Study to Evaluate Immunogenicity and Safety of an Investigational Influenza Vaccine (H1N1)

Study Overview
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Brief Summary
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This trial will assess the immunogenicity and safety elicited by the adjuvanted GSK Biologicals' influenza investigational vaccine GSK2340274A in healthy Japanese adults aged 20-64 years.

Detailed Description
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This Protocol Posting has been updated following Protocol amendment 1& 2, October 2009. The sections impacted are study design and outcome measures

Official Title
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Immunogenicity and Safety Study of GSK Biologicals' Influenza Candidate Vaccine GSK2340274A

Conditions
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Influenza

Intervention / Treatment
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* Biological: Influenza investigational vaccine GSK2340274A


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Japanese male and female adults 20 to 64 years of age at time of the first vaccination, inclusive. Good general health as assessed by medical history and physical examination Subjects who the investigator believes that they can and will comply with the requirements of the protocol. Written informed consent obtained from the subject. Access to a consistent means of telephone contact, which may be either in the home or at the workplace, land line or mobile, but NOT a pay phone or other multiple-user device. Females of non-childbearing potential may be enrolled in the study. Female of childbearing potential may be enrolled in the study, if she: 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 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(s) within 30 days preceding the first dose of study vaccine, or planned use during the study period. History of previous administration of a novel [H1N1]v vaccine. Previous participation in study NCT00742885. Presence of significant acute or chronic, uncontrolled medical or psychiatric illness. Presence or evidence of substance abuse or of neurological or psychiatric diagnoses which, although stable, are deemed by the investigator to render the potential subject unable/unlikely to provide accurate safety reports. Presence of an axillary temperature >= 37.5 °C, or acute symptoms greater than mild severity on the scheduled date of first vaccination. Diagnosed with cancer, or treatment for cancer within 3 years. Any confirmed or suspected immunosuppressive or immunodeficient condition including history of human immunodeficiency virus (HIV) infection. Chronic administration of immunosuppressants or other immune modifying drugs within 6 months of study enrolment or planned administration during the study period. Receipt of any immunoglobulins and/or any blood products within 3 months of study enrolment or planned administration of any of these products during the study period. Any significant disorder of coagulation or treatment with warfarin derivatives or heparin. An acute evolving neurological disorder or history of Guillain-Barré syndrome. Administration of any vaccines within 30 days before vaccination or planned administration within the first vaccination up to blood sampling at Day 42 and within 30 days prior to blood sampling at Day 182, with the exception of seasonal influenza vaccine. Administration of any seasonal influenza vaccine within 14 days before vaccination on Day 0, or planned administration within the first vaccination up to blood sampling at Day 42 and within 14 days prior to blood sampling at Day 182. Any known or suspected allergy to any constituent of influenza vaccines or component used in the manufacturing process of the study vaccine; a history of anaphylactic-type reaction to any constituent of influenza vaccines; or a history of severe adverse reaction to a previous influenza vaccine. Known pregnancy or a positive urine test result prior to the time of first vaccination. Lactating or nursing female. Excessive underweight (Body Mass Index [BMI] < 18.5) or excessive obesity (BMI >= 30). Any conditions which, in the opinion of the investigator, prevents the subjects from participating in the study. Clinically or virologically confirmed influenza infection within 6 months preceding the study start.

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 64 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: GSK2340274A GROUP<br>Healthy subjects, aged 20 to 64 years, male and female, received 2 doses of GSK2340274A vaccine, injected intramuscularly in the deltoid region of the non-dominant arm at Day 0 and of the dominant arm at Day 21. | Biological: Influenza investigational vaccine GSK2340274A<br>* Two intramuscular injections on Day 0 and Day 21, respectively<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Titers for Serum Hemagglutination Inhibition (HI) Antibodies Against A/California/7/2009 (H1N1)V-like Antigen | Titers are presented as geometric mean titers (GMTs). | At Day 0 | 
| Titers for Serum Hemagglutination Inhibition (HI) Antibodies Against A/California/7/2009 (H1N1)V-like Antigen | Titers are presented as geometric mean titers (GMTs). | At Day 21 | 
| Titers for Serum Hemagglutination Inhibition (HI) Antibodies Against A/California/7/2009 (H1N1)V-like Antigen | Titers are presented as geometric mean titers (GMTs). | At Day 42 | 
| Number of Seropositive Subjects for Haemagglutination Inhibition (HI) Antibodies A/California/7/2009 (H1N1)V-like Antigen | A seropositive subject was defined as a subject whose serum antibody titer was greater than or equal to (≥) 1:10. | At Day 0 | 
| Number of Seropositive Subjects for Haemagglutination Inhibition (HI) Antibodies Against A/California/7/2009 (H1N1)V-like Antigen | A seropositive subject was defined as a subject whose serum antibody titer was greater than or equal to (≥) 1:10. | At Day 21 | 
| Number of Seropositive Subjects for Haemagglutination Inhibition (HI) Antibodies Against A/California/7/2009 (H1N1)V-like Antigen | A seropositive subject was defined as a subject whose serum antibody titer was greater than or equal to (≥) 1:10. | At Day 42 | 
| Number of Seroconverted Subjects for Haemagglutination Inhibition (HI) Antibodies Against A/California/7/2009 (H1N1)V-like Antigen | A seroconverted subject was defined as a vaccinated subject who had either a pre-vaccination titer smaller than (<) 1:10 and a post-vaccination titer greater than or equal to (≥) 1:40 or a pre-vaccination titer ≥ 1:10 and at least a four-fold increase in post-vaccination titer. | At Day 21 | 
| Number of Seroconverted Subjects for Haemagglutination Inhibition (HI) Antibodies Against A/California/7/2009 (H1N1)V-like Antigen | A seroconverted subject was defined as a vaccinated subject who had either a pre-vaccination titer smaller than (<) 1:10 and a post-vaccination titer greater than or equal to (≥) 1:40 or a pre-vaccination titer ≥ 1:10 and at least a four-fold increase in post-vaccination titer. | At Day 42 | 
| Number of Seroprotected Subjects Against A/California/7/2009 (H1N1)V-like Antigen | A seroprotected subject was defined as a vaccinated subject with serum Hemagglutination Inhibition (HI) titer ≥ 1:40. | At Day 0 | 
| Number of Seroprotected Subjects Against A/California/7/2009 (H1N1)V-like Antigen | A seroprotected subject was defined as a vaccinated subject with serum Hemagglutination Inhibition (HI) titer ≥ 1:40. | At Day 21 | 
| Number of Seroprotected Subjects Against A/California/7/2009 (H1N1)V-like Antigen | A seroprotected subject was defined as a vaccinated subject with serum Hemagglutination Inhibition (HI) titer ≥ 1:40. | At Day 42 | 
| Seroconversion Factor for Hemagglutination Inhibition (HI) Antibodies Against A/California/7/2009 (H1N1)V-like Antigen | 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. | At Day 21 | 
| Seroconversion Factor for Hemagglutination Inhibition (HI) Antibodies Against A/California/7/2009 (H1N1)V-like Antigen | 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. | At Day 42 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Seropositive Subjects for Haemagglutination Inhibition (HI) Antibodies A/California/7/2009 (H1N1)V-like Antigen | A seropositive subject was defined as a subject whose serum antibody titer was greater than or equal to (≥) 1:10. | At Days 0, 21, 42 and 182 | 
| Titers for Serum Hemagglutination Inhibition (HI) Antibodies Against A/California/7/2009 (H1N1)V-like Antigen | Titers are presented as geometric mean titers (GMTs). | At Days 0, 21, 42 and 182 | 
| Number of Seroconverted Subjects for Haemagglutination Inhibition (HI) Antibodies Against A/California/7/2009 (H1N1)V-like Antigen | A seroconverted subject was defined as a vaccinated subject who had either a pre-vaccination titer smaller than (<) 1:10 and a post-vaccination titer greater than or equal to (≥) 1:40 or a pre-vaccination titer ≥ 1:10 and at least a four-fold increase in post-vaccination titer. | At Days 21, 42 and 182 | 
| Number of Seroprotected Subjects Against A/California/7/2009 (H1N1)V-like Antigen | A seroprotected subject was defined as a vaccinated subject with serum Hemagglutination Inhibition (HI) titer ≥ 1:40. | At Days 0, 21, 42 and 182 | 
| Seroconversion Factor for Hemagglutination Inhibition (HI) Antibodies Against A/California/7/2009 (H1N1)V-like Antigen | 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. | At Days 21, 42 and 182 | 
| Titers for Serum Neutralizing Antibodies Against A/Neth/602/09 (H1N1)V-like Antigen | Titers are presented as geometric mean titers (GMTs). | At Days 0, 21, 42 and 182 | 
| Number of Seropositive Subjects for Neutralizing Antibodies Against A/Neth/602/09 (H1N1)V-like Antigen | A seropositive subject was defined as a subject whose serum antibody titer was greater than or equal to (≥) 1:8. | At Days 0, 21, 42 and 182 | 
| Number of Seroconverted Subjects for Neutralizing Antibodies Against A/Neth/602/09 (H1N1)V-like Antigen | A seroconverted subject was defined as a vaccinated subject with a minimum 4-fold increase in post vaccination neutralizing titer. | At Days 21, 42 and 182 | 
| Number of Subjects With Any and Grade 3 Solicited Local Symptoms | Assessed solicited local symptoms were pain, redness and swelling. Any = occurrence of the symptom regardless of intensity grade. Grade 3 pain = pain that prevented normal activity. Grade 3 redness/swelling = redness/swelling spreading beyond 100 millimeters (mm) of injection site. | During a 7-day (Days 0-6) follow-up after each vaccination | 
| Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Assessed solicited general symptoms were fatigue, headache, joint pain at other location, muscle aches, shivering, sweating and temperature [defined as axillary temperature equal to or above 37.5 degrees Celsius (°C)]. Any = occurrence of the symptom regardless of intensity grade. Grade 3 symptom = symptom that prevented normal activity. Grade 3 temperature = fever > 39.0 °C. Related = symptom assessed by the investigator as related to the vaccination. | During a 7-day (Days 0-6) follow-up after each 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 AE = an AE which prevented normal, everyday activities. Related = AE assessed by the investigator as related to the vaccination. | During a 21-day (Days 0-20) follow-up period after the first vaccination and during a 63-day (Days 21-84) follow-up after the second 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 (Days 0-182) | 
| Number of Subjects With Any Adverse Events of Specific Interest (AESIs). | An AESI was defined as an AE including autoimmune diseases and other mediated inflammatory disorders and assessed by the investigator as specific to the treatment administration. | During the entire study period (Days 0-182) | 
| Number of Days With Any Solicited Local Symptoms | Assessed solicited local symptoms were pain, redness and swelling. Any = occurrence of the symptom regardless of intensity grade. The number of days with any solicited local symptom was assessed in subjects who have reported at least once the symptom. | During a 7-day (Days 0-6) follow-up after each vaccination | 
| Number of Days With Any Solicited General Symptoms | Assessed solicited general symptoms were fatigue, headache, joint pain at other location, muscle aches, shivering, sweating and temperature [defined as axillary temperature equal to or above 37.5 degrees Celsius (°C)]. Any = occurrence of the symptom regardless of intensity grade. The number of days with any solicited general symptom was assessed in subjects who have reported at least once the symptom. | During a 7-day (Days 0-6) follow-up after each vaccination | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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influenza infection, GSK Biologicals' influenza vaccine GSK2340272A