Pandemic H5N1 influenza vaccine for adult organ transplant recipients

Pandemic Influenza Vaccine in Organ Transplantation (PIVOT Trial): Safety and Immunogenicity of Pandemic Influenza Vaccine in Organ Transplant Recipients

This trial will test whether two doses of an AS03-adjuvanted H5N1 vaccine are safe and produce protective immune responses in adult organ transplant recipients.

Quick facts

• Phase: Phase 3
• Study type: Interventional
• Enrollment: 120 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: University Health Network, Toronto (Academic / other)
• Drugs / interventions: Rituximab
• Locations: 1 site (Toronto, Ontario)
• Trial ID: NCT07240558 on ClinicalTrials.gov

What this trial studies

This randomized, placebo-controlled, double-blind, single-centre Phase 3 trial will enroll 120 stable adult organ transplant recipients at the University Health Network in Toronto and randomize them 1:1 to receive two intramuscular doses of an AS03-adjuvanted inactivated H5N1 vaccine (Arepanrix, GSK) or saline placebo three weeks apart. Blood samples at baseline, 3 weeks, and 6 weeks will be tested with hemagglutination inhibition assays to measure antibody responses against vaccine and circulating H5N1 strains, and a subset of 60 participants will provide peripheral blood mononuclear cells for cellular immunity assays including H5-specific CD4+ and CD8+ T-cell responses and B-cell analyses. Participants will be monitored for local and systemic reactions for seven days after each dose and followed for six months for adverse events including graft rejection, influenza-like illness, and laboratory-confirmed influenza, with long-term immunogenicity assessed at six months in vaccine recipients. Key eligibility includes age ≥18, more than three months post-transplant with stable graft function and eGFR >30 mL/min/1.73 m2, and exclusion criteria include recent rituximab, active CMV viremia, recent influenza or other vaccinations, pregnancy, and life expectancy under three months.

Who should consider this trial

Good fit: Adults at least three months after an organ transplant with stable graft function, eGFR >30 mL/min/1.73 m2, and ability to attend study visits at the Toronto site are ideal candidates.

Not a fit: Patients with recent rituximab, active infections or high CMV viral load, recent IVIG or vaccinations, pregnancy, prior life-threatening influenza vaccine reactions, or life expectancy under three months are unlikely to benefit or be eligible.

Why it matters

Potential benefit: If successful, the vaccine could give transplant patients stronger antibody and T-cell protection against H5N1 and reduce the risk of severe pandemic influenza.

How similar studies have performed: AS03-adjuvanted H5N1 vaccines have produced robust antibody responses in healthy adults and prior H5N1 vaccine trials, but data are limited in immunosuppressed organ transplant recipients making this application relatively novel for that population.

Eligibility criteria

Inclusion Criteria:

* Age ≥ 18 and greater than 3 months post-transplant
* Stable graft function
* eGFR \>30mL/min/1.73m2
* Able to provide informed consent

Exclusion Criteria:

* Allergy to vaccine components;
* Previous life-threatening reaction to influenza vaccine (ie Guillain Barré Syndrome);
* Ongoing or recent therapy for acute rejection (within the previous 30 days);
* Ongoing active cytomegalovirus (CMV) infection with viral load of greater or equal to 1000 international units/ml in the last 7 days;
* Febrile illness in the past 2 weeks;
* Rituximab in the last 6 months;
* Receiving treatment for active or acute infection;
* Unable to provide informed consent;
* 2025 seasonal influenza vaccination in preceding 6 weeks;
* Recent other vaccination in last 14 days;
* Receipt of intravenous immunoglobulin in last 30 days or expected to receive in next 30 days; Life expectancy \< 3 months;
* Diagnosis of influenza virus infection in the last 90 days.
* Pregnancy known at the time of enrolment

Where this trial is running

Toronto, Ontario

• University Health Network — Toronto, Ontario, Canada (Recruiting)

Study contacts

• Study coordinator: Victoria G Hall, MBBS MPH

Conditions Influenza; Avian Influenza; Vaccination