Study to Demonstrate the Lot-to-lot Consistency and to Evaluate the Safety of an Adjuvanted Influenza Vaccine Candidate

Study Overview
=================
Brief Summary
-----------------
The purpose of this phase IIb study is to demonstrate the consistency of three lots of an adjuvanted influenza vaccine candidate and to evaluate the safety of this vaccine compared to Fluarix™ administered intramuscularly in elderly aged 60 years old and above.

Detailed Description
-----------------
The Protocol Posting has been updated in order to comply with the FDA Amendment Act, Sep 2007.

Official Title
-----------------
Demonstrate the Lot-to-lot Consistency of 3 Consecutive Production Lots of an Adjuvanted Influenza Vaccine Candidate and Evaluate the Safety of an Adjuvanted Influenza Vaccine Candidate Versus Fluarix™ Administered Intramuscularly in Elderly

Conditions
-----------------
Influenza

Intervention / Treatment
-----------------
* Biological: Candidate Influenza Vaccine GSK1247446A - 3 different formulations
* Biological: Fluarix TM


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: A male or female age 60 years or older at the time of the vaccination. Subjects who the investigator believes can and will comply with the requirements of the protocol Written informed consent obtained from the subject. Free of an acute aggravation of the health status as established by clinical examination before entering into the study. Exclusion Criteria: Use of any investigational or non-registered product (drug or vaccine) within 30 days preceding the administration of the study vaccine, or planned use during the study period. Acute clinically significant pulmonary, cardiovascular, hepatic or renal functional abnormality, as determined by physical examination or laboratory screening tests. Chronic administration (defined as more than 14 days) of immunosuppressants or other immune-modifying drugs within three months prior to the first vaccine dose. Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination Administration of immunoglobulins and/or any blood products within the 3 months preceding the first dose of study vaccine or planned administration 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 30 days after vaccination. History of hypersensitivity to a previous dose of influenza vaccine. History of confirmed influenza infection within the last 12 months. History of allergy or reactions likely to be exacerbated by any component of the vaccine(s) Acute disease at the time of enrolment

Ages Eligible for Study
-----------------
Minimum Age: 60 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: GSK1247446A Lot 1 Group<br>Subjects aged 60 years or older at the time of vaccination received 1 dose of Lot 1 GSK1247446A vaccine adjuvanted with AS03 at Day 0. The vaccine was administered intramuscularly into the deltoid region of the non-dominant arm. | Biological: Candidate Influenza Vaccine GSK1247446A - 3 different formulations<br>* Single dose, Intramuscular injection<br>|
| Experimental: GSK1247446A Lot 2 Group<br>Subjects aged 60 years or older at the time of vaccination received 1 dose of Lot 2 GSK1247446A vaccine adjuvanted with AS03 at Day 0. The vaccine was administered intramuscularly into the deltoid region of the non-dominant arm. | Biological: Candidate Influenza Vaccine GSK1247446A - 3 different formulations<br>* Single dose, Intramuscular injection<br>|
| Experimental: GSK1247446A Lot 3 Group<br>Subjects aged 60 years or older at the time of vaccination received 1 dose of Lot 3 GSK1247446A vaccine adjuvanted with AS03 at Day 0. The vaccine was administered intramuscularly into the deltoid region of the non-dominant arm. | Biological: Candidate Influenza Vaccine GSK1247446A - 3 different formulations<br>* Single dose, Intramuscular injection<br>|
| Experimental: GSK1247446A Pooled Group<br>Subjects aged 60 years or older at the time of vaccination received 1 dose of Lot 1, 2 or 3 GSK1247446A vaccines adjuvanted with AS03 at Day 0. The vaccines were administered intramuscularly into the deltoid region of the non-dominant arm. | Biological: Candidate Influenza Vaccine GSK1247446A - 3 different formulations<br>* Single dose, Intramuscular injection<br>|
| Active Comparator: Fluarix Group<br>Subjects aged 60 years or older at the time of vaccination received 1 dose of FluarixTM vaccine adjuvanted with AS03 at Day 0. The vaccines were administered intramuscularly into the deltoid region of the non-dominant arm. | Biological: Fluarix TM<br>* Single dose, Intramuscular injection<br>|

What is the study measuring?
-----------------
Primary 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 influenza strains assessed were A/New Caledonia, A/New York and B/Malaysia. The seropositivity cut-off assay was 1:10. The results for the GSK1247446A Lot 1, 2, 3 and Pooled Groups are the primary efficacy variables. | At Days 0 and 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 assessed influenza strains were A/New Caledonia, A/New York and B/Malaysia. The results for the GSK1247446A Lot 1, 2, 3 and Pooled Groups are the primary efficacy variables. | At Day 21 | 
| Number of Seroprotected Subjects Against 3 Strains of Influenza Disease. | A seroprotected subject was defined as a vaccinated subject who had a serum HI titer ≥ 1:40. The 3 assessed influenza strains were A/New Caledonia, A/New York and B/Malaysia. The results for the GSK1247446A Lot 1, 2, 3 and Pooled Groups are the primary efficacy variables. | At Days 0 and 21 | 
| Seroconversion Factor for Hemagglutination Inhibition (HI) Antibodies Against 3 Strains of Influenza Disease. | The seroconversion factor (SCF) was defined as the fold increase in serum Hemagglutination Inhibition (HI) geometric mean titers (GMTs) post vaccination compared to Day 0. The 3 assessed influenza strains were A/New Caledonia, A/New York and B/Malaysia. The results for the GSK1247446A Lot 1, 2, 3 and Pooled Groups are the primary efficacy variables. | At Day 21 | 
| Number of Subjects With Any, Grade 3 and Related Solicited Local Symptoms. | Assessed solicited local symptoms were ecchymosis, pain, redness and swelling at injection site. Any = incidence of a particular symptom regardless of intensity grade. Grade 3 pain = pain that prevented normal activity. Grade 3 redness/swelling/ecchymosis = redness/swelling/ecchymosis spreading beyond 50 millimeters (mm) of the injection site. All solicited local symptoms were assessed by the investigator as being related to study vaccination. | During the 7-day (Days 0-6) post vaccination period | 
| Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms. | Assessed solicited general symptoms were arthralgia, fatigue, fever [oral temperature equal to or above (≥) 37.5 degrees Celsius (°C)], headache, muscle aches and shivering. Any = incidence of a particular symptom regardless of grade intensity or relationship with the study vaccination. Grade 3 symptom = symptom that prevented normal activity. Grade 3 fever = fever > 39.0°C. Related = symptom considered by the investigator to have a causal relationship to study vaccination. | During the 7-day (Days 0-6) post vaccination period | 
| Number of Subjects With New Onset of Chronic Diseases (NOCDs). | NOCDs include conditions such as diabetes, autoimmune disease, asthma, allergies etc. This table includes rare events, defined as events with an occurrence rate of 0.1 % and belonging to the NOCDs. | From Day 0 to Day 180 | 
| Number of Subjects With Medically Significant Conditions (MSCs). | MSCs were defined as conditions prompting emergency room visits or physician visits that were not related to common diseases or routine visits. This table includes rare events, defined as events with an occurrence rate of 0.1 % and belonging to the MSCs. | From Day 0 to Day 180 | 
| Number of Subjects With Any, Grade 3 and Related Unsolicited Adverse Events (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 = any unsolicited AE regardless of intensity or relationship to vaccination. Grade 3 = unsolicited AE that prevented normal activity Related = unsolicited AE assessed by the investigator as related to the vaccination. This table includes rare events, defined as events with an occurrence rate of 0.1 % and belonging to the AEs. | During the 30-day (Days 0-29) post-vaccination period | 
| Number of Subjects With 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 = any SAE regardless of intensity or relationship to vaccination. Related (REL) = SAE assessed by the investigator as related to the vaccination. | During the entire study period (Days 0-180) | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Influenza, Influenza vaccine