Immunogenicity of Fluzone High Dose in Immunocompromised Children and Young Adults

Immunogenicity and Efficacy of High-dose Trivalent Inactivated Seasonal Influenza Vaccine (Fluzone High Dose) in Immunocompromised Children and Young Adults.

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.

Study Overview

• Status: Completed
• Conditions: Rheumatologic Disorder; Dialysis; Human Immunodeficiency Virus (HIV); Solid Organ Transplant Recipient (Liver, Kidney, Heart); Bone Marrow Transplant (BMT)
• Intervention / Treatment: Biological: Fluzone High Dose; Biological: Fluzone

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Children's Hospital Colorado

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 5 years to 35 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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
• If a subject has a temperature ≥ 100.4°F at the time of enrollment, then the subject must choose to not enroll or delay immunization until afebrile.
• Receiving influenza vaccination past December 15 of influenza season.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Fluzone High Dose; Fluzone High Dose 0.5 mL intramuscularly (IM) given once	Biological: Fluzone High Dose; A single-dose of high-dose influenza vaccine will be administered to subjects randomized to this arm; Other Names: influenza vaccine; high-dose influenza vaccine
Active Comparator: Fluzone; Fluzone 0.5mL IM given once	Biological: Fluzone; A single-dose of standard-dose influenza vaccine will be administered to subjects randomized to this arm; Other Names: influenza vaccine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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: Polymerase chain reaction (PCR)-proven diagnosis of influenza performed at Children's Hospital Colorado (CHC); Diagnosis of influenza by non-PCR rapid-influenza test; 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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Adverse Events Definitely or Possibly Related to Vaccination Reported Within 14 Days of Vaccination	Number of adverse events reported within the 14 days after vaccination by each subject within each patient group. Data collected from that reported in safety questionnaires and in Safety Diary that spanned the 14 days post-vaccination.	0-14 days after vaccination
Number of Subjects With Seroconversion From T1 to T2 in the High Dose and Standard Dose Vaccine Groups	HAI was measured on blood samples #1 and #2 for all subjects. Seroconversion is defined as a four-fold increase in antibody level between the high-dose and standard-dose recipients within each patient group was performed.	10-45 days post-vaccination
Number of Participants Seroprotected at Timepoint 3 in High Dose and Standard Dose Vaccination Groups	Measure HAI on blood sample #3, drawn May-September following vaccination. Report number who still have HAI ≥ 1:40 in the high-dose and standard-dose groups.	at least 5 months post vaccination
Change in Disease Status From Vaccination Through June of the Following Year	Evaluate disease status changes reported by subject on Questionnaire #2 as well as changes reported in clinic notes over the course of the influenza season. Subjects considered "worse" had worsening function of transplanted organ or complications related to underlying condition (e.g. dialysis) or new diagnosis of disease considered serious by PI.	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.	Data gathered from the following; Safety data in 1st 14 days (safety surveys and safety diary); Safety survey at day 30-45 regarding any unplanned health care visit or other AE during the 30 days after vaccine; On-going passive surveillance of adverse events (AEs)/serious adverse events (SAEs) throughout course of influenza season of enrollment; Chart review of each participant by PI through Sept 30 of the year following vaccine Data collection stopped in September following enrollment.	(1) Date of vaccine through day 30 post-vaccine; (2) Day 31 post-vaccine through September 30 of the year following vaccine

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Additional Measures of Immunogenicity in High Dose and Standard Dose Vaccinations	This secondary objective was included as exploratory and we plan to add additional analyses when funding is secured. There is no anticipated date when we will have this completed. (No immunogenicity studies have been done besides HAI.) For other immunogenicity: would compare results of blood draw #1 and #2 between the high-dose and standard-dose recipients for each patient group for any of the following: antibody avidity, microneutralization, T-cell interferon, T-cell IL-2, B-cell Immunoglobulin G (IgG) and B-cell Immunoglobulin A (IgA).	10-45 days post-vaccination
Numbers of Subjects Who Were Both Seroprotected and Who Seroconverted at T2 and T3 After Vaccination	Seroprotection (HAI>=1:40) and seroconversion (4-fold increase) together have been found to be a better predictor of vaccine effectiveness. Patients had to have both a 4-fold rise in HAI and have HAI>=40 to be counted	(1) T2 measured 14-45 days post-vaccination; (2) T3 measured June 1-Sept 30 post-vaccination (end-of season), following vaccination

Collaborators and Investigators

• Sponsor: University of Colorado, Denver
• Collaborators: Colorado Clinical & Translational Sciences Institute
• Investigators: Principal Investigator: Donna Curtis, MD, MPH, Children's Hospital Colorado, University of Colorado Denver School of Medicine

Study record dates

Study Major Dates

• Study Start: September 1, 2012
• Primary Completion (Actual): September 1, 2015
• Study Completion (Actual): September 1, 2017

Study Registration Dates

• First Submitted: August 27, 2012
• First Submitted That Met QC Criteria: September 13, 2012
• First Posted (Estimate): September 14, 2012

Study Record Updates

• Last Update Posted (Actual): January 23, 2018
• Last Update Submitted That Met QC Criteria: December 21, 2017
• Last Verified: December 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; Musculoskeletal Diseases; Connective Tissue Diseases; Slow Virus Diseases; HIV Infections; Acquired Immunodeficiency Syndrome; Rheumatic Diseases; Collagen Diseases; Physiological Effects of Drugs; Immunologic Factors; Vaccines
• Other Study ID Numbers: 12-0829

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: There is no plan to share data at the end of the study. Data management at the close of the study will occur according to IRB and FDA regulations.