Safety and Immunogenicity Study of GSK Biologicals' Seasonal Influenza Candidate Vaccine (GSK2321138A)

Study Overview
=================
Brief Summary
-----------------
This study is designed to assess the safety and immunogenicity of a GSK Biologicals' investigational vaccine GSK2321138A in adults 18 years old and older. This study is also designed to assess the lot-to-lot consistency of vaccine GSK2321138A. The blinding will be double blind for all groups except for the GSK2604409A Group which will be open.

Official Title
-----------------
Partially-blind Immunogenicity and Safety Study of GSK Biologicals' Seasonal Influenza Vaccine GSK2321138A in Adults.

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

Intervention / Treatment
-----------------
* Biological: Influenza vaccine GSK2321138A
* Biological: FluarixTM
* Biological: Influenza vaccine GSK2604409A


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: A male or female 18 years of age or older at the time of the first vaccination Subjects who the investigator believes can and will comply with the requirements of the protocol. Written informed consent obtained from the subject. Healthy subjects or those with chronic well-controlled disease as established by physical examination before entering into the study. Female subjects of non-childbearing potential may be enrolled in the study. 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 urine pregnancy test on the day of vaccination, and has agreed to continue adequate contraception during the entire treatment period and for 2 months after completion of the vaccination series Exclusion Criteria: Use of any investigational or non-registered product other than the study vaccine within 30 days preceding the dose of the study vaccine or planned use during the study period. Chronic administration of immunosuppressants or other immune-modifying drugs within three months prior to enrolment in this study or planned administration during the study period. Administration of an influenza vaccine during the 6 months preceding entry into the study. Planned administration / administration of a vaccine not foreseen by the study protocol within 30 days before vaccination and up to Day 21. Any contra-indication to intramuscular administration of the influenza vaccines. History of hypersensitivity/anaphylaxis to a previous dose of influenza vaccine, history of any reaction or hypersensitivity likely to be exacerbated by any component of the vaccines. Any administration of a long-acting immune-modifying drug within 3 months before study start, or planned administration during the study period. Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination. Acute disease and/or fever at the time of enrolment. Acute or chronic, clinically significant pulmonary, cardiovascular, hepatic or renal functional abnormality, as determined by physical examination or laboratory screening tests. History of Guillain-Barré syndrome within 6 weeks of receipt of prior inactivated influenza virus vaccine. Administration of immunoglobulins and/or any blood products within the three months prior to the enrolment in this study, or planned during the study. History of chronic alcohol consumption and/or drug abuse. Any condition which, in the opinion of the investigator, prevents the subject from participating in the study Pregnant or lactating female.

Ages Eligible for Study
-----------------
Minimum Age: 18 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: GSK2321138A Lot 1 Group<br>Subjects received one dose of the GSK2321138A vaccine, Lot 1, at Day 0. The GSK2321138A vaccine was administered as a single dose intramuscularly in the deltoid region of the non-dominant arm. | Biological: Influenza vaccine GSK2321138A<br>* One intramuscular injection<br>|
| Experimental: GSK2321138A Lot 2 Group<br>Subjects received one dose of the GSK2321138A vaccine, Lot 2, at Day 0. The GSK2321138A vaccine was administered as a single dose intramuscularly in the deltoid region of the non-dominant arm. | Biological: Influenza vaccine GSK2321138A<br>* One intramuscular injection<br>|
| Experimental: GSK2321138A Lot 3 Group<br>Subjects received one dose of the GSK2321138A vaccine, Lot 3, at Day 0. The GSK2321138A vaccine was administered as a single dose intramuscularly in the deltoid region of the non-dominant arm. | Biological: Influenza vaccine GSK2321138A<br>* One intramuscular injection<br>|
| Active Comparator: Fluarix Group<br>Subjects received one dose of the Fluarix™ vaccine at Day 0. The Fluarix™ vaccine was administered as a single dose intramuscularly in the deltoid region of the non-dominant arm. | Biological: FluarixTM<br>* One intramuscular injection<br>|
| Active Comparator: GSK2604409A Group<br>Subjects received one dose of the GSK2604409A vaccine at Day 0. The GSK2604409A vaccine was administered as a single dose intramuscularly in the deltoid region of the non-dominant arm. | Biological: Influenza vaccine GSK2604409A<br>* One intramuscular injection<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Titers for Hemagglutination Inhibition (HI) Antibodies Against 4 Strains of Influenza Disease | Titers are presented as geometric mean titers (GMTs). The reference cut-off value was 1:10. HI antibodies assessed were antibodies against the A/California/7/2009 (H1N1), A/Victoria/210/2009 (H3N2), B/Brisbane/60/2008 (Victoria), and B/Brisbane/3/2007 (Yamagata) flu strains. Subjects receiving the GSK2321138A vaccine were pooled for this outcome measure. | At Day 0 (D 0), and at Day 21 (D 21) | 
| Number of Seroconverted Subjects Against 4 Strains of Influenza Disease | A seroconverted subject was a vaccinated subject who had either a pre-vaccination hemagglutination inhibition (HI) antibody titer < 1:10 and a post-vaccination titer above or equal (>=) 1:40, or a pre-vaccination HI antibody titer >= 1:10 and at least a 4-fold increase in post-vaccination HI antibody titer. Antibodies assessed were HI antibodies against the A/California/7/2009 (H1N1), A/Victoria/210/2009 (H3N2), B/Brisbane/60/2008 (Victoria), and B/Brisbane/3/2007 (Yamagata) flu strains. Subjects receiving the GSK2321138A vaccine were pooled for this outcome measure. | At Day 21 (D 21) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Seropositive Subjects Against 4 Strains of Influenza Disease | A seropositive subject was a vaccinated subject with hemagglutination inhibition (HI) antibody titer above or equal (>=) the reference cut-off value of 1:10. Antibodies assessed were HI antibodies against the A/California/7/2009 (H1N1), A/Victoria/210/2009 (H3N2), B/Brisbane/60/2008 (Victoria), and B/Brisbane/3/2007 (Yamagata) flu strains. Subjects receiving the GSK2321138A vaccine were pooled for this outcome measure. | At Day 0 (D 0), and at Day 21 (D 21) | 
| Number of Seroprotected Subjects Against 4 Strains of Influenza Disease | A seroprotected subject was a vaccinated subject who had hemagglutination inhibition (HI) antibody titer above or equal (>=) 1:40. Antibodies assessed were HI antibodies against the A/California/7/2009 (H1N1), A/Victoria/210/2009 (H3N2), B/Brisbane/60/2008 (Victoria), and B/Brisbane/3/2007 (Yamagata) flu strains. Subjects receiving the GSK2321138A vaccine were pooled for this outcome measure. | At Day 0 (D 0), and at Day 21 (D 21) | 
| Increase in Hemagglutination Inhibition Antibodies Against 4 Strains of Influenza Disease | Increase in hemagglutination inhibition (HI) antibodies is presented in terms of mean geometric increase (MGI), defined as the geometric mean of the within subject ratios of the post-vaccination reciprocal HI titer to the Day 0 reciprocal HI titer , expressed using fold increase as unit . Antibodies assessed were HI antibodies against the A/California/7/2009 (H1N1), A/Victoria/210/2009 (H3N2), B/Brisbane/60/2008 (Victoria), and B/Brisbane/3/2007 (Yamagata) flu strains. Subjects receiving the GSK2321138A vaccine were pooled for this outcome measure. | At Day 21 (D 21) | 
| Number of Subjects With Any and Grade 3 Solicited Local Symptoms. | Assessed solicited local symptoms post vaccination were pain, redness and swelling at the injection site. Any = occurrence of a symptom regardless of intensity. Grade 3 pain = significant pain at rest/ that prevented normal every day activities. Grade 3 redness/swelling = redness/swelling spreading beyond 100 millimeters (mm) of injection site. | Within the 7-day (Days 0-6) follow-up period after vaccination | 
| Number of Days With Solicited Local Symptoms | Assessed solicited local symptoms post vaccination were pain, redness and swelling at the injection site. | Within 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 post vaccination were fatigue, gastrointestinal symptoms (Gastr.), headache, joint pain at other location (Joint Pain), muscle aches, shivering, and temperature [axillary temperature above or equal to (>=) 37.5 degrees Celsius (°C)]. Any = occurrence of a symptom regardless of intensity or relationship to vaccination. Grade 3 = symptom which prevented normal every day activities. Grade 3 temperature = axillary temperature > 39°C. Related = symptom assessed as causally related to study vaccination. | Within the 7-day (Days 0-6) follow-up period after vaccination | 
| Number of Days With Solicited General Symptoms | Assessed solicited general symptoms post vaccination were fatigue, gastrointestinal symptoms (Gastr.), headache, joint pain at other location (Joint Pain), muscle aches, shivering, and temperature [defined as axillary temperature above or equal to (≥) 37.5 degrees Celsius (°C)]. | Within the 7-day (Days 0-6) follow-up period after vaccination | 
| Number of Subjects With Any, Grade 3 and Related Unsolicited Adverse Events (AEs) | Unsolicited AEs cover 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 unsolicited AE = any unsolicited AE regardless of intensity or relationship to vaccination. Grade 3 unsolicited AE = unsolicited AE that prevented normal everyday activity Related unsolicited AE = unsolicited AE assessed by the investigator as related to the vaccination. | Within the 21-day (Days 0-20) follow-up period after vaccination | 
| Number of Subjects With Any and Related Adverse Events With Medically-attended Events (MAEs) | Medically-attended events (MAEs) refer to non-serious and serious events leading to an otherwise unscheduled visit to or from medical personnel for any reason, including emergency room visits. If a MAE was leading to hospitalisation (or met any other serious adverse event criterion), it was reported as serious adverse event. Related MAE = MAE assessed by the investigator as related to the vaccination. Subjects receiving the GSK2321138A vaccine were pooled for this outcome measure. | From the beginning of the study (Day 0) to study end (Day 180) | 
| Number of Subjects With Any and Related Potential Immune-mediated Diseases (pIMDs) | Potential immune-mediated diseases (pIMDs) are a subset of adverse events that include both clearly autoimmune diseases and also other inflammatory and/or neurologic disorders which may or may not have an autoimmune etiology. Related pIMD = pIMD assessed by the investigator as related to the vaccination. Subjects receiving the GSK2321138A vaccine were pooled for this outcome measure. | From the beginning of the study (Day 0) to study end (Day 180) | 
| Number of Subjects With Any and Related 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, result in disability/incapacity or are a congenital anomaly/birth defect in the offspring of a study subject. Any SAE = any SAE regardless of intensity or relationship to vaccination. Related SAE = SAE assessed by the investigator as related to the vaccination. | From the beginning of the study (Day 0) to study end (Day 180) | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
influenza infection, GSK Biologicals influenza vaccine GSK2321138A