Evaluate Safety & Immunogenicity of GSK Bio's Influenza Vaccine GSK576389A After Repeated Vaccination in Elderly Adults

Study Overview
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Brief Summary
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Since influenza vaccines are administered every year because of the frequent change in their antigenic composition, the safety and immunogenicity profile of GSK Biologicals' influenza vaccine GSK576389A will be re-evaluated after repeated vaccine administration. In this observer blind study, the subjects previously enrolled in study 104888 (NCT00377585) will receive a dose with the 2007-2008 season's formulations of Fluarix or GSK576389A. Only subjects who were previously enrolled in study 104888 (NCT00377585) are eligible for participation in this study.

Detailed Description
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This study involves 2 age groups (based on primary study): Subjects enrolled in the >= 65 yrs age group in the primary study. Subjects enrolled in the 18-40 yrs age group in the primary study. The study will be conducted in an open manner for this age group. The Protocol Posting has been updated in order to comply with the FDA Amendment Act, Sep 2007.

Official Title
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Observer Blind Study to Evaluate Safety, Reactogenicity and Immunogenicity of GSK Biologicals Influenza Vaccine GSK576389A Administered to Adults Over 65 Years Previously Vaccinated With the Same Vaccine, Compared to Fluarix™

Conditions
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Influenza

Intervention / Treatment
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* Biological: Fluarix
* Biological: GSK Biologicals Influenza Vaccine GSK576389A


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects who the investigator believes can and will comply with the requirements of the protocol should be enrolled in the study. Written informed consent obtained from the subject. Free of an acute aggravation of the health status as established by clinical evaluation 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 practice adequate contraception for 30 days prior to vaccination, have a negative pregnancy test and continue such precautions for 2 months after completion of the vaccination series. Male or female subjects who participated in the 104888 study (NCT00377585) and were enrolled in the >= 65 years age group or in the 18-40 years age group . Exclusion Criteria: Administration of other licensed vaccines within 2 weeks (for inactivated vaccines) or 4 weeks (for live vaccines) prior to enrolment in this study. Planned administration of a vaccine not foreseen by the study protocol up to 30 days after vaccination Planned administration of an influenza vaccine other than the study vaccines during the entire study period Any vaccination against influenza since January 2007 Chronic administration (defined as more than 14 days) of immunosuppressants or other immune-modifying drugs within six months prior to the first vaccine dose. Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination (no laboratory testing required). History of hypersensitivity to a previous dose of influenza vaccine History of allergy or reactions likely to be exacerbated by any component of the vaccine(s) Acute (active) clinically significant pulmonary, cardiovascular, hepatic or renal functional abnormality, as determined by physical examination or pre-existing laboratory screening tests Acute disease at the time of enrolment 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 Use of any investigational or non-registered product (drug or vaccine) other than the study vaccine(s) within 30 days prior to vaccination, or planned use during the study period Any medical conditions in which IM injections are contraindicated Pregnant or lactating female, or planning to become pregnant or to discontinue contraceptive precautions.

Ages Eligible for Study
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Minimum Age: 18 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: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: FluAS25 Group<br>Subjects aged 65 years and above, who had received one dose of GlaxoSmithKline (GSK) Biologicals' AS25 adjuvanted influenza vaccine (GSK576389A) in study NCT00377585, received one dose of GlaxoSmithKline (GSK) Biologicals' AS25 adjuvanted influenza vaccine (GSK576389A) in the current study. | Biological: GSK Biologicals Influenza Vaccine GSK576389A<br>* Single dose, Intramuscular injection<br>|
| Active Comparator: Fluarix ≥ 65 years age Group<br>Subjects aged 65 years and above, who had received one dose of Fluarix™ vaccine in study NCT00377585, received one dose of Fluarix™ vaccine in the current study. | Biological: Fluarix<br>* Single dose, Intramuscular injection<br>|
| Active Comparator: Fluarix 18-40 years age Group<br>Subjects aged between 18 and 40 years, who had received one dose of Fluarix™ vaccine in study NCT00377585, received one dose of Fluarix™ vaccine in the current study. | 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 |
| --- | --- | --- |
| Number of Subjects Reporting Any and Grade 3 Solicited Local Adverse Events (AEs) | Solicited local AEs assessed include ecchymosis, pain, redness and swelling. Any: any symptom regardless of intensity grade. Grade 3 pain: considerable pain at rest, which prevented normal everyday activities. Grade 3 ecchymosis, redness and swelling: more than 100 millimeter. | During a 7-day follow-up period after vaccination | 
| Duration of Solicited Local Adverse Events | Duration was expressed as the median number of days the symptom was experienced. | During a 7-day follow-up period after vaccination | 
| Number of Subjects Reporting Any, Grade 3 and Related Solicited General Adverse Events (AEs) | Solicited general AEs assessed include arthralgia, fatigue, headache, myalgia, nausea, shivering and fever. Any: any symptom regardless of intensity grade; any fever: oral temperature greater than or equal to 38 degrees Celsius (°C). Grade 3: symptoms that prevented normal activity ; Grade 3 fever: oral temperature greater than 40°C. Related: symptom assessed by the investigator as causally related to the study vaccination. | During a 7-day follow-up period after vaccination | 
| Duration of Solicited General Adverse Events | Duration was expressed as the median number of days the symptom was experienced. | During a 7-day follow-up period after vaccination | 
| Number of Subjects Reporting 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 AE regardless of intensity or relationship to vaccination. Grade 3: AE that prevented normal activity. Related: AE considered by the investigator to be causally related to the study vaccination. | During a 21-day follow-up period after vaccination | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects With Any and Related Serious Adverse Events (SAEs) | 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. | During the vaccination phase of the study (Day 0 to Day 20) and during the long term follow-up phase of the study (Day 21 to Day 179) | 
| Number of Subjects Reporting Any and Related Medically Significant Conditions (MSCs) | Medically significant conditions assessed include conditions prompting emergency room visits, hospitalizations or physician visits. | During the vaccination phase of the study (Day 0 to Day 20) and during the long term follow-up phase of the study (Day 21 to Day 179) | 
| Serum Hemagglutination-inhibition (HI) Antibody Titers Against Each of the Three Vaccine Strains | Titers were expressed as Geometric Mean Titers. The three vaccine strains assessed included A/Solomon Islands, A/Wisconsin and B/Malaysia. | At Days 0 and 21 | 
| Number of Subjects Seroconverted for HI Antibodies Against Each of the Three Vaccine Strains | A seroconverted subject was defined as a subject who had either a pre-vaccination titer below1:10 and a post-vaccination titer greater than or equal to1:40 or a pre-vaccination titer greater than or equal to1:10 and at least a four-fold increase in post-vaccination titer. The three vaccine strains assessed included A/Solomon Islands, A/Wisconsin and B/Malaysia. | At Day 21 | 
| Seroconversion Factors for HI Antibodies Against Each of the Three Vaccine Strains | Seroconversion factor was defined as the fold increase in serum HI Geometric Mean Titers post-vaccination compared to Day 0. | At Day 21 | 
| Number of Subjects Seroprotected for HI Antibodies Against Each of the Three Vaccine Strains | A seroprotected subject was defined as a subject with a serum HI titer greater than or equal to1:40 that is usually accepted as indicating protection. The three vaccine strains assessed included A/Solomon Islands, A/Wisconsin and B/Malaysia. | At Days 0 and 21 | 
| Number of Cluster of Differentiation 4 (CD4) T-cells (Per Million CD4 T-cells) Producing at Least 2 Different Immune Markers | Results are presented as the geometric mean number of immune response marker-positive CD4 T-cells (per million CD4 T-cells) for pooled vaccine strains. Immune markers assessed include Cluster of Differentiation 40 Ligand (CD40L), interleukin-2 (IL-2), tumor necrosis factor alpha (TNF-α) and interferon gamma (IFN-γ). | At Day 0 and 21 | 
| Number of CD4 T-cells (Per Million CD4 T-cells) Producing at Least CD40L and Another Immune Marker | Results are presented as the geometric mean number of CD40L-positive CD4 T-cells (per million CD4 T-cells) for pooled vaccine strains. Other immune markers assessed include interleukin-2 (IL-2), tumor necrosis factor alpha (TNF-α) and interferon gamma (IFN-γ). | At Day 0 and 21 | 
| Number of CD4 T-cells (Per Million CD4 T-cells) Producing at Least IFN-γ and Another Immune Marker | Results are presented as the geometric mean number of IFN-γ -positive CD4 T-cells (per million CD4 T-cells) for pooled vaccine strains. Other immune markers assessed include Cluster of Differentiation 40 Ligand (CD40L), interleukin-2 (IL-2) and tumor necrosis factor alpha (TNF-α). | At Day 0 and 21 | 
| Number of CD4 T-cells (Per Million CD4 T-cells) Producing at Least IL-2 and Another Immune Marker | Results are presented as the geometric mean number of IFN-γ -positive CD4 T-cells (per million CD4 T-cells) for pooled vaccine strains. Other immune markers assessed include Cluster of Differentiation 40 Ligand (CD40L), tumor necrosis factor alpha (TNF-α) and interferon gamma (IFN-γ). | At Day 0 and 21 | 
| Number of CD4 T-cells (Per Million CD4 T-cells) Producing at Least TNF-α and Another Immune Marker | Results are presented as the geometric mean number of IFN-γ -positive CD4 T-cells (per million CD4 T-cells) for pooled vaccine strains. Other immune markers assessed include Cluster of Differentiation 40 Ligand (CD40L) and interferon gamma (IFN-γ). | At Day 0 and 21 | 
| Number of Cluster of Differentiation 8 (CD8) T-cells (Per Million CD8 T-cells) Expressing at Least 2 Different Immune Markers | Results are presented as the geometric mean number of immune response marker-positive CD8 T-cells (per million CD8 T-cells) for pooled vaccine strains. Immune markers assessed include Cluster of Differentiation 40 Ligand (CD40L), interleukin-2 (IL-2), tumor necrosis factor alpha (TNF-α) and interferon gamma (IFN-γ). | At Day 0 and 21 | 
| Number of CD8 T-cells (Per Million CD8 T-cells) Producing at Least CD40L and Another Immune Marker | Results are presented as the geometric mean number of CD40L-positive CD8 T-cells (per million CD8 T-cells) for pooled vaccine strains. Other immune markers assessed include interleukin-2 (IL-2), tumor necrosis factor alpha (TNF-α) and interferon gamma (IFN-γ). | At Day 0 and 21 | 
| Number of CD8 T-cells (Per Million CD8 T-cells) Producing at Least IFN-γ and Another Immune Marker | Results are presented as the geometric mean number of IFN-γ -positive CD8 T-cells (per million CD8 T-cells) for pooled vaccine strains. Other immune markers assessed include Cluster of Differentiation 40 Ligand (CD40L), interleukin-2 (IL-2) and tumor necrosis factor alpha (TNF-α). | At Day 0 and 21 | 
| Number of CD8 T-cells (Per Million CD8 T-cells) Producing at Least IL-2 and Another Immune Marker | Results are presented as the geometric mean number of IFN-γ -positive CD8 T-cells (per million CD8 T-cells) for pooled vaccine strains. Other immune markers assessed include Cluster of Differentiation 40 Ligand (CD40L), tumor necrosis factor alpha (TNF-α) and interferon gamma (IFN-γ). | At Day 0 and 21 | 
| Number of CD8 T-cells (Per Million CD8 T-cells) Producing at Least TNF-α and Another Immune Marker | Results are presented as the geometric mean number of IFN-γ -positive CD8 T-cells (per million CD8 T-cells) for pooled vaccine strains. Other immune markers assessed include Cluster of Differentiation 40 Ligand (CD40L) and interferon gamma (IFN-γ). | At Day 0 and 21 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Fluarix, GSK Bio's influenza vaccine GSK576389A, Influenza infection