day 1.

Group Type: EXPERIMENTAL

mRNA-1273.211

Intervention Type: BIOLOGICAL

Sterile liquid for injection

Part B: mRNA-1273 100 μg

Participants will receive 1 intramuscular booster dose of 100 μg of mRNA-1273 on Day 1.

Group Type: EXPERIMENTAL

mRNA-1273

Intervention Type: BIOLOGICAL

Sterile liquid for injection

Part C: mRNA-1273.617.2 100 μg

Participants will receive 1 intramuscular booster dose of 100 μg of mRNA-1273.617.2 on Day 1.

Group Type: EXPERIMENTAL

mRNA-1273.617.2

Intervention Type: BIOLOGICAL

Sterile liquid for injection

Part C: mRNA-1273.617.2 50 μg

Participants will receive 1 intramuscular booster dose of 50 μg of mRNA-1273.617.2 on Day 1.

Group Type: EXPERIMENTAL

mRNA-1273.617.2

Intervention Type: BIOLOGICAL

Sterile liquid for injection

Part D: mRNA-1273.213 50 μg

Participants will receive 1 intramuscular booster dose of 50 μg of mRNA-1273.213 on Day 1.

Group Type: EXPERIMENTAL

mRNA-1273.213

Intervention Type: BIOLOGICAL

Sterile liquid for injection

Part D: mRNA-1273.213 100 μg

Participants will receive 1 intramuscular booster dose of 100 μg of mRNA-1273.213 on Day 1.

Group Type: EXPERIMENTAL

mRNA-1273.213

Intervention Type: BIOLOGICAL

Sterile liquid for injection

Part E: mRNA-1273.213 100 μg

Participants will receive 1 intramuscular booster dose of 100 μg of mRNA-1273.213 on Day 1.

Group Type: EXPERIMENTAL

mRNA-1273.213

Intervention Type: BIOLOGICAL

Sterile liquid for injection

Part F Cohort 1: mRNA-1273.529 50 μg

Participants will receive 1 intramuscular first booster dose of 50 μg of mRNA-1273.529 on Day 1.

Group Type: EXPERIMENTAL

mRNA-1273.529

Intervention Type: BIOLOGICAL

Sterile liquid for injection

Part F Cohort 2: mRNA-1273.529 50 μg and mRNA-1273 50 μg

Participants will receive 1 intramuscular second booster dose of 50 μg of mRNA-1273.529 or mRNA-1273 enrolled sequentially (after receiving a primary series of mRNA-1273 and a single booster dose of mRNA-1273 50 μg) on Day 1.

Group Type: EXPERIMENTAL

mRNA-1273

Intervention Type: BIOLOGICAL

Sterile liquid for injection

mRNA-1273.529

Intervention Type: BIOLOGICAL

Sterile liquid for injection

Part G: mRNA-1273.214 50 μg

Participants will receive 1 intramuscular second booster dose of mRNA-1273.214 50 μg on Day 1.

Group Type: EXPERIMENTAL

mRNA-1273.214

Intervention Type: BIOLOGICAL

Sterile liquid for injection

Part A.2: mRNA-1273.214 50 μg

Participants will receive 1 intramuscular booster dose of 50 μg of mRNA-1273.214 on Day 1.

Group Type: EXPERIMENTAL

mRNA-1273.214

Intervention Type: BIOLOGICAL

Sterile liquid for injection

Part H: mRNA-1273.222 50 μg

Participants will receive 1 intramuscular second booster dose of 50 μg of mRNA-1273.222 on Day 1.

Group Type: EXPERIMENTAL

mRNA-1273.222

Intervention Type: BIOLOGICAL

Sterile liquid for injection

Part J: mRNA-1273.815 or mRNA-1273.231

Participants will receive 1 intramuscular booster dose of 50 μg of mRNA-1273.815 or 50 ug of mRNA-1273.231 on Day 1.

Group Type: EXPERIMENTAL

mRNA-1273.815

Intervention Type: BIOLOGICAL

Sterile liquid for injection

mRNA-1273.231

Intervention Type: BIOLOGICAL

Sterile liquid for injection

Interventions

mRNA-1273.211

Sterile liquid for injection

Intervention Type: BIOLOGICAL

mRNA-1273

Sterile liquid for injection

Intervention Type: BIOLOGICAL

mRNA-1273.617.2

Sterile liquid for injection

Intervention Type: BIOLOGICAL

mRNA-1273.213

Sterile liquid for injection

Intervention Type: BIOLOGICAL

mRNA-1273.529

Sterile liquid for injection

Intervention Type: BIOLOGICAL

mRNA-1273.214

Sterile liquid for injection

Intervention Type: BIOLOGICAL

mRNA-1273.222

Sterile liquid for injection

Intervention Type: BIOLOGICAL

mRNA-1273.815

Sterile liquid for injection

Intervention Type: BIOLOGICAL

mRNA-1273.231

Sterile liquid for injection

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

• 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 Day 1, agreement to continue adequate contraception or abstinence through 3 months following the vaccination, and not currently breastfeeding.
• Participants must have been either previously enrolled in the mRNA-1273-P301 (COVE) study, must have received 2 doses of mRNA-1273 in that study, with their second dose at least 6 months prior to enrollment in this study (mRNA-1273-P205), and must be currently enrolled and compliant in that study (that is, has not withdrawn or discontinued early); or participant must have received 2 doses of mRNA-1273 under the EUA with their second dose at least 6 months prior to enrollment in mRNA-1273-P205; or have received a 2 dose primary series of mRNA-1273 followed by a 50 μg booster dose of mRNA-1273 in the mRNA-1273-P301 (COVE) study or under EUA at least 3 months prior to enrolment in mRNA-1273-P205; and able to provide proof of vaccination status at the time of screening (Day 1); or for enrollment in Part A.2, participant must be currently enrolled and compliant in Part A.1 of the mRNA 1273 P205 study and must have received their first booster dose of mRNA 1273.211 50 μg; or for enrollment in Part J, participant must meet at least 1 of the following criteria: completed enrollment in Part H of the mRNA-1273-P205 study; or received a 2-dose primary series of mRNA-1273 (100 μg) followed by a 50 μg booster dose of mRNA-1273 in the mRNA-1273-P301 (COVE) study or under EUA, followed by a 50 μg booster dose of mRNA-1273.222 under EUA at least 3 months prior to enrollment in Part J of mRNA-1273-P205; or previously received a 2-dose primary series of mRNA vaccine against SARS-CoV-2 followed by a booster dose of a monovalent mRNA vaccine, followed by a second booster dose of a bivalent mRNA vaccine. Participants in Part J must also provide proof of vaccination status at the time of screening (Day 0 or Day 1).

Exclusion Criteria

• Significant exposure to someone with SARS-CoV-2 infection or COVID-19 in the past 14 days, as defined by the US Centers for Disease Control and Prevention (CDC) as a close contact of someone who has had COVID-19.
• Known history of SARS-CoV-2 infection within 3 months prior to enrollment.
• Is acutely ill or febrile (temperature ≥38.0°Celsius/[100.4°Fahrenheit]) less than 72 hours prior to or at the Screening Visit (Day 0) or Day 1.
• 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.
• Has received systemic immunosuppressants or immune-modifying drugs for >14 days in total within 6 months prior to Screening (for corticosteroids ≥10 milligrams (mg)/day of prednisone equivalent) or is anticipating the need for immunosuppressive treatment at any time during participation in the study.
• Known or suspected allergy or history of anaphylaxis, urticaria, or other significant AR to the vaccine or its excipients.
• Has a documented history of myocarditis or pericarditis within 2 months prior to Screening Visit (Day 0).
• Has received or plans to receive any licensed vaccine ≤28 days prior to the injection (Day 1) or a licensed vaccine within 28 days before or after they study injection, with the exception of influenza vaccines, which may be given 14 days before or after receipt of a study vaccine.
• Has received systemic immunoglobulins or blood products within 3 months prior to the Screening Visit (Day 0) or plans for receipt during the study.
• 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.
• Is currently experiencing an SAE in Study mRNA-1273-P301 (COVE) at the time of screening for this study.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

ModernaTX, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Benchmark Research (California)

Sacramento, California, United States

Research Centers of America

Hollywood, Florida, United States

Jacksonville Center For Clinical Research

Jacksonville, Florida, United States

Meridian Clinical Research-(Savannah Georgia)

Savannah, Georgia, United States

Meridian Clinical Research (Iowa)

Sioux City, Iowa, United States

Johnson County Clinical Trials

Lenexa, Kansas, United States

Meridian Clinical Research-(Baton Rouge, Louisiana)

Baton Rouge, Louisiana, United States

Benchmark Research

Metairie, Louisiana, United States

Meridian Clinical Research-(Rockville Maryland)

Rockville, Maryland, United States

Brigham and Women's Hospital

Boston, Massachusetts, United States

Washington State University

St Louis, Missouri, United States

Sundance Clinical Research

St Louis, Missouri, United States

Meridian Clinical Research (Grand Island, Nebraska)

Grand Island, Nebraska, United States

Meridian Clinical Research (Norfolk-Nebraska)

Norfolk, Nebraska, United States

Meridian Clinical Research-(Omaha Nebraska)

Omaha, Nebraska, United States

Meridian Clinical Research, LLC

New York, New York, United States

Trial Management Associates

Wilmington, North Carolina, United States

Lynn Health Science Institute

Oklahoma City, Oklahoma, United States

Benchmark Research - Austin - HyperCore

Austin, Texas, United States

Tekton Research, Inc.

Austin, Texas, United States

Benchmark Research - Fort Worth - HyperCore

Fort Worth, Texas, United States

Texas Center for Drug Development, Inc.

Houston, Texas, United States

DM Clinical Research

Tomball, Texas, United States

Countries

United States

References

Chalkias S, Whatley JL, Eder F, Essink B, Khetan S, Bradley P, Brosz A, McGhee N, Tomassini JE, Chen X, Zhao X, Sutherland A, Shen X, Girard B, Edwards DK, Feng J, Zhou H, Walsh S, Montefiori DC, Baden LR, Miller JM, Das R. Original SARS-CoV-2 monovalent and Omicron BA.4/BA.5 bivalent COVID-19 mRNA vaccines: phase 2/3 trial interim results. Nat Med. 2023 Sep;29(9):2325-2333. doi: 10.1038/s41591-023-02517-y. Epub 2023 Aug 31.

Reference Type: DERIVED

PMID: 37653342 (View on PubMed)

Chalkias S, Harper C, Vrbicky K, Walsh SR, Essink B, Brosz A, McGhee N, Tomassini JE, Chen X, Chang Y, Sutherland A, Montefiori DC, Girard B, Edwards DK, Feng J, Zhou H, Baden LR, Miller JM, Das R. A Bivalent Omicron-Containing Booster Vaccine against Covid-19. N Engl J Med. 2022 Oct 6;387(14):1279-1291. doi: 10.1056/NEJMoa2208343. Epub 2022 Sep 16.

Reference Type: DERIVED

PMID: 36112399 (View on PubMed)

Chalkias S, Schwartz H, Nestorova B, Feng J, Chang Y, Zhou H, Dutko FJ, Edwards DK, Montefiori D, Pajon R, Leav B, Miller JM, Das R. Safety and Immunogenicity of a 100 mug mRNA-1273 Vaccine Booster for Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). medRxiv [Preprint]. 2022 Mar 7:2022.03.04.22271830. doi: 10.1101/2022.03.04.22271830.

Reference Type: DERIVED

PMID: 35291289 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

mRNA-1273-P205

Identifier Type: -

Identifier Source: org_study_id