Safety Study of Four Candidate Influenza Vaccines to Prevent Influenza Disease in the Elderly Population

Study Overview
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Brief Summary
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As influenza vaccine efficacy is reported to be lower in elderly subjects compared to healthy adults, probably as a result of immunosenescence, there is a desire to devise ways to increase the current vaccines efficacy for this target population. Adjuvants are known to boost immune responses, thus representing one way to increase the efficacy of the current GlaxoSmithKline Fluarix™ influenza vaccine in elderly subjects. The purpose of this study is to evaluate the immunogenicity and the reactogenicity of a vaccination with four different adjuvanted GlaxoSmithKline influenza vaccines administered to elderly subjects. For immunogenicity and safety evaluations, healthy adults aged 18 to 40 years old and elderly aged 65 years and older will receive Fluarix™ and form the control groups of this trial.

Official Title
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Demonstrate the Non-inferiority in Term of Cellular Mediated Immune Response of GSK Biologicals' Influenza Candidate Vaccines Containing Various Adjuvants Administered in Elderly Population (Aged 65 Years &Amp; Older) vs Fluarix™ (Known as Alpha-Rix™ in Belgium) Administered in Adults (18-40 Years)

Conditions
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Influenza

Intervention / Treatment
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* Biological: Fluarix
* Biological: Fluarix-AS25
* Biological: Fluarix-AS50
* Biological: Fluarix-AS01B
* Biological: Fluarix-AS01E


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: A male or female aged between 18 and 40 years or aged 65 years or older at the time of the vaccination. Free of obvious health problems as established by medical history and clinical examination 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 preceding the administration of the study vaccine, or planned use during the study period. 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. History of confirmed influenza infection since a year from the date of previous vaccination. Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination History of hypersensitivity to vaccines. History of allergic disease or reactions likely to be exacerbated by any component of the vaccine. Acute clinically significant pulmonary, cardiovascular, hepatic or renal functional abnormality, as determined by physical examination or laboratory screening tests. Acute disease at the time of enrolment. Administration of immunoglobulins and/or any blood products within the three months preceding the administration of the study vaccine or during the study.

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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Fluarix 18-40 Y Group<br>Subjects (aged 18-40 years [Y]) received 1 dose of the Fluarix vaccine, administered intramuscularly in the deltoid region of the non-dominant arm. | Biological: Fluarix<br>* 1 dose administered intramuscularly in the deltoid region of the non-dominant arm<br>* Other names: GlaxoSmithKline Biologicals' licensed influenza vaccine;|
| Experimental: Fluarix ≥65 Y Group<br>Subjects (aged ≥ 65 years) received 1 dose of the Fluarix vaccine, administered intramuscularly in the deltoid region of the non-dominant arm. | Biological: Fluarix<br>* 1 dose administered intramuscularly in the deltoid region of the non-dominant arm<br>* Other names: GlaxoSmithKline Biologicals' licensed influenza vaccine;|
| Experimental: Fluarix-AS25 Group<br>Subjects (aged ≥ 65 years) received 1 dose of the Fluarix vaccine adjuvanted with AS25, administered intramuscularly in the deltoid region of the non-dominant arm. | Biological: Fluarix-AS25<br>* 1 dose administered intramuscularly into the deltoid region of the non-dominant arm<br>* Other names: Fluarix vaccine adjuvanted with AS25;|
| Experimental: Fluarix-AS50 Group<br>Subjects (aged ≥ 65 years) received 1 dose of the Fluarix vaccine adjuvanted with AS50, administered intramuscularly in the deltoid region of the non-dominant arm. | Biological: Fluarix-AS50<br>* 1 dose administered intramuscularly into the deltoid region of the non-dominant arm<br>* Other names: Fluarix vaccine adjuvanted with AS25;|
| Experimental: Fluarix- AS01B Group<br>Subjects (aged ≥ 65 years) received 1 dose of the Fluarix vaccine adjuvanted with AS01B, administered intramuscularly in the deltoid region of the non-dominant arm. | Biological: Fluarix-AS01B<br>* 1 dose administered intramuscularly into the deltoid region of the non-dominant arm<br>* Other names: Fluarix vaccine adjuvanted with AS01B;|
| Experimental: Fluarix- AS01E Group<br>Subjects (aged ≥ 65 years) received 1 dose of the Fluarix vaccine adjuvanted with AS01E, administered intramuscularly in the deltoid region of the non-dominant arm. | Biological: Fluarix-AS01E<br>* 1 dose administered intramuscularly into the deltoid region of the non-dominant arm<br>* Other names: Fluarix vaccine adjuvanted with AS01E;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequency of Influenza-specific Cluster of Differentiation 4+ (CD4+) T-cells Expressing at Least 2 Markers | The frequency was expressed as the geometric mean of influenza-specific CD4 T-cells, expressing at least 2 markers among CD40 Ligand (CD40L), Interleukin 2 (IL-2), Tumor Necrosis Factor-α (TNF-α) and Interferon-γ (IFN-γ ) upon in vitro stimulation. | At Day 21 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Titers for Serum Hemagglutination Inhibition (HI) Antibodies Against 3 Strains of Influenza Disease | Titers are presented as geometric mean titers (GMTs). The 3 flu strains assessed were A/New Caledonia (H1N1), A/New York (H3N2) and B/Jiangsu (B). Seropositivity was defined as a serum HI titer greater than or equal to (≥) 1:10. | At Day 0 and at Day 21 | 
| Titers for Serum HI Antibodies Against 3 Strains of Influenza Disease | Titers are presented as geometric mean titers (GMTs). The 3 flu strains assessed were A/New Caledonia (H1N1), A/New York (H3N2) and B/Jiangsu (B). Seropositivity was defined as a serum HI titer of ≥ 1:10. | At Day 90 and Day 180 | 
| Number of Seroconverted Subjects Against 3 Strains of Influenza Disease | A seroconverted subject was defined as a vaccinated 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 four-fold increase in post-vaccination titer. The 3 flu strains assessed were A/New Caledonia (H1N1), A/New York (H3N2) and B/Jiangsu (B). | At Day 21 | 
| Number of Seroconverted Subjects Against 3 Strains of Influenza Disease | A seroconverted subject was defined as a vaccinated 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 four-fold increase in post-vaccination titer. The 3 flu strains assessed were A/New Caledonia (H1N1), A/New York (H3N2) and B/Jiangsu (B). | At Day 90 and Day 180 | 
| Seroconversion Factor for Hemagglutination Inhibition (HI) Antibodies Against 3 Strains of Influenza Disease | The seroconversion factor (SCF) was defined as the fold change in serum Hemagglutination Inhibition (HI) geometric mean titers (GMTs) post vaccination compared to pre-vaccination time point. The 3 flu strains assessed were A/New Caledonia (H1N1), A/New York (H3N2) and B/Jiangsu (B). | At Day 21 | 
| Seroconversion Factor for Hemagglutination Inhibition (HI) Antibodies Against 3 Strains of Influenza Disease | The seroconversion factor (SCF) was defined as the fold change in serum Hemagglutination Inhibition (HI) geometric mean titers (GMTs) post vaccination compared to pre-vaccination time point. The 3 flu strains assessed were A/New Caledonia (H1N1), A/New York (H3N2) and B/Jiangsu (B). | At Day 90 and Day 180 | 
| Number of Seroprotected Subjects Against 3 Strains of Influenza Disease | A seroprotected subject was defined as a vaccinated subject with serum Hemagglutination Inhibition (HI) titer ≥ 1:40. The 3 flu strains assessed were A/New Caledonia (H1N1), A/New York (H3N2) and B/Jiangsu (B). | At Day 0 and at Day 21 | 
| Number of Seroprotected Subjects Against 3 Strains of Influenza Disease | A seroprotected subject was defined as a vaccinated subject with serum Hemagglutination Inhibition (HI) titer ≥ 1:40. The 3 flu strains assessed were A/New Caledonia (H1N1), A/New York (H3N2) and B/Jiangsu (B). | At Day 90 and Day 180 | 
| Number of Subjects With Any and Grade 3 Solicited Local Symptoms. | Assessed solicited local symptoms were haematoma, pain, redness and swelling. Any = occurrence of any local symptom regardless of intensity grade. Grade 3 pain = pain which prevented normal everyday activity. Grade 3 haematoma/redness/swelling = haematoma/redness/swelling spreading beyond 50 millimeters (mm). | During the 7-day (Days 0-6) follow-up period after vaccination | 
| Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms. | Assessed solicited general symptoms were fatigue, fever [defined as axillary temperature equal to or above 37.5 degrees Celsius (°C)], headache, joint pain, muscle aches and shivering. Any = occurrence of any general symptom regardless of intensity grade and relationship to vaccination. Grade 3 = symptoms that prevented normal activity. Grade 3 fever = fever >39°C. Related = general symptom assessed by the investigator as causally related to the study vaccination. | During the 7-day (Days 0-6) follow-up period after vaccination | 
| Number of Subjects With Any, Grade 3 and Related Unsolicited Adverse Events (AEs). | An unsolicited AE covers any untoward medical occurrence in a clinical investigation subject temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product and 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 the occurrence of any unsolicited AE regardless of intensity grade or relation to vaccination. Grade 3 =event that prevented normal everyday activity. Related = event assessed by the investigator as causally related to the study vaccination. | During the 21-day (Days 0-20) follow-up period after vaccination | 
| Number of Subjects With Serious Adverse Events (SAEs). | Serious adverse events (SAEs) assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity. | During the entire study period (Day 0 - Day 180) |