High vs. Standard Dose Influenza Vaccines in Lung Transplant (Repeater)

Vanderbilt University Medical Center

Status and phase: Enrolling; Phase 2

Conditions: Influenza; Immunization; Infection|Transplantation Infection|Influenza

Treatments: Biological: Fluzone High Dose Inactivated Influenza Vaccine; Biological: Fluzone Standard Dose Inactivated Influenza Vaccine

Study type: Interventional

Funder types: Other

Identifiers

NCT07192458

251037

Details and patient eligibility

About

This will be a follow-up study to the "Comparison of High Dose vs. Standard Dose Influenza Vaccine in Lung Allograft Recipient" study (DMID Protocol Number 22-0014) at Vanderbilt University Medical Center.

Lung transplantation is a life-saving therapy for patients with advanced lung disease, and is also associated with an improvement in quality of life. However, due to the need for life-long immunosuppression to prevent acute cellular rejection and chronic lung allograft dysfunction ("chronic rejection"), lung transplant recipients are at risk for developing major infections. In fact, one-year survival is 85%, with infection being the leading cause of death within the first year post-transplant. We will conduct a follow-up phase II, randomized, double-blind trial to assess the impact of subsequent administration of two doses of HD-IIV compared to two doses of SD-IIV among lung recipients during the early post-transplant period. Demonstration of improved immunogenicity from two doses of HD-IIV over consecutive influenza seasons would provide potential broad benefit in reducing influenza disease and its associated complications in lung transplant recipients. Moreover, studying vaccine immunogenicity and safety in the same participants over consecutive years can provide insight into the influence of immunosuppression levels and allograft aging on vaccine-mediated immune modulation. This proposed study design will contribute significantly to influenza vaccination guidance and policy for the highly vulnerable lung transplant population. This proposed study is designed to address several key knowledge gaps in vaccine-mediated protection of lung transplant recipients against influenza:

• Is there increased immunogenicity with administration of one or two doses of HD-IIV or SD-IIV in the subsequent season compared to two doses of HD-IIV or SD-IIV in the first season?
• What is the durability of the humoral and cellular immune response between influenza seasons and does two doses of HD-IIV or SD-IIV sustain higher HAI titers compared to two doses of HD-IIV or SD-IIV in the first season?
• What is the impact of maintenance immunosuppression levels on influenza vaccine immunogenicity within the same participant?
• Will the optimal immunogenic vaccination strategy be associated with an acceptable long-term safety profile over successive influenza seasons, including injection-site and systemic reactions, allosensitization, and organ rejection?

Full description

The study is a phase II, single-center, double-blind, randomized controlled immunogenicity and safety trial comparing two doses of HD-IIV to two doses of SD-IIV over two consecutive years in lung transplant recipients. At study enrollment, following consent, participants will receive either HD-IIV or SD-IIV , with study arm assignments based on DMID protocol number 22-0014. Therefore, participants will ultimately receive four total doses of either HD-IIV or four total doses of SD-IIV over two consecutive influenza seasons.

Enrollment: 60 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Lung transplant recipient who enrolled and completed Visits 1, 2, and 3 of the DMID protocol number 22-0014 during the prior 2024-2025 or 2025-2026 influenza season, respectively

  • Anticipated to be available for the duration of the study
  • Can be reached by telephone, text message, email, or electronic health record messaging

Exclusion criteria

• Recipient of multi-organ, extra-pulmonary, and/or hematopoietic stem cell transplant

• Recipient of a re-do lung transplant

• History of Guillain-Barre syndrome

• History of receiving the current season's influenza vaccine prior to study enrollment and/or Visit 1 of this follow-up study

• Pregnant person

• Laboratory-confirmed influenza disease after September 1st in the current influenza season and before enrollment in this follow-up study (patient can still receive the second influenza vaccination despite proven influenza disease after enrollment)

• CMVIG/IVIG/SCIG receipt within 28 days of each vaccine

• Receipt of rituximab or other B-cell depleting antibody (including proteasome inhibitors) therapy within 3 months of 1st vaccine dose (Day 0)

• Receipt of T-cell depleting therapies (anti-thymocyte globulin, alemtuzumab, daratumumab) between the completion of Visit 3 of the initial study and enrollment in this follow-up study

• Investigator concern about study participation

• Note: Criteria for temporarily delaying vaccine administration: The following conditions are temporary or self-limiting, and a participant may be included in the study once the condition has resolved, provided that the participant is otherwise eligible:

  • Fever ≥100.4ºF/38.0ºC (oral measurement), or an acute severe illness within 48 hours of enrollment
  • Receipt of any live vaccines within four weeks or any inactivated vaccines within two weeks prior to potential study vaccination

No children have been enrolled in the DMID protocol number 22-0014; therefore, only adults will be enrolled in this current study

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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60 participants in 2 patient groups

Fluzone: Two Doses High Dose Inactivated Influenza Vaccine

Experimental group

Description:

Fluzone: Two Doses of HD-IIV

Treatment:

Biological: Fluzone High Dose Inactivated Influenza Vaccine

Fluzone: Two Doses Standard Dose Inactivated Influenza Vaccine

Experimental group

Description:

Fluzone: Two Doses of of SD-IIV

Treatment:

Biological: Fluzone Standard Dose Inactivated Influenza Vaccine