Study to Evaluate Immunogenicity and Safety of GlaxoSmithKline (GSK) Biologicals' Quadrivalent Influenza Vaccine GSK2282512A When Administered to Children 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 investigate the immunogenicity, reactogenicity and safety of the new influenza vaccine GSK2282512A (FLU-Q-QIV) and compare its activity to the marketed vaccine Fluarix® (TIV) in young children 6 to 35 months of age.

Detailed Description
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The subjects will be randomized (1:1) in the 2 treatment groups to explore responses to vaccination in a sub-group analysis based on age (6 to 17 months, 18 to 35 months).

Official Title
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Immunogenicity and Safety Study of GSK Biologicals' Quadrivalent Influenza Vaccine (GSK2282512A) When Administered in Children

Conditions
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Influenza

Intervention / Treatment
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* Biological: Quadrivalent influenza GSK2282512A vaccine
* Biological: Fluarix


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject's 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 the 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. 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. Chronic administration of immunosuppressants or other immune-modifying drugs within six months prior to the first vaccine dosed. 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 enrolment. 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: GSK2282512A Group<br>Subjects aged between 6 to 35 months inclusive received 1 dose (primed subjects) at Day 0 and 2 doses (unprimed subjects) at Days 0 and 28 of quadrivalent influenza GSK2282512A vaccine. Quadrivalent influenza GSK2282512A vaccine was administered intramuscularly in the left anterolateral thigh (subjects < 12 months of age) or the deltoid muscle (subjects ≥ 12 months of age). | Biological: Quadrivalent influenza GSK2282512A vaccine<br>* 1 or 2 doses administered intramuscularly (IM) in deltoid muscle or anterolateral thigh on Day 0 (primed subjects) and on Day 0 and Day 28 (unprimed subjects) respectively.<br>|
| Active Comparator: Fluarix Group<br>Subjects aged between 6 to 35 months inclusive received 1 dose (primed subjects) at Day 0 and 2 doses (unprimed subjects) at Days 0 and 28 of Fluarix vaccine. Fluarix vaccine was administered intramuscularly in the left anterolateral thigh (subjects < 12 months of age) or the deltoid muscle (subjects ≥ 12 months of age). | Biological: Fluarix<br>* 1 or 2 doses administered IM in deltoid muscle or anterolateral thigh, 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 Anti- Haemagglutination Inhibition (HI) Antibodies Against Each of the Four Vaccine Influenza Strains of Quadrivalent Influenza GSK2282512A 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/CAL/7/09 (H1N1), Flu A/Victoria/361/11 (H3N2), Flu B/Hubei-Wujiagang/158/09 (Yamagata) and Flu B/Bri/60/08 (Victoria). This outcome concerns solely subjects in the GSK2282512A Group. | 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 prevented normal everyday activities. Grade 3 swelling was greater than 100 millimeters (mm) i.e. >100mm. | During the 7-day (Days 0-6) post-vaccination period | 
| Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms (Excluding Fever). | 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. | During the 7-day (Days 0-6) post-vaccination period | 
| 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. | During the 7-day (Days 0-6) post-vaccination period | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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/CAL/7/09 (H1N1), Flu A/Victoria/361/11 (H3N2), Flu B/Hubei-Wujiagang/158/09 (Yamagata) and Flu B/Bri/60/08 (Victoria) | At Day 0 (for all subjects) and 28 days after the last vaccine dose (at Day 28 for primed subjects and at Day 56 for unprimed subjects) | 
| Number of Seroconverted Subjects for Anti- Haemagglutination Inhibition (HI) Antibodies Against Each of the Four Vaccine Influenza Strains of Fluarix 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/CAL/7/09 (H1N1), Flu A/Victoria/361/11 (H3N2), Flu B/Hubei-Wujiagang/158/09 (Yamagata) and Flu B/Bri/60/08 (Victoria). This outcome concerns solely subjects in the Fluarix Group. | At Day 28 for primed subjects and at Day 56 for unprimed subjects | 
| Number of Subjects Who Were Seroprotected for Haemagglutination Inhibition (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/CAL/7/09 (H1N1), Flu A/Victoria/361/11 (H3N2), Flu B/Hubei-Wujiagang/158/09 (Yamagata) and Flu B/Bri/60/08 (Victoria) | 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 Haemagglutination Inhibition (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/CAL/7/09 (H1N1), Flu A/Victoria/361/11 (H3N2), Flu B/Hubei-Wujiagang/158/09 (Yamagata) and Flu B/Bri/60/08 (Victoria) | 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, Grade 3 and Related Fever | Any fever was defined as any fever ≥38.0 °C irrespective of intensity and relationship to vaccination. Related was defined as symptoms considered by the investigator to have a causal relationship to vaccination. Grade 3 fever was defined as fever ≥39.0 °C. | During the 4-day (Days 0-3) post-vaccination period | 
| 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). | During the entire study period (Day 0 to Day 180) | 
| Number of Subjects Reporting Any Potential Immune-Mediated Diseases (pIMDs) | Potential immune-mediated diseases (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. | 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. | During the 28-day (Days 0-27) post-vaccination period. | 
| 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. | 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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Immunogenicity, Children, Safety, Seasonal influenza, Fluarix