Study Comparing the Immune Response and Safety of Fluarix and Fluzone Influenza Vaccines in Children

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to compare two influenza vaccines (Fluzone and Fluarix) in terms of the immune response elicited and safety with a six month follow-up after first vaccination. The Protocol Posting has been updated in order to comply with the FDA Amendment Act, Sep 2007.

Official Title
-----------------
A Phase III, Single-blind, Randomized Study to Evaluate the Immunogenicity and Safety of Fluarix® (GSK Biologicals') Compared With Fluzone® (Aventis Pasteur/Sanofi) Administered Intramuscularly in Children (6 Months and Older)

Conditions
-----------------
Influenza

Intervention / Treatment
-----------------
* Biological: Fluarix™
* Biological: Fluzone


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: A male or female child age 6 months to < 18 years at the time of the 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 should be enrolled in the study. Written informed consent obtained from the subject's parent/guardian; assent obtained in subjects > 10 years. Female subjects of childbearing potential must agree to take a pregnancy test. Exclusion Criteria: Use of any investigational or non-registered product (drug or vaccine, other than the study 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. 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 enrollment. History of Guillain Barré syndrome within 6 weeks of receipt of prior inactivated influenza virus vaccine. Pregnant or lactating female. Receipt of an influenza vaccine outside of this study, during current (2006-07) flu season.

Ages Eligible for Study
-----------------
Minimum Age: 6 Months
Maximum Age: 17 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Fluarix Group<br>Subjects in this group received Fluarix™ and will be further stratified by 3 age groups 1:1 in 6 months to < 36 months 1:1 in 3 to < 5 years 3:1 in 5 to < 18 years | Biological: Fluarix™<br>* Subjects were administered 1 or 2 doses* intramuscularly, into the non-dominant upper arm for children > 12 months of age, in the anterolateral thigh for children < 12 months. *Only those subjects between the age of 6 months and < 9 years, who had no history of prior influenza vaccination, received 2 doses at months 0 & 1.<br>|
| Active Comparator: Fluzone Group<br>Subjects in this group received Fluzone and will be further stratified by 3 age groups 1:1 in 6 months to < 36 months 1:1 in 3 to < 5 years 3:1 in 5 to < 18 years | Biological: Fluzone<br>* Subjects were administered 1 or 2 doses* intramuscularly, into the non-dominant upper arm for children > 12 months of age, in the anterolateral thigh for children < 12 months. *Only those subjects between the age of 6 months and < 9 years, who had no history of prior influenza vaccination, received 2 doses at months 0 & 1.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Geometric Mean Titer (GMT) of Serum Haemagglutination-inhibition (HI) Antibodies | GMTs and their 95% confidence interval are presented for all 3 viral strains comprised in the vaccine. | 21 or 28 days after last vaccine dose | 
| Number of Seroconverted Subjects | Seroconverted subjects are defined as subjects with either a pre-vaccination HI 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. Data are presented for all 3 viral strains comprised in the vaccine. | 21 or 28 days after last vaccine dose | 
| Number of Subjects Reporting Rare Serious Events | Rare serious event is defined as any untoward medical event with an occurrence rate of ≥1/300 that: resulted in death, was life-threatening, required hospitalization or prolongation of existing hospitalization, resulted in disability/incapacity, or was a congenital anomaly/birth defect in the offspring of a study subject. | Up to 6 months after vaccination | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Seroprotected Subjects | Seroprotected subjects are defined as vaccinees with a serum HI titer ≥ 1:40. Data are presented for all 3 viral strains comprised in the vaccine. | Before (PRE) and 21 or 28 days after (POST) the last vaccine dose | 
| Number of Initially Unprotected Subjects With at Least a 4 Fold Increase in HI Titer | Initially unprotected subjects are subjects with a baseline HI titer < 1:40. Data are presented for all 3 viral strains comprised in the vaccine. | 21 or 28 days after last vaccine dose | 
| Number of Subjects Reporting Solicited Local and General Symptoms | Solicited local symptoms assessed include pain, redness, and swelling. Solicited general symptoms assessed include drowsiness, fever, irritability, loss of appetite, arthralgia, fatigue, headache, muscle aches, and shivering. Data across doses are presented. Any = at least one symptom irrespective of intensity/relationship to vaccination; Grade 3: symptom that prevented normal everyday activities; Related: considered by the investigator as related to the study vaccination. | During a 4-day follow-up period after each vaccination | 
| Number of Subjects Reporting Unsolicited Adverse Events | An Adverse Event 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. Any = at least one symptom irrespective of intensity and relationship to vaccination; Grade 3 = preventing normal activity; Related = considered by the investigator to be causally related to the study vaccination. | Within 28 days following vaccination | 
| Number of Subjects Reporting New Onset Chronic Illnesses and/or Serious Adverse Events (SAE) | SAE: any untoward medical occurrence that resulted in death, was life-threatening, required hospitalization or prolongation of existing hospitalization, resulted in disability/incapacity, or was a congenital anomaly/birth defect in the offspring of a study subject. Examples of possible new onset chronic illnesses include but are not limited to diabetes, asthma, allergies, autoimmune disease, cancer, neuropathic disorders. | Up to 6 months after vaccination | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Fluarix, Influenza