Evaluation of 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 104887 will receive a dose with the 2007-2008 season's formulations of Fluarix or GSK576389A. Only subjects who were previously enrolled in study 104887 are eligible for participation in this study.

Detailed Description
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This study is a year 2 revaccination study. First year revaccination was done in study 104887 (NCT00386698). Primary study was study 104886 (NCT00318149). This study involves 2 age groups (based on primary study): Subjects enrolled in the ≥ 65 years age group in the primary study. Subjects enrolled in the 18-40 years age group in the primary study. 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 (≥66 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: Fluarix™
* Biological: GSK Bio's Influenza Vaccine GSK576389A


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 investigational vaccines in the 104887 study (NCT00386698). 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 between 19 and 42 years or 66 years and 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. 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. 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. 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. History of confirmed influenza infection since the date of previous vaccination. 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. (For corticosteroids, this will mean prednisone, or equivalent, ≥0.5 mg/kg/day. Inhaled and topical steroids are allowed.) 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. (Acute disease is defined as the presence of a moderate or severe illness with or without fever. All vaccines can be administered to persons with a minor illness such as diarrhea, mild upper respiratory infection with or without low-grade febrile illness, i.e. Axillary temperature <37.5°C / Oral temperature of <37.5°C). 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. Pregnant or lactating female. Female planning to become pregnant or planning to discontinue contraceptive precautions.

Ages Eligible for Study
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Minimum Age: 19 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: Adjuvanted influenza vaccine GSK576389A Group<br>Subjects aged ≥ 66 years who previously received 1 dose of adjuvanted influenza vaccine GSK576389A in NCT00318149 and NCT00386698 studies were administered 1 dose of adjuvanted influenza vaccine GSK576389A. | Biological: GSK Bio's Influenza Vaccine GSK576389A<br>* Single dose, Intramuscular injection<br>|
| Active Comparator: Fluarix young Group<br>Subjects aged 19-42 years who previously received 1 dose of Fluarix vaccine in NCT00318149 and NCT00386698 studies were administered 1 dose of Fluarix vaccine. | Biological: Fluarix™<br>* Single dose, Intramuscular injection<br>|
| Active Comparator: Fluarix elderly Group<br>Subjects aged ≥ 66 years who previously received 1 dose of Fluarix vaccine in NCT00318149 and NCT00386698 studies were administered 1 dose of Fluarix vaccine. | 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) | Grade 3 ecchymosis, redness and swelling was greater than 100 millimeter i.e. >100 mm 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. | Day 0-6 | 
| Duration of Solicited Local AEs | Duration was defined as number of days with any grade of local symptoms. | Day 0-6 | 
| Number of Subjects Reporting Any, Grade 3 and Related Solicited General AEs | Any temperature was defined as axillary temperature ≥38.0 degree centigrade (°C), grade 3 temperature was axillary 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 general symptom that prevented normal activity. Related was general symptom assessed by the investigator as causally related to the study vaccination. | Day 0-6 | 
| Duration of Solicited General AEs | Duration was defined as number of days with any grade of general symptoms. | Day 0-6 | 
| 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 event that prevented normal activities and related was defined as unsolicited AE assessed by the investigator to be causally related to the study vaccination. | Day 0-20 | 
| Number of Subjects Reporting at Least One, Grade 3 and Related Medically Significant Conditions (MSCs) | MSCs were defined as AEs with a medically-attended visit i.e. prompting emergency room (ER) visits, hospitalizations or physician visits and that were not routine visits for physical examination or vaccination. At least one MSC was defined as at least one MSC experienced. Grade 3 was MSC that prevented normal activities and Related was defined as MSC assessed by the investigator to be causally related to the study vaccination. | Day 0-20 | 
| 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 and related was event assessed by the investigator as causally related to the study vaccination. | Day 0-20 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Haemagglutination Inhibition (HI) Antibody Titers | Antibody titers were expressed as Geometric mean titers (GMTs). The vaccine strains included A/Solomon Islands, A/Wisconsin and B/Malaysia antigens. | At Days 0 and 21 | 
| The Number of Subjects Seropositive to HI Antibodies | Seropositivity was defined as antibody titer greater than or equal to the cut-off value i.e. ≥ 1:10. The vaccine strains included A/Solomon Islands, A/Wisconsin and B/Malaysia antigens. | At Days 0 and 21 | 
| The Number of Subjects Seroconverted to HI Antibodies | Seroconversion was defined as 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 4-fold increase in post-vaccination titer. The vaccine strains included A/Solomon Islands, A/Wisconsin and B/Malaysia antigens. | At Day 21 | 
| HI Antibody Seroconversion Factors (SCF) | SCF was defined as the fold increase in serum HI GMTs post-vaccination compared to Day 0. The vaccine strains included A/Solomon Islands, A/Wisconsin and B/Malaysia antigens. | At Day 21 | 
| The Number of Subjects Seroprotected to HI Antibodies | Seroprotection was defined as serum HI titer ≥1:40 that usually is accepted as indicating protection. The vaccine strains included A/Solomon Islands, A/Wisconsin and B/Malaysia antigens. | At Days 0 and 21 | 
| The Geometric Mean (GM) Number of CD4 T-cells Per Million CD4+ T-cells for Each Vaccine Strain and for Pooled Vaccine Strains Producing at Least Two Different Immune Markers or Producing Each of the Immune Markers Plus Another Immune Marker | The vaccine strains included A/Solomon Islands, A/Wisconsin, B/Malaysia and Pool FLU antigens and the markers assessed were Cluster of Differentiation 4-All doubles i.e. CD4-All doubles, CD40 Ligand (CD40L), interferon-gamma (IFN-γ), interleukin-2 (IL-2) and tumor necrosis factor alpha (TNF-α). | At Days 0 and 21 | 
| The GM Number of CD8 T-cells Per Million CD8+ T-cells for Each Vaccine Strain and for Pooled Vaccine Strains Producing at Least Two Different Immune Markers or Producing Each of the Immune Markers Plus Another Immune Marker | The vaccine strains included A/Solomon Islands, A/Wisconsin, B/Malaysia and Pool FLU antigens and the markers assessed were CD8-All doubles, CD40L, IFN-γ, IL-2 and TNF-α. | At Days 0 and 21 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Influenza vaccine GSK576389A, Fluarix, Influenza infection