Study to Evaluate the Immunogenicity and Safety of GlaxoSmithKline (GSK) Biologicals' Quadrivalent Influenza Vaccine (GSK2282512A) Compared to Fluzone® Quadrivalent in 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 assess the immunogenicity and safety of GSK Biologicals' quadrivalent influenza vaccine (GSK2282512A) compared to Sanofi Pasteur's Fluzone® Quadrivalent in children 6 to 35 months of age.

Official Title
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Immunogenicity and Safety Study of GSK Biologicals' Quadrivalent Influenza Vaccine (GSK2282512A) Compared to Fluzone® Quadrivalent 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® Quadrivalent


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 (drug or vaccine) 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 (defined as more than 14 days in total) of immunosuppressants or other immune-modifying drugs within six months prior to the first vaccine dose. For corticosteroids, this will mean a dose equivalent to either > 2 mg/kg/day of body weight, or to ≥ 20 mg/day of prednisone for persons who weigh ≥ 10 kg, when administered for more than 2 weeks. Inhaled and topical steroids are allowed. Prior receipt of any seasonal or pandemic influenza vaccine (registered or investigational) 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 (including egg proteins); 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. Fever is defined as temperature ≥ 38.0°C/100.4°F by any route. Subjects with a minor illness (such as mild diarrhoea, mild upper respiratory infection) 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 in this group received 1 dose (primed subjects) at Day 0 and 2 doses (unprimed subjects) at Days 0 and 28 of FluLaval™ Quadrivalent vaccine. The vaccine was administered intramuscularly into the anterolateral region of the thigh (subjects below 12 months of age) or in the deltoid muscle of the non-dominant arm (subjects ≥12 months of age). | Biological: FluLaval™ Quadrivalent<br>* 1 or 2 doses administered intramusculary (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: FLU Q-QIV (GSK2282512A);|
| Active Comparator: Fluzone® Quadrivalent Group<br>Subjects in this group received 1 dose (primed subjects) at Day 0 and 2 doses (unprimed subjects) at Days 0 and 28 of Fluzone® Quadrivalent vaccine. The vaccine was administered intramuscularly into the anterolateral region of the thigh (subjects below 12 months of age) or in the deltoid muscle of the non-dominant arm (subjects ≥12 months of age). | Biological: Fluzone® Quadrivalent<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>* Other names: F-QIV;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Haemagglutination Inhibition (HI) Antibody Titers Against Each of the 4 Vaccine Influenza Strains | Antibody titers were expressed as Seroconversion rate (SCR) and SCR difference. SCR was defined as the proportion of vaccinees who had either a pre-vaccination titer < 1:10 and a post-vaccination titer ≥ 1:40 or a pre-vaccination titer ≥ 1:10 and at least a four-fold increase in post-vaccination titer. The vaccine strains assessed were Flu A/California/7/2009 (H1N1), A/Texas/50/2012 (H3N2), B/Massachusetts/2/2012 (Yamagata) and B/Brisbane/60/2008 (Victoria). | 28 days after last vaccine dose (i.e. Day 28 for vaccine-primed subjects and Day 56 for vaccine-unprimed subjects) | 
| Humoral Immune Response in Terms of Haemagglutination Inhibition (HI) Antibodies by Calculating Serum Antihaemagglutination (HA) Antibody Titers Against the 4 Vaccine Strains. | HI antibody titres were expressed as geometric mean titers (GMTs) and adjusted GMT ratios. The vaccine strains assessed were Flu A/California/7/2009 (H1N1) HI, A/Texas/50/2012 (H3N2) HI, B/Massachusetts/2/2012 (Yamagata) HI and B/Brisbane/60/2008 (Victoria). | At 28 days after the last vaccine dose (i.e. Day 28 for vaccine-primed subjects and Day 56 for vaccine-unprimed subjects) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Haemagglutination Inhibition (HI) Antibody Titers Against Each of the 4 Vaccine Influenza Strains, Overall, by Age Group (6-17 and 18-35 Months of Age) and by Priming Status (Vaccine-primed and Vaccine-unprimed) | Antibody titers were expressed as Geometric mean titers (GMTs). The vaccine strains assessed were A/California/7/2009 (H1N1), A/Texas/50/2012 (H3N2), B/Massachusetts/2/2012 (Yamagata) and B/Brisbane/60/2008 (Victoria). | At Day 0 and 28 days after last vaccine dose (i.e. Day 28 for vaccine-primed subjects and Day 56 for vaccine-unprimed subjects) | 
| Number of Subjects Who Were Seroprotected for Anti-HI Antibodies Against Each of the 4 Vaccine Influenza Strains, Overall, by Age Group (6-17 and 18-35 Months of Age) and by Priming Status (Vaccine-primed and Vaccine-unprimed) | A seroprotected subject was defined as a vaccinated subject with a serum HI titer greater than or equal to (≥) 1:40. The vaccine strains assessed were Flu A/California/7/2009 (H1N1) HI, A/Texas/50/2012 (H3N2) HI, B/Massachusetts/2/2012 (Yamagata) HI and B/Brisbane/60/2008 (Victoria). | At Day 0 and 28 days after last vaccine dose (i.e. Day 28 for vaccine-primed subjects and Day 56 for vaccine-unprimed subjects) | 
| Number of Seroconverted Subjects for Anti-HA Antibodies Against Each of the 4 Vaccine Influenza Strains, Overall, by Age Group (6-17 and 18-35 Months of Age) and by Priming Status (Vaccine-primed and Vaccine-unprimed) | A seroconverted subject was defined as a vaccinated subject with either a pre-vaccination titer less than (<) 1:10 and a post-vaccination titer ≥ 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) HI, A/Texas/50/2012 (H3N2) HI, B/Massachusetts/2/2012 (Yamagata) HI and B/Brisbane/60/2008 (Victoria). | 28 days after last vaccine dose (i.e. Day 28 for vaccine-primed subjects and Day 56 for vaccine-unprimed subjects) | 
| Mean Geometric Increase (MGI) for Haemagglutination Inhibition (HI) Antibody Titer Against Each of the 4 Vaccine Influenza Strains, Overall, by Age Group (6-17 and 18-35 Months of Age) and by Priming Status (Vaccine-primed and Vaccine-unprimed) | MGI was defined as the fold increase in serum HI GMTs post-vaccination compared to pre-vaccination (Day 0). The vaccine strains assessed were Flu A/California/7/2009 (H1N1) HI, A/Texas/50/2012 (H3N2) HI, B/Massachusetts/2/2012 (Yamagata) HI and B/Brisbane/60/2008 (Victoria). | 28 days after last vaccine dose (i.e. Day 28 for vaccine-primed subjects and Day 56 for vaccine-unprimed subjects) | 
| Number of Subjects Reporting Any and Grade 3 Solicited Local Symptoms, Overall, by Age Group (6-17 and 18-35 Months of Age) and by Priming Status (Vaccine-primed and Vaccine-unprimed) | Solicited local symptoms assessed were pain, redness and swelling. Any was defined as any solicited local symptom reported irrespective of intensity and all subjects reporting 'Yes' for solicited symptom occurred but with missing values for at least one day during the solicited period. Grade 3 pain = Cried when limb is moved/spontaneously painful. Grade 3 redness and swelling was greater than 100 millimeters (mm) i.e. >100mm. | During a 7-day (Day 0 - Day 6) follow-up period after each vaccination | 
| Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms, Overall, by Age Group (6-17 and 18-35 Months of Age) and by Priming Status (Vaccine-primed and Vaccine-unprimed) | Solicited general symptoms assessed were drowsiness, irritability/fussiness, loss of appetite and fever. 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. Any fever was defined as subjects with a documented temperature of greater than or equal to (≥) 38°C/100.4°F by any route and all subjects reporting temperature less than (< )38°C but with missing values for at least one day during the solicited period. Grade 3 fever was defined as temperature greater than (>) 39.0°C. | During the 7-day (Days 0-6) follow-up period after each vaccination | 
| Duration of Solicited Local and General AEs, Overall, by Age Group (6-17 and 18-35 Months of Age) and by Priming Status (Vaccine-primed and Vaccine-unprimed) | Duration was defined as number of days with any grade of local and general symptoms. | During the 7-day (Days 0-6) follow-up period after each vaccination. | 
| Number of Subjects Reporting Any Fever Following Each Dose and Across Doses. | Any Fever = all subjects with a documented temperature of ≥38.0°C /100.4°F by axillary route and all subjects reporting temperature < 38.0°C but with missing values for at least one day during the solicited period. Grade 3 fever was defined as temperature greater than (>) 39.0°C. | During a 2-day (Days 0-1) follow-up period after each vaccination | 
| Number of Subjects Reporting the Occurrence of All Medically Attended Events (MAEs), Overall, by Age Group (6-17 and 18-35 Months of Age) and by Priming Status (Vaccine-primed and Vaccine-unprimed). | 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 (Days 0 -180) | 
| Number of Subjects Reporting the Occurrence of Any and Related Potential Immune-Mediated Disease (pIMDs), Overall, by Age Group (6-17 and 18-35 Months of Age) and by Priming Status (Vaccine-primed and Vaccine-unprimed) | pIMDs are a subset of adverse events (AEs) that include both clearly autoimmune diseases and also other inflammatory and/or neurologic disorders which may or may not have an autoimmune etiology. Related = symptom assed by the investigator as causally related to the study vaccination. | During the entire study period (Days 0 -180) | 
| Number of Subjects Reporting Any, Grade 3 and Related Unsolicited Adverse Events (AEs), Overall, by Age Group (6-17 and 18-35 Months of Age) and by Priming Status (Vaccine-primed and Vaccine-unprimed) | 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 unsolicited AE was defined as an event that prevented normal activity. Related unsolicited AE was defined as an event assessed by the investigator to be causally related to the study vaccination. | During a 28-day (Days 0-27 for primed and unprimed subjects and Days 28-56 for unprimed subjects) post-vaccination period | 
| Number of Subjects Reporting Any and Related Serious Adverse Events (SAEs), Overall, by Age Group (6-17 and 18-35 Months of Age) and by Priming Status (Vaccine-primed and Vaccine-unprimed) | SAEs assessed include medical occurrences that results in death, are life threatening, require hospitalization or prolongation of hospitalization, results in disability/incapacity or are a congenital anomaly/birth defect in the offspring of a study subjects. Related = symptom assessed by the investigator as causally related to the study vaccination. | During the entire study period (Days 0 -180) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Safety, Fluzone Quadrivalent, Comparator, Children, Seasonal influenza, Immunogenicity