Study to Evaluate an Influenza Vaccine Candidate

Study Overview
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Brief Summary
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In order to find the formulation leading to a maximal increase of the immune response while maintaining an acceptable safety profile, this study is designed to evaluate the immunogenicity, safety and reactogenicity of the different formulations of GSK Biologicals' influenza vaccine administered in adults aged 18-64 years.

Detailed Description
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The Protocol Posting has been updated in order to comply with the FDA Amendment Act, Sep 2007.

Official Title
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Immunogenicity, Safety and Reactogenicity of GSK Biologicals' Influenza Vaccine GSK1247446A With Various Formulations in Subjects Aged 18-64 Years

Conditions
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Influenza

Intervention / Treatment
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* Biological: Influenza Vaccine GSK1247446A - 4 different formulations
* Biological: Fluarix™


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Only subjects who the investigator believes that they can and will comply with the requirements of the protocol . A male or female between, and including, 18 - 64 years of age at the time of vaccination. Written informed consent obtained from the subject. Healthy subjects as established by medical history and clinical examination before entering into the study. If the subject is female, she must be of non-childbearing potential or if she is of childbearing potential, she must have a negative pregnancy test, practice adequate contraception for 30 days prior to vaccination, and continue such precautions for 2 months after completion of the vaccination series. Exclusion Criteria: Use of any investigational or non-registered product (drug or vaccine) other than the study vaccine(s) within 30 days preceding the first dose of study vaccine, or planned use during the study period. Chronic administration (defined as more than 14 days) of immunosuppressants or other immune-modifying drugs within three months prior to the first vaccine dose Administration of a vaccine not foreseen by the study protocol from 30 days before vaccination, up to 21 days after vaccination. History of hypersensitivity to a previous dose of influenza vaccine. Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination History of allergic disease or reactions likely to be exacerbated by any component of the vaccine(s) Acute or chronic, clinically significant pulmonary, cardiovascular, hepatic or renal functional abnormality, as determined by physical examination or laboratory screening tests. Confirmed influenza infection within a year preceding the study start. Administration of an influenza vaccine within a year preceding the study start. 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. Pregnant or lactating female. Concurrent participation 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 Acute disease at the time of enrolment. History of chronic alcohol consumption and/or drug abuse. Female planning to become pregnant or planning to discontinue contraceptive precautions. Any condition which, in the opinion of the investigator, prevents the subject from participating in the study. History of administration of experimental/licensed vaccine containing squalene and/or tocopherol within the last 12 months.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 64 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: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: GSK1247446A 1 Group<br>Subjects aged 18-64 years at the time of enrolment received 1 dose of GSK1247446A with a full dose of AS03 adjuvant at Day 0. The vaccine was administered intramuscularly in the deltoid region of the non-dominant arm. | Biological: Influenza Vaccine GSK1247446A - 4 different formulations<br>* Single dose, Intramuscular injection<br>|
| Experimental: GSK1247446A 2 Group<br>Subjects aged 18-64 years at the time of enrolment received 1 dose of GSK1247446A with 1/2 dose of AS03 adjuvant at Day 0. The vaccine was administered intramuscularly in the deltoid region of the non-dominant arm. | Biological: Influenza Vaccine GSK1247446A - 4 different formulations<br>* Single dose, Intramuscular injection<br>|
| Experimental: GSK1247446A 3 Group<br>Subjects aged 18-64 years at the time of enrolment received 1 dose of GSK1247446A with 1/4 dose of AS03 adjuvant at Day 0. The vaccine was administered intramuscularly in the deltoid region of the non-dominant arm. | Biological: Influenza Vaccine GSK1247446A - 4 different formulations<br>* Single dose, Intramuscular injection<br>|
| Experimental: GSK1247446A 4 Group<br>Subjects aged 18-64 years at the time of enrolment received 1 dose of GSK1247446A with 1/8 dose of AS03 adjuvant at Day 0. The vaccine was administered intramuscularly in the deltoid region of the non-dominant arm. | Biological: Influenza Vaccine GSK1247446A - 4 different formulations<br>* Single dose, Intramuscular injection<br>|
| Active Comparator: Fluarix Group<br>Subjects aged 18-64 years at the time of enrolment received 1 dose of FluarixTM at Day 0. The vaccine was administered intramuscularly in the deltoid region of the non-dominant arm. | Biological: Fluarix™<br>* Single dose, Intramuscular injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Titers for Serum Hemagglutination Inhibition (HI) Antibodies Against 3 Strains of Influenza Disease. | Titers are presented as geometric mean titers (GMTs). The 3 influenza strains assessed were A/Solomon Islands (SOLO), A/Wisconsin (WISC) and B/Malaysia (MALA). The seropositivity cut-off assay was 1:10. The results for Day 0 and Day 21 are the primary efficacy variables. | At Days 0, 21 and 180 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Seroconverted Subjects Against 3 Strains of Influenza Disease. | A seroconverted subject was defined as a vaccinated subject 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 3 influenza strains assessed were A/Solomon Islands (SOLO), A/Wisconsin (WISC) and B/Malaysia (MALA). | At Days 21 and 180 | 
| Seroconversion Factor for Hemagglutination Inhibition (HI) Antibodies Against 3 Strains of Influenza Disease. | The seroconversion factor (SCF) was defined as the fold increase in serum Hemagglutination Inhibition (HI) geometric mean titers (GMTs) post vaccination compared to Day 0. The 3 influenza strains assessed were A/Solomon Islands (SOLO), A/Wisconsin (WISC) and B/Malaysia (MALA). | At Days 21 and 180 | 
| Number of Seroprotected Subjects Against 3 Strains of Influenza Disease. | A seroprotected subject was defined as a vaccinated subject who had a serum HI titer ≥ 1:40. The 3 influenza strains assessed were A/Solomon Islands (SOLO), A/Wisconsin (WISC) and B/Malaysia (MALA). | At Days 0, 21 and 180 | 
| Titers for Serum Hemagglutination Inhibition (HI) Antibodies Against 4 Strains of Influenza Disease. | Titers are presented as geometric mean titers (GMTs). The 4 influenza strains assessed were A/Wisconsin (WISC), B/Malaysia (MALA), A/Brisbane (BRIS) and B/Florida (FLOR). The seropositivity cut-off assay was 1:28. | At Days 0 and 21 | 
| Geometric Mean of Influenza-specific Cluster of Differentiation (CD) 4 T-cells. | The mean was calculated for CD4 T-cells (per million CD4 T-cells) producing at least two different cytokines (All Doubles), at least CD40L, at least INF gamma (IFN-γ), at least IL2 and at least TNF alpha (TNF-α). | At Days 0, 21 and 180 | 
| Geometric Mean of Influenza-specific Cluster of Differentiation (CD) 8 T-cells. | The mean was calculated for CD8 T-cells (per million CD8 T-cells) producing at least two different cytokines (All Doubles), at least CD40L, at least INF gamma (IFN-γ), at least IL2 and at least TNF alpha (TNF-α). | At Days 0, 21 and 180 | 
| Number of Subjects With Any and Grade 3 Solicited Local Symptoms. | Assessed solicited local symptoms were ecchymosis, pain, redness and swelling at injection site. Any = incidence of a particular symptom regardless of intensity grade. Grade 3 pain = pain that prevented normal everyday activity. Grade 3 redness/swelling/ecchymosis = redness/swelling/ecchymosis spreading beyond 50 millimeters (mm) of the injection site. | During the 7-day (Days 0-6) post vaccination period | 
| Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms. | Assessed solicited general symptoms were arthralgia, fatigue, fever [oral temperature above (>) 38.0 degrees Celsius (°C)], headache, myalgia, nausea and shivering. Any = incidence of a particular symptom regardless of grade intensity or relationship with the study vaccination. Grade 3 symptom = symptom that prevented normal activity. Grade 3 fever = fever ≥ 39.0°C. Related = symptom considered by the investigator to have a causal relationship to study vaccination. | During the 7-day (Days 0-6) post vaccination period | 
| Number of Subjects With Any, Grade 3 and Related Medically Significant Conditions (MSCs). | MSCs were defined as conditions prompting emergency room visits or physician visits that were not related to common diseases or routine visits. Any = incidence of a particular symptom regardless of grade intensity or relationship with the study vaccination. Grade 3 = event which prevented normal activities. Related = event assessed by the investigator as causally related to the study vaccination | From Day 0 to Day 180 | 
| Number of Subjects With Any, Grade 3 and Related Unsolicited Adverse Events (AEs). | Unsolicited AE covers any AE 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 = any unsolicited AE regardless of intensity or relationship to vaccination. Grade 3 = unsolicited AE that prevented normal activity Related = unsolicited AE assessed by the investigator as related to the vaccination. | During the 21-day (Days 0-20) 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, result in disability/incapacity or are a congenital anomaly/birth defect in the offspring of a study subject. | From Day 0 to Day 180 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Influenza, Influenza Vaccine