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

A Phase 2/3 Study to Evaluate the Immunogenicity and Safety of mRNA Vaccine Boosters for SARS-CoV-2 Variants

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.

Study Overview

• Status: Completed
• Conditions: SARS-CoV-2
• Intervention / Treatment: Biological: mRNA-1273.214; Biological: mRNA-1273; Biological: mRNA-1273.529; Biological: mRNA-1273.211; Biological: mRNA-1273.617.2; Biological: mRNA-1273.213; Biological: mRNA-1273.222; Biological: mRNA-1273.815; Biological: mRNA-1273.231

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.

• Study Type: Interventional
• Enrollment (Actual): 5404
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• United States
  • California
    • Sacramento, California, United States, 95864
      • Benchmark Research (California)
  • Florida
    • Hollywood, Florida, United States, 33024
      • Research Centers of America
    • Jacksonville, Florida, United States, 32216
      • Jacksonville Center for Clinical Research
  • Georgia
    • Savannah, Georgia, United States, 31406
      • Meridian Clinical Research-(Savannah Georgia)
  • Iowa
    • Sioux City, Iowa, United States, 51106
      • Meridian Clinical Research (Iowa)
  • Kansas
    • Lenexa, Kansas, United States, 66219
      • Johnson County Clinical Trials
  • Louisiana
    • Baton Rouge, Louisiana, United States, 70809
      • Meridian Clinical Research-(Baton Rouge, Louisiana)
    • Metairie, Louisiana, United States, 70006
      • Benchmark Research
  • Maryland
    • Rockville, Maryland, United States, 20854
      • Meridian Clinical Research-(Rockville Maryland)
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Brigham and Women's Hospital
  • Missouri
    • Saint Louis, Missouri, United States, 63141
      • Sundance Clinical Research
    • Saint Louis, Missouri, United States, 63110
      • Washington State University
  • Nebraska
    • Grand Island, Nebraska, United States, 68803
      • Meridian Clinical Research (Grand Island, Nebraska)
    • Norfolk, Nebraska, United States, 68701
      • Meridian Clinical Research (Norfolk-Nebraska)
    • Omaha, Nebraska, United States, 68134
      • Meridian Clinical Research-(Omaha Nebraska)
  • New York
    • New York, New York, United States, 13901
      • Meridian Clinical Research, LLC
  • North Carolina
    • Wilmington, North Carolina, United States, 28403
      • Trial Management Associates
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73112
      • Lynn Health Science Institute
  • Texas
    • Austin, Texas, United States, 78745
      • Tekton Research, Inc.
    • Austin, Texas, United States, 78705
      • Benchmark Research - Austin - HyperCore
    • Fort Worth, Texas, United States, 76135
      • Benchmark Research - Fort Worth - HyperCore
    • Houston, Texas, United States, 77081
      • Texas Center for Drug Development, Inc.
    • Tomball, Texas, United States, 77375
      • DM Clinical Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Key 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).

Key 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.

Note: Other inclusion and exclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

14

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Biological: mRNA-1273.211; Sterile liquid for injection
Experimental: 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.	Biological: mRNA-1273.211; Sterile liquid for injection
Experimental: Part B: mRNA-1273 100 μg; Participants will receive 1 intramuscular booster dose of 100 μg of mRNA-1273 on Day 1.	Biological: mRNA-1273; Sterile liquid for injection
Experimental: 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.	Biological: mRNA-1273.617.2; Sterile liquid for injection
Experimental: 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.	Biological: mRNA-1273.617.2; Sterile liquid for injection
Experimental: Part D: mRNA-1273.213 50 μg; Participants will receive 1 intramuscular booster dose of 50 μg of mRNA-1273.213 on Day 1.	Biological: mRNA-1273.213; Sterile liquid for injection
Experimental: Part D: mRNA-1273.213 100 μg; Participants will receive 1 intramuscular booster dose of 100 μg of mRNA-1273.213 on Day 1.	Biological: mRNA-1273.213; Sterile liquid for injection
Experimental: Part E: mRNA-1273.213 100 μg; Participants will receive 1 intramuscular booster dose of 100 μg of mRNA-1273.213 on Day 1.	Biological: mRNA-1273.213; Sterile liquid for injection
Experimental: 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.	Biological: mRNA-1273.529; Sterile liquid for injection
Experimental: Part G: mRNA-1273.214 50 μg; Participants will receive 1 intramuscular second booster dose of mRNA-1273.214 50 μg on Day 1.	Biological: mRNA-1273.214; Sterile liquid for injection
Experimental: 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.	Biological: mRNA-1273.214; Sterile liquid for injection
Experimental: 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.	Biological: mRNA-1273.222; Sterile liquid for injection
Experimental: 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.	Biological: mRNA-1273; Sterile liquid for injection; Biological: mRNA-1273.529; Sterile liquid for injection
Experimental: 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.	Biological: mRNA-1273.815; Sterile liquid for injection; Biological: mRNA-1273.231; Sterile liquid for injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Geometric Mean Titer (GMT) of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)-Specific Antibody at Day 29	Day 29
GMT of SARS-CoV-2-Specific Antibody at Day 91 (For Part G only)	Day 91
GMT of Omicron-Specific Antibody at Day 91 (For Part G only)	Day 91
Seroresponse Rate of Vaccine Recipients at Day 29	Day 29
Seroresponse Rate of Vaccine Recipients at Day 91 (For Part G only)	Day 91
Number of Participants with Solicited Local and Systemic Reactogenicity Adverse Reactions (ARs)	Up to Day 7 (7 days post-vaccination)
Number of Participants with Unsolicited Adverse Events (AEs)	Up to Day 28 (28 days post-vaccination)
Number of Participants with Serious AEs (SAEs), Medically Attended AEs (MAAEs), AEs Leading to Withdrawal, and AEs of Special Interest (AESIs)	Up to Day 366
GMT of Omicron-Specific Antibody (For Part J only) at Day 15	Day 15
GMT of Omicron-Specific Antibody (For Parts F, G, H and J only) at Day 29	Day 29
Geometric mean fold rise (GMFR) of Omicron-Specific Antibody (For Part J only) at Day 15	Day 15
Seroresponse Rate of Vaccine Recipients at Day 15 (For Part J only)	Day 15

Secondary Outcome Measures

Outcome Measure	Time Frame
GMT of SARS-CoV-2-Specific Antibody	Days 1, 15, 181, and 366
Seroresponse Rate of Vaccine Recipients	Days 1, 15, 181, and 366

Collaborators and Investigators

• Sponsor: ModernaTX, Inc.

Publications and helpful links

General Publications

• 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.
• 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. 2022 Mar 7:2022.03.04.22271830. doi: 10.1101/2022.03.04.22271830. Preprint.

Study record dates

Study Major Dates

• Study Start (Actual): May 28, 2021
• Primary Completion (Actual): November 17, 2023
• Study Completion (Actual): November 17, 2023

Study Registration Dates

• First Submitted: June 14, 2021
• First Submitted That Met QC Criteria: June 14, 2021
• First Posted (Actual): June 15, 2021

Study Record Updates

• Last Update Posted (Estimated): December 21, 2023
• Last Update Submitted That Met QC Criteria: December 15, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: SARS-CoV-2; COVID 19; Coronavirus; SARS-CoV-2 Vaccine; Virus Diseases; Moderna; Messenger RNA; mRNA-1273 vaccine; mRNA-1273; mRNA-1273.214; COVID 19 Vaccine; mRNA-1273.529; mRNA-1273.211; mRNA-1273.617.2; mRNA-1273.213; mRNA-1273.815; mRNA-1273.231
• Other Study ID Numbers: mRNA-1273-P205

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No