Study to Evaluate the Safety and Immunogenicity of GlaxoSmithKline Biologicals' Influenza Vaccine in Elderly People

Study Overview
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Brief Summary
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The purpose of the study is to evaluate the safety of GSK Biologicals' influenza vaccine. Elderly subjects were randomized in the primary study (NCT00760617) and will now receive the same vaccine for the third time. For this study the masking is observer-blind for elderly subjects and open for young adult subjects.

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 investigational vaccine 2186877A
* Biological: FluarixTM


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: All subjects must satisfy ALL the following criteria at study entry: Subjects who the investigator believes that they can and will comply with the requirements of the protocol should be enrolled in the study. Specific attention should be given to the compliance potential of subjects with suspected drug or alcohol abuse. A male or female aged 19-43 years or >=66 years at the time of the vaccination and who participated in the study NCT00760617 and completed the 6-month follow-up. 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. Female subjects of non-childbearing potential may be enrolled in the study. Non-childbearing potential is defined as pre-menarche, current tubal ligation, hysterectomy, ovariectomy or post-menopause. Female subjects of childbearing potential may be enrolled in the study if the subject: has practiced adequate contraception for 30 days prior to vaccination, and has a negative pregnancy test on the day of vaccination, and has agreed to continue adequate contraception for 2 months after the vaccination. Exclusion Criteria: The following criteria should be checked at the time of study entry. If ANY exclusion criterion applies, the subject must not be included in the study: Use of any investigational or non-registered product 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 2009 with a seasonal influenza vaccine. Chronic administration 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 clinically significant pulmonary, cardiovascular, hepatic, renal, neurological and psychiatric disorders, as determined by clinical evaluation or pre-existing laboratory screening tests. Acute disease and/or fever at the time of enrolment. Fever is defined as temperature >=37.5°C on oral setting. Subjects with a minor illness without fever may be enrolled at the discretion of the investigator. Administration of immunoglobulins and/or any blood products within the three months preceding the administration of the study vaccine or planned administration during the study. Any medical conditions in which IM 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: 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 ≥ 66 years receiving 1 dose of New generation influenza vaccine GSK2186877A | Biological: GSK investigational vaccine 2186877A<br>* Single dose, intramuscular injection<br>|
| Active Comparator: Fluarix elderly Group<br>Subjects aged ≥ 66 years receiving 1 dose of Fluarix vaccine | Biological: FluarixTM<br>* Single dose, intramuscular injection<br>|
| Active Comparator: Fluarix young Group<br>Subjects aged 19-43 years receiving 1 dose of Fluarix vaccine | Biological: FluarixTM<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 ≥ 100 millimeter (mm) and grade 3 pain was considerable pain at rest, that prevented normal everyday activities. | 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 fever was defined as oral temperature ≥ 38.0 degree centigrade (°C), grade 3 fever was oral temperature ≥ 39.0°C-≤ 40.0°C. For other symptoms, any was defined as occurrence of any general symptom regardless of intensity grade, grade 3 was defined as general symptom that prevented normal activity and 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, grade 3 was unsolicited symptom that prevented normal activity and related was event assessed by the investigator as causally related to the study vaccination. | Day 0-20 | 
| Number of Subjects Reporting Any, Grade 3 and Related AEs With a Medically Attended Visit | 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 causally related to the study vaccination. | Day 0-179 | 
| Number of Subjects Reporting AEs of Specific Interest (AESI) | 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 autoimmune 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 causally related to the study vaccination. | Day 0-179 | 
| Number of Subjects Reporting Any and Related Serious Adverse Events (SAEs) up to Day 180 | 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. | Up to Day 180 | 
| Number of Subjects Reporting Any and Related Serious Adverse Events (SAEs) After Day 180 | 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. | After Day 180 | 

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 titers (GMTs) against separate vaccine strains. The vaccine strains included A/Brisbane, A/Uruguay and B/Brisbane antigens. | Day 0 and Day 21 | 
| HI Antibody Titers at Day 180 | Antibody titers were expressed as GMTs against 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 Days 0 and 21 | Seropositivity was defined as antibody titer greater than or equal to the cut-off value i.e ≥ 1:10. | Day 0 and Day 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. | Day 180 | 
| The Number of Subjects Seroconverted to HI Antibodies at Day 21 | A seroconverted subject was defined as a subject who had 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. | Day 21 | 
| The Number of Subjects Seroconverted to HI Antibodies at Day 180 | A seroconverted subject was defined as a subject who had 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. | Day 180 | 
| HI Antibody Seroconversion Factors (SCF) at Day 21 | SCF was defined as the fold increase in serum HI GMTs post-vaccination compared to Day 0. | At 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. | At Day 180 | 
| The Number of Subjects Seroprotected to HI Antibodies at Days 0 and 21 | A seroprotected subject was defined as a subject with a serum HI titer ≥ to 1:40 that usually is accepted as indicating protection. | At Day 0 and Day 21 | 
| The Number of Subjects Seroprotected to HI Antibodies at Day 180 | A seroprotected subject was defined as a subject with a serum HI titer ≥ 1:40 that usually is accepted as indicating protection. | At 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 Strains Expressing at Least Two Different Markers or Expressing Different Combinations of Markers at Days 0 and 21 | The markers assessed were Cluster of Differentiation 40 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 Day 21 | 
| The 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 Day 180 | The markers assessed were CD40L, IL-2, TNF-α and IFN-γ and vaccine strains tested included A/Brisbane, A/Uruguay and B/Brisbane antigens. | At Day 180 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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influenza infection, Influenza Vaccines, GSK Bio's influenza vaccine GSK2186877A