High vs. Standard Dose Influenza Vaccine in Lung Allograft Recipients

NCT05215327 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 212201
• Study Type: interventional
• Target: 270
• Locations: 1 country
• Sites: 1

Brief Summary

Lung allograft recipients have a higher burden of influenza disease and greater associated morbidity and mortality compared with healthy controls. Induction and early maintenance immunosuppression is thought to impair immunogenicity to standard dose inactivated influenza vaccine. This early post-transplant period is when immunity is most desirable, since influenza disease during this time frame is associated with adverse consequences. Thus, strategies to reduce severe influenza disease in this highly susceptible population are critical. No trials in lung transplant recipients have evaluated two doses of HD-IIV within the same influenza season as a strategy to improve immunogenicity and durability of influenza prevention. Furthermore, no influenza vaccine trials have focused on enrollment of subjects at early post-transplant timepoints. Very few studies have been performed in solely lung allograft recipients. Immunosuppression intensity is highest in lung patients, thereby limiting comparisons to recipients of heart, liver, and kidney transplants. Therefore, studies to assess both HD-IIV and two-dose strategies in the same influenza season in post-lung transplant recipients are greatly needed. The central hypothesis of our proposal is that lung allograft recipients who are 1-35 months post-transplant and receiving two doses of HD-quadrivalent inactivated influenza vaccine (QIV) will have higher HAI geometric mean titers (GMT) to influenza antigens compared to those receiving two doses of SD-QIV. To test this hypothesis and address the above critical knowledge gaps, we propose to conduct a phase II, multi-center, randomized, double-blind, controlled immunogenicity and safety trial comparing the administration of two doses of HD-QIV to two doses of SD-QIV in lung allograft recipients 1-35 months post-transplant. The results of this clinical trial will address significant knowledge gaps regarding influenza vaccine strategies (e.g., one vs. two doses and HD-QIV vs. SD-QIV) and immune responses in lung transplant recipients and will guide vaccine recommendations during the post-transplant period.

Conditions

Transplantation Infection; Influenza; Immunization; Infection

Keywords

Influenza; Vaccination; Immunization; Lung Transplantation; High Dose; Fluzone; Standard Dose; Influenza, Human; Communicable Diseases

Outcome Measures

Primary Outcomes (2)

• Geometric Mean Titers of influenza vaccine antibodies.

  Antibody titers will be measured by hemagglutination inhibition assay.

  Day 56 (post-vaccination)

• The number of participants reporting solicited injection site reactions and systemic reactions.

  Post-vaccination local adverse events (pain, tenderness, swelling/induration, erythema/redness, swelling/induration size, and erythema/redness size) and systemic adverse events (Fatigue/malaise, headache, nausea, body ache/myalgia (not at the injection site), general activity level, vomiting, and fever).

  Within 7 days post-vaccination

Secondary Outcomes (2)

• Geometric Mean Titers Ratio of influenza vaccine antibodies (post-/pre-vaccination).

  Day 56 (post-vaccination)

• The number of participants achieving seroprotection and seroconversion for influenza virus.

  Day 56 (post-vaccination)

Study Arms (2)

Two Doses High Dose Quadrivalent Inactivated Influenza Vaccine

EXPERIMENTAL

two doses of HD-QIV (0.7 mL; 60µg of each influenza antigen) 28-42 days apart

Biological: High Dose Quadrivalent Inactivated Influenza Vaccine

Two Doses Standard Dose Quadrivalent Inactivated Influenza Vaccine

EXPERIMENTAL

receive two doses of SD-QIV (0.5 mL; 15µg of each influenza antigen) 28-42 days apart

Biological: Standard Dose Quadrivalent Inactivated Influenza Vaccine

Interventions

Standard Dose Quadrivalent Inactivated Influenza Vaccine BIOLOGICAL

Fluzone ® Quadrivalent is a vaccine indicated for active immunization for the prevention of influenza disease caused by two influenza A subtype viruses and two type B viruses contained in the vaccine.

Also known as: Fluzone

Two Doses Standard Dose Quadrivalent Inactivated Influenza Vaccine

High Dose Quadrivalent Inactivated Influenza Vaccine BIOLOGICAL

Fluzone High-Dose (Influenza Vaccine) for intramuscular injection is an inactivated influenza vaccine, prepared from influenza viruses propagated in embryonated chicken eggs. The virus-containing allantoic fluid is harvested and inactivated with formaldehyde. Influenza virus is concentrated and purified in a linear sucrose density gradient solution using a continuous flow centrifuge. The virus is then chemically disrupted using a non-ionic surfactant, octylphenol ethoxylate (Triton® X-100), producing a "split virus". The split virus is further purified and then suspended in sodium phosphatebuffered isotonic sodium chloride solution. The Fluzone High-Dose process uses an additional concentration factor after the ultrafiltration step in order to obtain a higher hemagglutinin (HA) antigen concentration.

Also known as: Fluzone High Dose

Two Doses High Dose Quadrivalent Inactivated Influenza Vaccine

Eligibility Criteria

• Age: 16 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Lung allograft recipients
• Age ≥16 years at time of enrollment
• ≥1 month (30 days) and \<36 months post-lung transplant
• Anticipated to be available for duration of the study
• Can be reached by telephone, email, or text message

You may not qualify if:

• Recipient of multi-organ, extra-pulmonary, and/or hematopoietic stem cell transplant
• Recipient of a re-do lung transplant
• History of severe hypersensitivity to previous influenza vaccination or anaphylaxis to eggs/egg protein
• History of Guillain-Barre syndrome
• HIV positive patients, by history or documentation from previous test
• History of known severe latex hypersensitivity
• History of receiving the current season's influenza vaccine post-transplant prior to enrollment in the study
• Pregnant female
• Proven influenza disease after September 1st and before first study vaccine (patient can still receive the second influenza vaccination despite proven influenza disease once enrolled)
• 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 study vaccine (Day 0).
• Receipt of augmented T-cell depleting therapy within 3-months of 1st study vaccine (Day 0)
• Investigator concern about study participation

Sponsors & Collaborators

• Vanderbilt University Medical Center: lead
• Northwestern University Feinberg School of Medicine: collaborator
• University of Alabama at Birmingham: collaborator
• Duke University: collaborator
• University of Washington: collaborator
• Emory University: collaborator
• Baylor College of Medicine: collaborator
• NYU Langone Health: collaborator

Study Sites (1)

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

RECRUITING

MeSH Terms

Conditions

Infections; Influenza, Human; Communicable Diseases

Interventions

Influenza Vaccines; Fluzone High-Dose

Condition Hierarchy (Ancestors)

Respiratory Tract Infections; Orthomyxoviridae Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Viral Vaccines; Vaccines; Biological Products; Complex Mixtures

Study Officials

• Natasha Halasa, MD. MPH

  Vanderbilt University Medical Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Natasha Halasa, MD, MPH

CONTACT

615-322-2250; natasha.halasa@vumc.org

Laura Stewart, PhD

CONTACT

615-343-0218; laura.s.stewart@vumc.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: All study staff, and subjects will be blinded to which vaccine the subject will receive, except for an un-blinded vaccinator. This individual will not inform the study team or the subjects which vaccine they administered to the subject. The un-blinded vaccinator will not participate in any other study activities. If the study vaccine is provided in a blinded manner, then research staff will be able to administer the vaccine, and an un-blinded vaccinator will not be necessary. The pharmacy will be un-blinded and will have a record of which vaccine was given to each subject.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Pediatric Infectious Diseases

Model Details: The primary goal of this study is to compare influenza vaccine immunogenicity and safety between two doses of HD-QIV and two doses of SD-QIV in a population of lung transplant recipients. The study will be powered on a comparison of the primary immunogenicity outcome. A nominal level of α = 0.05 (two-sided) will be used to determine statistical significance

Study Record Dates

• First Submitted: January 18, 2022
• First Posted: January 31, 2022
• Study Start: November 8, 2022
• Primary Completion (Estimated): July 31, 2027
• Study Completion (Estimated): December 31, 2027
• Last Updated: December 8, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)