RSV/hMPV Vaccine for Respiratory Syncytial Virus Immunization

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

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Sanofi Pasteur, a Sanofi Company

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

Disqualifiers: Immunodeficiency, Myocarditis, Thrombocytopenia, others

Compensation: Varies

Number of Visits: Unknown

1470 Participants Needed

Trial Summary

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 immunosuppressive therapy or long-term systemic corticosteroids, you may not be eligible to participate.

What data supports the effectiveness of the RSV/hMPV mRNA Vaccine treatment?

Research shows that vaccines using similar approaches, like mRNA-based vaccines, have been effective in generating immune responses against respiratory viruses such as RSV and hMPV in animal models and older adults. This suggests potential effectiveness for the RSV/hMPV mRNA Vaccine in preventing these infections. ^{1 2 3 4 5}

How is the RSV/hMPV mRNA Vaccine different from other RSV treatments?

The RSV/hMPV mRNA Vaccine is unique because it uses mRNA technology to instruct cells to produce proteins that trigger an immune response against both RSV and hMPV, unlike traditional vaccines that often use weakened or inactivated viruses. This approach is similar to the mRNA-1345 vaccine, which targets RSV alone, but the combination vaccine aims to protect against two viruses simultaneously. ^{3 6 7 8 9}

What is the purpose of this trial?

The aim of this study is to evaluate the safety and immunogenicity of a human metapneumovirus (hMPV) / respiratory syncytial virus (RSV) mRNA vaccine candidate encapsulated in a lipid nanoparticle (LNP) based formulation (hereafter referred to as hMPV/RSV vaccine) for the prevention of lower respiratory tract disease (LRTD) caused by hMPV and/or RSV among adults aged 60 years and older. Overall, the study is designed to address the following goals: * Assess the safety profile of the candidate formulations. * Describe the immunogenicity profile of the candidate formulations. * Select the vaccine formulations (dose) for future development. * Assess the safety and immunogenicity of a booster vaccination of the selected formulation administered 12 months after the primary vaccination in a subset of the study population. The study duration is as follows: -Six months each for the Sentinel and Main Cohorts; up to 12 months for the Expansion Cohort, and 12 additional months for the Booster Cohort Treatment duration: * Stage 1 Sentinel Cohort: 1 intra-muscular (IM) injection. Participants will be followed for 6 months post vaccination * Stage 1 Main Cohort: 1 IM injection. Participants will be followed for 6 months post vaccination * Stage 2 Expansion Cohort: 1 IM injection. Participants in the selected formulation arm will be followed for 12 months post-vaccination; the remainder of the participants will be followed for 8 months post-vaccination * Stage 2 Booster Cohort: 1 IM injection 12 months post-primary vaccination. Participants will be followed for 12 months post-booster vaccination

Eligibility Criteria

This trial is for adults aged 60 and older who are not pregnant or breastfeeding. Women must be postmenopausal for at least a year or surgically sterile to participate. The study aims to prevent lower respiratory tract disease caused by hMPV/RSV.

Inclusion Criteria

Are you 60 years old or older?

Exclusion Criteria

Do you have an autoimmune disorder or are you on any immunosuppressive medication?

Have you ever experienced a severe allergic reaction to a vaccine?

Have you ever been diagnosed with or received vaccination for RSV (respiratory syncytial virus)?

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment - Stage 1 Sentinel Cohort

Participants receive 1 intra-muscular (IM) injection and are followed for 6 months post-vaccination

6 months

Treatment - Stage 1 Main Cohort

Participants receive 1 IM injection and are followed for 6 months post-vaccination

6 months

Treatment - Stage 2 Expansion Cohort

Participants receive 1 IM injection; selected formulation arm followed for 12 months, others for 8 months post-vaccination

8-12 months

Booster - Stage 2 Booster Cohort

Participants receive 1 IM injection 12 months post-primary vaccination and are followed for 12 months post-booster

12 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• hMPV/RSV mRNA Vaccine

Trial Overview The study tests the safety and immune response of an mRNA vaccine candidate targeting human metapneumovirus (hMPV) and respiratory syncytial virus (RSV), comparing it with a placebo, licensed RSV vaccine, and other investigational vaccines.

Participant Groups

Group I: Group X Stage 2 Expansion Cohort Experimental Treatment 1 Intervention

1 IM injection of selected investigational hMPV/RSV vaccine formulation from Group 1-9 of Stage 1 Main Cohort

Group II: Group B Stage 1 Sentinel Cohort Experimental Treatment 1 Intervention

1 IM injection of investigational hMPV/RSV vaccine formulation B

Group III: Group A Stage 1 Sentinel Cohort Experimental Treatment 1 Intervention

1 IM injection of investigational hMPV/RSV vaccine formulation A

Group IV: Group 9 Stage 1 Main Cohort Experimental Treatment 1 Intervention

1 IM injection of investigational hMPV/RSV vaccine formulation I

Group V: Group 8 Stage 1 Main Cohort Experimental Treatment 1 Intervention

1 IM injection of investigational hMPV/RSV vaccine formulation H

Group VI: Group 7 Stage 1 Main Cohort Experimental Treatment 1 Intervention

1 IM injection of investigational hMPV/RSV vaccine formulation B

Group VII: Group 6 Stage 1 Main Cohort Experimental Treatment 1 Intervention

1 IM injection of investigational hMPV/RSV vaccine formulation A

Group VIII: Group 5 Stage 1 Main Cohort Experimental Treatment 1 Intervention

1 IM injection of investigational hMPV/RSV vaccine formulation G

Group IX: Group 4 Stage 1 Main Cohort Experimental Treatment 1 Intervention

1 IM injection of investigational hMPV/RSV vaccine formulation F

Group X: Group 3 Stage 1 Main Cohort Experimental Treatment 1 Intervention

1 IM injection of investigational hMPV/RSV vaccine formulation E

Group XI: Group 2 Stage 1 Main Cohort Experimental Treatment 1 Intervention

1 IM injection of investigational hMPV/RSV vaccine formulation D

Group XII: Group 15 Stage 2 Booster Cohort Experimental Treatment 1 Intervention

1 IM injection of selected investigational hMPV/RSV vaccine formulation from Group X of Expansion Cohort

Group XIII: Group 14 Stage 2 Expansion Cohort Experimental Treatment 1 Intervention

1 IM injection of licensed RSV vaccine

Group XIV: Group 13 Stage 2 Expansion Cohort Experimental Treatment 1 Intervention

1 IM injection of investigational hMPV monovalent vaccine

Group XV: Group 12 Stage 2 Expansion Cohort Experimental Treatment 1 Intervention

1 IM injection of investigational RSV monovalent vaccine

Group XVI: Group 10 Stage 1 Main Cohort Experimental Treatment 1 Intervention

1 IM injection of investigational hMPV/RSV vaccine formulation J

Group XVII: Group 1 Stage 1 Main Cohort Experimental Treatment 1 Intervention

1 IM injection of investigational hMPV/RSV vaccine formulation C

Group XVIII: Group C Stage 1 Sentinel Cohort Placebo Group 1 Intervention

1 IM injection of placebo

Group XIX: Group 11 Stage 1 Main Cohort Placebo Group 1 Intervention

1 IM injection of placebo

Group XX: Group 16 Stage 2 Booster Cohort Placebo Group 1 Intervention

1 IM injection of placebo

Who Is Running the Clinical Trial?

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

A recombinant Sendai virus (SeV) carrying a gene for a truncated hMPV fusion protein was developed, showing promise as a vaccine against human metapneumovirus (hMPV) infections, particularly in vulnerable young children.

The vaccine successfully induced binding and neutralizing antibody responses and provided protection against hMPV in a cotton rat model, suggesting its potential for preventing serious health risks associated with hMPV infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Sendai virus recombinant vaccine expressing a gene for truncated human metapneumovirus (hMPV) fusion protein protects cotton rats from hMPV challenge. Russell, CJ., Jones, BG., Sealy, RE., et al.[2018]

Human metapneumovirus (HMPV) is a significant cause of respiratory infections in infants, and despite extensive research, no effective vaccines for HMPV or respiratory syncytial virus (RSV) have been developed in over 50 years.

Recombinant chimeric viruses that express antigens from HMPV and other viruses show promise as potential vaccine candidates, with ongoing studies validating their effectiveness and suggesting optimization strategies based on RSV research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Engineering of Live Chimeric Vaccines against Human Metapneumovirus. Ogonczyk Makowska, D., Hamelin, MÈ., Boivin, G.[2020]

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]

A novel vaccine candidate, b/h PIV3/hMPV F2, was engineered and shown to generate strong immune responses in African green monkeys, providing protection against human metapneumovirus (hMPV) infection.

The vaccine demonstrated safety and attenuation in rhesus monkeys, indicating its potential for further evaluation in humans to prevent hMPV-related respiratory diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A host-range restricted parainfluenza virus type 3 (PIV3) expressing the human metapneumovirus (hMPV) fusion protein elicits protective immunity in African green monkeys. Tang, RS., Mahmood, K., Macphail, M., et al.[2020]

Respiratory syncytial virus (RSV) poses a significant health risk not only to infants but also to older adults, prompting urgent vaccine development efforts, with 19 candidates currently in clinical trials.

Advancements in understanding the RSV surface fusion glycoprotein have led to innovative vaccine strategies, including particle-based, live-attenuated, subunit, and vector-based approaches, although past trial failures indicate the need for improved knowledge on immunological protection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The respiratory syncytial virus vaccine landscape: lessons from the graveyard and promising candidates. Mazur, NI., Higgins, D., Nunes, MC., et al.[2023]

The bivalent RSVpreF vaccine was found to be safe and well-tolerated in a study of 618 adults aged 18-49, with mostly mild or moderate local and systemic reactions and no serious adverse events reported within 12 months post-vaccination.

The vaccine induced strong virus-neutralizing responses, with antibody levels significantly higher than those needed for protection in high-risk infants, suggesting its potential effectiveness for maternal immunization against RSV.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Randomized Phase 1/2 Study of a Respiratory Syncytial Virus Prefusion F Vaccine. Walsh, EE., Falsey, AR., Scott, DA., et al.[2022]

The study evaluated recombinant murine pneumonia virus (rMPV) as a potential vaccine vector for respiratory syncytial virus (RSV), demonstrating that it can effectively express the RSV F protein and induce high levels of neutralizing antibodies in rhesus macaques.

rMPV showed low levels of replication in the respiratory tracts of the macaques while maintaining stable expression of the RSV F protein, suggesting it could be a safe and immunogenic vaccine candidate for both RSV-naive and RSV-experienced populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Murine Pneumonia Virus Expressing the Fusion Glycoprotein of Human Respiratory Syncytial Virus from an Added Gene Is Highly Attenuated and Immunogenic in Rhesus Macaques. Brock, LG., Liu, X., Liang, B., et al.[2019]

The investigational RSV vaccine ChAd155-RSV was well-tolerated in healthy adults aged 18-45, with no dose-related toxicity or serious adverse events observed during a 1-year follow-up.

ChAd155-RSV effectively increased specific immune responses, including neutralizing antibodies and T-cell activity, indicating its potential efficacy in generating protection against RSV.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-in-Human Randomized Study to Assess the Safety and Immunogenicity of an Investigational Respiratory Syncytial Virus (RSV) Vaccine Based on Chimpanzee-Adenovirus-155 Viral Vector-Expressing RSV Fusion, Nucleocapsid, and Antitermination Viral Proteins in Healthy Adults. Cicconi, P., Jones, C., Sarkar, E., et al.[2022]

Respiratory syncytial virus (RSV) is a leading cause of lower respiratory infections in infants and the elderly, and despite its prevalence, there is currently no licensed vaccine available.

Promising vaccine candidates are in development, with nanoparticle and subunit vaccines showing potential for pregnant women and the elderly, while live-attenuated or vector-based vaccines may be more suitable for children.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Respiratory syncytial virus vaccines: an update on those in the immediate pipeline. Esposito, S., Di Pietro, G.[2020]

References

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

A Sendai virus recombinant vaccine expressing a gene for truncated human metapneumovirus (hMPV) fusion protein protects cotton rats from hMPV challenge. [2018]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Engineering of Live Chimeric Vaccines against Human Metapneumovirus. [2020]

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

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

4. Netherlands pubmed.ncbi.nlm.nih.gov

A host-range restricted parainfluenza virus type 3 (PIV3) expressing the human metapneumovirus (hMPV) fusion protein elicits protective immunity in African green monkeys. [2020]

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

The respiratory syncytial virus vaccine landscape: lessons from the graveyard and promising candidates. [2023]

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

A Randomized Phase 1/2 Study of a Respiratory Syncytial Virus Prefusion F Vaccine. [2022]

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

Murine Pneumonia Virus Expressing the Fusion Glycoprotein of Human Respiratory Syncytial Virus from an Added Gene Is Highly Attenuated and Immunogenic in Rhesus Macaques. [2019]

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

First-in-Human Randomized Study to Assess the Safety and Immunogenicity of an Investigational Respiratory Syncytial Virus (RSV) Vaccine Based on Chimpanzee-Adenovirus-155 Viral Vector-Expressing RSV Fusion, Nucleocapsid, and Antitermination Viral Proteins in Healthy Adults. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Respiratory syncytial virus vaccines: an update on those in the immediate pipeline. [2020]