Immunogenicity of Fluzone High Dose in Immunocompromised Children and Young Adults - Full Text View

Purpose

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.

Condition	Intervention	Phase
Rheumatologic Disorder Human Immunodeficiency Virus (HIV) Bone Marrow Transplant(BMT) Hemodialysis	Biological: Fluzone High Dose Biological: Fluzone	Phase 2

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator) Primary Purpose: Prevention
Official Title:	Immunogenicity and Efficacy of High-dose Trivalent Inactivated Seasonal Influenza Vaccine(Fluzone High Dose) in Immunocompromised Children and Young Adults.

Resource links provided by NLM:

Genetics Home Reference related topics: complement factor I deficiency

MedlinePlus related topics: Flu HIV/AIDS

Drug Information available for: Influenza Vaccines

U.S. FDA Resources

Further study details as provided by University of Colorado, Denver:

Primary Outcome Measures:

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. 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 questionnaires #2 and #3). [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.

Secondary Outcome Measures:

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 adverse events (AEs)/serious adverse events (SAEs) throughout course of influenza season of enrollment. Data collection will stop in September following enrollment.

Estimated Enrollment:	420
Study Start Date:	September 2012
Estimated Study Completion Date:	September 2014
Estimated Primary Completion Date:	September 2014 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Fluzone High Dose Fluzone High Dose 0.5mL intramuscularly (IM) given once	Biological: Fluzone High Dose Other Names: high-dose influenza vaccine influenza vaccine
Active Comparator: Fluzone Fluzone 0.5mL IM given once	Biological: Fluzone Other Name: influenza vaccine

Eligibility

Ages Eligible for Study:	5 Years to 35 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01685372

Locations

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

Sponsors and Collaborators

University of Colorado, Denver

Colorado Clinical & Translational Sciences Institute

Investigators

Principal Investigator:

Donna Curtis, MD, MPH

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

More Information

No publications provided

Responsible Party:	University of Colorado, Denver
ClinicalTrials.gov Identifier:	NCT01685372 History of Changes
Other Study ID Numbers:	12-0829
Study First Received:	August 27, 2012
Last Updated:	March 14, 2013
Health Authority:	United States: Food and Drug Administration United States: Data and Safety Monitoring Board United States: Institutional Review Board

Additional relevant MeSH terms:

Acquired Immunodeficiency Syndrome
HIV Infections
Collagen Diseases
Immunologic Deficiency Syndromes
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections

Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Slow Virus Diseases
Immune System Diseases
Connective Tissue Diseases

ClinicalTrials.gov processed this record on May 22, 2013