Study to Evaluate Immunogenicity and Safety of GlaxoSmithKline (GSK) Biologicals' Quadrivalent Influenza Vaccine GSK2282512A When Administered to Children From 6 to 35 Months of Age

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the immunogenicity and safety of the new influenza vaccine GSK2282512A (FLU Q-QIV) and compare its activity to Sanofi Pasteur's Fluzone® (TIV) in children 6 to 35 months of age.

Detailed Description
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The subjects will be randomised (1:1) in the two treatment groups (Q-QIV and TIV-YB) to explore response to vaccination.

Official Title
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Immunogenicity and Safety Study of GSK Biologicals' Quadrivalent Influenza Vaccine (GSK2282512A) in Children 6 to 35 Months of Age

Conditions
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Influenza

Intervention / Treatment
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* Biological: FluLaval® Quadrivalent
* Biological: Fluzone®


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects' parent(s)/Legally Acceptable Representative(s) [LAR(s)] who, in the opinion of the investigator, can and will comply, with the requirements of the protocol. A male or female between, and including, 6 and 35 months of age at the time of the first vaccination. Written informed consent obtained from the parent(s)/LAR(s) of the subject. Subjects in stable health as determined by investigator's clinical examination and assessment of subject's medical history. Subjects are eligible regardless of history of administration of influenza vaccine in a previous season. Exclusion Criteria: Use of any investigational or non-registered product other than the study vaccine within 30 days preceding the first dose of study vaccine, or planned use during the study period. Routine registered childhood vaccinations are permitted. Child in care. Chronic administration of immunosuppressants or other immune-modifying drugs within six months prior to the first vaccine dose. For corticosteroids, this will mean prednisone ≥ 0.5 mg/kg/day, or equivalent. Inhaled and topical steroids are allowed. Prior receipt of any seasonal or pandemic influenza vaccine within six months preceding the first dose of study vaccine, or planned use during the study period. Administration of immunoglobulins and/or any blood products within the three months preceding the first dose of study vaccine or planned administration during the study period. History of Guillain-Barré syndrome within six weeks of receipt of prior influenza vaccine. Any known or suspected allergy to any constituent of influenza vaccines; a history of anaphylactic-type reaction to consumption of eggs; or a history of severe adverse reaction to a previous influenza vaccine. Acute disease and/or fever at the time of enrollment. Fever is defined as temperature ≥ 38.0°C/100.4°F by any method. Subjects with a minor illness without fever may be enrolled at the discretion of the investigator. Any significant disorder of coagulation or treatment with warfarin derivatives or heparin. Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination. Any other condition which, in the opinion of the investigator, prevents the subject from participating in the study.

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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: FluLaval Quadrivalent Group<br>Subjects received 1 or 2 doses of FluLaval® Quadrivalent vaccine at Day 0 or Days 0 and 28, depending on age and vaccine priming status. | Biological: FluLaval® Quadrivalent<br>* 1 or 2 doses administered intramuscularly (IM) in deltoid region of non-dominant arm (for subjects ≥12 months of age) or anterolateral region of left thigh (for subjects <12 months of age) on Day 0 (primed subjects) and on Day 0 and Day 28 (unprimed subjects), respectively.<br>* Other names: GSK2282512A;|
| Active Comparator: Fluzone Group<br>Subjects received 1 or 2 doses of Fluzone® vaccine at Day 0 or Days 0 and 28, depending on age and priming status. | Biological: Fluzone®<br>* 1 or 2 doses administered IM in deltoid region of non-dominant arm (for subjects ≥12 months of age) or anterolateral region of left thigh (for subjects <12 months of age) on Day 0 (primed subjects) and on Day 0 and Day 28 (unprimed subjects), respectively.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Seroconverted Subjects for Haemagglutination Inhibition (HI) Antibodies Against Each of the Four Vaccine Influenza Strains of FluLaval® Quadrivalent Vaccine. | A seroconverted subject was defined as a vaccinated subject with either a pre-vaccination titer less than (<) 1:10 and a post-vaccination titer greater than or equal to (≥) 1:40, or a pre-vaccination titer ≥ 1:10 and at least a 4-fold increase in post-vaccination titer. The vaccine strains assessed were Flu A/California/7/2009 (H1N1), Flu A/Texas/50/2012 (H3N2), Flu B/Massachusetts/2/2012 (Yamagata), Flu B/Brisbane/60/2008 (Victoria). This outcome concerns solely subjects in the FluLaval Quadrivalent Group. Vaccine primed subjects are subjects who had received a total of 2 or more doses of seasonal influenza vaccine since 01 July 2010. Vaccine unprimed subjects are subjects who had never received any seasonal influenza vaccine or had received only one dose of seasonal influenza vaccine since 01 July 2010. | 28 days after the last vaccine dose (at Day 28 for primed subjects and at Day 56 for unprimed subjects) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Seroconverted Subjects for HI Antibodies Against Each of the Four Vaccine Influenza Strains. | A seroconverted subject was defined as a vaccinated subject with either a pre-vaccination titer less than (<) 1:10 and a post-vaccination titer greater than or equal to (≥) 1:40, or a pre-vaccination titer ≥ 1:10 and at least a 4-fold increase in post-vaccination titer. The vaccine strains assessed were Flu A/California/7/2009 (H1N1), Flu A/Texas/50/2012 (H3N2), Flu B/Massachusetts/2/2012 (Yamagata), Flu B/Brisbane/60/2008 (Victoria). This outcome concerns solely subjects in the Fluzone Group. Vaccine primed subjects are subjects who had received a total of 2 or more doses of seasonal influenza vaccine since 01 July 2010. Vaccine unprimed subjects are subjects who had never received any seasonal influenza vaccine or had received only one dose of seasonal influenza vaccine since 01 July 2010. | 28 days after the last vaccine dose (at Day 28 for primed subjects and at Day 56 for unprimed subjects) | 
| Haemagglutination Inhibition (HI) Antibody Titers Against Each of the Four Vaccine Influenza Strains | HI antibody titres were expressed as Geometric mean titers (GMTs). The vaccine strains assessed were Flu A/California/7/2009 (H1N1), Flu A/Texas/50/2012 (H3N2), Flu B/Massachusetts/2/2012 (Yamagata), Flu B/Brisbane/60/2008 (Victoria). Vaccine primed subjects are subjects who had received a total of 2 or more doses of seasonal influenza vaccine since 01 July 2010. Vaccine unprimed subjects are subjects who had never received any seasonal influenza vaccine or had received only one dose of seasonal influenza vaccine since 01 July 2010. | On Day 0 and 28 days after the last vaccine (Day 28 and Day 56 for primed and unprimed subjects respectively) | 
| Number of Subjects Who Were Seroprotected for HI Antibodies Against Each of the Four Vaccine Influenza Strains. | A seroprotected subject was defined as a vaccinated subject with a serum HI titer greater than or equal to (≥) 1:40 that usually is accepted as indicating protection in adults. The vaccine strains assessed were Flu A/California/7/2009 (H1N1), Flu A/Texas/50/2012 (H3N2), Flu B/Massachusetts/2/2012 (Yamagata), Flu B/Brisbane/60/2008 (Victoria). Vaccine primed subjects are subjects who had received a total of 2 or more doses of seasonal influenza vaccine since 01 July 2010. Vaccine unprimed subjects are subjects who had never received any seasonal influenza vaccine or had received only one dose of seasonal influenza vaccine since 01 July 2010. | At Day 0 (for all subjects) and Day 28 after last vaccine dose (Day 28 for primed subjects and Day 56 for unprimed subjects) | 
| Mean Geometric Increase (MGI) for HI Antibody Titer Against Each of the Four Vaccine Influenza Strains. | MGI was defined as the fold increase in serum haemagglutination inhibition (HI) GMTs post-vaccination compared to pre-vaccination (Day 0). The vaccine strains assessed were Flu A/California/7/2009 (H1N1), Flu A/Texas/50/2012 (H3N2), Flu B/Massachusetts/2/2012 (Yamagata), Flu B/Brisbane/60/2008 (Victoria). Vaccine primed subjects are subjects who had received a total of 2 or more doses of seasonal influenza vaccine since 01 July 2010. Vaccine unprimed subjects are subjects who had never received any seasonal influenza vaccine or had received only one dose of seasonal influenza vaccine since 01 July 2010. | 28 days after the last vaccine dose (at Day 28 for primed subjects and at Day 56 for unprimed subjects) | 
| Number of Subjects Reporting Any and Grade 3 Solicited Local Symptoms. | Solicited local symptoms assessed were pain, redness and swelling. Any was defined as occurrence of the specified solicited local symptom regardless of its intensity. Grade 3 pain was defined as pain that made the subject cry when limb was moved/spontaneously painful. Grade 3 swelling was greater than 100 millimeters (mm) i.e. >100mm. Vaccine primed subjects are subjects who had received a total of 2 or more doses of seasonal influenza vaccine since 01 July 2010. Vaccine unprimed subjects are subjects who had never received any seasonal influenza vaccine or had received only one dose of seasonal influenza vaccine since 01 July 2010. | During a 7-day follow-up period (i.e. day of vaccination and six subsequent days) after each vaccination | 
| Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms. | Solicited general symptoms assessed were drowsiness, irritability/fussiness and loss of appetite. Any was defined as any solicited general symptom reported irrespective of intensity and relationship to vaccination. Related was defined as symptoms assessed by the investigator to have a causal relationship to vaccination. Grade 3 irritability/fussiness was defined as crying that could not be comforted/prevented normal activity. Grade 3 loss of appetite was defined as not eating at all. Grade 3 drowsiness was defined as drowsiness that prevented normal activity.Grade 3 fever was defined as axillary temperature above 39.0°C. Vaccine primed subjects are subjects who had received a total of 2 or more doses of seasonal influenza vaccine since 01 July 2010. Vaccine unprimed subjects are subjects who had never received any seasonal influenza vaccine or had received only one dose of seasonal influenza vaccine since 01 July 2010. | During a 7-day follow-up period (i.e. day of vaccination and six subsequent days) after each vaccination | 
| Number of Subjects Reporting Any, Grade 3 and Related Fever | Any fever was defined as any fever ≥38.0 degrees Celsius (°C) irrespective of intensity and relationship to vaccination. Related was defined as symptoms assessed by the investigator to have a causal relationship to vaccination. Grade 3 fever was defined as fever ≥39.0 °C. Vaccine primed subjects are subjects who had received a total of 2 or more doses of seasonal influenza vaccine since 01 July 2010. Vaccine unprimed subjects are subjects who had never received any seasonal influenza vaccine or had received only one dose of seasonal influenza vaccine since 01 July 2010. | During a 4-day follow-up period (i.e. day of vaccination and 3 subsequent days) after each vaccination | 
| Duration of Solicited Local and General Symptoms | Duration was defined as number of days with any grade of local and general symptoms. Vaccine primed subjects are subjects who had received a total of 2 or more doses of seasonal influenza vaccine since 01 July 2010. Vaccine unprimed subjects are subjects who had never received any seasonal influenza vaccine or had received only one dose of seasonal influenza vaccine since 01 July 2010. | During a 7-day follow-up period (i.e. day of vaccination and six subsequent days) after each vaccination | 
| Number of Subjects Reporting Any Medically Attended Adverse Events (MAEs) | MAEs were defined as adverse events with medically-attended visits that were not routine visits for physical examination or vaccination, such as visits for hospitalization, an emergency room visit, or an otherwise unscheduled visit to or from medical personnel (medical doctor) for any reason. Any was defined as any occurrence of MAE(s). Related was defined as a MAE assessed by the investigator to be causally related to the study vaccination. Vaccine primed subjects are subjects who had received a total of 2 or more doses of seasonal influenza vaccine since 01 July 2010. Vaccine unprimed subjects are subjects who had never received any seasonal influenza vaccine or had received only one dose of seasonal influenza vaccine since 01 July 2010. | During the entire study period (Day 0 to Day 180) | 
| Number of Subjects Reporting Any Potential Immune-Mediated Diseases (pIMDs) | pIMDs were defined as a subset of adverse events that included both clearly autoimmune diseases and also other inflammatory and/or neurologic disorders which might or might not have an autoimmune aetiology. Any pIMD was defined as at least one pIMD experienced by the study subject. Related pIMD was defined as a pIMD assessed by the investigator to be causally related to the study vaccination. Vaccine primed subjects are subjects who had received a total of 2 or more doses of seasonal influenza vaccine since 01 July 2010. Vaccine unprimed subjects are subjects who had never received any seasonal influenza vaccine or had received only one dose of seasonal influenza vaccine since 01 July 2010. | During the entire study period (Day 0 to Day 180) | 
| Number of Subjects Reporting Any, Grade 3 and Related Unsolicited Adverse Events (AEs). | An unsolicited AE was defined as an untoward medical occurrence in a patient or clinical investigation subject, temporally associated with use of a medicinal product, whether or not considered related to the medicinal product and reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for solicited symptoms. Any was defined as occurrence of any unsolicited symptom regardless of intensity grade or relation to vaccination. Grade 3 was an event that prevented normal activities and related was defined as an unsolicited AE assessed by the investigator to be causally related to the study vaccination Vaccine primed subjects are subjects who had received a total of 2 or more doses of seasonal influenza vaccine since 01 July 2010. Vaccine unprimed subjects are subjects who had never received any seasonal influenza vaccine or had received only one dose of seasonal influenza vaccine since 01 July 2010 | During a 28-day follow-up period (i.e. day of vaccination and 27 subsequent days) after each vaccination | 
| Number of Subjects Reporting Any and Related Serious Adverse Events (SAEs) | A serious adverse event was defined as any untoward medical occurrence that: resulted in death, was life threatening, required hospitalization or prolongation of hospitalization, resulted in disability/incapacity or was a congenital anomaly/birth defect in the offspring of a study subject. Any was defined as occurrence of any symptom regardless of intensity grade or relation to vaccination and related was an event assessed by the investigator as causally related to the study vaccination. Vaccine primed subjects are subjects who had received a total of 2 or more doses of seasonal influenza vaccine since 01 July 2010. Vaccine unprimed subjects are subjects who had never received any seasonal influenza vaccine or had received only one dose of seasonal influenza vaccine since 01 July 2010. | During the entire study period (Day 0 - Day 180) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Children, Immunogenicity, Fluzone®, 6 to 35 months of age, Seasonal influenza, Safety