High vs.Standard Dose Influenza Vaccine in Pediatric Solid Organ Transplant (SOT) Recipients

NCT05947071 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: DAIT RTB-019
• Study Type: interventional
• Target: 312
• Locations: 1 country
• Sites: 8

Brief Summary

Influenza virus is a significant pathogen in pediatric solid organ transplant (SOT) recipients. However, these individuals respond poorly to 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. One study compared HD-IIV vs. SD-IIV in adult SOT recipients and noted that HD-IIV was safe and more immunogenic; however, the median post-transplant period was 38 months. A phase I pediatric study comparing a single dose of HD-IIV vs. SD-IIV was safe with higher immunogenicity, but the study was limited by small sample size and median post-transplant vaccine administration was 26 months. In another phase II trial of adult SOT recipients, two doses of SD-IIV one month apart compared to one-dose of SD-IIV revealed modestly increased immunogenicity when given at a median of 18 months post-transplant. Therefore, these studies lack both evaluation in the early post-transplant period and substantive pediatric populations. Additionally, the administration of two-doses of HD-IIV in the same influenza season has not been evaluated in pediatric SOT recipients. Thus, the optimal immunization strategy for pediatric SOT recipients less than 24 months post-transplant is unknown. In addition, immunologic predictors and correlates of influenza vaccine immunogenicity in pediatric SOT recipients have not been well-defined. The central hypothesis of our proposal is that pediatric SOT recipients 1-23 months post-transplant who receive two doses of HD-quadrivalent inactivated influenza vaccine (QIV) will have similar safety but higher Hemagglutination Inhibition (HAI) geometric mean titers (GMTs) to influenza antigens compared to pediatric SOT recipients receiving two doses of SD-QIV.

Conditions

Immunization; Infection; Transplantation Infection; Influenza

Keywords

Influenza; Vaccination; Immunization; High Dose; Fluzone; Standard Dose; Influenza, Human; Communicable Diseases; Pediatric transplantation

Outcome Measures

Primary Outcomes (2)

• Immunogenicity: Hemagglutination Inhibition (HAI) titers

  Antibody titers will be measured by hemagglutination inhibition assay.

  4 weeks following the 2nd study vaccine

• Safety: solicited local and systemic post-administration 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).

  in the first 7 days following each study vaccine

Secondary Outcomes (3)

• Immunogenicity: Hemagglutination Inhibition (HAI) titers

  4 weeks following 1st and 2nd doses of each study vaccine

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

  4 weeks following the 1st and 2nd study vaccination

• Durability of immunogenicity

  180 days after vaccine 2

Study Arms (2)

Two Doses Standard Dose Quadrivalent Inactivated Influenza Vaccine

EXPERIMENTAL

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

Biological: Standard Dose Quadrivalent Inactivated Influenza Vaccine

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

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: 3 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Male or female, 3-17 years of age at time of enrollment
• Pediatric kidney, heart, and/or liver transplant recipient ≥1 month and \<24 months post-transplant at the time of study immunization
• Note: Participants undergoing re-transplantation are permitted
• Anticipated to be available for duration of the study
• Available by telephone, email, or text message

You may not qualify if:

• Inability (i.e. not able to understand and provide consent) or unwillingness of a participant/parent/legal guardian to give written informed consent or comply with study protocol
• History of severe hypersensitivity to influenza vaccination or anaphylaxis to eggs/egg protein
• History of severe latex hypersensitivity
• History of Guillain-Barre syndrome
• History of lung or intestine transplant
• HIV positive patients (testing within 24 months of enrollment)
• Receipt of current season's influenza vaccine post-transplant prior to enrollment in the study
• Currently pregnant or lactating (females of childbearing age may be enrolled based on self-report, urine pregnancy test must be performed prior to each influenza vaccine)
• Past or current medical problems or findings from physical examination or laboratory testing that are not listed above, which, in the opinion of the investigator, may pose additional risks from participation in the study, may interfere with the participant's ability to comply with study requirements or that may impact the quality or interpretation of the data obtained from the study.

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (8)

Stanford University

Stanford, California, 94305, United States

RECRUITING

Children's Healthcare of Atlanta

Atlanta, Georgia, 30322, United States

RECRUITING

Ann Robert H. Lurie Children's Hospital of Chicago

Chicago, Illinois, 60614, United States

RECRUITING

Children's Mercy Hospital

Kansas City, Missouri, 64108, United States

RECRUITING

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

RECRUITING

UPMC Children's Hospital of Pittsburgh

Pittsburgh, Pennsylvania, 15224, United States

RECRUITING

Monroe Carell Jr. Children's Hospital at Vanderbilt

Nashville, Tennessee, 37232, United States

RECRUITING

Texas Children's Hospital

Houston, Texas, 77030, 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 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. 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: NIH
• Responsible Party: SPONSOR

Model Details: The primary goal of this two-arm, double blind, randomized controlled trial is to compare influenza vaccine immunogenicity and safety between (a) two doses of SD-QIV and (b) two doses of HD-QIV over one influenza season in a population of pediatric SOT recipients who are ≥1 month and \<24 months post-transplant at the time of study immunization.

Study Record Dates

• First Submitted: March 1, 2023
• First Posted: July 17, 2023
• Study Start: September 26, 2024
• Primary Completion (Estimated): July 1, 2027
• Study Completion (Estimated): September 1, 2027
• Last Updated: April 21, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (8)