Immunogenicity of Fluzone High Dose in Immunocompromised Children and Young Adults

NCT01685372 | Completed Phase 2 Results DMC

• 1 other identifier: 12-0829
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to determine whether Fluzone High Dose increases the immune response to the influenza antigens contained in the vaccine compared to standard-dose Fluzone in immunocompromised children and young adults. Safety and efficacy data will also be collected.

Conditions

Solid Organ Transplant Recipient (Liver, Kidney, Heart); Rheumatologic Disorder; Human Immunodeficiency Virus (HIV); Bone Marrow Transplant (BMT); Dialysis

Outcome Measures

Primary Outcomes (2)

• Number of Episodes of Influenza and Influenza-Like-Illness Reported in High Dose and Standard Dose Vaccination Groups

  Gathered data on influenza and influenza-like-illness during the influenza season for which the subject was vaccinated. Reported numbers of episodes of PCR-diagnosed influenza and rates of reported Influenza-Like-Illness (ILI) from Questionnaire #2 and also that were obtained from medical records. Data were categorized by the following: 1. Polymerase chain reaction (PCR)-proven diagnosis of influenza performed at Children's Hospital Colorado (CHC) 2. Diagnosis of influenza by non-PCR rapid-influenza test 3. Diagnosis of ILI (from questionnaire #2). \[Centers for Disease Control (CDC) definition of ILI: Fever ≥ 100°F AND cough or sore throat in the absence of another known cause other than influenza for the illness.\]

  up to 10 months after vaccination

• Number of Subjects Seroprotected at Timepoint 2 in High Dose and Standard Dose Vaccination Groups

  Measure hemagglutinin inhibition (HAI) on blood samples #2 for all subjects, which is the sample drawn at the "peak" of the immune response. Compare number of subjects who are seroprotected (reaching HAI ≥ 1:40) between the high-dose and standard-dose recipients..

  blood draw at 10-45 days post-vaccination

Secondary Outcomes (5)

• Number of Adverse Events Definitely or Possibly Related to Vaccination Reported Within 14 Days of Vaccination

  0-14 days after vaccination

• Number of Subjects With Seroconversion From T1 to T2 in the High Dose and Standard Dose Vaccine Groups

  10-45 days post-vaccination

• Number of Participants Seroprotected at Timepoint 3 in High Dose and Standard Dose Vaccination Groups

  at least 5 months post vaccination

• Change in Disease Status From Vaccination Through June of the Following Year

  up to 9 months post-vaccination

• Number of Adverse Events Considered Definitely or Possibly Related to Vaccination Through Sept 30 of the Year Following Vaccination.

  (1) Date of vaccine through day 30 post-vaccine; (2) Day 31 post-vaccine through September 30 of the year following vaccine

Other Outcomes (2)

• Additional Measures of Immunogenicity in High Dose and Standard Dose Vaccinations

  10-45 days post-vaccination

• Numbers of Subjects Who Were Both Seroprotected and Who Seroconverted at T2 and T3 After Vaccination

  (1) T2 measured 14-45 days post-vaccination; (2) T3 measured June 1-Sept 30 post-vaccination (end-of season), following vaccination

Study Arms (2)

Fluzone High Dose

EXPERIMENTAL

Fluzone High Dose 0.5 mL intramuscularly (IM) given once

Biological: Fluzone High Dose

Fluzone

ACTIVE COMPARATOR

Fluzone 0.5mL IM given once

Biological: Fluzone

Interventions

Fluzone High Dose BIOLOGICAL

A single-dose of high-dose influenza vaccine will be administered to subjects randomized to this arm

Also known as: high-dose influenza vaccine, influenza vaccine

Fluzone High Dose

Fluzone BIOLOGICAL

A single-dose of standard-dose influenza vaccine will be administered to subjects randomized to this arm

Also known as: influenza vaccine

Fluzone

Eligibility Criteria

• Age: 5 Years - 35 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Age ≥ 5 years and ≤ 35 years
• Receiving influenza vaccination in Children's Hospital Colorado (CHC) clinic as part of routine clinical care
• Only supposed to receive one dose of influenza vaccine
• Rheumatology patients: must be on some type of immunosuppressive or immunomodulatory medication at the time of immunization and considered at least moderately immunosuppressed in the opinion of the primary rheumatologist. Basic guidelines for rheumatology patients: (1) Any patient receiving monoclonal antibody therapy (i.e., infliximab, etanercept, tocilizumab, anakinra) must also be taking another immunosuppressive/immunomodulatory medication; (2) Patients taking steroids as monotherapy must be on a dose of ≥ 2mg/kg/day OR ≥ 20mg/day; (3) Patients on combination therapy where the dose of a single drug may not be very high, but the combination is considered moderately or severely immunosuppressive will be eligible.
• Bone Marrow Transplant patients: all patients in clinic eligible
• Oncology patients: must be on some type of chemotherapy
• Hemodialysis patients: must be on dialysis
• Child Health Immunodeficiency Program (CHIP) patients: must have a known diagnosis of HIV
• Solid Organ Transplant patients: post-transplant, influenza vaccine recommended by primary transplant physician

You may not qualify if:

• Rheumatology patients: if receiving any of the monoclonal antibodies, etanercept, infliximab, adalimumab, tocilizumab, atlizumab, or anakinra, must also be taking at least one other immunosuppressive/immunomodulatory medication
• Unable to come for scheduled follow-up appointments
• History of anaphylaxis reaction to influenza vaccination in the past
• Severe allergic reaction to any component of the vaccine, including egg protein, or after previous dose of any influenza vaccine
• History of Guillain-Barre syndrome ever in the past in the subject or in a parent or a sibling of the subject
• Allergy to latex
• Intravenous immuneglobulin (IVIG) within in 4 weeks preceding any blood draw
• Receiving an investigational agent as part of another study or other medical treatment (investigational = not-FDA approved for any indication)
• Subject not enrolled in other studies that prohibit him/her from enrolling in this study
• Blood draw contraindicated
• Pregnancy
• Breastfeeding
• Received a polysaccharide vaccine (pneumovax) w/in 3 weeks of the vaccination
• Absolute neutrophil count (ANC) \< 500/uL at the time of vaccination or could potentially have ANC 500/uL during the 5 days after vaccination
• Platelet count \< 50,000/uL at the time of vaccination

Sponsors & Collaborators

• University of Colorado, Denver: lead
• Colorado Clinical & Translational Sciences Institute: collaborator

Study Sites (1)

Children's Hospital Colorado

Aurora, Colorado, 80045, United States

Location

MeSH Terms

Conditions

Collagen Diseases; Acquired Immunodeficiency Syndrome

Interventions

Fluzone High-Dose; Influenza Vaccines

Condition Hierarchy (Ancestors)

Connective Tissue Diseases; Skin and Connective Tissue Diseases; HIV Infections; Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Slow Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Viral Vaccines; Vaccines; Biological Products; Complex Mixtures

Limitations and Caveats

The number of participants was very low, limiting statistical analysis and limiting the ability to perform any subgroup analysis. Data at T3, were even more limited given loss-to-follow-up.

Results Point of Contact

• Title: Donna Curtis, MD, MPH
• Organization: University of Colorado School of Medicine

donna.curtis@childrenscolorado.org

720-777-6981

Study Officials

• Donna Curtis, MD, MPH

  Children's Hospital Colorado, University of Colorado Denver School of Medicine

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 27, 2012
• First Posted: September 14, 2012
• Study Start: September 1, 2012
• Primary Completion: September 1, 2015
• Study Completion: September 1, 2017
• Last Updated: January 23, 2018
• Results First Posted: November 30, 2017

Record last verified: 2017-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)