Pandemic Flu Vaccine for Kidney Transplant Recipients

(PIVOT Trial)

Overseen By Victoria G Hall, MBBS MPH

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: University Health Network, Toronto

Must not be taking: Rituximab, Intravenous immunoglobulin

Disqualifiers: Allergy, CMV infection, Pregnancy, others

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

Compensation: Varies

Number of Visits: 3

Duration: 6 weeks

120 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new flu vaccine designed to protect kidney transplant recipients from a potential bird flu pandemic. It evaluates the vaccine's safety and effectiveness in this high-risk group. Participants will receive either the H5N1 vaccine (Arepanrix, GSK) or a placebo (a harmless substance with no therapeutic effect) for comparison. Individuals who had a kidney transplant at least three months ago and have stable organ function may be eligible to join. As a Phase 3 trial, this is the final step before FDA approval, offering participants a chance to contribute to a potentially groundbreaking treatment.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, if you are receiving treatment for an active or acute infection, you may not be eligible to participate.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that the H5N1 vaccine, Arepanrix, is generally safe for individuals with long-term illnesses and weakened immune systems. One study found that this vaccine did not cause serious side effects or harm kidney function in transplant patients.

Additionally, flu vaccines have proven safe for kidney transplant recipients, with no serious side effects reported and no damage to the transplanted kidney. Although the vaccine might not prevent the flu as effectively in those with weaker immune systems, its safety remains reassuring.

Overall, current evidence suggests that the H5N1 vaccine is safe for kidney transplant patients. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about the H5N1 vaccine, Arepanrix, for kidney transplant recipients because it offers targeted protection against the H5N1 flu strain, which is a specific type of avian influenza. Most existing flu vaccines for transplant patients are designed for seasonal flu strains and may not effectively cover this high-risk group against pandemic threats. The H5N1 vaccine uses a unique formulation specifically approved for pandemic flu, potentially providing a more tailored immune response for individuals who have undergone kidney transplants, whose immune systems are often compromised. This specificity in targeting H5N1 could mean better protection and peace of mind for these vulnerable patients.

What evidence suggests that the H5N1 vaccine might be an effective treatment for kidney transplant recipients?

Research has shown that the H5N1 vaccine, Arepanrix, has been safely used in thousands of healthy adults. Studies have found that this vaccine helps the body fight infections by triggering an immune response. However, it may not work as well in people with weakened immune systems, such as those who have had a kidney transplant. This trial will compare the H5N1 vaccine with a placebo to gather more information on its effectiveness in protecting kidney transplant patients against H5N1 flu. ^{2 6 7 8 9}

Are You a Good Fit for This Trial?

This trial is for kidney transplant recipients who may be at high risk of serious infection from influenza. It's designed to test how safe and effective the H5N1 avian flu vaccine is in this group. Specific eligibility criteria are not provided, but typically include being a certain time post-transplant without rejection, and not having conditions that could interfere with vaccine efficacy or safety.

Inclusion Criteria

Able to provide informed consent

I am over 18 and it's been more than 3 months since my transplant.

My kidney function is stable with an eGFR over 30.

Exclusion Criteria

Allergy to vaccine components

Recent other vaccination in last 14 days

Previous life-threatening reaction to influenza vaccine (i.e., Guillain Barré Syndrome)

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive two doses of the H5N1 vaccine or placebo, administered 3 weeks apart

6 weeks

3 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including adverse events and long-term immunogenicity

6 months

Multiple visits (in-person and virtual)

What Are the Treatments Tested in This Trial?

Interventions

• H5N1 vaccine (Arepanrix, GSK)

Trial Overview The PIVOT Trial is testing the safety and immune response generated by two doses of an H5N1 avian flu vaccine (Arepanrix) compared to a placebo in kidney transplant patients. The goal is to determine if the vaccine can safely induce immunity against pandemic influenza in these individuals.

How Is the Trial Designed?

Group I: H5N1 vaccine Active Control 1 Intervention

This arm will receive 2 doses of approved H5N1 vaccine, 3 weeks apart

Group II: Placebo Placebo Group 1 Intervention

This arm will receive 2 doses of normal saline (placebo), 3 weeks apart

Who Is Running the Clinical Trial?

University Health Network, Toronto

Lead Sponsor

Trials

1,555

Recruited

526,000+

Laval University

Collaborator

Trials

439

Recruited

178,000+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5519647/

Adjuvanted (AS03) A/H1N1 2009 Pandemic Influenza ... The clinical database included one report of corneal transplant rejection in an adjuvanted (AS03) A/H5N1 vaccine trial. The event was reported ...

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0264410X11010954

Pandemic influenza A H1N1 vaccine in recipients of solid ... B.A. Crowe et al. Evaluation of the cellular immune responses induced by a non-adjuvanted inactivated whole virus A/H5N1/VN/1203 pandemic influenza vaccine in ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3359578/

Influenza A/H1N1 Vaccine in Patients Treated by Kidney ... Although this adjuvant has been safely administered with the H1N1 and the H5N1 strains to thousands of healthy adults (18), more data are needed about the ...

4. amjtransplant.org amjtransplant.org/article/S1600-6135(22)28051-4/fulltext

De Novo Anti-HLA Antibody After Pandemic H1N1 and ... 2. Schwarz, TF ∙ Horacek, T ∙ Knuf, M ... Single dose vaccination with AS03-adjuvanted H5N1 vaccines in a randomized ...

5. fda.gov fda.gov/media/182872/download

Individuals using assistive technology may not be able to fully Vaccination with AREPANRIX may not be as effective in preventing disease caused by influenza A (H5N1) virus in immunosuppressed individuals, including ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT07240558

Study Details | NCT07240558 | Pandemic Influenza ... We plan to study the safety and immunogenicity of a two-dose regimen of the pandemic influenza H5N1 vaccine in kidney transplant patients.

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4054238/

Safety and Immunogenicity of a Vero Cell Culture-Derived ... The results of this study demonstrate that nonadjuvanted whole-virus H5N1 vaccines are safe and immunogenic in chronically ill and immunocompromised patients, ...

8. sciencedirect.com sciencedirect.com/science/article/pii/S1600613522057768

Influenza Vaccination Is Efficacious and Safe in Renal ... Booster vaccination did not enhance SP. Influenza vaccination did neither cause renal dysfunction nor triggered acute rejection and adverse events were limited.

9. mdpi.com mdpi.com/2076-393X/13/2/189

Safety and Efficacy of Influenza Vaccination in Kidney Graft ... Influenza vaccination prevents severe infections in KTx recipients, with good serological response and no impact on graft function or severe adverse events.