Evaluate Safety and 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 study, the subjects previously enrolled in study 107973 will receive a dose with the 2007-2008 season's formulations of Fluarix or GSK576389A. Only subjects who were previously enrolled in study 107973 (NCT00386113) are eligible for participation in this study.

Detailed Description
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This study is a year 3 revaccination study. Second year revaccination was done in study 107973 (NCT00386113). First year revaccination was done in study 104540 (NCT00318058). Primary study was study 103304. The Protocol Posting has been updated in order to comply with the FDA Amendment Act, Sep 2007

Official Title
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Reactogenicity and Immunogenicity of GSK Biologicals' Influenza Vaccine GSK576389A in Elderly Adults (≥67 Years) Previously Vaccinated With the Same Candidate Vaccine. Fluarix™ Will be Used as Reference.

Conditions
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Influenza

Intervention / Treatment
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* Biological: GSK Biologicals' influenza vaccine GSK576389A
* Biological: Fluarix™


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects who were previously vaccinated with GlaxoSmithKline Biologicals Fluarix™ or GSK576389A vaccines in the 107973 study (NCT00386113). Subjects who the investigator believes that they can and will comply with the requirements of the protocol should be enrolled in the study. A male or female aged >= 67 years at the time of re-vaccination. Written informed consent obtained from the subject. Free of an acute aggravation of the health status as established by clinical evaluation (medical history and medical history directed examination) before entering into the study. Exclusion Criteria: Use of any investigational or non-registered product (drug or vaccine) other than the study vaccines within 30 days prior to vaccination, or planned use during the study period. 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 21 days after vaccination. Confirmed influenza infection since the date of previous vaccination. Planned administration of an influenza vaccine other than the study vaccines during the entire study period. Vaccination against influenza since January 2007 with the Northern Hemisphere 2007/2008 influenza vaccine or 2006/2007 influenza vaccine. Administration of more than 14 days of immunosuppressants or other immune-modifying drugs within six months prior to the administration of the study vaccine. 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 clinical evaluation (medical history and medical history directed 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 administration of the study vaccine or planned administration during the study. Any medical conditions in which intramuscular injections are contraindicated.

Ages Eligible for Study
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Minimum Age: 67 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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: FluAS25 (GSK576389A) Group<br>Subjects received 1 dose of GlaxoSmithKline (GSK) Biologicals' AS25 adjuvanted influenza vaccine (GSK576389A). | Biological: GSK Biologicals' influenza vaccine GSK576389A<br>* Single dose, intramuscular injection<br>|
| Active Comparator: Fluarix Group<br>Subjects received 1 dose of Fluarix™. | 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 Symptoms | Solicited local symptoms 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 Symptoms | Duration was expressed as median number of days any symptom persisted. Solicited local symptoms assessed include ecchymosis, pain, redness and swelling. Any: occurrence of any local symptom regardless of their intensity grade. | During a 7-day follow-up period after vaccination | 
| Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms | Solicited general symptoms 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 39°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 Symptoms | Duration was expressed as median number of days any symptom persisted. Solicited general symptoms assessed include arthralgia, fatigue, headache, myalgia, nausea, shivering and fever. Any: occurrence of any general symptom regardless of their intensity grade or relationship to vaccination. | 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: occurrence of any unsolicited AE regardless of their intensity grade or relationship to vaccination. Grade 3: unsolicited AE that prevented normal everyday activities. Related: unsolicited AE assessed by the investigator as causally related to the study vaccination. | During a 21-day follow-up period after vaccination | 
| Number of Subjects Reporting Any, Grade 3 and Related Medically Significant Conditions (MSCs) | Medically Significant Conditions (MSCs) included all unsolicited adverse events that resulted in a medically attended visit. Any: occurrence of any MSC regardless of their intensity grade or relationship to vaccination. Grade 3: MSC that prevented normal everyday activities. Related: MSC assessed by the investigator as causally related to the study vaccination. | During a 21-day follow-up period after vaccination | 
| Number of Subjects Reporting 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. Any: occurrence of any SAE regardless of their relationship to vaccination. Related: SAE assessed by the investigator as causally related to the study vaccination. | Throughout the entire study (up to Day 21) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum Haemagglutination 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 Seropositive for HI Antibodies Against Each of the Three Vaccine Strains | A seropositive subject was defined as a subject with a serum HI titer greater than or equal to 1:10. 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 (SCFs) for HI Antibodies Against Each of the Three Vaccine Strains | Seroconversion factor was defined as the fold increase in serum HI GMTs post-vaccination compared to Day 0. The three vaccine strains assessed included A/Solomon Islands, A/Wisconsin and B/Malaysia. | 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 to 1:40 that usually is accepted as indicating protection. | At Days 0 and 21 | 
| Number of Cytokine-positive Cluster of Differentiation 4 (CD4) T Lymphocytes Per Million T Lymphocytes for Each of the Three Vaccine Strains | Results are presented as geometric mean number of specific influenza CD4 T lymphocytes per million T lymphocytes. The three vaccine strains assessed included A/Solomon Islands, A/Wisconsin and B/Malaysia. Results are given for All doubles (i.e. CD4 T lymphocytes expressing at least 2 different cytokines [Cluster of Differentiation 40L (CD40L), Interleukin-2 (IL-2), Tumor Necrosis Factor alpha (TNF-α), Interferon gamma (IFN-γ)]) and for CD4 T lymphocytes expressing one particular cytokine (CD40L, IL-2, TNF-α, or IFN-γ) and least one other. | At Days 0 and 21 | 
| Number of Cytokine-positive Cluster of Differentiation 8 (CD8) T Lymphocytes Per Million T Lymphocytes for Each of the Three Vaccine Strains | Results are presented as geometric mean number of specific influenza CD8 T lymphocytes per million T lymphocytes. The three vaccine strains assessed included A/Solomon Islands, A/Wisconsin and B/Malaysia. Results are given for All doubles (i.e. CD8 T lymphocytes expressing at least 2 different cytokines [Cluster of Differentiation 40L (CD40L), Interleukin-2 (IL-2), Tumor Necrosis Factor alpha (TNF-α), Interferon gamma (IFN-γ)]) and for CD8 T lymphocytes expressing one particular cytokine (CD40L, IL-2, TNF-α, or IFN-γ) and least one other. | At Days 0 and 21 | 

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