Pandemic Influenza Vaccine in Organ Transplantation (PIVOT Trial)

Официальное название

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

Обзор

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.

Подробное описание

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.

Вмешательства

• Биопрепарат H5N1 vaccine (Arepanrix, GSK)
  2 doses of H5N1 vaccine, 3 weeks apart, given IM (deltoid)
• Биопрепарат Placebo
  2 doses of 0.5mls normal saline, 3 weeks apart, given IM (deltoid)

Первичные конечные точки

• Seroprotection and seroconversion 6 weeks after dose 1 [Срок оценки: 6 weeks after dose 1 and 3 weeks after dose 2]

Вторичные конечные точки (6)

• Seroprotection and seroconversion after dose 1 and comparison with after dose 2 [Срок оценки: 6 weeks after dose 1]
• T and B cell immunity after dose 1 and dose of vaccine [Срок оценки: 3 and 6 weeks post dose 1]
• Durability of immunity at 6 months post dose 1 [Срок оценки: 6 months post dose 1]
• Local and systemic adverse events to vaccination [Срок оценки: Until 6 months post dose 2]
• Other safety factors [Срок оценки: Until 6 months post dose 2]
• Seroprotection and seroconversion after dose 1 and 2 to H5, H1, H3 [Срок оценки: 6 weeks and 3 weeks post dose 1]

Критерии участия

Критерии включения

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

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Четверное слепое

Основная цель

Профилактика

Центры проведения

Канада · 1 центр

• University Health Network — Toronto

Идентификаторы

NCT: NCT07240558 · TID-2024-002 · 196762

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗