RSV/hMPV Vaccine for Respiratory Infections

Recruiting at 12 trial locations

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, Anticoagulants, others

Disqualifiers: Immunodeficiency, Myocarditis, Substance abuse, others

Compensation: Varies

Number of Visits: 2

Duration: 1 day

646 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 anticoagulants, you may not be eligible to participate. It's best to discuss your specific medications with the trial investigator.

What data supports the effectiveness of the RSV/hMPV vaccine candidate treatment for respiratory infections?

Research on RSV vaccines shows promising results, with some candidates inducing strong immune responses without causing enhanced disease. Advances in understanding the virus's structure have led to new vaccine designs, and some protein-based vaccines have shown potential in clinical trials for providing protection, especially in populations already exposed to RSV. ^{1 2 3 4 5}

Is the RSV/hMPV vaccine generally safe for humans?

Research on different RSV vaccines, including those using adenoviral vectors, shows they generally have an acceptable safety profile in both infants and adults. However, past trials with a different type of RSV vaccine in the 1960s showed increased risk of severe disease, which has since informed the development of safer vaccines. ^{3 6 7 8 9}

How is the RSV/hMPV vaccine treatment different from other treatments for respiratory infections?

The RSV/hMPV vaccine is unique because it targets both respiratory syncytial virus (RSV) and human metapneumovirus (hMPV), which are major causes of respiratory infections, and there are currently no approved vaccines for these viruses. This vaccine uses a novel approach by combining antigens (substances that trigger an immune response) from both viruses, potentially offering protection against multiple pathogens with a single immunization. ^{3 4 7 10 11}

What is the purpose of this trial?

This trial is testing a new vaccine for lung infections caused by RSV and hMPV in adults aged 60 and older. The vaccine aims to help the immune system recognize and fight these viruses.

Eligibility Criteria

Adults aged 60 or older can join this vaccine study if they're not pregnant, breastfeeding, and don't have a history of severe allergies to the vaccine's ingredients. They should be generally healthy or have stable chronic diseases. People with recent serious infections, heart inflammation history, bleeding disorders, or on certain medications may not qualify.

Inclusion Criteria

I am not pregnant, breastfeeding, and cannot become pregnant.

My doctor agrees I am fit for the trial and my condition has been stable without major treatment changes for 6 weeks.

I am 60 years old or older.

Exclusion Criteria

Participation at the time of study enrollment (or in the 4 weeks preceding the first study intervention administration) or planned participation during the present study period in another clinical study investigating a vaccine, drug, medical device, or medical procedure

I have a weak immune system or I am taking medication that weakens my immune system, but I am stable if I have HIV.

I have not had COVID-19 or its symptoms in the last 10 days.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a single intramuscular (IM) injection of the RSV/hMPV vaccine candidate or placebo

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and immunogenicity for 12 months post-vaccination

12 months

Multiple visits (in-person and virtual)

Booster

A subset of participants receive a booster vaccination 12 months after the primary vaccination

1 day

1 visit (in-person)

Booster Follow-up

Participants are monitored for safety and immunogenicity for 12 months after the booster dose

12 months

Multiple visits (in-person and virtual)

Treatment Details

Interventions

• RSV/hMPV vaccine candidate

Trial Overview The trial is testing different doses of an RSV/hMPV vaccine candidate in seniors to see how safe it is and how well it works (immunogenicity). Participants will get one shot and some will receive a booster after 12 months. A placebo group is included for comparison.

Participant Groups

Group I: Sentinel Cohort: RSV/hMPV Group 2 (Dose B) Experimental Treatment 1 Intervention

Participants will be randomized to receive a single IM injection of RSV/hMPV vaccine candidate

Group II: Sentinel Cohort: RSV/hMPV Group 1 (Dose A) Experimental Treatment 1 Intervention

Participants will be randomized to receive a single IM injection of RSV/hMPV vaccine candidate

Group III: Sentinel Cohort: RSV/hMPV Group 0 (Dose L) Experimental Treatment 1 Intervention

Participants will be randomized to receive a single IM injection of RSV/hMPV vaccine candidate

Group IV: Main Cohort: RSV/hMPV Group 2 (Dose B) Experimental Treatment 1 Intervention

Participants will be randomized to receive a single IM injection of RSV/hMPV vaccine candidate

Group V: Main Cohort: RSV/hMPV Group 1 (Dose A) Experimental Treatment 1 Intervention

Participants will be randomized to receive a single IM injection of RSV/hMPV vaccine candidate

Group VI: Booster Cohort-RSV/hMPV Experimental Treatment 2 Interventions

Participants will be randomized to receive a determined dose of single IM injection of RSV/hMPV vaccine candidate from a subset of Main cohort

Group VII: Main Cohort: Placebo-Group 3 Placebo Group 1 Intervention

Participants will be randomized to receive a single IM injection of placebo

Group VIII: Booster Cohort-Placebo Placebo Group 1 Intervention

Participants will be randomized to receive of single IM injection of placebo from a subset of Main cohort

Group IX: Sentinel Cohort: Placebo-Group 3 Placebo Group 1 Intervention

Participants will be randomized to receive a single 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

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 study evaluated an adjuvanted RSV vaccine in 1900 adults aged 60 and older, using a reliable patient-reported outcome tool (FLU-PRO) to assess RSV disease symptoms and virologic confirmation, demonstrating the tool's effectiveness in capturing relevant data.

Self-collection of nasal swabs significantly improved the detection of RSV cases, identifying 9 additional cases that site-swabbing alone would have missed, highlighting the importance of participant engagement in monitoring respiratory illnesses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of Efficacy Endpoints for a Phase IIb Study of a Respiratory Syncytial Virus Vaccine in Older Adults Using Patient-Reported Outcomes With Laboratory Confirmation. Yu, J., Powers, JH., Vallo, D., et al.[2020]

Respiratory syncytial virus (RSV) is a significant cause of illness and death in children, highlighting the urgent need for an effective vaccine.

Recent advancements in molecular technologies have improved the safety of live-attenuated vaccines, and protein-based vaccines are showing promise in clinical trials for both RSV-primed individuals and maternal vaccination to protect infants early in life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Respiratory syncytial virus vaccine: Is it coming? Sales, V., Wang, EE.[2021]

The Gcf A/Bac M2 vaccine candidate successfully induced strong Th1 and CD8+ T-cell responses in mice, leading to effective protective immunity against respiratory syncytial virus (RSV) without causing vaccine-enhanced disease (VED).

This vaccine formulation also resulted in a significant increase in IgG responses compared to Gcf A alone, suggesting that Bac M2 acts as an effective adjuvant, enhancing the immune response to RSV.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vaccine containing G protein fragment and recombinant baculovirus expressing M2 protein induces protective immunity to respiratory syncytial virus. Jo, YM., Kim, J., Chang, J.[2022]

The investigational ChAd155-RSV vaccine was found to have a safety profile similar to other childhood vaccines, with most adverse events occurring at rates comparable to or lower than those of active comparators.

The vaccine induced a strong immune response in infants, with higher RSV neutralizing titers and antibody concentrations compared to the comparator group, and there was no evidence of vaccine-associated enhanced respiratory disease (VAERD).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and immunogenicity of a ChAd155-vectored respiratory syncytial virus vaccine in infants 6-7 months of age: a phase 1/2 randomized trial. Sáez-Llorens, X., Norero, X., Mussi-Pinhata, MM., et al.[2023]

The RSVPreF3 vaccine candidate was found to be safe for use in 213 healthy pregnant women, with no significant adverse events related to the vaccine or placebo reported during the study.

The vaccine effectively increased RSV-specific neutralizing antibody levels in mothers and successfully transferred these antibodies to newborns, indicating strong immunogenicity and potential protection for infants against RSV.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Immunogenicity of an Investigational Respiratory Syncytial Virus Vaccine (RSVPreF3) in Mothers and Their Infants: A Phase 2 Randomized Trial. Bebia, Z., Reyes, O., Jeanfreau, R., et al.[2023]

The historical use of a formalin-inactivated RSV vaccine in the 1960s led to enhanced respiratory disease in infants, highlighting the need to understand the immunological mechanisms behind this adverse effect before developing new vaccines.

Recent discussions among experts and the FDA suggest that if new candidate vaccines demonstrate safety in preclinical and early clinical studies, they may be tested in RSV-naïve infants, marking a potential advancement in preventive measures against RSV.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Summary of the Vaccines and Related Biological Products Advisory Committee meeting held to consider evaluation of vaccine candidates for the prevention of respiratory syncytial virus disease in RSV-naïve infants. Browne, SK., Beeler, JA., Roberts, JN.[2021]

The Ad26.RSV.preF vaccine candidate showed good safety and immunogenicity in a study involving 12 adults and 36 RSV-seropositive children, with no serious adverse events reported and only mild to moderate reactions observed.

The vaccine significantly increased RSV neutralization titers in children and resulted in fewer RSV infections compared to the placebo group, indicating its potential effectiveness in preventing RSV.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 1/2a Safety and Immunogenicity of an Adenovirus 26 Vector Respiratory Syncytial Virus (RSV) Vaccine Encoding Prefusion F in Adults 18-50 Years and RSV-Seropositive Children 12-24 Months. Stuart, ASV., Virta, M., Williams, K., 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]

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]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

In Vitro Evaluation of Glycoengineered RSV-F in the Human Artificial Lymph Node Reactor. [2020]

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

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

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

Evaluation of Efficacy Endpoints for a Phase IIb Study of a Respiratory Syncytial Virus Vaccine in Older Adults Using Patient-Reported Outcomes With Laboratory Confirmation. [2020]

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

Respiratory syncytial virus vaccine: Is it coming? [2021]

5. Korea (South) pubmed.ncbi.nlm.nih.gov

Vaccine containing G protein fragment and recombinant baculovirus expressing M2 protein induces protective immunity to respiratory syncytial virus. [2022]

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

Safety and immunogenicity of a ChAd155-vectored respiratory syncytial virus vaccine in infants 6-7 months of age: a phase 1/2 randomized trial. [2023]

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

Safety and Immunogenicity of an Investigational Respiratory Syncytial Virus Vaccine (RSVPreF3) in Mothers and Their Infants: A Phase 2 Randomized Trial. [2023]

8. Netherlands pubmed.ncbi.nlm.nih.gov

Summary of the Vaccines and Related Biological Products Advisory Committee meeting held to consider evaluation of vaccine candidates for the prevention of respiratory syncytial virus disease in RSV-naïve infants. [2021]

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

Phase 1/2a Safety and Immunogenicity of an Adenovirus 26 Vector Respiratory Syncytial Virus (RSV) Vaccine Encoding Prefusion F in Adults 18-50 Years and RSV-Seropositive Children 12-24 Months. [2023]

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

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

11. Switzerland pubmed.ncbi.nlm.nih.gov

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