Evaluation of Safety and Immunogenicity of GSK Biologicals' Influenza Vaccine GSK2186877A in Adults 65 Years and Older

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety and immunogenicity of GlaxoSmithKline Biologicals' influenza vaccine GSK2186877A in adults 65 year of age and older. This protocol posting deals with objectives & outcome measures of the extension phase at year 1. The objectives & outcome measures of the primary phase are presented in a separate protocol posting (NCT number = 00540592).

Official Title
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Observer-blind Safety and Immunogenicity Study of GlaxoSmithKline Biologicals' Influenza Vaccine GSK2186877A When Administered to Elderly Subjects.

Conditions
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Influenza

Intervention / Treatment
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* Biological: GSK Bio's influenza vaccine GSK2186877A
* Biological: Fluarix


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. A male or female aged 18-41 years or ≥65 years at the time of the vaccination and who participated in the 110847 study and completed the 6 month follow-up. Written informed consent obtained from the subject. Fee of acute aggravation of the health status as established by clinical evaluation (medical history and medical history directed examination) before entering into the study. Female subjects must be of non-childbearing potential. 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 an influenza vaccine other than the study vaccines or of a vaccine not foreseen in the study protocol during the entire study period. Vaccination against influenza since January 2008 with a seasonal 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. 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 (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 IM injections are contraindicated. Lactating female, female planning to become pregnant or planning 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: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: New generation influenza vaccine GSK2186877A Group<br>Subjects aged ≥65 years received 1 dose of New generation influenza vaccine GSK2186877A | Biological: GSK Bio's influenza vaccine GSK2186877A<br>* Intramuscular (IM) administration, 1 dose<br>|
| Active Comparator: Fluarix elderly Group<br>Subjects aged ≥65 years received 1 dose of Fluarix vaccine | Biological: Fluarix<br>* Intramuscular (IM) administration, 1 dose<br>|
| Active Comparator: Fluarix young Group<br>Subjects aged 18-40 years received 1 dose of Fluarix vaccine | Biological: Fluarix<br>* Intramuscular (IM) administration, 1 dose<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 or equal to 100 millimeter (mm) 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 and grade for quantifiable symptoms: ecchymosis, redness and swelling was greater than (>) 20mm. | Day 0-6 | 
| Number of Subjects Reporting Any, Grade 3 and Related Solicited General AEs | Any fever was defined as oral temperature ≥38.0 degree centigrade (°C), grade 3 fever was oral temperature >40.0°C. For other symptoms, any was defined as occurrence of any general symptom regardless of intensity grade or relationship to vaccination, grade 3 was defined as a general symptom that prevented normal activity and related was a 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 adverse event (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, grade 3 was unsolicited symptom that prevented normal activity and related was event assessed by the investigator as possibly related to the study vaccination. | Day 0-20 | 
| Number of Subjects Reporting Any, Grade 3 and Related AEs With a Medically Attended Visit Between Day 0 to 20 | For each solicited and unsolicited AE the subject experienced, the subject was asked if they had received medical attention defined as hospitalization, an emergency room visit or a visit to or from medical personnel (medical doctor) for any reason. Any was defined as occurrence of any symptom regardless of intensity grade, grade 3 was defined as symptom that prevented normal activity and related was general symptom assessed by the investigator as possibly related to the study vaccination. | Day 0-20 | 
| Number of Subjects Reporting Any, Grade 3 and Related AEs With a Medically Attended Visit Between Day 21 to 179 | For each solicited and unsolicited AE the subject experienced, the subject was asked if they had received medical attention defined as hospitalization, an emergency room visit or a visit to or from medical personnel (medical doctor) for any reason. Any was defined as occurrence of any symptom regardless of intensity grade, grade 3 was defined as symptom that prevented normal activity and related was general symptom assessed by the investigator as possibly related to the study vaccination. | Day 21-179 | 
| Number of Subjects Reporting AEs of Specific Interest (AESI) Including Autoimmune Disease (AID) | AESI for safety monitoring are a subset of AEs that include both clearly autoimmune diseases and also other inflammatory and/or neurologic disorders which may or may not have an autoiimune etiology. Any was defined as occurrence of any symptom regardless of intensity grade, grade 3 was defined as symptom that prevented normal activity and related was general symptom assessed by the investigator as possibly related to the study vaccination. | Day 0-179 | 
| Number of Subjects Reporting Any and Related Serious Adverse Events (SAEs) Between Day 0 to Day 20 | 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 | 
| Number of Subjects Reporting Any and Related Serious Adverse Events (SAEs) Between Day 21 to Day 179 | 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 21-179 | 
| Number of Subjects Reporting Any and Related Serious Adverse Events (SAEs) From Day 180 to Day 209 | 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 180 to Day 209 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Haemagglutination Inhibition (HI) Antibody Titers at Days 0 and 21 | Antibody titers were expressed as Geometric mean titres (GMTs) with separate vaccine strains. The vaccine strains included A/Brisbane, A/Uruguay and B/Brisbane antigens. | At Day 0 and 21 | 
| HI Antibody Titers at Day 180 | Antibody titers were expressed as GMTs with separate vaccine strains. The vaccine strains included A/Brisbane, A/Uruguay and B/Brisbane antigens. | Day 180 | 
| The Number of Subjects Seropositive to HI Antibodies at Day 0 and 21 | Seropositivity was defined as antibody titer greater than or equal to the cut-off value i.e ≥ 1:10. The vaccine strains included A/Brisbane, A/Uruguay and B/Brisbane antigens. | At Day 0 and 21 | 
| The Number of Subjects Seropositive to HI Antibodies at Day 180 | Seropositivity was defined as antibody titer greater than or equal to the cut-off value i.e ≥ 1:10. The vaccine strains included A/Brisbane, A/Uruguay and B/Brisbane antigens. | Day 180 | 
| The Number of Subjects Seroconverted to HI Antibodies at Day 21 | Seroconversion was defined as the percentage of vaccinees who had either a pre-vaccination titre less than (<) 1:10 and a post-vaccination titre ≥1:40 or a pre-vaccination titre ≥1:10 and at least a 4-fold increase in post-vaccination titre. The vaccine strains included A/Brisbane, A/Uruguay and B/Brisbane antigens. | Day 21 | 
| The Number of Subjects Seroconverted to HI Antibodies at Day 180 | Seroconversion was defined as the percentage of vaccinees who had either a pre-vaccination titre <1:10 and a post-vaccination titre ≥1:40 or a pre-vaccination titre ≥1:10 and at least a 4-fold increase in post-vaccination titre. The vaccine strains included A/Brisbane, A/Uruguay and B/Brisbane antigens. | Day 180 | 
| HI Antibody Seroconversion Factor (SCF) at Day 21 | SCF was defined as the fold increase in serum HI GMTs post-vaccination compared to Day 0. The vaccine strains included A/Brisbane, A/Uruguay and B/Brisbane antigens. | Day 21 | 
| HI Antibody SCF at Day 180 | SCF was defined as the fold increase in serum HI GMTs post-vaccination compared to Day 0. The vaccine strains included A/Brisbane, A/Uruguay and B/Brisbane antigens. | Day 180 | 
| The Number of Subjects Seroprotected to HI Antibodies at Day 0 and Day 21 | Seroprotection was defined as the percentage of vaccinees with a serum HI titre ≥1:40 that usually is accepted as indicating protection. The vaccine strains included A/Brisbane, A/Uruguay and B/Brisbane antigens. | At Day 0 and 21 | 
| The Number of Subjects Seroprotected to HI Antibodies at Day 180 | Seroprotection was defined as the percentage of vaccinees with a serum HI titre ≥1:40 that usually is accepted as indicating protection. The vaccine strains included A/Brisbane, A/Uruguay and B/Brisbane antigens. | Day 180 | 
| The Geometric Mean (GM) Number of Influenza Specific Cluster of Differentiation 4 (CD4) T-cells Per Million CD4 T-cells for Each Vaccine Strain Expressing at Least Two Different Markers or Expressing Different Combinations of Markers at Days 0 and 21 | The markers assessed were CD4-ALL DOUBLES, CD40 Ligand (CD40L), interleukin 2 (IL-2), tumour necrosis factor alpha (TNF-α) and interferon gamma (IFN-γ) and vaccine strains tested included A/Brisbane, A/Uruguay and B/Brisbane antigens. | At Day 0 and 21 | 

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