Study to Evaluate the Safety and Immunogenicity of a Pandemic Influenza Vaccine in Adults Aged 18 Years and Above

Study Overview
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Brief Summary
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Today, the leading contender for the next pandemic of influenza is H5N1, a strain of avian virus. Prevention and control will depend on the rapid production and worldwide distribution of specific pandemic vaccines. Candidate 'pandemic-like' vaccines must be developed and tested in clinical trials to determine the most optimal formulation and the best vaccination schedule. This study is designed to test in healthy adults aged above 18 years the reactogenicity and immunogenicity of one and two administrations of a candidate pandemic H5N1 vaccine formulated from Split Virus.

Detailed Description
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This study has 2 phases: The study ID 107064 corresponds to objectives & outcome measures evaluated from day 0 until day 51. The study ID 107217 corresponds to objectives & outcome measures evaluated at day 180. The Protocol Posting has been updated in order to comply with the FDA Amendment Act, Sep 2007.

Official Title
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A Phase III, Observer-blind, Randomised Study to Evaluate the Safety and Immunogenicity of One and Two Administrations of Pandemic Monovalent (H5N1) Influenza Vaccine (Adjuvanted Split Virus Formulation) in Adults Aged 18 Years and Older

Conditions
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Influenza

Intervention / Treatment
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* Biological: Adjuvanted pandemic influenza candidate vaccine
* Biological: Fluarix
* Biological: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects who the investigator believes that they can and will comply with the requirements of the protocol. A male or female aged 18 years or above at the time of the first vaccination. Written informed consent obtained from the subject. Healthy subjects as established by medical history and clinical examination before entering into the study. If the subject is female, she must be of non-childbearing potential, for 30 days prior to first vaccination, have a negative pregnancy test and must agree to continue such precautions for two months after completion of the vaccination series. Exclusion Criteria: 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 the second vaccination. Administration of interpandemic influenza vaccine between Day 0 and Day 51of the study. Those study participants belonging to risk groups eligible to receive the annual interpandemic influenza vaccine (in accordance with local regulations) can receive the annual vaccination after day 51 and before the end of the study on Day 180. Chronic administration (defined as more than 14 days) of immunosuppressants or other immune-modifying drugs within 6 months prior to the first administration of the study vaccine. Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination History of chronic alcohol consumption and/or drug abuse. 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. Major congenital defects or serious chronic disease including any medically significant chronic pulmonary, cardiovascular, renal, neurological, psychiatric or metabolic disorder, as determined by medical history and physical examination. (Subjects suffering from seasonal allergies or asthma under inhalative treatment can be included). Acute disease at the time of enrolment. Administration of immunoglobulins and/or any blood products within the 3 months preceding the first administration of the study vaccine or during the study. Lactating women Use of any investigational or non-registered product (drug or vaccine) other than the study vaccine(s) within 30 days prior to the first vaccination, or planned use during the study period.

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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: GSK1562902A Group<br>Male and female subjects aged 18 or over received two intramuscular doses of the GSK1562902A study vaccine, at Day 0 and Day 21, into the non-dominant arm. The group was further stratified by age for analyses. | Biological: Adjuvanted pandemic influenza candidate vaccine<br>* 2 doses, intramuscular injection<br>|
| Active Comparator: Fluarix+Placebo Group<br>Male and female subjects aged 18 or over received one dose of Fluarix™ vaccine at Day 0 and one dose of placebo at Day 21, intramuscularly into de non-dominant arm. The group was further stratified by age for analyses. | Biological: Fluarix<br>* One intramuscular injection<br>Biological: Placebo<br>* One intramuscular injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects With Solicited Local Symptoms | Assessed solicited local symptoms were ecchymosis, induration, pain, redness and swelling. Any = occurrence of symptom regardless of intensity grade. Grade 3 Pain = pain that prevented normal everyday activities Grade 3 ecchymosis/induration/redness/swelling = redness/swelling spreading beyond (>) 50 millimeters (mm) in diameter | During a 7 day follow-up period after each dose of vaccine and overall. | 
| Number of Subjects With Solicited General Symptoms (Dose 1) | Assessed solicited general symptoms were arthralgia, fatigue, fever [defined as axillary temperature equal to or above (≥) 37.5 degrees Celsius (°C)], headache, myalgia, shivering, sweating. Any = occurrence of symptom regardless of intensity grade and relationship to vaccination. Grade 3 symptom = symptoms that prevented normal activity. Grade 3 Fever = fever higher than (>) 39.0 °C. Related = symptom considered by the investigator to be casually related with the study vaccination. | During the 7-day (Days 0-6) after Dose 1 | 
| Number of Subjects With Solicited General Symptoms (Dose 2) | Assessed solicited general symptoms were arthralgia, fatigue, fever [defined as axillary temperature equal to or above (≥) 37.5 degrees Celsius (°C)], headache, myalgia, shivering, sweating. Any = occurrence of symptom regardless of intensity grade and relationship to vaccination. Grade 3 symptom = symptoms that prevented normal activity. Grade 3 Fever = fever higher than (>) 39.0 °C. Related = symptom considered by the investigator to be casually related with the study vaccination. | During the 7-day (Days 0-6) after Dose 2 | 
| Number of Subjects With Solicited General Symptoms (Across Doses) | Assessed solicited general symptoms were arthralgia, fatigue, fever [defined as axillary temperature equal to or above (≥) 37.5 degrees Celsius (°C)], headache, myalgia, shivering, sweating. Any = occurrence of symptom regardless of intensity grade and relationship to vaccination. Grade 3 symptom = symptoms that prevented normal activity. Grade 3 Fever = fever higher than (>) 39.0 °C. Related = symptom considered by the investigator to be casually related with the study vaccination. | During the 7-day (Days 0-6) post vaccination across dosses | 
| Number of Subjects With 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. Related symptoms were not available. | During the 21st Day (Days 0-20) post Dose 1 | 
| Number of Subjects With 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. Related symptoms were not available. | During the 30 Day (Days 0-29) post Dose 2 | 
| Number of Subjects With Serious Adverse Events (SAEs) | SAEs assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity. | From Day 0 to Day 180 | 
| Number of Subjects With New Onset Chronic Diseases (NOCDs) | NOCDs include autoimmune disorders, asthma, type I diabetes, allergies. | From Day 0 to Day 180 | 
| Number of Subjects With Medically Significant Conditions (MSCs) | MSCs prompting emergency room or physician visits that were not related to common diseases or routine visits. Common diseases included upper respiratory infections, sinusitis, pharyngitis, gastroenteritis, urinary tract infections, cervico-vaginal yeast infections, menstrual cycle abnormalities and injury. | From Day 0 to Day 51 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Anti- Haemagglutinin Antibody (Anti-HA) Titers Against Avian Influenza A Subtype H5N1 | Anti-HA antibody titers were expressed as Geometric Mean Tiyers (GMTs). | At Day 0 (PRE), 21 and 42 | 
| Number of Seroconverted Subjects Against H5N1 | Seroconversion rate for Haemagglutinin antibody response was defined as the number of vaccinees who had either a pre-vaccination titer lower 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 fourfold increase in post-vaccination titer. Seroconversion rate for Neutralising antibody response was defined as the percentage of vaccinees with a minimum 4-fold increase in titer at post-vaccination. | At Day 21 and Day 42 | 
| Seroconversion Factor for Hemagglutination Inhibition (HI) Antibodies Against A/Vietnam Influenza Strain | Seroconversion factor was defined as the fold increase in serum HI GMTs post-vaccination compared to day 0. | At Day 21 and Day 42 | 
| Number of Seroprotected Subjects Against A/Vietnam Influenza Strain | Seroprotection rate was defined as the number of vaccinees with a serum HI titer ≥1:40 that usually is accepted as indicating protection. | At Day 0 (PRE), Day 21 and Day 42 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Adjuvanted pandemic influenza candidate vaccine, Influenza