Non-Inferiority of Various GSK Bio's Influenza Vaccine Presentations in Adults Aged 65 Years and Over

Study Overview
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Brief Summary
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This observer blind study is designed to compare the immune response of GSK Biologicals' influenza vaccine GSK576389A when administered using various presentations in adults aged 65 years and older. The Protocol Posting has been updated in order to comply with the FDA Amendment Act, Sep 2007.

Detailed Description
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The study contains 6 parallel groups, stratified by two age groups: 65-74 years and ≥ 75 years and by two influenza vaccination histories: no influenza vaccination in the last 3 seasons and at least one influenza vaccination in the last 3 seasons.

Official Title
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Non-Inferiority of GlaxoSmithKline Biologicals' Influenza Vaccine (GSK576389A) 1 Container Over 2 Container Presentation in Adults Aged 65 Years and Over

Conditions
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Influenza

Intervention / Treatment
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* Biological: GSK Bio's influenza vaccine GSK576389A [NH 2006/07 season]
* Biological: GSK Bio's influenza vaccine GSK576389A [NH 2007/08 season]
* Biological: Fluarix [NH 2006/07 season]
* Biological: Fluarix [NH 2007/08 season]


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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 65 years or older at the time of the vaccination. 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. Exclusion Criteria: 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. 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 Visit 2 after vaccination. Planned administration of an influenza vaccine other than the study vaccines during the entire study period. Vaccination against influenza since January 2007 (including the Northern Hemisphere NH 2006/2007 or NH 2007/08 influenza vaccine). Chronic administration (defined as 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 hypersensivity to a previous dose of influenza vaccine. History of allergy or reactions likely to be exacerbated by any component of the vaccine(s) Acute clinically significant pulmonary, cardiovascular, hepatic or renal functional abnormality, as determined by clinical evaluation 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: 65 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: GSK576389A- 2006/2007 Season - 1 container Group<br>Subjects aged ≥ 65 years received adjuvanted influenza vaccine GSK576389A for the Northern Hemisphere 2006/2007 influenza season presented in 1 container. | Biological: GSK Bio's influenza vaccine GSK576389A [NH 2006/07 season]<br>* Single dose, intramuscular injection, GSK Bio's influenza vaccine GSK576389A formulation recommended for the Northern Hemisphere 2006-2007 influenza season.<br>|
| Experimental: GSK576389A - 2006/2007 Season - 2 containers Group<br>Subjects aged ≥ 65 years received adjuvanted influenza vaccine GSK576389A for the Northern Hemisphere 2006/2007 influenza season presented in 2 containers. | Biological: GSK Bio's influenza vaccine GSK576389A [NH 2006/07 season]<br>* Single dose, intramuscular injection, GSK Bio's influenza vaccine GSK576389A formulation recommended for the Northern Hemisphere 2006-2007 influenza season.<br>|
| Active Comparator: Fluarix 2006/2007 Season Group<br>Subjects aged ≥ 65 years received a single dose of Fluarix vaccine formulation recommended for the Northern Hemisphere 2006-2007 influenza season. | Biological: Fluarix [NH 2006/07 season]<br>* Single dose, intramuscular injection, Fluarix vaccine formulation recommended for the Northern Hemisphere 2006-2007 influenza season.<br>|
| Experimental: GSK576389A - 2007/2008 Season - 1 container Group<br>Subjects aged ≥ 65 years received adjuvanted influenza vaccine GSK576389A for the Northern Hemisphere 2007/2008 influenza season presented in 1 container. | Biological: GSK Bio's influenza vaccine GSK576389A [NH 2007/08 season]<br>* Single dose, intramuscular injection, GSK Bio's influenza vaccine GSK576389A formulation recommended for the Northern Hemisphere 2007-2008 influenza season.<br>|
| Experimental: GSK576389A - 2007/2008 Season - 2 containers Group<br>Subjects aged ≥ 65 years received adjuvanted influenza vaccine GSK576389A for the Northern Hemisphere 2007/2008 influenza season presented in 2 containers. | Biological: GSK Bio's influenza vaccine GSK576389A [NH 2007/08 season]<br>* Single dose, intramuscular injection, GSK Bio's influenza vaccine GSK576389A formulation recommended for the Northern Hemisphere 2007-2008 influenza season.<br>|
| Active Comparator: Fluarix 2007/2008 Season Group<br>Subjects aged ≥ 65 years received a single dose of Fluarix vaccine formulation recommended for the Northern Hemisphere 2007-2008 influenza season. | Biological: Fluarix [NH 2007/08 season]<br>* Single dose, intramuscular injection, Fluarix vaccine formulation recommended for the Northern Hemisphere 2007-2008 influenza season.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Haemagglutination Inhibition (HI) Antibody Titers for the H1N1 Vaccine Strain | Antibody titers were expressed as Geometric mean titers (GMTs). The H1N1 vaccine strains included A/New Caledonia and A/Solomon Islands antigens. A/New Caledonia vaccine strain was administered to both groups receiving the adjuvanted influenza vaccine GSK576389A for the Northern Hemisphere 2006/2007 influenza season. A/Solomon Islands vaccine strain was administered to both groups receiving the adjuvanted influenza vaccine GSK576389A for the Northern Hemisphere 2007/2008 influenza season. | At Days 0 and 21 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| HI Antibody Titers Against Each of the Three Vaccine Strains for the Two Season Formulations | Antibody titers were expressed as GMTs. The vaccine strains included A/New Caledonia or A/Solomon Islands, A/Wisconsin and B/Malaysia antigens. A/New Caledonia vaccine strain was administered to all groups receiving the Northern Hemisphere 2006/2007 influenza season vaccine formulations. A/Solomon Islands vaccine strain was administered to all groups receiving the Northern Hemisphere 2007/2008 influenza season vaccine formulations. A/Wisconsin and B/Malaysia vaccine strains were administered to all groups. | At Days 0 and 21 | 
| The Number of Subjects Seroconverted for HI Antibodies Against Each of the Three Vaccine Strains for the Two Season Formulations | A seroconverted subject was defined as a subject who had either a pre-vaccination titer below 1:10 and a post-vaccination titer greater than or equal to 1:40 or a pre-vaccination titer greater than or equal to 1:10 and at least a 4-fold increase in post-vaccination titer. The vaccine strains included A/New Caledonia (for all groups receiving vaccine formulations for the Northern Hemisphere [NH] 2006/2007 influenza season) or A/Solomon Islands (for all groups receiving vaccine formulations for the NH 2007/2008 influenza season), A/Wisconsin and B/Malaysia antigens. | At Day 21 | 
| HI Antibody Seroconversion Factors | Seroconversion factors were defined as the fold increase in serum HI GMTs post-vaccination compared to Day 0. The vaccine strains included A/New Caledonia (for all groups receiving vaccine formulations for the Northern Hemisphere [NH] 2006/2007 influenza season) or A/Solomon Islands (for all groups receiving vaccine formulations for the NH 2007/2008 influenza season), A/Wisconsin and B/Malaysia antigens. | At Day 21 | 
| The Number of Subjects Seroprotected for HI Antibodies Against Each of the Three Vaccine Strains for the Two Season Formulations | 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. The vaccine strains included A/New Caledonia (for all groups receiving vaccine formulations for the Northern Hemisphere [NH] 2006/2007 influenza season) or A/Solomon Islands (for all groups receiving vaccine formulations for the NH 2007/2008 influenza season), A/Wisconsin and B/Malaysia antigens. | At Days 0 and 21 | 
| Number of Subjects Reporting Any and Grade 3 Solicited Local Adverse Events (AEs) | Grade 3 ecchymosis, redness and swelling was greater than 100 millimeter (mm) i.e. >100mm and grade 3 pain was considerable pain at rest that prevented normal everyday activities. Any was occurrence of any local symptom regardless of their intensity grade. Any for ecchymosis, redness and swelling was >20mm. | During a 7-day follow-up period (Day 0-6) after vaccination | 
| Duration of Solicited Local AEs | Duration was defined as number of days with any grade of local symptoms. | During a 7-day follow-up period (Day 0-6) after vaccination | 
| Number of Subjects Reporting Any, Grade 3 and Related Solicited General AEs | Any temperature was defined as oral temperature greater than or equal to 38.0 degree centigrade i.e ≥38.0°C, grade 3 temperature was oral temperature ≥39.0°C. For other symptoms, any was defined as occurrence of any general symptom regardless of intensity grade or relation to vaccination and grade 3 was defined as a general symptom that prevented normal activity. Related was a general symptom assessed by the investigator as causally related to the study vaccination. | During a 7-day follow-up period (Day 0-6) after vaccination | 
| Duration of Solicited General AEs | Duration was defined as number of days with any grade of general symptoms. | During a 7-day follow-up period (Day 0-6) after vaccination | 
| Number of Subjects Reporting Any, Grade 3 and Related Unsolicited 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 was defined as occurrence of any unsolicited symptom regardless of intensity grade or relation to vaccination. Grade 3 was an event that prevented normal activities and related was defined as an unsolicited AE assessed by the investigator to be causally related to the study vaccination. | During a 21-day follow-up period (Day 0-20) after vaccination | 
| Number of Subjects Reporting Any, Grade 3 and Related Medically Significant Conditions (MSCs) | MSCs were defined as an AEs with a medically-attended visit (MAE) i.e. prompting emergency room (ER) visits, hospitalizations or physician visits and that were not routine visits for physical examination or vaccination. Any MSC was defined as at least one MSC experienced. Grade 3 was a MSC that prevented normal activities and related was defined as a MSC assessed by the investigator to be causally related to the study vaccination. | During a 21-day follow-up period (Day 0-20) 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 was defined as occurrence of any symptom regardless of intensity grade or relation to vaccination and related was an event assessed by the investigator as causally related to the study vaccination. | During a 21-day follow-up period (Day 0-20) after vaccination | 

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