mRNA-1345 Vaccine for RSV

Recruiting at 47 trial locations

Overseen By Moderna Clinical Trials Support Center

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: ModernaTX, Inc.

Must be taking: Immunosuppressive therapy

Must not be taking: Alemtuzumab, Rituximab, Immunosuppressants

Disqualifiers: Myocarditis, Pericarditis, Anaphylaxis, 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

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

1150 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests the safety and immune response of the mRNA-1345 vaccine in high-risk adults and those with organ transplants. The vaccine uses genetic instructions to help the body recognize and fight the virus.

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 in Part A, you should not have been on chronic immunosuppressants or immune-modifying drugs for more than 14 days within 180 days before starting the trial. If you are in Part B, you should not have had certain treatments like alemtuzumab or rituximab within 2 years before starting the trial.

What data supports the effectiveness of the mRNA-1345 vaccine for RSV?

Research shows that mRNA-based vaccines targeting the RSV F protein, like mRNA-1345, can increase protective antibodies and are generally well tolerated in older adults, suggesting potential effectiveness in preventing RSV infections. ^{1 2 3 4 5}

How is the mRNA-1345 vaccine for RSV different from other treatments?

The mRNA-1345 vaccine is unique because it uses mRNA technology to target the RSV prefusion F glycoprotein, which is a new approach compared to traditional vaccines. This vaccine is designed to boost the immune response specifically against RSV, and it is currently being tested for its effectiveness and safety in older adults, a group at high risk for severe RSV infections. ^{1 2 4 6 7}

Eligibility Criteria

This trial is for adults aged 18-59 with heart disease, chronic lung conditions, or stable diabetes on medication. It's also for those over 18 who've had an organ transplant and are on anti-rejection drugs. People can't join if they're in another study, have unstable health issues that could affect safety or results, severe allergies to the vaccine ingredients, recent use of immune-modifying drugs, a history of certain heart inflammations, or recent organ rejection.

Inclusion Criteria

You are 18 years of age or older.

You have received a lung transplant at least 6 months ago.

You have received a lung transplant at least 6 months ago.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment Part A

Single injection of mRNA-1345 administered intramuscularly (IM) on Day 1 for high-risk adults aged ≥18 to <60 years

1 day

Treatment Part B

Two injections of mRNA-1345 administered IM on Day 1 and Day 57 for adults who received solid organ transplant (SOT)

8 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• mRNA-1345

Trial Overview The trial tests mRNA-1345 vaccine's safety and immune response in two groups: high-risk adults (Part A) and adult solid organ transplant recipients (Part B). The goal is to see how well the vaccine works in these different populations who are at higher risk from respiratory syncytial virus.

Participant Groups

Group I: Part B: mRNA-1345 Dose 2 Experimental Treatment 1 Intervention

Two injections of mRNA-1345 administered IM on Day 1 and Day 57.

Group II: Part A: mRNA-1345 Dose 2 Experimental Treatment 1 Intervention

Single injection of mRNA-1345 administered IM on Day 1.

Group III: Part A: mRNA-1345 Dose 1 Experimental Treatment 1 Intervention

Single injection of mRNA-1345 administered intramuscularly (IM) on Day 1.

mRNA-1345 is already approved in United States for the following indications:

Approved in United States as mRESVIA for:

• Prevention of lower respiratory tract disease caused by RSV infection in adults aged 60 years and older

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

Findings from Research

The mRNA-based vaccine V172, designed to target the pre-fusion form of the RSV F glycoprotein, was found to be safe and well-tolerated in a Phase 1 clinical trial involving 112 older adults and 48 younger adults, with common side effects being mild and manageable.

V172 induced higher neutralizing antibody levels compared to a previous vaccine candidate (V171.2) and demonstrated protective effects in an animal model, suggesting it could be an effective option for preventing RSV infections in humans.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of a stabilized RSV pre-fusion F mRNA vaccine: Preclinical studies and Phase 1 clinical testing in healthy adults. Nussbaum, J., Cao, X., Railkar, RA., et al.[2023]

The Ad26.RSV.preF vaccine, tested in a phase 1/2a study with 352 adults aged 60 and older, was found to be well tolerated, showing similar side effects across different regimens.

Combining Ad26.RSV.preF with RSV preF protein significantly enhanced humoral immune responses while maintaining cellular responses, suggesting this combination could be more effective in generating immunity against RSV.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety, Immunogenicity, and Regimen Selection of Ad26.RSV.preF-based Vaccine Combinations: A Randomized, Double-blind, Placebo-Controlled, Phase 1/2a Study. Comeaux, CA., Bart, S., Bastian, AR., et al.[2023]

Vaccination with Arexvy and Abrysvo can significantly reduce the health burden of respiratory syncytial virus (RSV) in older adults, leading to fewer hospitalizations and deaths, making it a valuable intervention for this age group.

The cost-effectiveness analysis suggests that these vaccines could be economically viable, with a maximum price-per-dose of $127 for Arexvy and $118 for Abrysvo, potentially rising to $235 and $245 respectively if benefits extend into a second RSV season.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cost-effectiveness of Prefusion F Protein-based Vaccines Against Respiratory Syncytial Virus Disease for Older Adults in the United States. Moghadas, SM., Shoukat, A., Bawden, CE., et al.[2023]

The mRNA-1345 vaccine demonstrated high efficacy, with 83.7% effectiveness in preventing RSV-associated lower respiratory tract disease with at least two symptoms, and 68.4% efficacy against RSV-associated acute respiratory disease in a study involving 35,541 older adults.

The vaccine was generally safe, with most adverse reactions being mild to moderate and transient, although there was a higher incidence of local and systemic reactions compared to the placebo group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of an mRNA-Based RSV PreF Vaccine in Older Adults. Wilson, E., Goswami, J., Baqui, AH., et al.[2023]

The investigational mRNA vaccine (mRNA-1777) targeting Respiratory Syncytial Virus (RSV) was found to be safe and well-tolerated in both younger (72 participants) and older adults (107 participants), with no serious adverse events reported.

The vaccine successfully triggered a strong immune response, indicated by increased levels of RSV neutralizing antibodies and other immune markers, suggesting its potential effectiveness in protecting against RSV infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase 1, randomized, placebo-controlled study to evaluate the safety and immunogenicity of an mRNA-based RSV prefusion F protein vaccine in healthy younger and older adults. Aliprantis, AO., Shaw, CA., Griffin, P., et al.[2021]

Advancements in understanding the RSV surface fusion glycoprotein have led to the development of various vaccine approaches, including mRNA vaccines, which are currently showing promising results in clinical trials for preventing RSV in infants and the elderly.

The mRNA-1345 vaccine has received FDA fast-track designation for adults over 60, highlighting its potential as a safe and effective preventative measure against RSV, especially following the success of mRNA technology in COVID-19 vaccines.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Development of mRNA vaccines against respiratory syncytial virus (RSV). Qiu, X., Xu, S., Lu, Y., et al.[2023]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

Evaluation of a stabilized RSV pre-fusion F mRNA vaccine: Preclinical studies and Phase 1 clinical testing in healthy adults. [2023]

2. United States pubmed.ncbi.nlm.nih.gov

Safety, Immunogenicity, and Regimen Selection of Ad26.RSV.preF-based Vaccine Combinations: A Randomized, Double-blind, Placebo-Controlled, Phase 1/2a Study. [2023]

3. United States pubmed.ncbi.nlm.nih.gov

Cost-effectiveness of Prefusion F Protein-based Vaccines Against Respiratory Syncytial Virus Disease for Older Adults in the United States. [2023]

4. United States pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of an mRNA-Based RSV PreF Vaccine in Older Adults. [2023]

5. United States pubmed.ncbi.nlm.nih.gov

Prevention strategies for respiratory syncytial virus: passive and active immunization. [2015]

6. United States pubmed.ncbi.nlm.nih.gov

A phase 1, randomized, placebo-controlled study to evaluate the safety and immunogenicity of an mRNA-based RSV prefusion F protein vaccine in healthy younger and older adults. [2021]

7. England pubmed.ncbi.nlm.nih.gov

Development of mRNA vaccines against respiratory syncytial virus (RSV). [2023]