mRNA Vaccines Comparison for COVID-19 Prevention

(NextCOVE Trial)

No longer recruiting at 266 trial locations

Overseen By Moderna Clinical Trials Support Center

Age: Any Age

Sex: Any

Trial Phase: Phase 3

Sponsor: ModernaTX, Inc.

Must not be taking: Immunosuppressants, Immune-modifying drugs

Disqualifiers: Substance abuse, Acute illness, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 30

Duration: 1 day

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to compare the effectiveness and safety of two different mRNA vaccines for preventing COVID-19. Researchers will test two sets of vaccines, each with two versions, to determine which works better and how they affect the immune response. Individuals who have completed a COVID-19 vaccine series and at least one booster, as well as those unvaccinated, may qualify to participate. Participants should be prepared to follow study procedures and must not have had recent close contact with someone with COVID-19. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to the development of potentially groundbreaking vaccines.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are on systemic immunosuppressants or immune-modifying drugs, you may not be eligible to participate.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Previous studies have shown that mRNA-1283.222 is well tolerated, with participants mostly reporting mild side effects, such as soreness at the injection site. These studies noted no serious safety issues. Research also indicates that mRNA-1273.222 is safe, with consistent safety data showing mild to moderate side effects as the most common.

Reports have shown that mRNA-1273.815 is safe and well tolerated, with most side effects being mild, like slight pain or swelling at the injection site. Lastly, mRNA-1283.815 has demonstrated a safety profile similar to the approved Spikevax vaccine, with mild reactions being the most common.

These findings suggest that all four vaccines are generally safe and well tolerated in humans. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the mRNA-1273.222 and mRNA-1283.222 vaccines because they are designed to provide enhanced protection against COVID-19 variants. Unlike existing vaccines, which target the original strain of the virus, these new mRNA vaccines are tailored to address specific mutations found in recent variants. This targeted approach can potentially offer better immunity and longer-lasting protection. Additionally, the mRNA-1283.222 vaccine is being investigated for its ability to be effective at lower doses, which could mean fewer side effects and easier mass production and distribution.

What evidence suggests that this trial's treatments could be effective for COVID-19 prevention?

This trial will compare different mRNA vaccines for COVID-19 prevention. Research has shown that the mRNA-1283.222 vaccine, one of the vaccines tested in this trial, performs as well as the original mRNA-1273 vaccine in preventing COVID-19, with similar infection rates in both groups. Participants in this trial may receive mRNA-1273.222, which studies have found to be more effective than other two-part vaccines at preventing COVID-19 hospitalizations. The mRNA-1273.815 vaccine, another option in this trial, was reported to be 51% effective in preventing severe COVID-19 cases, such as hospitalizations. While there is less direct data on mRNA-1283.815, it is being compared to mRNA-1273.815, which has shown strong protection against COVID-19 hospitalizations. Overall, these vaccines have demonstrated promise in providing strong protection against COVID-19. ^{1 6 7 8 9}

Are You a Good Fit for This Trial?

This trial is for people ≥12 years old who've had a full initial COVID-19 vaccination series, and if they're ≥18, at least one booster. They must show proof of vaccination, be able to follow the study plan, and not be pregnant or become pregnant during the study. People can't join if they've been exposed to COVID-19 recently, are sick or have a fever before starting the trial, have conditions that could risk their health in the study or affect results, plan to get other vaccines close to this trial's timeline, received certain treatments like blood products or immunosuppressants near the start of the trial.

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 the first injection, and agreement to continue adequate contraception or abstinence through 90 days following the vaccine administration.

I understand and can follow the study's requirements.

I have completed the initial COVID-19 vaccine series and, if over 18, received a booster.

Exclusion Criteria

I have not received any blood products or immunoglobulins in the last 90 days and do not plan to receive any during the study.

I have not taken strong immune system drugs for more than 2 weeks in the last 6 months.

I have not had, nor plan to have, any vaccines 60 days before or after the study injection.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a single intramuscular injection of either mRNA-1283 or mRNA-1273 on Day 1

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety, immunogenicity, and vaccine efficacy

365 days

Multiple visits (in-person and virtual) on Days 29, 91, 181, and 365

What Are the Treatments Tested in This Trial?

Interventions

• mRNA-1273.222
• mRNA-1283.222

Trial Overview The study compares two mRNA vaccines: mRNA-1283.222 (new) versus mRNA-1273.222 (existing). It looks at how safe they are and how bodies react to them ('reactogenicity'), as well as comparing their effectiveness ('relative vaccine efficacy') and immune response ('immunogenicity').

How Is the Trial Designed?

Group I: Part 2: mRNA-1283.815 Experimental Treatment 1 Intervention

Participants will receive single IM injection of mRNA-1283.815 on Day 1.

Group II: Part 2: mRNA-1273.815 Experimental Treatment 1 Intervention

Participants will receive single IM injection of mRNA-1273.815 on Day 1.

Group III: Part 1: mRNA-1283.222 Experimental Treatment 1 Intervention

Participants will receive single intramuscular (IM) injection of mRNA-1283.222 on Day 1.

Group IV: Part 1: mRNA-1273.222 Experimental Treatment 1 Intervention

Participants will receive single IM injection of mRNA-1273.222 on Day 1.

Who Is Running the Clinical Trial?

ModernaTX, Inc.

Lead Sponsor

Trials

127

Recruited

66,790,000+

Dr. Stephen Hoge

ModernaTX, Inc.

Chief Medical Officer

MD from Harvard Medical School

Stéphane Bancel

ModernaTX, Inc.

Chief Executive Officer since 2011

MBA from Harvard Business School, MSc in Engineering from École Centrale Paris

Published Research Related to This Trial

The mRNA-1273 Moderna COVID-19 vaccine was found to have a safety profile in a real-world setting in Japan that is consistent with clinical trial data, indicating it is well-tolerated among participants.

In a survey of 301 respondents, 98% reported local and systemic adverse events following the second dose, with younger individuals (18-29 years) and females experiencing higher rates of adverse events after the first dose, although these differences diminished with subsequent doses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-Time Survey of Vaccine Safety of the mRNA-1273 SARS-CoV-2 Vaccine in Workplace Vaccination at Keio University. Okumura, K., Hara, A., Inada, I., et al.[2022]

In a phase 1 clinical trial involving 104 healthy adults, the mRNA-1283 vaccine was found to be safe, with no serious adverse events reported, indicating a favorable safety profile.

All doses of the mRNA-1283 vaccine (10, 30, and 100 µg) produced strong immune responses comparable to the established mRNA-1273 vaccine, suggesting its potential effectiveness in generating immunity against SARS-CoV-2.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Interim analysis of a phase 1 randomized clinical trial on the safety and immunogenicity of the mRNA-1283 SARS-CoV-2 vaccine in adults. Yassini, P., Hutchens, M., Paila, YD., et al.[2023]

The mRNA-1273 Covid-19 vaccine was found to be safe for children aged 6 months to 5 years, with mostly low-grade and transient adverse events, and no new safety concerns identified during the trial.

The vaccine elicited immune responses in young children that were comparable to those in young adults, meeting noninferiority criteria, with estimated efficacy rates of 36.8% for children aged 2-5 years and 50.6% for those aged 6-23 months against Covid-19.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of mRNA-1273 Vaccine in Children 6 Months to 5 Years of Age. Anderson, EJ., Creech, CB., Berthaud, V., et al.[2023]

Citations

1. thelancet.com thelancet.com/journals/laninf/article/PIIS1473-3099(25)00236-1/fulltext

Efficacy, immunogenicity, and safety of a next-generation ... We evaluated the relative vaccine efficacy (rVE), immunogenicity, and safety of mRNA-1283 compared to the first-generation vaccine (mRNA-1273).

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40639387/

results from a phase 3, randomised, observer- ... We evaluated the relative vaccine efficacy (rVE), immunogenicity, and safety of mRNA-1283 compared to the first-generation vaccine (mRNA-1273).

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05815498

NCT05815498 | A Study of mRNA-1283 Injection ... The purpose of this study (Part 1 and Part 2) is to evaluate the relative vaccine efficacy (rVE), safety, reactogenicity, and immunogenicity of mRNA-1283.222 ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10675676/

Comparative Effectiveness of Bivalent (Original/Omicron ... Overall, we found greater effectiveness of mRNA-1273.222 compared with the BNT162b2 Bivalent vaccine in preventing COVID-19-related hospitalizations and ...

5. nature.com nature.com/articles/s41467-023-41537-7

mRNA-1273 bivalent (original and Omicron) COVID-19 ... This study reports results that support early estimates of the effectiveness of bivalent COVID-19 boosters against an array of COVID-19 outcomes ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39332418/

Safety and immunogenicity of a single-dose omicron ... We aimed to determine the safety and immunogenicity of an omicron-containing COVID-19 vaccine (mRNA-1273.222) in vaccine-naive adolescents who were SARS-CoV-2 ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10504066/

Original SARS-CoV-2 monovalent and Omicron BA.4/BA.5 ... Herein, we summarize the interim safety and immunogenicity results of the mRNA-1273.222 clinical study and we include neutralization information ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT04649151

NCT04649151 | A Study to Evaluate the Safety, ... 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 ...

9. fda.gov fda.gov/media/164810/download

COVID-19 Moderna Bivalent Vac ▫ Consistent safety and immunogenicity data observed in preclinical and ... (mRNA-1273.222). Original Vaccine. (mRNA-1273). Non-Contemporaneous ...