Immunogenicity and Safety of GSK Biologicals' Influenza Vaccine Versus a Licensed Comparator in Children

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the immunogenicity and the safety of GlaxoSmithKline Biologicals' seasonal influenza vaccine, Fluarix, compared to Fluzone (a US-licensed vaccine) in children, 6 to 35 months of age.

Official Title
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Immunogenicity and Safety of GSK Biologicals' Thimerosal-free TIV Flu Vaccine Versus a Licensed Comparator in Children

Conditions
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Influenza

Intervention / Treatment
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* Biological: Fluarix
* Biological: Fluzone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: A male or female child aged 6 to 35 months at the time of the first vaccination; children who may or may not have had previous administration of influenza vaccine in a previous season are acceptable. Subjects having a parent/guardian who the investigator believes can and will comply with the requirements of the protocol. Written informed consent obtained from the subject's parent/guardian. Exclusion Criteria: Use of any investigational or non-registered product (drug or vaccine) within 30 days preceding the administration of the study vaccine, or planned use during the study period. Routine, registered childhood vaccinations are not an exclusion criterion. History of hypersensitivity to any vaccine. History of allergy or reactions likely to be exacerbated by any component of the vaccine. Acute disease at the time of enrolment. History of Guillain Barré syndrome within 6 weeks of receipt of prior inactivated influenza virus vaccine. Receipt of an influenza vaccine outside of this study, during current (2008-09) flu season. Administration of immunoglobulins and/or blood products within the 3 months preceding the first dose of study vaccine or planned administration during the study period.

Ages Eligible for Study
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Minimum Age: 6 Months
Maximum Age: 35 Months

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Fluarix Dose A Group<br>Subjects were administered 1 or 2 doses* of Fluarix vaccine (at Day 0 or at Days 0 and 28) intramuscularly, in the non-dominant upper arm (children >12 months of age) or in the anterolateral thigh (children <12 months of age). * Only those subjects who had no history of prior influenza vaccination (i.e. unprimed subjects) received 2 doses. | Biological: Fluarix<br>* One (Day 0) or two (Day 0 and Day 28) doses by intramuscular injection. Two different doses are tested.<br>|
| Experimental: Fluarix Dose B Group<br>Subjects were administered 1 or 2 doses*, half the volume of dose A, of Fluarix vaccine (at Day 0 or at Days 0 and 28) intramuscularly, in the non-dominant upper arm (children >12 months of age) or in the anterolateral thigh (children <12 months of age). * Only those subjects who had no history of prior influenza vaccination (i.e. unprimed subjects) received 2 doses. | Biological: Fluarix<br>* One (Day 0) or two (Day 0 and Day 28) doses by intramuscular injection. Two different doses are tested.<br>|
| Active Comparator: Fluzone Group<br>Subjects were administered 1 or 2 doses* of Fluzone vaccine (at Day 0 or at Days 0 and 28) intramuscularly, in the non-dominant upper arm (children >12 months of age) or in the anterolateral thigh (children <12 months of age). * Only those subjects who had no history of prior influenza vaccination (i.e. unprimed subjects) received 2 doses. | Biological: Fluzone<br>* One (Day 0) or two (Day 0 and Day 28) doses by intramuscular injection.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Geometric Mean Titer (GMT) of Serum Anti-hemagglutinin (HA) Antibodies Against Each of the Influenza Vaccine Strains | GMTs and their 95% confidence interval are presented for all 3 viral strains comprised in the vaccine. Post-vaccination timepoints: Day 28 for primed or Day 56 for unprimed subjects | Day 0 (PRE), Day 28 or Day 56 (POST) | 
| Number of Subjects Who Seroconverted | Seroconversion is defined as the number of subjects with either a pre-vaccination anti-HA titer < 1:10 and a post-vaccination titer ≥ 1:40, or a pre-vaccination titer ≥ 1:10 and a minimum 4-fold increase at post-vaccination titer. Post-vaccination timepoints: Day 28 for primed or Day 56 for unprimed subjects | Day 28 or Day 56 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Seroprotected Subjects | A seroprotected subject is a subject with a serum anti-HA titer ≥ 1:40 Post-vaccination timepoints: Day 28 for primed or Day 56 for unprimed subjects | Day 0 (PRE), Day 28 or Day 56 (POST) | 
| Seroconversion Factor | Seroconversion factor is defined as the fold increase in serum anti-HA GMTs post-vaccination (Day 28 or 56) compared to pre-vaccination (Day 0). Post-vaccination timepoints: Day 28 for primed or Day 56 for unprimed subjects | Day 28 or Day 56 | 
| Number of Subjects Reporting Solicited Local Symptoms | Solicited local symptoms assessed include pain, redness and swelling. | During a 4-day follow-up period after vaccination | 
| Number of Subjects Reporting Solicited General Symptoms | Solicited general symptoms assessed include drowsiness, irritability, loss of appetitie, and temperature. | During a 4-day follow-up period after vaccination | 
| Number of Subjects Reporting Unsolicited Adverse Events (AE) | An AE is any untoward medical occurrence in a clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product | During a 28-day follow-up period after vaccination | 
| Number of Subjects Reporting Serious Adverse Events (SAE) and New Onset of Chronic Diseases (NOCD) | An SAE is any untoward medical occurrence that: results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect in the offspring of a study subject, or may evolve into one of the outcomes listed above. NOCDs assessed include for example: diabetes, asthma, allergies, autoimmune disease, cancer, neuropathic disorders | During the entire study (Day 0 until Month 6) | 
| Number of Subjects Reporting Rare Serious Events | Rare serious events have an occurrence rate of 1/300 (0.3%). | During the entire study (Day 0 until Month 6) |