Immunogenicity and Safety of GSK Biologicals' (Pre-) Pandemic Influenza Candidate Vaccine

Study Overview
=================
Brief Summary
-----------------
This trial will assess the immunogenicity and safety elicited by the adjuvanted GSK Biologicals' (pre-) pandemic influenza candidate vaccine in healthy Japanese adults.

Official Title
-----------------
Immunogenicity and Safety of GSK Biologicals' (Pre-) Pandemic Influenza Candidate Vaccine GSK 1557484A.

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

Intervention / Treatment
-----------------
* Biological: Influenza A (H5N1) Virus Monovalent Vaccine, Adjuvanted


Participation Criteria
=================
Eligibility Criteria
-----------------
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. 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. Written informed consent obtained from the subject. Comprehension of the study requirements, expressed availability for the required study period, and ability to attend scheduled visits. Subjects who the investigator believes that they can and will comply with the requirements of the protocol should be enrolled in the study. Exclusion Criteria: 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. Diagnosed with cancer, or treatment for cancer within 3 years. Presence of an axillary temperature >= 37.5 °C, or acute symptoms greater than mild severity on the scheduled date of first vaccination. Any confirmed or suspected immunosuppressive or immunodeficient condition including history of human immunodeficiency virus (HIV) infection. Receipt of systemic glucocorticoids within 1 month of study enrolment, or any other cytotoxic or immunosuppressive drug within 6 months of study enrolment. Any significant disorder of coagulation or treatment with Coumadin derivatives or heparin. Administration of any registered vaccine within 30 days before study enrolment 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. Use of any investigational or non-registered product within 30 days prior to study enrolment or planned use during the study period. History of previous H5N1 vaccination, or history of H5N1 influenza infection. Receipt of any immunoglobulins and/or any blood products within 6 months of study enrolment or planned administration of any of these products during the study period. 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 consumption of eggs; or a history of severe adverse reaction to a previous influenza vaccine. Known pregnancy or a positive urine beta-human chorionic gonadotropin test result prior to the time of first vaccination. Lactating or nursing. Women of child-bearing potential who lack a history of reliable contraceptive practices. The provision of this history does NOT replace the requirement to perform, and obtain negative results in pregnancy urine tests prior to treatments; all women will have urine pregnancy tests regardless of their status. Known receipt of analgesic or antipyretic medication on the day of treatment (Day 0).

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Influenza A (H5N1) 20-40 Years Group<br>Subjects aged between 20 and 40 years inclusive received 2 doses of Influenza A (H5N1) Virus Monovalent Vaccine, Adjuvanted at Days 0 and 21 administered intramuscularly in the deltoid region of the non-dominant arm. | Biological: Influenza A (H5N1) Virus Monovalent Vaccine, Adjuvanted<br>* All subjects will receive 2 doses administered as an intramuscular (IM) injection.<br>* Other names: PumarixTM;|
| Experimental: Influenza A (H5N1) 41-64 Years Group<br>Subjects aged between 41 and 64 years inclusive received 2 doses of Influenza A (H5N1) Virus Monovalent Vaccine, Adjuvanted at Days 0 and 21 administered intramuscularly in the deltoid region of the non-dominant arm. | Biological: Influenza A (H5N1) Virus Monovalent Vaccine, Adjuvanted<br>* All subjects will receive 2 doses administered as an intramuscular (IM) injection.<br>* Other names: PumarixTM;|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Haemagglutination Inhibition (HI) Antibody Titers for the H5N1 Vaccine Strain | Antibody titers were expressed as Geometric mean titers (GMTs). The H5N1 vaccine strain included A/Indonesia/05/2005 antigen (A/Indonesia). | At Day 0 and Day 42 | 
| Number of Subjects Seroconverted for H5N1 HI Antibodies | A seroconverted subject was defined as a subject who had either a pre-vaccination titer below 1:10 and a post-vaccination titer greater than or equal to 1:40 or a pre-vaccination titer greater than or equal to 1:10 and at least a 4-fold increase in post-vaccination titer. The H5N1 vaccine strain included A/Indonesia antigen. | At Day 42 | 
| HI Antibody Seroconversion Factors for H5N1 HI Antibodies | Seroconversion factors (SCF) were defined as the fold increase in serum H5N1 HI antibody GMTs post-vaccination compared to Day 0, at Day 42. The H5N1 vaccine strain included A/Indonesia antigen. | At Day 0 and Day 42 | 
| Number of Subjects Seroprotected for H5N1 HI Antibodies | A seroprotected subject was defined as a subject with a serum H5N1 HI antibody titer greater than or equal to 1:40, at Day 42. The H5N1 vaccine strain included A/Indonesia antigen. | At Day 42 | 
| Haemagglutination Inhibition (HI) Antibody Titers for the H5N1 Vaccine Strain | Antibody titers were expressed as Geometric mean titers (GMTs). The H5N1 vaccine strain included A/Indonesia antigen. | At Day 0, Day 21 and Day 182 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects Seroconverted for H5N1 HI Antibodies | A seroconverted subject was defined as a subject who had either a pre-vaccination titer below 1:10 and a post-vaccination titer greater than or equal to 1:40 or a pre-vaccination titer greater than or equal to 1:10 and at least a 4-fold increase in post-vaccination titer, at Days 21 and 182. The H5N1 vaccine strain included A/Indonesia antigen. | At Day 21 and Day 182 | 
| Seroconversion Factors for H5N1 HI Antibodies | Seroconversion factors (SCF) were defined as the fold increase in serum H5N1 HI antibody GMTs post-vaccination compared to Day 0, at Days 21 and 182. The H5N1 vaccine strain included A/Indonesia antigen. | At Day 21 and Day 182 | 
| Number of Subjects Seroprotected for H5N1 HI Antibodies | A seroprotected subject was defined as a subject with a serum H5N1 HI antibody titer greater than or equal to 1:40, at Days 21 and 182. The H5N1 vaccine strain included A/Indonesia antigen. | At Day 0, Day 21 and Day 182 | 
| Antibody Titers for Serum Anti-H5N1 Neutralising Antibodies | Antibody titers were expressed as Geometric mean titers (GMTs). The H5N1 vaccine strain included A/Indonesia antigen. | At Day 0, Day 42 and Day 182 | 
| Number of Subjects Seroconverted for Serum Anti-H5N1 Neutralising Antibodies | A seroconverted subject was defined as a subject with a minimum 4 fold increase in titer at post-vaccination for neutralising antibody response at Days 42 and 182. The H5N1 vaccine strain included A/Indonesia antigen. | At Day 42 and Day 182 | 
| Number of Subjects With Any Biochemical and Haematological Laboratory Abnormalities | Biochemical and haematological parameters assessed in blood samples include alanine aminotransferase (ALT), aspartate aminotransferase (AST), basophils (BAS) and blood urea nitrogen (BUN ). Categories = unknown, below, within, or above the normal ranges. | At Day 0, Day 7 and Day 42 | 
| Number of Subjects With Any Biochemical and Haematological Laboratory Abnormalities | Biochemical and haematological parameters assessed in blood samples include creatinine (CREA), eosinophils (EOS), hemoglobin (HB) and hematocrit (HC). Categories = unknown, below, within, or above the normal ranges. | At Day 0, Day 7 and Day 42 | 
| Number of Subjects With Any Biochemical and Haematological Laboratory Abnormalities | Biochemical and haematological parameters assessed in blood samples include lymphocytes (LYM), monocytes (MON) and neutrophils (NEU). Categories = unknown, below, within, or above the normal ranges. | At Day 0, Day 7 and Day 42 | 
| Number of Subjects With Any Normal or Abnormal Urine Values | Urine parameters assessed were blood, glucose, protein and urobilinogen. Categories = negative, positive | At Day 0, Day 7 and Day 42 | 
| Number of Subjects Reporting Any and Grade 3 Solicited Local Symptoms | Solicited local symptoms assessed were pain, redness and swelling/induration. Any=any solicited local symptom reported regardless of their intensity. Grade 3 pain= significant pain at rest that prevented normal activities as assessed by inability to attend/do work or school. Grade 3 redness and swelling/induration=redness and swelling/induration above 100 millimetres (mm). | During the 7-day post vaccination period (Days 0-6) after any vaccination | 
| Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms | Solicited general symptoms assessed were fatigue, headache, joint pain, muscle aches, shivering, increase sweating and fever. Any=any solicited general symptom reported regardless of their intensity grade or their relationship to vaccination. Any fever was ≥ 38.0 degrees celsius (°C). Grade 3 = general symptom that prevented normal everyday activities as assessed by inability to attend/do work or school, or required intervention of a physician/healthcare provider. Grade 3 fever was≥ 39.0°C. Related= general symptom assessed by the investigator as causally related to the study vaccination. | During the 7-day post vaccination period (Days 0-6) after any vaccination | 
| Number of Subjects Reporting Any, Grade 3 and Related Unsolicited Adverse Events (AEs) | Unsolicited AE is 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 AE regardless of intensity grade or relation to vaccination. Grade 3 was an event that prevented normal activities and related was defined as an unsolicited AE assessed by the investigator to be causally related to the study vaccination. | During the 21-day (Days 0-20) following vaccination | 
| Number of Subjects Reporting Any, Grade 3 and Related Unsolicited AEs | Unsolicited AE is 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 AE regardless of intensity grade or relation to vaccination. Grade 3 was an event that prevented normal activities and related was defined as an unsolicited AE assessed by the investigator to be causally related to the study vaccination. | From Day 0 to Day 83 following vaccination | 
| Number of Subjects Reporting Any Medically-significant Conditions (MSCs) | MSCs were defined as AEs with a medically-attended visit (s) i.e. prompting emergency room (ER) visits, hospitalizations or physician visits and that were not routine visits for physical examination or vaccination. | During the 182-day (Days 0-181) post-vaccination period | 
| Number of Subjects Reporting 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. | During the entire study period (Day 0 to Day 181) | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Immunogenicity, Safety, Pandemic Influenza