High vs. Standard Dose Influenza Vaccine in Adult SOT Recipients

NCT04613206 | Active Not Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 12345
• Study Type: interventional
• Target: 396
• Locations: 1 country
• Sites: 1

Brief Summary

The influenza virus is a significant cause of morbidity in adult solid organ transplant (SOT) recipients. However, these individuals show a suboptimal response to vaccines including the standard-dose (SD) inactivated influenza vaccine (IIV). Recent studies have investigated two strategies to overcome poor immune responses in SOT recipients: (1) administration of high-dose (HD)-IIV compared to SD-IIV and (2) two doses of SD-IIV compared to one dose of SD-IIV in the same influenza season. The first study compared HD-IIV vs. SD-IIV in adult SOT and noted HD-IIV was safe and reported higher immunogenicity; however, the median post-transplant period was 38 months. In another phase II trial of adult SOT recipients, two doses of SD-IIV a month apart compared to one-dose SD-IIV revealed increased immunogenicity, with a median post-transplantation period of 18 months. Therefore, these studies lack evaluation in the early post-transplantation period in this vulnerable population when influenza disease is most severe. The administration of two-doses of HD-IIV in the same influenza season has also not been studied in SOT recipients. Moreover, the vast majority of SOT influenza vaccinations studies have not substantively evaluated prolonged immunogenicity. Thus, the optimal immunization strategy for SOT recipients less than 12 months post-transplant is poorly-defined. In addition, the immunologic predictors and correlates of influenza vaccine immunogenicity in SOT recipients have not been defined. The investigators hypothesize that adult solid organ transplant recipients that are 1-11 months out from transplant and are receiving high-dose inactivated influenza vaccine will have higher hemagglutination inhibition (HAI) geometric mean titers to influenza A antigens compared to adult SOT recipients receiving standard-dose inactivated influenza vaccine. To test this hypothesis and address the above critical knowledge gaps, The investigators propose to conduct a phase II multicenter randomized controlled trial comparing either two doses HD-IIV, two doses of SD-IIV, or one-dose of HD-IIV in adult kidney, heart, and liver SOT recipients 1-11 months post-transplantation. The results of this study will address significant gaps in knowledge regarding influenza vaccine strategies and immune responses in adult SOT recipients and will guide vaccine recommendations in this vulnerable population.

Conditions

Immunization; Infection; Transplantation Infection; Influenza; Solid Organ Transplant

Keywords

Influenza; Vaccination; Solid Organ Transplant; Immunization; High Dose; Fluzone; Standard Dose

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 (3)

Two Doses High Dose Quadrivalent Inactivated Influenza Vaccine

EXPERIMENTAL

two doses of 0.7 mL HD-IIV (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

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

Biological: Standard Dose Quadrivalent Inactivated Influenza Vaccine

One Dose High Dose Quadrivalent Inactivated Influenza Vaccine

EXPERIMENTAL

one dose of 0.7 mL HD-IIV (60µg of each influenza antigen) followed by placebo 28-42 days later

Biological: High Dose Quadrivalent Inactivated Influenza Vaccine

Interventions

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

One Dose High Dose Quadrivalent Inactivated Influenza Vaccine; Two Doses High Dose Quadrivalent Inactivated Influenza Vaccine

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

Eligibility Criteria

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

You may qualify if:

• Adult SOT recipients who have undergone kidney, heart, and/or liver transplantation I. Multiple organ recipients are permitted (i.e. any combination of organs including kidney, heart and/or liver).
• II. Subjects undergoing re-transplantation are permitted
• Age ≥18 years at vaccination
• ≥1 month and \<12 months post-SOT
• Anticipated to be available for duration of study
• Can be reached by telephone, email, or text message

You may not qualify if:

• History of severe hypersensitivity to previous influenza vaccination or anaphylaxis to eggs/egg protein
• History of Guillain-Barre syndrome
• History of known active infection with HIV
• 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)
• History of lung or intestine transplant
• CMVIG/IVIG/SCIG receipt in the 28 days prior to or planned administration within 84-126 days of the calendar date of first vaccination
• Subjects must have a platelet count of \<20,000 to receive the immunizations

Sponsors & Collaborators

• Vanderbilt University Medical Center: lead
• University of Alabama at Birmingham: collaborator
• Northwestern University Feinberg School of Medicine: collaborator
• University of Washington: collaborator

Study Sites (1)

Vanderbilt Univeristy Medical Center

Nashville, Tennessee, 37232, United States

Location

MeSH Terms

Conditions

Infections; Influenza, Human

Interventions

Influenza Vaccines; Fluzone High-Dose

Condition Hierarchy (Ancestors)

Respiratory Tract Infections; Orthomyxoviridae Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Viral Vaccines; Vaccines; Biological Products; Complex Mixtures

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator, Professor of Pediatric Infectious Diseases

Study Record Dates

• First Submitted: October 13, 2020
• First Posted: November 3, 2020
• Study Start: January 11, 2021
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: January 21, 2026

Record last verified: 2026-01

Locations

US (1)