mRNA-1283 COVID-19 variant vaccine: safety and immune response in older and high-risk younger adults

A Phase 3b/4, Open-label Study to Evaluate the Immunogenicity and Safety of mRNA-1283 COVID-19 Variant-containing Vaccine Formulations

This tests whether the mRNA-1283 variant COVID-19 vaccine is safe and increases immune protection in adults 65+ and in 12–64 year-olds with at least one high-risk condition.

Quick facts

• Phase: Phase 4
• Study type: Interventional
• Enrollment: 832 (estimated)
• Ages: 12 Years and up
• Sex: All
• Sponsor: ModernaTX, Inc. (Industry-sponsored)
• Drugs / interventions: infliximab, prednisone
• Locations: 5 sites (Atlanta, Georgia and 4 other locations)
• Trial ID: NCT07089706 on ClinicalTrials.gov

What this trial studies

The protocol is a master design that allows multiple subprotocols to test updated variant-containing formulations of the mRNA-1283 vaccine. Subprotocol 01 is a single-arm evaluation of the 2025-2026 mRNA-1283 variant formulation, enrolling adults aged 65 and older and ages 12–64 who have at least one condition that raises their risk for severe COVID-19. The study moved from an initial Part A to a Part B design to collect hypothesis-driven immunogenicity endpoints, reactogenicity data, and longer safety follow-up. Each new variant formulation will be evaluated under a separate subprotocol using the same overall framework.

Who should consider this trial

Good fit: Adults aged 65 or older, and people aged 12–64 who have at least one medical condition that increases COVID-19 risk and who can attend study visits and follow contraception requirements if applicable, are the intended participants.

Not a fit: People younger than 65 without high-risk conditions, those unable to comply with follow-up visits, or those who cannot meet the contraception/screening requirements are unlikely to gain direct benefit from this subprotocol.

Why it matters

Potential benefit: If successful, the vaccine could provide stronger, variant-targeted immune protection and reduce severe COVID-19 outcomes in older and high-risk participants.

How similar studies have performed: Previous mRNA COVID-19 booster studies, including earlier Moderna mRNA formulations, have increased neutralizing antibodies and reduced severe disease, so testing variant-updated boosters builds on established mRNA vaccine success.

Eligibility criteria

Inclusion Criteria:

Subprotocol 1:

* ≥65 years of age at the time of signing the informed consent or ≥12 to \<65 years of age at the time of signing the informed consent with at least 1 risk factor for severe outcomes from COVID-19.
* Investigator's assessment that the participant understands and is willing and physically able to comply with protocol-mandated follow-up, including all procedures.
* Participants who are assigned female at birth or could become pregnant:

  i) Has a negative pregnancy test at the Screening Visit and on the day of vaccination prior to vaccine dose being administered on Day 1.

ii) Has practiced adequate contraception or has abstained from all activities that could result in pregnancy for at least 28 days prior to the first dose (Day 1).

iii) Has agreed to continue adequate contraception through 28 days following vaccine administration.

Exclusion Criteria:

Subprotocol 1:

* History of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection within 6 months prior to enrollment.
* Acutely ill or febrile (temperature ≥38.0°Celsius/≥100.4°Fahrenheit) within 72 hours prior to or at the Screening Visit or Day 1. Participants meeting this criterion may be rescheduled within the Screening window and will retain their initially assigned participant number.
* History of a diagnosis or condition that, in the judgment of the Investigator, is clinically unstable or may affect participant safety, assessment of study endpoints, assessment of immune response, or adherence to study procedures.
* Receipt of the COVID-19 vaccine within 6 months prior to enrollment.
* Receipt of any licensed non-COVID-19 vaccine within 28 days before or planned receipt within 28 days after the study intervention, except an influenza vaccine, which may be given 14 days before or after receipt of the study intervention.
* Receipt of systemic immunosuppressants for \>14 days in total, within 180 days prior to Screening Visit (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.
* Receipt of systemic immunoglobulins, long-acting biological therapies that affect immune responses (for example, infliximab) or blood products within 90 days prior to the Screening Visit or plans to receive them during the study.
* History of anaphylaxis or severe hypersensitivity reaction requiring medical intervention after receipt of any mRNA vaccine or therapeutic or any components of an mRNA vaccine or therapeutic.
* Has donated ≥450 milliliters (mL) of blood products within 28 days prior to the Screening Visit or plans to donate blood products within 28 days after the study injection.

Note: Other protocol-specified inclusion and exclusion criteria may apply.

Where this trial is running

Atlanta, Georgia and 4 other locations

• DelRicht Research-Atlanta — Atlanta, Georgia, United States (Recruiting)
• DelRicht Research-Baton Rouge — Baton Rouge, Louisiana, United States (Recruiting)
• DelRicht Research-New Orleans — New Orleans, Louisiana, United States (Recruiting)
• DelRicht Research-Gulfport — Gulfport, Mississippi, United States (Recruiting)
• DelRicht Research-Tulsa — Tulsa, Oklahoma, United States (Recruiting)

Study contacts

• Study coordinator: Moderna WeCare Team

Conditions COVID-19; mRNA-1283; mRNA-1283 vaccine; SARS-CoV-2; SARS-CoV-2 Vaccine; Coronavirus; Coronavirus Infections; Virus Diseases