Study to Evaluate the Safety and Immunogenicity of GSK Biological Pandemic Candidate Influenza Vaccine (H1N1) in Children

Study Overview
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Brief Summary
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The objective of this study is to evaluate the safety and immunogenicity study of GSK Biologicals' pandemic influenza candidate vaccine (GSK2340272A) in children aged 3 to 9 years.

Official Title
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Safety and Immunogenicity Study of GSK Biologicals' Pandemic Influenza Candidate Vaccine (GSK2340272A) in Children Aged 3 to 9 Years

Conditions
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Influenza

Intervention / Treatment
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* Biological: GSK pandemic vaccine GSK2340272A


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects who the investigator believes that their parent(s)/Legally Acceptable Representative(s) (LAR) can and will comply with the requirements of the protocol. Children, male or female, aged between 3 and 9 years at the time of first study vaccination. Written informed consent obtained from the parent(s) or LAR(s) of the subject. Healthy children, as established by medical history and clinical examination when entering the study. Exclusion Criteria: Use of any investigational or non-registered product other than the study vaccine within 30 days preceding the first dose of the study vaccine or planned use during the study period. Clinically or virologically confirmed influenza infection within six months preceding the study start. Planned administration of any vaccine 30 days prior and 30 days after any study vaccine administration. Have received any seasonal flu vaccine since last year. Previous administration of any H1N1 A/California-like vaccine Chronic administration of immunosuppressants or other immune-modifying drugs within three months prior to enrolment in this study or planned administration during the study period. For corticosteroids, this will mean prednisone >= 0.5 mg/kg/day, or equivalent. Inhaled and topical steroids are allowed. Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination. Acute or chronic, clinically-significant pulmonary, cardiovascular, hepatic or renal functional abnormality, as determined by medical history and physical examination. History of hypersensitivity to vaccines. History of allergic disease or reactions likely to be exacerbated by any component of the vaccines. History of any neurological disorders or seizures. Acute disease and/or fever at the time of enrolment: Fever is defined as temperature >= 37.5°C on oral, axillary or tympanic setting, or >= 38°C on rectal setting. Subjects with a minor illness (such as mild diarrhoea, mild upper respiratory infection) without fever may be enrolled at the discretion of the investigator. Administration of immunoglobulins and/or any blood products within the three months prior to the enrolment in this study, or planned during the study. Any condition which, in the opinion of the investigator, renders the subject unfit for participation in the study. Child in Care.

Ages Eligible for Study
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Minimum Age: 3 Years
Maximum Age: 9 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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: GSK2340272A F1 Y3-5 GROUP<br>Healthy male or female children, between 3 and 5 years of age (Y3-5) at the time of first study vaccination, who intramuscularly received 2 doses of GSK2340272A vaccine formulation 1 (F1) in the deltoid region of the arm, according to a 0-21 day schedule. | Biological: GSK pandemic vaccine GSK2340272A<br>* 2 intramuscular injections<br>|
| Experimental: GSK2340272A F1 Y6-9 GROUP<br>Healthy male or female children, between 6 and 9 years of age (Y6-9) at the time of first study vaccination, who intramuscularly received 2 doses of GSK2340272A vaccine formulation 1 (F1) in the deltoid region of the arm, according to a 0-21 day schedule. | Biological: GSK pandemic vaccine GSK2340272A<br>* 2 intramuscular injections<br>|
| Experimental: GSK2340272A F2 Y3-5 GROUP<br>Healthy male or female children, between 3 and 5 years of age (Y3-5) at the time of first study vaccination, who intramuscularly received 2 doses of GSK2340272A vaccine formulation 2 (F2) in the deltoid region of the arm, according to a 0-21 day schedule. | Biological: GSK pandemic vaccine GSK2340272A<br>* 2 intramuscular injections<br>|
| Experimental: GSK2340272A F2 Y6-9 GROUP<br>Healthy male or female children, between 6 and 9 years of age (Y6-9) at the time of first study vaccination, who intramuscularly received 2 doses of GSK2340272A vaccine formulation 2 (F2) in the deltoid region of the arm, according to a 0-21 day schedule. | Biological: GSK pandemic vaccine GSK2340272A<br>* 2 intramuscular injections<br>|
| Experimental: GSK2340272A F3 Y3-5 GROUP<br>Healthy male or female children, between 3 and 5 years of age (Y3-5) at the time of first study vaccination, who intramuscularly received 2 doses of GSK2340272A vaccine formulation 3 (F3) in the deltoid region of the arm, according to a 0-21 day schedule. | Biological: GSK pandemic vaccine GSK2340272A<br>* 2 intramuscular injections<br>|
| Experimental: GSK2340272A F3 Y6-9 GROUP<br>Healthy male or female children, between 6 and 9 years of age (Y6-9) at the time of first study vaccination, who intramuscularly received 2 doses of GSK2340272A vaccine formulation 3 (F3) in the deltoid region of the arm, according to a 0-21 day schedule. | Biological: GSK pandemic vaccine GSK2340272A<br>* 2 intramuscular injections<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Haemagglutination Inhibition (HI) Antibody Titers Against Vaccine H1N1 Antigen | Humoral immune response in terms of vaccine H1N1 haemagglutination inhibition (HI) antibodies against A/California/7/2009 (H1N1)v-like virus (Flu A/CAL/7/09) has been assessed. Antibody titers were presented as geometric mean titers (GMTs). | At Day 42 | 
| Number of Seropositive Subjects for HI Antibodies | A seropositive subject was defined as a subject with a serum HI titer equal to or above (≥) 1:10. The flu strain assessed was Flu A/CAL/7/09. | At Day 42 | 
| Number of Seroconverted Subjects in Terms of HI Antibodies | Seroconversion (SCR) was defined as: For initially seronegative subjects [pre-vaccination titer below (<) 1:10], a post-vaccination titer ≥ 1:40. For initially seropositive subjects (pre-vaccination titer ≥ 1:10), at least a 4-fold increase in post-vaccination titer. The flu strain assessed was Flu A/CAL/7/09. | At Day 42 | 
| Number of Seroprotected Subjects for HI Antibodies | A seroprotected subject was defined as a vaccinated subject with a serum HI titer ≥ 1:40, which is usually accepted as indicating protection. The flu strain assessed was Flu A/CAL/7/09. | At Day 42 | 
| Geometric Mean Fold Increase (GMFR) for Serum HI Antibody Titer | GMFR, also called seroconversion factor (SCF), was defined as the fold increase in serum HI geometric mean titers (GMTs) post-vaccination compared to pre-vaccination. The flu strain assessed was Flu A/CAL/7/09. | At Day 42 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Seropositive Subjects for HI Antibodies | A seropositive subject was defined as a subject with a serum HI titer equal to or above (≥) 1:10. The flu strain assessed was Flu A/CAL/7/09. | At Day 0, Day 21 and Month 7 | 
| HI Antibody Titers Against Vaccine H1N1 Antigen | Humoral immune response in terms of vaccine H1N1 haemagglutination inhibition (HI) antibodies against A/California/7/2009 (H1N1)v-like virus (Flu A/CAL/7/09) has been assessed. Antibody titers were presented as geometric mean titers (GMTs). | At Day 0, Day 21 and Month 7 | 
| Number of Seroconverted Subjects in Terms of HI Antibodies | Seroconversion (SCR) was defined as: For initially seronegative subjects (pre-vaccination titer below < 1:10), a post-vaccination titer ≥ 1:40. For initially seropositive subjects (pre-vaccination titer ≥ 1:10), at least a 4-fold increase in post-vaccination titer. The flu strain assessed was Flu A/CAL/7/09. | At Day 21 and Month 7 | 
| Number of Seroprotected Subjects for HI Antibodies | A seroprotected subject was defined as a vaccinated subject with a serum HI titer ≥ 1:40, which is usually accepted as indicating protection. The flu strain assessed was Flu A/CAL/7/09. | At Day 0, Day 21 and Month 7 | 
| Geometric Mean Fold Increase (GMFR) for Serum HI Antibody Titer | GMFR, also called seroconversion factor (SCF), was defined as the fold increase in serum HI geometric mean titers (GMTs) post-vaccination compared to pre-vaccination. The flu strain assessed was Flu A/CAL/7/09. | At Day 21 and Month 7 | 
| Number of Subjects With Any and Grade 3 Solicited Local Symptoms | Assessed solicited local symptoms were pain, redness and swelling. Any = incidence of a particular symptom regardless of intensity grade or relationship to vaccinations. Grade 3 pain (children below 6 years of age) = cried when limb was moved/spontaneously painful. Grade 3 pain (children above 6 years of age) = significant pain at rest; pain that prevented normal everyday activities. Grade 3 redness/swelling = redness/swelling spreading beyond 50 millimeters (mm) of injection site. | During the 7-day (Days 0-6) post-vaccination period following each dose and across doses | 
| Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Assessed solicited general symptoms were drowsiness, irritability, loss of appetite and fever [defined as axillary temperature equal to or above 37.5 degrees Celsius (°C)]. Any = incidence of a particular symptom regardless of intensity grade or relationship to vaccinations. Grade 3 drowsiness = drowsiness which prevented normal everyday activities. Grade 3 irritability = crying that could not be comforted/prevented normal activity. Grade 3 loss of appetite = not eating at all. Grade 3 fever = fever > 39.0 °C. Related = symptom assessed by the investigator as causally related to the vaccination | During the 7-day (Days 0-6) post-vaccination period following each dose and across doses | 
| Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Assessed solicited general symptoms were fatigue, gastrointestinal, headache and temperature [defined as axillary temperature equal to or above 37.5 degrees Celsius (°C)]. Any = incidence of a particular symptom regardless of intensity grade or relationship to vaccinations. Grade 3 = symptom which prevented normal everyday activity. Related = symptom assessed by the investigator as causally related to the vaccination. Grade 3 fever = fever > 39.0 °C. | During the 7-day (Days 0-6) post-vaccination period following each dose and across doses | 
| Number of Subjects With Any Medically-attended Events (MAEs) | MAEs were defined as events for which the subject received medical attention defined as hospitalization, an emergency room visit, or a visit to or from medical personnel (medical doctor) for any reason. Any MAE(s) = Occurrence of any MAE(s) regardless of intensity grade or relation to vaccination. | During the entire study period (from Month 0 up to Month 12) | 
| Number of Subjects With Adverse Events of Specific Interest (AESIs)/Potential Immune-mediated Disease (pIMDs) | Adverse events of specific interest (AESI) were defined as AEs including autoimmune diseases and other mediated inflammatory disorders and assessed by the investigator as specific to the treatment administration. Potential immune-mediated diseases (pIMDs) are a subset of AEs that include autoimmune diseases and other inflammatory and/or neurologic disorders of interest which may or may not have an autoimmune aetiology. | During the entire study period (from Month 0 up to Month 12) | 
| Number of Subjects With Unsolicited Adverse Events (AEs) | An unsolicited AE covers 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 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 the occurrence of any unsolicited AE regardless of intensity grade or relation to vaccination. Grade 3 AE = an AE which prevented normal, everyday activities. Related = AE assessed by the investigator as related to the vaccination. | Within the 42-day (Days 0-41) post-vaccination period | 
| Number of Subjects With Serious Adverse Events (SAEs) | Serious adverse events (SAEs) assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity. | During the entire study period (from Month 0 to Month 12) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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influenza infection, GSK Bio's influenza vaccine GSK2340272A