Study to Evaluate the Safety and Immune Response of Two-Doses of Candidate Influenza Vaccine GSK 1557484A in Adults

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety and immune response of two-doses of GSK Biologicals' candidate influenza vaccine GSK 1557484A with or without adjuvant in adults. The Protocol Posting has been updated in order to comply with the FDA Amendment Act, Sep 2007.

Detailed Description
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The study has five core arms and the stratification is based on site and age. In addition, there are 4 possible contingent groups of which 2 will be studied based on an analysis concerning immunogenicity performance at Day 42 in core groups above.

Official Title
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A Phase I/II, Observer-Blind, Randomized, Active-Controlled Trial to Evaluate the Safety and Immunogenicity of a Two-Dose Series of GSK Biologicals' Candidate Influenza Vaccine GSK 1557484A Antigens With or Without Adjuvant

Conditions
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Influenza

Intervention / Treatment
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* Biological: Pumarix™
* Biological: Pandemrix ™


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and female adults 18 to 64 years of age at time of first vaccination, inclusive. Good general health as assessed by medical history and physical examination. Access to a consistent means of telephone contact 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 of 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. Blood pressure abnormalities Diagnosed with cancer, or treatment for cancer, within 3 years. Persons with a history of cancer who are disease-free without treatment for 3 years or more are eligible. Persons with a history of histologically-confirmed basal cell carcinoma of the skin successfully treated with local excision only are excepted and may enroll, but other histologic types of skin cancer are exclusionary. Women who are disease-free 3 years or more after treatment for breast cancer and receiving long-term prophylactic tamoxifen are excepted and may enroll. Presence of an oral temperature ≥ 37.8º 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 cytotoxic or immunosuppressive drug within 6 months of study enrollment. Any significant disorder of coagulation or treatment with Coumadin derivatives or heparin. Administration of any non-influenza vaccines within 30 days before study enrollment or during the study period. Use of any investigational or non-registered product (drug or vaccine) or planned participation in another investigational study within 30 days prior to study enrollment, or during the study period. Receipt of any immunoglobulins and/or any blood products within 3 months of study enrollment or planned administration of any of these products during the study period. Any known or suspected allergy to any constituent of influenza vaccines. Known pregnancy or a positive urine beta-human chorionic gonadotropin (ß-hCG) test result prior to dosing on Study Days 0 or 21. Lactating or nursing. Women of child bearing potential who lack a history of reliable contraceptive practices. Known receipt of analgesic or antipyretic medication on the day of treatment

Ages Eligible for Study
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Minimum Age: 18 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pumarix Formulation 1 Group<br>Healthy subjects aged between 18 and 64 years at the time of vaccination received two doses of formulation 1 of Pumarix™ vaccine at Day 0 and Day 21. The vaccine was administered intramuscularly in the deltoid region of the arm (non-dominant arm for the first injection and dominant arm for the second one). | Biological: Pumarix™<br>* Two doses administered intramuscularly (IM), the first in the deltoid region of the non-dominant arm and the second in the deltoid region of the dominant arm.<br>|
| Experimental: Pumarix Formulation 2 Group<br>Healthy subjects aged between 18 and 64 years at the time of vaccination received two doses of formulation 2 of Pumarix™ vaccine at Day 0 and Day 21. The vaccine was administered intramuscularly in the deltoid region of the arm (non-dominant arm for the first injection and dominant arm for the second one). | Biological: Pumarix™<br>* Two doses administered intramuscularly (IM), the first in the deltoid region of the non-dominant arm and the second in the deltoid region of the dominant arm.<br>|
| Experimental: Pumarix Formulation 3 Group<br>Healthy subjects aged between 18 and 64 years at the time of vaccination received two doses of formulation 3 of Pumarix™ vaccine at Day 0 and Day 21. The vaccine was administered intramuscularly in the deltoid region of the arm (non-dominant arm for the first injection and dominant arm for the second one). | Biological: Pumarix™<br>* Two doses administered intramuscularly (IM), the first in the deltoid region of the non-dominant arm and the second in the deltoid region of the dominant arm.<br>|
| Experimental: Pandemrix Formulation A Group<br>Healthy subjects aged between 18 and 64 years at the time of vaccination received two doses of formulation A of Pandemrix™ vaccine at Day 0 and Day 21. The vaccine was administered intramuscularly in the deltoid region of the arm (non-dominant arm for the first injection and dominant arm for the second one). | Biological: Pandemrix ™<br>* Two doses administered intramuscularly (IM), the first in the deltoid region of the non-dominant arm and the second in the deltoid region of the dominant arm.<br>|
| Experimental: Pandemrix Formulation B Group<br>Healthy subjects aged between 18 and 64 years at the time of vaccination received two doses of formulation B of Pandemrix ™ vaccine at Day 0 and Day 21. The vaccine was administered intramuscularly in the deltoid region of the arm (non-dominant arm for the first injection and dominant arm for the second one). | Biological: Pandemrix ™<br>* Two doses administered intramuscularly (IM), the first in the deltoid region of the non-dominant arm and the second in the deltoid region of the dominant arm.<br>|
| Experimental: Pumarix Formulation 4 Group<br>Healthy subjects aged between 18 and 64 years at the time of vaccination received two doses of formulation 4 of Pumarix™ vaccine at Day 0 and Day 21. The vaccine was administered intramuscularly in the deltoid region of the arm (non-dominant arm for the first injection and dominant arm for the second one). | Biological: Pumarix™<br>* Two doses administered intramuscularly (IM), the first in the deltoid region of the non-dominant arm and the second in the deltoid region of the dominant arm.<br>|
| Experimental: Pumarix Formulation 5 Group<br>Healthy subjects aged between 18 and 64 years at the time of vaccination received two doses of formulation 5 of Pumarix™ vaccine at Day 0 and Day 21. The vaccine was administered intramuscularly in the deltoid region of the arm (non-dominant arm for the first injection and dominant arm for the second one). | Biological: Pumarix™<br>* Two doses administered intramuscularly (IM), the first in the deltoid region of the non-dominant arm and the second in the deltoid region of the dominant arm.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Seroconverted Subjects Against the A/Indonesia/5/2005 (H5N1) Strain of Influenza Disease. | A seroconverted subject was defined as a vaccinated subject who had either a pre-vaccination titer less than (<) 1:10 and a post-vaccination reciprocal titer greater than or equal to (≥) 1:40 or a pre-vaccination reciprocal titer ≥ 1:10 and at least a 4-fold increase in post-vaccination titer on the specified day. | At Day 42 | 
| Titers for Serum Hemagglutination Inhibition (HI) Antibodies Against the A/Indonesia/5/2005 (H5N1) Strain of Influenza Disease. | Titers are presented as geometric mean titers (GMTs). | At Day 42 | 
| Number of Seroprotected Subjects Against the A/Indonesia/5/2005 (H5N1) Strain of Influenza Disease. | A seroprotected subject was defined as a vaccinated subject who had a serum HI titer ≥ 1:40. | At Day 42 | 
| Number of Subjects With Solicited Local Symptoms. | Assessed solicited local symptoms were pain, redness and swelling. Any = occurrence of any solicited local symptoms regardless of their intensity grade. Any redness and swelling were ≥ 20 millimeters (mm). | Within the 7-day follow-up period (Days 0-6) after any vaccination | 
| Number of Subjects With Solicited General Symptoms. | Assessed solicited general symptoms were fatigue, headache, joint pain at other location (joint pain), muscle aches, shivering, sweating and fever. Fever was defined as oral temperature (≥) 38 degrees Celsius (°C). Any = occurrence of any solicited general symptoms regardless of intensity grade or relationship to vaccination. | Within the 7-day follow-up period (Days 0-6) after any vaccination | 
| Number of Subjects With Medically Attended Adverse Events (MAEs) and New Onset Chronic Diseases (NOCDs). | A MAE was defined as any unsolicited symptom that received medical attention such as hospitalization, an emergency room visit, or an otherwise unscheduled visit to or from medical personnel (medical doctor) for any reason. NOCDs included autoimmune diseases, diabetes mellitus. | From Day 0 to 182 | 
| Number of Subjects With Unsolicited Adverse Events (AEs). | An unsolicited AE was defined as an untoward medical occurrence in a patient or clinical investigation subject, temporally associated with 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. | During the 21-day follow-up period (Days 0-20) after vaccination. | 
| Number of Subjects With Unsolicited Adverse Events (AEs). | An unsolicited AE was defined as an untoward medical occurrence in a patient or clinical investigation subject, temporally associated with 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. | Between Day 0 and Day 84 after vaccination. | 
| Number of Subjects With Any Serious Adverse Events (SAEs). | A serious adverse event (SAE) was defined as any untoward medical occurrence that resulted in death, was life-threatening, required hospitalization or prolongation of existing hospitalization, resulted in disability/incapacity or resulted in a congenital anomaly/birth defect in the offspring of a study subject. | From Day 0 to 182 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Titers for Serum HI Antibodies Against the A/Indonesia/5/2005 (H5N1) Strain of Influenza Disease. | Titers are presented as geometric mean titers (GMTs). | At Day 21 and Day 182 | 
| Number of Seroconverted Subjects Against the A/Indonesia/5/2005 (H5N1) Strain of Influenza Disease. | A seroconverted subject was defined as a vaccinated subject who had either a pre-vaccination titer less than (<) 1:10 and a post-vaccination reciprocal titer greater than or equal to (≥) 1:40 or a pre-vaccination reciprocal titer ≥ 1:10 and at least a 4-fold increase in post-vaccination titer on the specified day. | At Days 21 and 182 | 
| Geometric Mean Fold-rise (GMFR) Against the A/Indonesia/5/2005 (H5N1) Strain of Influenza Disease. | GMFR was defined as the geometric mean fold increase in serum HI antibody reciprocal titer on the specified study day compared to Day 0. | At Days 21 and 182 | 
| Number of Seroprotected Subjects Against the A/Indonesia/5/2005 (H5N1) Strain of Influenza Disease. | A seroprotected subject was defined as a vaccinated subject who had a serum HI antibody reciprocal titer ≥ 1:40 on the specified study day. | At Days 0, 21 and 182 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Influenza, GSK 1557484A vaccine