Immunogenicity of Fluzone High Dose in Immunocompromised Children and Young Adults

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2014 by University of Colorado, Denver
Sponsor:
Collaborator:
Colorado Clinical & Translational Sciences Institute
Information provided by (Responsible Party):
University of Colorado, Denver
ClinicalTrials.gov Identifier:
NCT01685372
First received: August 27, 2012
Last updated: September 2, 2014
Last verified: September 2014

August 27, 2012
September 2, 2014
September 2012
September 2015   (final data collection date for primary outcome measure)
  • Efficacy [ Time Frame: up to 10 months after vaccination ] [ Designated as safety issue: No ]

    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 Questionnaire #2 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. 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 (diagnosed outside of main-campus CHC)
    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.]
  • Seroprotection [ Time Frame: blood draw at 10-45 days post-vaccination ] [ Designated as safety issue: No ]
    Measure hemagglutinin inhibition (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.
  • Efficacy [ Time Frame: up to 10 months after vaccination ] [ Designated as safety issue: No ]

    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 ] [ Designated as safety issue: No ]
    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
  • Safety [ Time Frame: 0-14 days after vaccination ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 Immunoglobulin G (IgG) and B-cell Immunoglobulin A (IgA).
  • End of season seroprotection [ Time Frame: at least 5 months post vaccination ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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. 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 ] [ Designated as safety issue: Yes ]
    1. Will survey subjects at day 30-45 regarding any unplanned health care visit
    2. Will have on-going passive surveillance of adverse events (AEs)/serious adverse events (SAEs) throughout course of influenza season of enrollment. Data collection will stop in September following enrollment.
  • Safety [ Time Frame: 0-14 days after vaccination ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: Yes ]
    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.
Not Provided
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
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, 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
    Other Names:
    • high-dose influenza vaccine
    • influenza vaccine
  • Biological: Fluzone
    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.
 
Recruiting
360
September 2015
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.
Both
5 Years to 35 Years
No
Contact: Donna Curtis, MD, MPH 720-777-8810 donna.curtis@childrenscolorado.org
United States
 
NCT01685372
12-0829
Yes
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
September 2014

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