RSV mRNA Vaccine for Respiratory Syncytial Virus Immunization

Recruiting at 80 trial locations

Overseen By Trial Transparency email recommended (Toll free for US & Canada)

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Sanofi

Must not be taking: Immunosuppressants, Corticosteroids, Anticoagulants, others

Disqualifiers: Immunodeficiency, Myocarditis, HIV, others

Compensation: Varies

Number of Visits: 43

865 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests a new RSV vaccine that uses tiny fat particles to help deliver it into the body. It aims to see if the vaccine is safe and effective in healthy adults aged 18-50 and those aged 60 and older. The vaccine works by teaching the immune system to recognize and fight RSV.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are on immunosuppressive therapy, long-term corticosteroids, or have received certain vaccines recently, you may not be eligible to participate.

What data supports the effectiveness of the RSV mRNA vaccine for respiratory syncytial virus immunization?

Research shows that an mRNA-based RSV vaccine, similar to the one being tested, was well tolerated and successfully triggered an immune response in both younger and older adults, increasing antibodies that help fight RSV. ^{1 2 3 4 5}

What safety data exists for mRNA vaccines, including those for RSV?

mRNA vaccines, like those for RSV, have shown acceptable safety profiles in studies, with common mild side effects such as local pain and fatigue. Research on similar mRNA vaccines, like those for COVID-19, supports their general safety in humans, with most adverse reactions being mild and temporary. ^{6 7 8 9 10}

How is the RSV mRNA vaccine treatment different from other RSV treatments?

The RSV mRNA vaccine is unique because it uses messenger RNA (mRNA) to instruct cells to produce a part of the RSV virus, specifically the F protein, which helps the immune system recognize and fight the virus. This approach is different from traditional vaccines that often use weakened or inactivated viruses. The vaccine is delivered using lipid nanoparticles (tiny fat particles) that protect the mRNA and help it enter cells, making it a novel method for RSV immunization. ^{3 4 5 11 12}

Research Team

Clinical Sciences & Operations

Principal Investigator

Sanofi

Eligibility Criteria

Adults aged 18-50 and those 60 or older can join this trial if they're not pregnant, breastfeeding, or planning to become pregnant soon. They must be able to follow the study schedule and agree to use effective contraception. People with weakened immune systems, recent RSV illness, chronic diseases affecting study participation, substance abuse issues, other vaccine receipts close to the trial period, certain medication intakes recently, or involvement in another clinical study cannot participate.

Inclusion Criteria

I am not pregnant or breastfeeding, can't have children, or will use birth control.

I am 60 years old or older.

I am not pregnant or breastfeeding, cannot have children, and can follow the study plan.

Exclusion Criteria

Known or suspected congenital or acquired immunodeficiency; receipt of immunosuppressive therapy within the preceding 6 months; long-term systemic corticosteroid therapy; known systemic hypersensitivity to any of the study intervention components; history of life-threatening reaction to study interventions or products containing the same substances; allergic reaction after administration of mRNA COVID-19 vaccine; history of RSV-associated illness in the last 12 months; previous history of myocarditis, pericarditis, and/or myopericarditis; thrombocytopenia or bleeding disorder contraindicating IM injection; bleeding disorder or receipt of anticoagulants in the 3 weeks preceding inclusion; chronic illness that might interfere with study conduct or completion; alcohol, prescription drug, or substance abuse that might interfere with study conduct or completion; receipt of any vaccine other than mRNA vaccine in the 4 weeks preceding or planned receipt in the 4 weeks following any study intervention administration; receipt of any mRNA vaccine in the 60 days preceding or planned receipt in the 60 days following any study intervention administration; previous vaccination against RSV with an investigational vaccine; receipt of immune globulins, blood, or blood-derived products in the past 3 months; receipt of oral or injectable antibiotic therapy within 72 hours prior to the first blood draw; participation in another clinical study investigating a vaccine, drug, medical device, or medical procedure; deprived of freedom by an administrative or court order, in an emergency setting, or hospitalized involuntarily; self-reported or documented HIV, HBsAg, HBcAb, HCV Abs, or positive SARS-CoV-2 RT-PCR or antigen test; identified as an investigator, employee, or immediate family member with direct involvement in the proposed study

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment (Stage 1)

Participants receive a single intramuscular injection of the RSV vaccine candidate or placebo and are followed for safety and immunogenicity

12 months

Multiple visits for safety analyses at Day 7, Day 28, and additional as data are available

Booster (Stage 1)

A subset of participants receive a booster vaccination 12 months after the primary vaccination and are followed for an additional 12 months

12 months post-booster

Follow-up visits at Day 29, Month 3, Month 6, and Month 12 post-booster

Treatment (Stage 2)

Participants aged 60 years and older receive a single intramuscular injection of the RSV vaccine candidate or placebo and are followed for safety and immunogenicity

6 months

Safety analyses at Day 7 and Day 28

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Placebo
• RSV mRNA LNP CL-0059 High Dose
• RSV mRNA LNP CL-0059 Low dose
• RSV mRNA LNP CL-0059 Medium Dose
• RSV mRNA LNP CL-0137 High Dose
• RSV mRNA LNP CL-0137 Low dose
• RSV mRNA LNP CL-0137 Medium Dose

Trial Overview The trial is testing a new RSV mRNA vaccine candidate given as an injection at low, medium, and high doses using two different lipid nanoparticles (CL-0059 or CL-0137). Participants will be monitored for safety and how well their bodies respond to the vaccine over a year; some will get a booster shot after 12 months.

Participant Groups

Group I: Group 6: Sentinel and Main Cohorts (Stage 1) Experimental Treatment 1 Intervention

1 injection of RSV vaccine candidate (Dose C) via intramuscular injection

Group II: Group 5: Sentinel and Main Cohorts (Stage 1) Experimental Treatment 1 Intervention

1 injection of RSV vaccine candidate (Dose C) via intramuscular injection

Group III: Group 4: Sentinel and Main Cohorts (Stage 1) Experimental Treatment 1 Intervention

1 injection of RSV vaccine candidate (Dose B) via intramuscular injection

Group IV: Group 3: Sentinel and Main Cohorts (Stage 1) Experimental Treatment 1 Intervention

1 injection of RSV vaccine candidate (Dose B) via intramuscular injection

Group V: Group 2: Sentinel and Main Cohorts (Stage 1) Experimental Treatment 1 Intervention

1 injection of RSV vaccine candidate (Dose A) via intramuscular injection

Group VI: Group 1: Sentinel and Main Cohorts (Stage 1) Experimental Treatment 1 Intervention

1 injection of RSV vaccine candidate (Dose A) via intramuscular injection

Group VII: Group 1: Phase IIa/Dose-ranging (Stage 2) Experimental Treatment 1 Intervention

1 injection of RSV vaccine candidate (Dose B) via intramuscular injection

Group VIII: Group 0: Phase IIa/Dose-ranging (Stage 2) Experimental Treatment 1 Intervention

1 injection of RSV vaccine candidate (Dose A) via intramuscular injection

Group IX: Group 7: Main, Sentinel and Booster Cohorts (Stage 1) Placebo Group 1 Intervention

1 injection of placebo via intramuscular injection

Group X: Group 2: Phase 11a/Dose-ranging (Stage 2) Placebo Group 1 Intervention

1 injection of placebo via intramuscular injection

Who Is Running the Clinical Trial?

Sanofi

Lead Sponsor

Trials

2,246

Recruited

4,085,000+

Paul Hudson

Sanofi

Chief Executive Officer since 2019

Degree in Economics from Manchester Metropolitan University

Christopher Corsico

Sanofi

Chief Medical Officer

MD from Cornell University, MPH in Chronic Disease Epidemiology from Yale University

Sanofi Pasteur, a Sanofi Company

Lead Sponsor

Trials

429

Recruited

6,140,000+

Paul Hudson

Sanofi Pasteur, a Sanofi Company

Chief Executive Officer since 2019

Degree in Economics from Manchester Metropolitan University

Dr. Thomas Triomphe

Sanofi Pasteur, a Sanofi Company

Chief Medical Officer since 2020

MD from Tehran University of Medical Sciences

Findings from Research

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]

In a study involving 122 older adults, a third dose of the RSVPreF3-AS01E vaccine was found to be well tolerated, with mostly mild-to-moderate side effects and no serious adverse events reported, indicating a good safety profile.

The third dose significantly boosted RSV-specific neutralizing antibodies and T-cell responses, demonstrating its immunogenicity, although the antibody levels after the third dose were lower than those observed one month after the first dose.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Immunogenicity of a Revaccination With a Respiratory Syncytial Virus Prefusion F Vaccine in Older Adults: A Phase 2b Study. Leroux-Roels, I., Van Ranst, M., Vandermeulen, C., et al.[2023]

A study analyzing 4838 reports from the European database EudraVigilance found that mRNA COVID-19 vaccines, particularly BNT162b2, have a favorable safety profile in children aged 5-11, with serious adverse events reported in 38.7% of cases, but most were manageable.

The most common side effects included fever, headache, and vomiting, with only 20 cases of Multisystem Inflammatory Syndrome reported, indicating that while monitoring is essential, the benefits of vaccination in this age group outweigh the risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety Monitoring of mRNA COVID-19 Vaccines in Children Aged 5 to 11 Years by Using EudraVigilance Pharmacovigilance Database: The CoVaxChild Study. Zinzi, A., Gaio, M., Liguori, V., et al.[2023]

A survey of 222 resident physicians who received a third dose of the BNT162b2 mRNA vaccine found that the most common side effects were local pain (88.3%), fatigue (58.1%), and muscle/joint pain (44.1%), all of which resolved within 48-72 hours.

Compared to the second dose, systemic reactions were less common and milder, although 36.1% of participants reported that side effects interfered with their normal activities, indicating that while the booster is generally well-tolerated, some individuals may still experience significant reactions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse Reactions after the Third Dose of the BNT162b2 mRNA COVID-19 Vaccine among Medical School Residents in a Regional Reference University Hospital in Italy. Rahmani, A., Dini, G., Montecucco, A., et al.[2022]

The novel ionizable lipid nanoparticle (244cis) demonstrated enhanced protein expression of human erythropoietin while significantly reducing immunogenicity compared to conventional lipid nanoparticles, making it safer for therapeutic use.

In a study involving tdTomato transgenic mice with pulmonary fibrosis, 244cis LNP achieved high levels of transfection in lung endothelial cells and fibroblasts, indicating its potential for effective mRNA delivery in chronic lung diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Novel piperazine-based ionizable lipid nanoparticles allow the repeated dose of mRNA to fibrotic lungs with improved potency and safety. Kim, M., Jeong, M., Lee, G., et al.[2023]

References

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

Evaluation of the safety, tolerability and pharmacokinetics of ALN-RSV01, a novel RNAi antiviral therapeutic directed against respiratory syncytial virus (RSV). [2008]

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

Evaluation of combined live, attenuated respiratory syncytial virus and parainfluenza 3 virus vaccines in infants and young children. [2007]

3. 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]

4. England pubmed.ncbi.nlm.nih.gov

Development and qualification of cell-based relative potency assay for a human respiratory syncytial virus (RSV) mRNA vaccine. [2023]

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

Safety and Immunogenicity of a Revaccination With a Respiratory Syncytial Virus Prefusion F Vaccine in Older Adults: A Phase 2b Study. [2023]

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

Nonclinical safety evaluation of a novel ionizable lipid for mRNA delivery. [2022]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Safety Monitoring of mRNA COVID-19 Vaccines in Children Aged 5 to 11 Years by Using EudraVigilance Pharmacovigilance Database: The CoVaxChild Study. [2023]

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

Split-Dose Administration Enhances Immune Responses Elicited by a mRNA/Lipid Nanoparticle Vaccine Expressing Respiratory Syncytial Virus F Protein. [2023]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Adverse Reactions after the Third Dose of the BNT162b2 mRNA COVID-19 Vaccine among Medical School Residents in a Regional Reference University Hospital in Italy. [2022]

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

Novel piperazine-based ionizable lipid nanoparticles allow the repeated dose of mRNA to fibrotic lungs with improved potency and safety. [2023]

11. England pubmed.ncbi.nlm.nih.gov

Carriers for the delivery of a vaccine against respiratory syncytial virus. [2022]

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

Respiratory syncytial virus vaccines. [2021]