Immunogenicity of Fluzone High Dose in Immunocompromised Children and Young Adults

Study Overview
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Brief Summary
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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.

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

Conditions
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Solid Organ Transplant Recipient (Liver, Kidney, Heart), Rheumatologic Disorder, Human Immunodeficiency Virus (HIV), Bone Marrow Transplant (BMT), Dialysis

Intervention / Treatment
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* Biological: Fluzone High Dose
* Biological: Fluzone


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 5 Years
Maximum Age: 35 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

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

What is the study measuring?
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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 |