Study to Assess the Immunogenicity and Safety of an Investigational Influenza Vaccine in Children

Study Overview
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Brief Summary
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The objective of this study is to evaluate the immunogenicity and safety of GSK Biologicals' investigational vaccine GSK1557482A.

Official Title
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Immunogenicity & Safety Study of GSK Biologicals' Thimerosal-free Trivalent Influenza Vaccine (TIV) Versus a Licensed Comparator in Children

Conditions
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Influenza

Intervention / Treatment
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* Biological: GSK investigational vaccine GSK1557482A
* Biological: Fluzone®


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects and/or subject parent(s)/Legally Acceptable Representative(s) (LAR) who the investigator believes can and will comply with the requirements of the protocol. A male or female child aged between 3 years and 17 years of age 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. Written informed consent obtained from the subject/from the parent(s)/LAR(s) of the subject. Healthy subjects as established by medical history and history-directed clinical examination before entering into the study. Female subjects of non-childbearing potential may be enrolled in the study. Female subjects of childbearing potential may be enrolled in the study, if the subject: has practiced adequate contraception for 30 days prior to vaccination, and has a negative pregnancy test on the day of vaccination, and has agreed to continue adequate contraception during the entire treatment period and for 2 months after completion of the vaccination series. Exclusion Criteria: Use of any investigational or non-registered product other than the study vaccines within 30 days preceding the administration of the study vaccine, or planned use during the study period. Routine, registered childhood vaccinations or registered and recommended pandemic influenza vaccine are not an exclusion. Receipt of a seasonal influenza vaccine outside of this study, during current (2009-2010) flu season. Child in care Receipt of systemic glucocorticoids within 1 month prior to study enrollment, or any other cytotoxic or immunosuppressive drug within 6 months of study enrollment. Topical, intra-articular or inhaled glucocorticoids are allowed. Concurrently participating in another clinical study, at any time during the study period, in which the subject has been or will be exposed to an investigational or a non-investigational product. History of hypersensitivity to any vaccine. History of Guillain-Barré-syndrome within 6 weeks of receipt of prior inactivated influenza virus vaccine. History of any reaction or hypersensitivity likely to be exacerbated by any component of the vaccine(s). Acute disease and/or fever at the time of enrolment. Administration of immunoglobulins and/or any blood products within the 3 months preceding the first dose of study vaccine or planned administration during the study period. Pregnant or lactating female. History of chronic alcohol consumption and/or drug abuse. Female planning to become pregnant or planning to discontinue contraceptive precautions. Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination.

Ages Eligible for Study
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Minimum Age: 3 Years
Maximum Age: 17 Years

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: Flulaval Group<br>subjects received Flulaval™ vaccine according to their priming status and age: 3-8 years: primed subjects 1 dose at Day 0; unprimed subjects 1 dose at Day 0 and a second dose at Day 28 9-17 years: 1 dose at Day 0 Flulaval vaccine was administered intramuscularly into the non-dominant deltoid. | Biological: GSK investigational vaccine GSK1557482A<br>* One intramuscular injection for primed subjects, two intramuscular injections for unprimed subjects<br>|
| Active Comparator: Fluzone Group<br>subjects received Fluzone® Sanofi Pasteur's vaccine according to their priming status and age: 3-8 years: primed subjects 1 dose at Day 0; unprimed subjects 1 dose at Day 0 and a second dose at Day 28 9-17 years: 1 dose at Day 0 Fluzone vaccine was administered intramuscularly into the non-dominant deltoid. | Biological: Fluzone®<br>* One intramuscular injection for primed subjects, two intramuscular injections for unprimed subjects<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Geometric Mean of Haemagglutination Inhibiting (HI) Antibodies Titers Against the Three Strains. | The three strains assessed were A/Brisbane/59/2007 (H1N1), A/Uruguay/716/2007 (H3N2) and B/Brisbane/60/2008. Titers were expressed as geometric mean antibody titers (GMTs). | At Day 0 and 28 after last vaccine dose. | 
| Number of Seroconverted Subjects for HI Antibodies Against the Three Strains. | The three strains assessed were A/Brisbane/59/2007 (H1N1), A/Uruguay/716/2007 (H3N2) and B/Brisbane/60/2008. Seroconversion was defined as the percentage of vaccinees that had either a pre-vaccination (Day 0) 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. | At Day 28 after last vaccine dose. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Geometric Mean of Haemagglutination Inhibiting (HI) Antibodies Titers Against the Three Strains, by Age-strata. | The three strains assessed were A/Brisbane/59/2007 (H1N1), A/Uruguay/716/2007 (H3N2) and B/Brisbane/60/2008. Titers were expressed as geometric mean antibody titers (GMTs). Subjects in each group were also stratified in the following age-strata: 3-4 years, 5-8 years and 9-17 years. | At Day 0 and 28 after last vaccine dose. | 
| Number of Seroconverted Subjects for HI Antibodies Titers Against the Three Strains, by Age-strata. | The three strains assessed were A/Brisbane/59/2007 (H1N1), A/Uruguay/716/2007 (H3N2) and B/Brisbane/60/2008. Seroconversion was defined as the percentage of vaccinees that had either a pre-vaccination (Day 0) 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. Subjects in each group were also stratified in the following age-strata: 3-4 years, 5-8 years and 9-17 years. | At Day 28 after last vaccine dose. | 
| Number of Seroprotected Subjects for HI Antibodies Titers Against the Three Strains. | The three strains assessed were A/Brisbane/59/2007 (H1N1), A/Uruguay/716/2007 (H3N2) and B/Brisbane/60/2008. Seroprotection rate (SPR) was defined as the percentage of vaccinees with a serum HI titer ≥ 1:40 that represents a putative protective level in adults. | At Day 0 and 28 after last vaccine dose. | 
| Number of Seroprotected Subjects for HI Antibodies Titers Against the Three Strains, by Age-strata. | The three strains assessed were A/Brisbane/59/2007 (H1N1), A/Uruguay/716/2007 (H3N2) and B/Brisbane/60/2008. Seroprotection rate (SPR) was defined as the percentage of vaccinees with a serum HI titer ≥ 1:40 that represents a putative protective level in adults. Subjects in each group were also stratified in the following age-strata: 3-4 years, 5-8 years and 9-17 years. | At Day 0 and 28 after last vaccine dose. | 
| Seroconversion Factor (SCF) for HI Antibodies Titers Against the Three Strains. | The three strains assessed were A/Brisbane/59/2007 (H1N1), A/Uruguay/716/2007 (H3N2) and B/Brisbane/60/2008. Seroconversion factor (SCF) was defined as the fold increase in serum HI GMTs post-vaccination compared to pre-vaccination. Seroconversion factor (SCF) was defined as the geometric mean of the within subjects ratios of the post-vaccination reciprocal HI titer to the Day 0 reciprocal HI titer. SCFs were calculated at Day 28 following the complete vaccination regimen. | At Day 0 and at Day 28 after last vaccine dose | 
| Seroconversion Factor (SCF) for HI Antibodies Titers Against the Three Strains, by Age-strata. | The three strains assessed were A/Brisbane/59/2007 (H1N1), A/Uruguay/716/2007 (H3N2) and B/Brisbane/60/2008. Seroconversion factor (SCF) was defined as the fold increase in serum HI GMTs post-vaccination compared to pre-vaccination. Seroconversion factor (SCF) was defined as the geometric mean of the within subjects ratios of the post-vaccination reciprocal HI titer to the Day 0 reciprocal HI titer. SCFs were calculated at Day 28 following the complete vaccination regimen. Subjects in each group were also stratified in the following age-strata: 3-4 years, 5-8 years and 9-17 years. | At Day 0 and at Day 28 after last vaccine dose | 
| Number of Subjects Below 5 Years of Age With Any, Severe (Grade 3) and Related to Vaccination Solicited General Adverse Events (AEs). | The general symptoms solicited from study subjects younger than 5 years of age were drowsiness, irritability, loss of appetite, and fever(= axillary temperature equal to or above 38.0 degrees Celsius (°C)). Any = occurrence of any solicited general symptom regardless of intensity grade or relationship to vaccination. Grade 3 drowsiness, irritability = symptom that prevented normal activity. Grade 3 loss of appetite = not eating at all. Grade 3 temperature = axillary temperature ≥ 39.0°C and ≤ 40.0°C. Related = symptom assessed by the investigator as causally related to the vaccination. | During a 4-day follow-up period (Days 0-3) after vaccination. | 
| Number of Subjects of 5 Years of Age and Above Reporting Any, Severe (Grade 3) and Related to Vaccination Solicited General Adverse Events (AEs). | The general symptoms solicited from study subjects 5 years of age and older were arthralgia (joint pain), fatigue, headache, muscle aches, shivering, and fever(= axillary temperature equal to or above 38.0 degrees Celsius (°C)). Any = occurrence of any solicited general symptom regardless of intensity grade or relationship to vaccination. Grade 3 symptoms = symptoms that prevented normal activity. Grade 3 temperature = axillary temperature ≥ 39.0°C and ≤ 40.0°C. Related = symptom assessed by the investigator as causaly related to the vaccination. | During a 4-day follow-up period (Days 0-3) after vaccination. | 
| Number of Subjects Reporting Any and Severe (Grade 3) Solicited Local Adverse Events (AEs). | Solicited local symptoms assessed were pain, redness and swelling. Any = occurrence of any solicited general symptom regardless of intensity grade. Grade 3 pain = pain that prevented normal activity. Grade 3 redness, swelling = redness, swelling above 100 millimeter (mm). All solicited local AEs were considered to be causally related to vaccination. | During a 4-day follow-up period (Days 0-3) after vaccination. | 
| Number of Subjects Reporting Any and Severe (Grade 3) Solicited Local Adverse Events (AEs), by Age-strata. | Solicited local symptoms assessed were pain, redness and swelling. Any = occurrence of any solicited general symptom regardless of intensity grade. Grade 3 pain = pain that prevented normal activity. Grade 3 redness, swelling = redness, swelling above 100 millimeter (mm). All solicited local AEs were considered to be causally related to vaccination. Subjects in each group were also stratified in the following age-strata: 3-4 years, 5-8 years and 9-17 years. | During a 4-day follow-up period (Days 0-3) after vaccination. | 
| Number of Subjects Reporting Any, Severe (Grade 3) and Related to Vaccination Unsolicited Adverse Events (AEs). | Any adverse event (AE) reported in addition to those solicited during the clinical study. Also any 'solicited' symptom with onset outside the specified period of follow-up for solicited symptoms was reported as an unsolicited adverse event. Grade 3 = event that prevented normal activities. Related = event assessed by the investigator as causally related to the study vaccination. | During a 28 day follow-up period (Days 0-27) after vaccination. | 
| Number of Subjects Reporting Any, Severe (Grade 3) and Related to Vaccination Unsolicited Adverse Events (AEs), by Age-strata. | Any adverse event (AE) reported in addition to those solicited during the clinical study. Also any 'solicited' symptom with onset outside the specified period of follow-up for solicited symptoms was reported as an unsolicited adverse event. Subjects in each group were also stratified in the following age-strata: 3-4 years, 5-8 years and 9-17 years. Grade 3 = event that prevented normal activities. Related = event assessed by the investigator as causally related to the study vaccination. | During a 28 day follow-up period (Days 0-27) after vaccination. | 
| Number of Subjects Reporting Medically Attended Adverse Events (MAEs). | For each solicited and unsolicited symptom the subject experiences, the subject/subject's parent(s)/ Legally Acceptable Representative (LAR(s)) was asked if they received medical attention defined as hospitalisation, an emergency room visit or a visit to or from medical personnel (medical doctor) for any reason. | During the entire study period (From Day 0 up to Day 180). | 
| Number of Subjects Reporting Serious Adverse Events (SAEs). | An SAE is defined as any untoward medical occurrence in a patient or clinical investigation subject that: results in death, is lifethreatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, or is a congenital anomaly/birth defect. | During the entire study period (From Day 0 up to Day 180). | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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GSK Biologicals influenza vaccine GSK1557482A, influenza infection