RSV Vaccine for Transplant Recipients

(RSVax Trial)

Overseen By Victoria Hall, MBBS

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: University Health Network, Toronto

Must not be taking: IVIg, Rituximab

Disqualifiers: Pregnancy, CMV, RSV, others

Stay on Your Current Meds You can continue your current medications while participating

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 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 4

100 Participants Needed

Trial Summary

Do I need to stop my current medications for the RSV vaccine trial?

The trial information does not specify if you need to stop your current medications. However, certain conditions like recent IVIg treatment, rituximab use, or active infections may affect your eligibility.

What data supports the effectiveness of the RSV Vaccine for Transplant Recipients?

Research shows that RSV vaccines like Arexvy and Abrysvo are effective in protecting older adults from serious RSV-related illnesses. These vaccines have been shown to work well in people with other health conditions, suggesting they might also help transplant recipients. ^{1 2 3 4 5}

How is the RSV vaccine different from other treatments for RSV in transplant recipients?

The RSV vaccine for transplant recipients is unique because it uses a prefusion F protein-based approach, which is designed to enhance the immune response against RSV. This is different from other treatments that may not specifically target this protein structure, making it potentially more effective in preventing RSV-related illnesses. ^{1 2 3 6 7}

What is the purpose of this trial?

Adjuvant, non-live RSV vaccine will be administered to adult lung and allogeneic hematopoietic stem cell transplant recipients. The safety and immunogenicity of this intervention will be studied. Blood work will be collected before and after the intervention, to assess humoral and cellular immunity. Participants will be followed for adverse reaction, hospitalization, RSV breakthrough infection, graft rejection or graft versus host disease. This study has Health Canada and UHN REB approval.

Research Team

Victoria G Hall, MBBS

Principal Investigator

UHN Toronto

Eligibility Criteria

This trial is for adult lung and allogeneic hematopoietic stem cell transplant recipients who are more than 6 months post-transplantation. They should be stable outpatients to qualify.

Inclusion Criteria

I am more than 6 months post lung or bone marrow transplant and my condition is stable.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Vaccination

Participants receive a single dose of adjuvanted RSV vaccine

1 day

1 visit (in-person)

Initial Follow-up

Blood work collected to assess humoral and cellular immunity at 4 weeks post-vaccination

4 weeks

1 visit (in-person)

Extended Follow-up

Participants are monitored for adverse events, RSV infection, and durability of immunity at 6 and 12 months post-vaccination

12 months

2 visits (in-person)

Treatment Details

Interventions

• RSV Vaccine

Trial Overview The trial is testing the safety and immune response to a non-live RSV vaccine given to transplant recipients. Blood tests will measure immunity before and after vaccination, tracking any adverse reactions or complications.

Participant Groups

Group I: RSV vaccine group Experimental Treatment 1 Intervention

Single arm open label study of RSV vaccine to all adult transplant participants enrolling into the study.

RSV Vaccine is already approved in Canada, United States for the following indications:

Approved in Canada as Arexvy for:

• Prevention of RSV lower respiratory tract infection in adults 60 years and older

Approved in United States as Arexvy for:

• Prevention of RSV lower respiratory tract infection in adults 60 years and older

Approved in United States as Abrysvo for:

• Prevention of RSV lower respiratory tract infection in adults 60 years and older
• Prevention of severe RSV disease in newborns when administered to pregnant women

Approved in Canada as Abrysvo for:

• Prevention of RSV lower respiratory tract infection in adults 60 years and older
• Prevention of severe RSV disease in newborns when administered to pregnant women

Who Is Running the Clinical Trial?

University Health Network, Toronto

Lead Sponsor

Trials

1,555

Recruited

526,000+

The PSI Foundation, Ontario

Collaborator

Trials

2

Recruited

160+

University of British Columbia

Collaborator

Trials

1,506

Recruited

2,528,000+

Findings from Research

Vaccination with the RSV vaccines Arexvy and Abrysvo can significantly reduce the health burden of RSV-related illnesses in older adults, providing substantial health benefits.

The cost-effectiveness analysis suggests that these vaccines are economically viable if priced under $120 per dose for Arexvy and $111 for Abrysvo, with potential budget impacts of up to $6.10 billion in the first 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 RSVPreF3 OA vaccine demonstrated high efficacy against RSV-related lower respiratory tract disease (94.6%) and acute respiratory illness (81.0%) in older adults with coexisting cardiorespiratory or endocrine/metabolic conditions, indicating it is effective for those at higher risk.

Immunogenicity results showed that post-vaccination neutralizing antibody levels in participants with these conditions were comparable to those without, suggesting that the vaccine is safe and effective across different health statuses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Respiratory Syncytial Virus Prefusion F Protein Vaccine Is Efficacious in Older Adults With Underlying Medical Conditions. Feldman, RG., Antonelli-Incalzi, R., Steenackers, K., 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]

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]

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]

The study involving 48 young adults and 1005 older adults demonstrated that the RSVPreF3 vaccine significantly boosted immune responses, particularly after the first dose, with higher levels of RSV-specific antibodies and T cells observed in participants receiving the AS01-adjuvanted formulation.

Safety assessments revealed that most side effects were mild to moderate and temporary, with no significant safety concerns identified, leading to the selection of the AS01E-adjuvanted vaccine for further clinical development.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Immunogenicity of a Respiratory Syncytial Virus Prefusion F (RSVPreF3) Candidate Vaccine in Older Adults: Phase 1/2 Randomized Clinical Trial. Leroux-Roels, I., Davis, MG., Steenackers, K., et al.[2023]

The RSV001 trial is a phase 1 study involving 70 healthy adults (ages 18-75) to evaluate the safety and immunogenicity of two novel RSV vaccines, PanAd3-RSV and MVA-RSV, using various prime/boost combinations.

Initial safety assessments showed that participants will monitor for adverse events for one week post-vaccination, ensuring that the vaccines are safe for both younger and older adults, which is crucial given the high-risk nature of RSV infection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and immunogenicity of novel respiratory syncytial virus (RSV) vaccines based on the RSV viral proteins F, N and M2-1 encoded by simian adenovirus (PanAd3-RSV) and MVA (MVA-RSV); protocol for an open-label, dose-escalation, single-centre, phase 1 clinical trial in healthy adults. Green, CA., Scarselli, E., Voysey, M., et al.[2019]

References

1. 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]

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

Respiratory Syncytial Virus Prefusion F Protein Vaccine Is Efficacious in Older Adults With Underlying Medical Conditions. [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

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

Safety and Immunogenicity of a Respiratory Syncytial Virus Prefusion F (RSVPreF3) Candidate Vaccine in Older Adults: Phase 1/2 Randomized Clinical Trial. [2023]

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

Safety and immunogenicity of novel respiratory syncytial virus (RSV) vaccines based on the RSV viral proteins F, N and M2-1 encoded by simian adenovirus (PanAd3-RSV) and MVA (MVA-RSV); protocol for an open-label, dose-escalation, single-centre, phase 1 clinical trial in healthy adults. [2019]