A Study for Evaluation of GSK Biologicals' Pandemic Influenza Vaccine.

Study Overview
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Brief Summary
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This observer-blind study is designed to show the immunological non-inferiority of Thiomersal-free-processed pandemic influenza vaccine as compared to the Thiomersal-containing-processed pandemic influenza vaccine.

Official Title
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Non-inferiority Study of GSK Biologicals' Pandemic Influenza Vaccine 1562902A.

Conditions
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Influenza

Intervention / Treatment
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* Biological: GSK1562902A
* Biological: GSK1562902A


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 should be enrolled in the study. A male or female aged 18 to 60 years at the time of the first vaccination. Written informed consent obtained from the subject. Good general health as established by medical history and clinical examination before entering into the study. 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 Comprehension of the study requirements, ability to comprehend and comply with procedures for collection of short- and long-term safety data, expressed availability for the required study period, and ability and willingness to attend scheduled visits. If the subject is female, she must be of non-childbearing potential, or if she is of childbearing potential, she must practice adequate contraception for 30 days prior to vaccination, have a negative pregnancy test and continue such precautions for 2 months after completion of the vaccination series. Exclusion Criteria: Evidence of substance abuse or of neurological or psychiatric diagnoses which, even if clinically 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. An oral temperature ≥ 37.8 º 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 (prednisone ≥ 5 mg/kg/day for more than 14 consecutive days) 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 Coumarin derivatives or Heparin. Administration of any vaccines within 30 days before study enrolment. Previous administration of any H5N1 vaccine. Previous administration of vaccines with adjuvants similar to those used in the investigational vaccine. Use of any investigational or non-registered product (drug or vaccine) or planned participation in another investigational study within 30 days prior to study enrolment, or during the 180 days following the first test article dose. Use of any investigational or non-registered product with immunosuppressive properties is exclusionary at any time during the trial. 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 known or suspected allergy to any constituent of influenza vaccines (including egg proteins or mercurial preservatives); 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 (β-hCG) test result prior to either vaccination. Lactating women. 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. Known use of an analgesic or antipyretic medication within 12 hours prior to first treatment.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 59 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: 1562902A NP GROUP<br>Healthy male or female adults, between and including 18 to 60 years of age, who received two doses of the new-processed (NP) 1562902A vaccine, administered intramuscularly in the deltoid region of the non-dominant arm, at Days 0 and 21. | Biological: GSK1562902A<br>* new-processed (NP), administered intramuscularly in the deltoid region of the non-dominant arm<br>|
| Experimental: 1562902A CP GROUP<br>Healthy male or female adults, between and including 18 to 60 years of age, who received two doses of the comparative-processed (CP) 1562902A vaccine, administered intramuscularly in the deltoid region of the non-dominant arm, at Days 0 and 21. | Biological: GSK1562902A<br>* comparative-processed (CP), administered intramuscularly in the deltoid region of the non-dominant arm<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Titers for Serum H5N1 Haemagglutination-inhibition (HI) Antibodies | Titers are presented as geometric mean titers (GMTs). The reference seropositivity cut-off value was equal to or above (≥) 1:10. The flu strain assessed was A/Indonesia/05/2005. | At Day 42 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Titers for Serum H5N1 HI Antibodies | Titers are presented as geometric mean titers (GMTs). The reference seropositivity cut-off value was equal to or above (≥) 1:10. The flu strains assessed were A/Indonesia/05/2005 and A/Vietnam/1194/2004. | At Day 0 and Day 180 | 
| Number of Subjects With H5N1 HI Antibody Concentrations Above the Cut-off Value | The cut-off values for the humoral immune response in terms of H5N1 HI antibodies were equal to or above (≥) 1:10. The flu strains assessed were A/Indonesia/05/2005 and A/Vietnam/1194/2004. | At Days 0, 42 and 180 | 
| Number of Seroconverted Subjects Against Two Strains of Influenza Disease | A seroconverted subject was defined as a vaccinated subject who had either a pre-vaccination titer below (<) 1:10 and a post-vaccination titer equal to or above (≥) 1:40, or a pre-vaccination titer ≥ 1:10 and at least a four-fold increase in post-vaccination titer. The flu strains assessed were A/Indonesia/05/2005 and A/Vietnam/1194/2004. | At Day 42 and Day 180 | 
| Seroconversion Factor (SCF) for H5N1 HI Antibodies | The seroconversion factor (SCF) was defined as the fold increase in H5N1 HI antibody GMTs post-vaccination compared to Day 0. The flu strains assessed were A/Indonesia/05/2005 and A/Vietnam/1194/2004. | At Day 42 and Day 180 | 
| Number of Seroprotected Subjects for H5N1 HI Antibodies | A seroprotected subject was defined as a vaccinated subject with a serum HI titer equal to or above (≥) 1:40. The flu strains assessed were A/Indonesia/05/2005 and A/Vietnam/1194/2004. | At Days 0, 42 and 180 | 
| Titers for Serum Neutralising Antibodies Against A/Vietnam/1194/2004 Strain of Influenza Disease | Titers are presented as geometric mean titers (GMTs). The reference seropositivity cut-off value was equal to or above (≥) 1:28. The flu strain assessed was A/Vietnam/1194/2004. | At Days 0, 42 and 180 | 
| Number of Subjects With Neutralizing Antibody Concentrations Above the Cut-off Value | Seropositivity cut-off values assessed were equal to or above (≥) 1:28 in the sera of subjects seronegative before vaccination. The flu strain assessed was A/Vietnam/1194/2004. | At Days 0, 42 and 180 | 
| Number of Seroconverted Subjects for Neutralizing Antibodies | A seroconverted subject was defined as a vaccinated subject who had either a pre-vaccination titer < 1:28 and a post-vaccination titer ≥ 1:56 or a pre-vaccination titer ≥ 1:28 and at least a four-fold increase in post-vaccination titer. The flu strain assessed was A/Vietnam/1194/2004. | At Day 42 and Day 180 | 
| 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 the 7-day (Days 0-6) post-vaccination period following each dose and across doses | 
| Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Assessed solicited general symptoms were arthralgia, fatigue, headache, myalgia, shivering, sweating and fever [defined as axillary temperature equal to or above (≥) 38 degrees Celsius (°C)]. Any = occurrence of the symptom regardless of intensity grade. Grade 3 symptom = symptom that prevented normal activity. Grade 3 fever = fever ≥ 39.0 °C. Related = symptom assessed by the investigator as causally related to the study vaccination. | During the 7-day (Days 0-6) post-vaccination period following each dose and across doses | 
| 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. | From Day 0 up to 51 days after the first vaccination | 
| Number of Subjects With Any 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 (from Day 0 up to Day 180) | 
| 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 the 21-day follow-up period after the first vaccination and 30-day follow-up period after the second 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 the entire study period (from Day 0 up to Day 180) | 
| 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 up to Day 51 | 
| Number of Subjects With SAEs | 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 (from Day 0 up to Day 180) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pandemic influenza