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Immunogenicity of Fluzone High Dose in Immunocompromised Children and Young Adults

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT01685372
First Posted: September 14, 2012
Last Update Posted: November 30, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborator:
Colorado Clinical & Translational Sciences Institute
Information provided by (Responsible Party):
University of Colorado, Denver
August 27, 2012
September 14, 2012
June 30, 2017
November 30, 2017
November 30, 2017
September 2012
September 2015   (Final data collection date for primary outcome measure)
  • Number of Episodes of Influenza and Influenza-Like-Illness Reported in High Dose and Standard Dose Vaccination Groups [ Time Frame: up to 10 months after vaccination ]

    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.]
  • Number of Subjects Seroprotected at Timepoint 2 in High Dose and Standard Dose Vaccination Groups [ Time Frame: blood draw at 10-45 days post-vaccination ]
    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..
  • Efficacy [ Time Frame: up to 10 months after vaccination ]

    Gathering data on influenza-like-illness during the influenza season for which the subject was vaccinated in the study. Influenza season typically lasts January through May. Compare rates of diagnosed influenza and rates of reported Influenza Like Illness (ILI) from Questionnaires #2 and #3 and also obtained from medical records between the high-dose and standard-dose recipients within each patient group for each influenza season included in the study. We will obtain 3 sets of data related to influenza/ILI and analyze combinations of them.

    1. PCR-proven diagnosis of influenza performed at Children's Hospital Colorado (CHC)
    2. Diagnosis of influenza by non-PCR rapid-influenza test (diagnosed outside of main-campus CHC)
    3. Diagnosis of ILI (from questionnaires #2 and #3). [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.]
  • Seroprotection [ Time Frame: blood draw at 10-45 days post-vaccination ]
    Measure HAI on blood samples #1 and #2 for all subjects, which is the sample drawn at the "peak" of the immune response. Compare percentage reaching HAI ≥ 1:32 (or 1:40) between the high-dose and standard-dose recipients within each patient group between timepoint 0 (pre-vaccination) and blood draw #2.
Complete list of historical versions of study NCT01685372 on ClinicalTrials.gov Archive Site
  • Number of Adverse Events Definitely or Possibly Related to Vaccination Reported Within 14 Days of Vaccination [ Time Frame: 0-14 days after 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 [ Time Frame: 10-45 days post-vaccination ]
    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 [ Time Frame: at least 5 months post vaccination ]
    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 [ Time Frame: up to 9 months post-vaccination ]
    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. [ Time Frame: (1) Date of vaccine through day 30 post-vaccine; (2) Day 31 post-vaccine through September 30 of the year following vaccine ]

    Data gathered from the following

    1. Safety data in 1st 14 days (safety surveys and safety diary)
    2. Safety survey at day 30-45 regarding any unplanned health care visit or other AE during the 30 days after vaccine
    3. On-going passive surveillance of adverse events (AEs)/serious adverse events (SAEs) throughout course of influenza season of enrollment
    4. Chart review of each participant by PI through Sept 30 of the year following vaccine Data collection stopped in September following enrollment.
  • Safety [ Time Frame: 0-14 days after vaccination ]
    Compare proportion of adverse events reported within the 14 days after vaccination by each subject. Compare types and rates of adverse events between the high-dose and standard-dose recipients within each patient group. Subjects will keep a Safety Diary for the 14 days post-vaccination.
  • Seroconversion [ Time Frame: 10-45 days post-vaccination ]
    Measure HAI on blood samples #1 and #2 for all subjects. Compare percentage reaching a four-fold increase in antibody level between the high-dose and standard-dose recipients within each patient group.
  • Other immunogenicity [ Time Frame: 10-45 days post-vaccination ]
    For other immunogenicity: Compare results of blood draw #1 and #2 between the high-dose and standard-dose recipients for each patient group for the following: antibody avidity, microneutralization, T-cell interferon, T-cell IL-2, B-cell IgG and B-cell IgA.
  • End of season seroprotection [ Time Frame: at least 5 months post vaccination ]
    Measure HAI on blood sample #3, to be drawn May-September following vaccination. Compare percentage who still have HAI ≥ 1:32 (1:40) between the high-dose and standard-dose recipients within each patient group.
  • Change in disease status after vaccination [ Time Frame: up to 6 months post-vaccination ]
    Evaluate disease status changes reported by subject on Questionnaire #3 as well as changes reported in clinic notes over the course of the influenza season. Statistical analysis will compare rates of progress or improvement of disease within the 2 months after vaccination and then within 6 months after vaccination between the high-dose and standard-dose recipients within each patient group.
  • Safety [ Time Frame: 12 months after vaccination ]
    1. Will survey subjects at day 30-45 regarding any unplanned health care visit
    2. Will have on-going passive surveillance of AEs/SAEs throughout course of influenza season of enrollment. Data collection will stop in September following enrollment.
  • Additional Measures of Immunogenicity in High Dose and Standard Dose Vaccinations [ Time Frame: 10-45 days post-vaccination ]
    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).
  • Numbers of Subjects Who Were Both Seroprotected and Who Seroconverted at T2 and T3 After Vaccination [ Time Frame: (1) T2 measured 14-45 days post-vaccination; (2) T3 measured June 1-Sept 30 post-vaccination (end-of season), following 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
Not Provided
 
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.
Not Provided
Interventional
Phase 2
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Prevention
  • Solid Organ Transplant Recipient (Liver, Kidney, Heart)
  • Rheumatologic Disorder
  • Human Immunodeficiency Virus (HIV)
  • Bone Marrow Transplant (BMT)
  • Dialysis
  • Biological: Fluzone High Dose
    A single-dose of high-dose influenza vaccine will be administered to subjects randomized to this arm
    Other Names:
    • high-dose influenza vaccine
    • influenza vaccine
  • Biological: Fluzone
    A single-dose of standard-dose influenza vaccine will be administered to subjects randomized to this arm
    Other Name: influenza vaccine
  • Experimental: Fluzone High Dose
    Fluzone High Dose 0.5 mL intramuscularly (IM) given once
    Intervention: Biological: Fluzone High Dose
  • Active Comparator: Fluzone
    Fluzone 0.5mL IM given once
    Intervention: Biological: Fluzone
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
16
September 2017
September 2015   (Final data collection date for primary outcome measure)

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.
Sexes Eligible for Study: All
5 Years to 35 Years   (Child, Adult)
No
Contact information is only displayed when the study is recruiting subjects
United States
 
 
NCT01685372
12-0829
Yes
Not Provided
Plan to Share IPD: No
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.
University of Colorado, Denver
University of Colorado, Denver
Colorado Clinical & Translational Sciences Institute
Principal Investigator: Donna Curtis, MD, MPH Children's Hospital Colorado, University of Colorado Denver School of Medicine
University of Colorado, Denver
October 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP