Pandemic Influenza Vaccine in Organ Transplantation (PIVOT Trial) (PIVOT)

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

Influenza is an important pathogen in transplant recipients. The current widespread outbreak of highly pathogenic H5N1 avian influenza (HPAI) in livestock, and the occurrence of several human cases of infection suggest that the next influenza pandemic may be soon approaching. Transplant patients will likely be uniquely predisposed to serious infection with high morbidity and mortality. There are a number of important reasons that evaluation of prevention strategies are critical in this highly vulnerable population. Currently, there is no data on the immunogenicity of H5Nx vaccines in this highly vulnerable population. The investigators plan to study the safety and immunogenicity of a two-dose regimen of the pandemic influenza H5N1 vaccine in organ transplant patients.

Study Overview

• Status: Recruiting
• Conditions: Vaccination; Avian Influenza; Influenza (Pandemic)
• Intervention / Treatment: Biological: H5N1 vaccine (Arepanrix, GSK); Biological: Placebo

Detailed Description

This randomized, placebo-controlled, double-blind, single-centre trial will evaluate the immunogenicity and safety of a two-dose regimen of the AS03-adjuvanted inactivated H5N1 vaccine (AREPANRIX™ H5N1, GSK) in adult organ transplant recipients. A total of 120 stable outpatient organ transplant recipients at the University Health Network (Toronto, Canada) will be enrolled and randomized 1:1 to receive two doses of H5N1 vaccine or placebo (0.9% saline) administered intramuscularly 3 weeks apart.

Blood samples collected at baseline (V0), 3 weeks (V1), and 6 weeks (V2) will be analyzed for serologic responses using hemagglutination inhibition (HAI) assays against vaccine and circulating H5N1 strains. In a subset of 60 participants (30 per arm), peripheral blood mononuclear cells will be obtained at each time point to assess cell-mediated immunity, including H5-specific CD4+ and CD8+ T-cell cytokine responses and B-cell immunity.

Participants will be monitored for local and systemic adverse events for 7 days following each dose and followed for 6 months for any adverse events, including rejection, influenza-like illness, and laboratory-confirmed influenza. Long-term immunogenicity will also be assessed at 6 months in vaccine recipients.

• Study Type: Interventional
• Enrollment (Estimated): 120
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Victoria G Hall, MBBS MPH; Phone Number: 1 416 340 4800; Email: victoria.hall@uhn.ca

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G2N2
      • Recruiting
      • University Health Network
      • Contact: Victoria G Hall, MBBS MPH; Phone Number: 4163404800; Email: victoria.hall@uhn.ca
      • Principal Investigator: Victoria G Hall, MBBS MPH

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: H5N1 vaccine; This arm will receive 2 doses of approved H5N1 vaccine, 3 weeks apart	Biological: H5N1 vaccine (Arepanrix, GSK); 2 doses of H5N1 vaccine, 3 weeks apart, given IM (deltoid)
Placebo Comparator: Placebo; This arm will receive 2 doses of normal saline (placebo), 3 weeks apart	Biological: Placebo; 2 doses of 0.5mls normal saline, 3 weeks apart, given IM (deltoid)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Seroprotection and seroconversion 6 weeks after dose 1	Participants with seroprotection (HAI titers greater than or equal to 1:40) after dose 2 AND seroconversion, defined as greater than or equal to 4-fold increase in HAI antibody titers from baseline to after dose 2 to the vaccine-matched H5 avian influenza strain.	6 weeks after dose 1 and 3 weeks after dose 2

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Seroprotection and seroconversion after dose 1 and comparison with after dose 2		6 weeks after dose 1
T and B cell immunity after dose 1 and dose of vaccine		3 and 6 weeks post dose 1
Durability of immunity at 6 months post dose 1		6 months post dose 1
Local and systemic adverse events to vaccination		Until 6 months post dose 2
Other safety factors	Transplant rejection, influenza like illness, confirmed influenza episodes	Until 6 months post dose 2
Seroprotection and seroconversion after dose 1 and 2 to H5, H1, H3		6 weeks and 3 weeks post dose 1

Collaborators and Investigators

• Sponsor: University Health Network, Toronto
• Collaborators: Laval University

Study record dates

Study Major Dates

• Study Start (Actual): November 3, 2025
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: November 16, 2025
• First Submitted That Met QC Criteria: November 16, 2025
• First Posted (Estimated): November 21, 2025

Study Record Updates

• Last Update Posted (Actual): December 18, 2025
• Last Update Submitted That Met QC Criteria: December 11, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Infections; Infections; Orthomyxoviridae Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases; Animal Diseases; Bird Diseases; Influenza, Human; Influenza in Birds; arepanrix; halofantrine
• Other Study ID Numbers: TID-2024-002; 196762 (Other Grant/Funding Number: CIHR)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Deidentified aggregated data will only be shared with appropriate request and ethical approval.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No