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Immunogenicity of Fluzone High Dose in Immunocompromised Children and Young Adults

Primary Purpose

Solid Organ Transplant Recipient (Liver, Kidney, Heart), Rheumatologic Disorder, Human Immunodeficiency Virus (HIV)

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Fluzone High Dose
Fluzone
Sponsored by
University of Colorado, Denver
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Solid Organ Transplant Recipient (Liver, Kidney, Heart)

Eligibility Criteria

5 Years - 35 Years (Child, Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Children's Hospital Colorado

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Fluzone High Dose

Fluzone

Arm Description

Fluzone High Dose 0.5 mL intramuscularly (IM) given once

Fluzone 0.5mL IM given once

Outcomes

Primary Outcome Measures

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.]
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..

Secondary Outcome Measures

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.
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.
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.
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.
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.

Full Information

First Posted
August 27, 2012
Last Updated
December 21, 2017
Sponsor
University of Colorado, Denver
Collaborators
Colorado Clinical & Translational Sciences Institute
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1. Study Identification

Unique Protocol Identification Number
NCT01685372
Brief Title
Immunogenicity of Fluzone High Dose in Immunocompromised Children and Young Adults
Official Title
Immunogenicity and Efficacy of High-dose Trivalent Inactivated Seasonal Influenza Vaccine (Fluzone High Dose) in Immunocompromised Children and Young Adults.
Study Type
Interventional

2. Study Status

Record Verification Date
December 2017
Overall Recruitment Status
Completed
Study Start Date
September 2012 (undefined)
Primary Completion Date
September 2015 (Actual)
Study Completion Date
September 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Colorado, Denver
Collaborators
Colorado Clinical & Translational Sciences Institute

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Solid Organ Transplant Recipient (Liver, Kidney, Heart), Rheumatologic Disorder, Human Immunodeficiency Virus (HIV), Bone Marrow Transplant (BMT), Dialysis

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
16 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Fluzone High Dose
Arm Type
Experimental
Arm Description
Fluzone High Dose 0.5 mL intramuscularly (IM) given once
Arm Title
Fluzone
Arm Type
Active Comparator
Arm Description
Fluzone 0.5mL IM given once
Intervention Type
Biological
Intervention Name(s)
Fluzone High Dose
Other Intervention Name(s)
high-dose influenza vaccine, influenza vaccine
Intervention Description
A single-dose of high-dose influenza vaccine will be administered to subjects randomized to this arm
Intervention Type
Biological
Intervention Name(s)
Fluzone
Other Intervention Name(s)
influenza vaccine
Intervention Description
A single-dose of standard-dose influenza vaccine will be administered to subjects randomized to this arm
Primary Outcome Measure Information:
Title
Number of Episodes of Influenza and Influenza-Like-Illness Reported in High Dose and Standard Dose Vaccination Groups
Description
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.]
Time Frame
up to 10 months after vaccination
Title
Number of Subjects Seroprotected at Timepoint 2 in High Dose and Standard Dose Vaccination Groups
Description
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..
Time Frame
blood draw at 10-45 days post-vaccination
Secondary Outcome Measure Information:
Title
Number of Adverse Events Definitely or Possibly Related to Vaccination Reported Within 14 Days of Vaccination
Description
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.
Time Frame
0-14 days after vaccination
Title
Number of Subjects With Seroconversion From T1 to T2 in the High Dose and Standard Dose Vaccine Groups
Description
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.
Time Frame
10-45 days post-vaccination
Title
Number of Participants Seroprotected at Timepoint 3 in High Dose and Standard Dose Vaccination Groups
Description
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.
Time Frame
at least 5 months post vaccination
Title
Change in Disease Status From Vaccination Through June of the Following Year
Description
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.
Time Frame
up to 9 months post-vaccination
Title
Number of Adverse Events Considered Definitely or Possibly Related to Vaccination Through Sept 30 of the Year Following Vaccination.
Description
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.
Time Frame
(1) Date of vaccine through day 30 post-vaccine; (2) Day 31 post-vaccine through September 30 of the year following vaccine
Other Pre-specified Outcome Measures:
Title
Additional Measures of Immunogenicity in High Dose and Standard Dose Vaccinations
Description
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).
Time Frame
10-45 days post-vaccination
Title
Numbers of Subjects Who Were Both Seroprotected and Who Seroconverted at T2 and T3 After Vaccination
Description
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
Time Frame
(1) T2 measured 14-45 days post-vaccination; (2) T3 measured June 1-Sept 30 post-vaccination (end-of season), following vaccination

10. Eligibility

Sex
All
Minimum Age & Unit of Time
5 Years
Maximum Age & Unit of Time
35 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Donna Curtis, MD, MPH
Organizational Affiliation
Children's Hospital Colorado, University of Colorado Denver School of Medicine
Official's Role
Principal Investigator
Facility Information:
Facility Name
Children's Hospital Colorado
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No
IPD Sharing 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.

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Immunogenicity of Fluzone High Dose in Immunocompromised Children and Young Adults

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