Evaluate Reactogenicity & Immunogenicity of an Influenza Pandemic Candidate Vaccine (GSK1562902A) in Primed Adults

Study Overview
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Brief Summary
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The present study is designed to evaluate the reactogenicity and immunogenicity of one or two booster administrations of an influenza pandemic candidate vaccine (GSK1562902A) in adults aged between 19 and 61 years, previously vaccinated with 2 doses of a pandemic candidate vaccine. Fifty new subjects who did not participate in a primary study (106750, NCT00309634) will be recruited. This protocol posting deals with objectives & outcome measures of the booster phase. The objectives & outcome measures of the primary phase are presented in a separate protocol posting (NCT00309634)

Detailed Description
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The present study is designed to evaluate the reactogenicity and immunogenicity of one or two booster administrations of an influenza pandemic candidate vaccine (GSK1562902A) in adults aged between 19 and 61 years, previously vaccinated with 2 doses of a pandemic candidate vaccine. The persistence of antibodies will be analysed at 6, 12, 18 and 24 months.

Official Title
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Evaluate the Reactogenicity & Immunogenicity of 1 or 2 Booster Administrations of an Influenza Pandemic Candidate Vaccine (GSK1562902A) in Primed Adults Aged Between 19 & 61 Years

Conditions
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Influenza

Intervention / Treatment
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* Biological: Pandemic influenza candidate vaccine (GSK1562902A) - 1 dose
* Biological: Pandemic influenza candidate vaccine (GSK1562902A) - 2 doses


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects who the investigator believes can and will comply with the requirements of the protocol should be enrolled in the study. For previously primed subjects: participation in the primary study (NCT00309634). For unprimed subjects: male or female between and including, 19 and 61 years of age 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 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: Use of any investigational or non-registered product (drug or vaccine) other than the study vaccine(s) within 30 days preceding the first dose of study vaccine, or planned use during the study period. For unprimed subjects who did not participate in the primary study (NCT00309634): Chronic administration (defined as more than 14 days) of immunosuppressants or other immune-modifying drugs within six months prior to the first vaccine dose. Planned administration/ administration of a licenced vaccine not foreseen by the study protocol within 2 weeks (for inactivated vaccines) or 4 weeks (for live vaccines) of the first dose of vaccine(s). Concurrently participating in another clinical study, at any time during the study period, in which the subject has been or will be exposed to an investigational or a non-investigational product (pharmaceutical product or device). Applicable for control group only: previous vaccination with a pandemic candidate vaccine or a vaccine containing the investigational vaccine adjuvant. History of hypersensitivity to vaccines. Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination (no laboratory testing required). History of allergic disease or reactions likely to be exacerbated by any component of the vaccine(s). Major congenital defects or serious chronic illness. History of any neurological disorders or seizures. Acute disease at the time of enrolment. Acute or chronic, clinically significant pulmonary, cardiovascular, hepatic or renal functional abnormality, as determined by physical examination or laboratory screening tests. Serious chronic disease including any medically significant chronic pulmonary, cardiovascular, renal, neurological, psychiatric or metabolic disorder, as determined by medical history and physical examination. Any condition which, in the opinion of the investigator, prevents the subject from participation in the study. Lactating female. History of chronic alcohol consumption and/or drug abuse

Ages Eligible for Study
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Minimum Age: 19 Years
Maximum Age: 61 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: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: GSK1562902A non-AD F1 Primed Group<br>Healthy male or female adults, between and including 19 to 61 years of age, primed with 2 doses of a non-adjuvanted (non-AD) investigational H5N1 vaccine (A/Vietnam/1194/04 strain) Formulation 1 (F1) in study 106750 (NCT00309634) receiving 2 doses of Pandemic influenza candidate vaccine (GSK1562902A) in this booster study, one at Day 0 and one at Day 21, administrated intramuscularly (IM) in the deltoid region of the non-dominant arm. | Biological: Pandemic influenza candidate vaccine (GSK1562902A) - 2 doses<br>* Two doses of Pandemic influenza candidate vaccine (GSK1562902A) administered intramuscularly in the deltoid region of the non-dominant arm at Day 0 and Day 21.<br>|
| Experimental: GSK1562902A non-AD F2 Primed Group<br>Healthy male or female adults, between and including 19 to 61 years of age, primed with 2 doses of a non-adjuvanted (non-AD) investigational H5N1 vaccine (A/Vietnam/1194/04 strain) Formulation 2 (F2) in study 106750 (NCT00309634) receiving 2 doses of Pandemic influenza candidate vaccine (GSK1562902A) in this booster study, one at Day 0 and one at Day 21, administrated IM in the deltoid region of the non-dominant arm. | Biological: Pandemic influenza candidate vaccine (GSK1562902A) - 2 doses<br>* Two doses of Pandemic influenza candidate vaccine (GSK1562902A) administered intramuscularly in the deltoid region of the non-dominant arm at Day 0 and Day 21.<br>|
| Experimental: GSK1562902A non-AD F3 Primed Group<br>Healthy male or female adults, between and including 19 to 61 years of age, primed with 2 doses of a non-adjuvanted (non-AD) investigational H5N1 vaccine (A/Vietnam/1194/04 strain) Formulation 3 (F3) in study 106750 (NCT00309634) receiving 2 doses of Pandemic influenza candidate vaccine (GSK1562902A) in this booster study, one at Day 0 and one at Day 21, administrated IM in the deltoid region of the non-dominant arm. | Biological: Pandemic influenza candidate vaccine (GSK1562902A) - 2 doses<br>* Two doses of Pandemic influenza candidate vaccine (GSK1562902A) administered intramuscularly in the deltoid region of the non-dominant arm at Day 0 and Day 21.<br>|
| Experimental: GSK1562902A non-AD F4 Primed Group<br>Healthy male or female adults, between and including 19 to 61 years of age, primed with 2 doses of a non-adjuvanted (non-AD) investigational H5N1 vaccine (A/Vietnam/1194/04 strain) Formulation 4 (F4) in study 106750 (NCT00309634) receiving 2 doses of Pandemic influenza candidate vaccine (GSK1562902A) in this booster study, one at Day 0 and one at Day 21, administrated IM in the deltoid region of the non-dominant arm. | Biological: Pandemic influenza candidate vaccine (GSK1562902A) - 2 doses<br>* Two doses of Pandemic influenza candidate vaccine (GSK1562902A) administered intramuscularly in the deltoid region of the non-dominant arm at Day 0 and Day 21.<br>|
| Experimental: GSK1562902A AD F1 Primed Group<br>Healthy male or female adults, between and including 19 to 61 years of age, primed with 2 doses of an adjuvanted (AD) investigational H5N1 vaccine (A/Vietnam/1194/04 strain) Formulation1 (F1) in study 106750 (NCT00309634) received 1 dose of Pandemic influenza candidate vaccine (GSK1562902A) in this booster study at Day 0, administrated IM in the deltoid region of the non-dominant arm. | Biological: Pandemic influenza candidate vaccine (GSK1562902A) - 1 dose<br>* A single dose of Pandemic influenza candidate vaccine (GSK1562902A) administered intramuscularly in the deltoid region of the non-dominant arm at Day 0.<br>|
| Experimental: GSK1562902A AD F2 Primed Group<br>Healthy male or female adults, between and including 19 to 61 years of age, primed with 2 doses of an adjuvanted (AD) investigational H5N1 vaccine (A/Vietnam/1194/04 strain) Formulation 2 (F2) in study 106750 (NCT00309634) received 1 dose of Pandemic influenza candidate vaccine (GSK1562902A) in this booster study at Day 0, administrated IM in the deltoid region of the non-dominant arm. | Biological: Pandemic influenza candidate vaccine (GSK1562902A) - 1 dose<br>* A single dose of Pandemic influenza candidate vaccine (GSK1562902A) administered intramuscularly in the deltoid region of the non-dominant arm at Day 0.<br>|
| Experimental: GSK1562902A AD F3 Primed Group<br>Healthy male or female adults, between and including 19 to 61 years of age, primed with 2 doses of an adjuvanted (AD) investigational H5N1 vaccine (A/Vietnam/1194/04 strain) Formulation 3 (F3)in study 106750 (NCT00309634) received 1 dose of Pandemic influenza candidate vaccine (GSK1562902A) in this booster study at Day 0, administrated IM in the deltoid region of the non-dominant arm. | Biological: Pandemic influenza candidate vaccine (GSK1562902A) - 1 dose<br>* A single dose of Pandemic influenza candidate vaccine (GSK1562902A) administered intramuscularly in the deltoid region of the non-dominant arm at Day 0.<br>|
| Experimental: GSK1562902A AD Approved F4 Primed Group<br>Healthy male or female adults, between and including 19 to 61 years of age, primed with 2 doses of approved Formulation (F) of adjuvanted (AD) H5N1 vaccine (A/Vietnam/1194/04 strain) in study 106750 (NCT00309634) received 1 dose of Pandemic influenza candidate vaccine (GSK1562902A) in this booster study at Day 0, administrated IM in the deltoid region of the non-dominant arm. | Biological: Pandemic influenza candidate vaccine (GSK1562902A) - 1 dose<br>* A single dose of Pandemic influenza candidate vaccine (GSK1562902A) administered intramuscularly in the deltoid region of the non-dominant arm at Day 0.<br>|
| Experimental: Control Group<br>Healthy male or female adults, between and including 19 to 61 years of age, unprimed receiving 2 doses of Pandemic influenza candidate vaccine (GSK1562902A) in this booster study, one at Day 0 and one at Day 21, administrated IM in the deltoid region of the non-dominant arm. | Biological: Pandemic influenza candidate vaccine (GSK1562902A) - 2 doses<br>* Two doses of Pandemic influenza candidate vaccine (GSK1562902A) administered intramuscularly in the deltoid region of the non-dominant arm at Day 0 and Day 21.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Titers for Serum H5N1 Haemagglutinin Inhibition (HI) Antibodies Against the A/Indonesia/05/2005 Strain | Titers were 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 0 | 
| Titers for Serum H5N1 Haemagglutinin Inhibition (HI) Antibodies Against the A/Indonesia/05/2005 Strain | Titers were 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 21 | 
| Number of Seroconverted Subjects for H5N1 HI Antibodies Against the A/Indonesia/05/2005 Strain | Seroconversion rate for HI antibody response was defined as the percentage of vaccines who have either a pre-vaccination titer < 1:10 and a post-vaccination titer ≥ 1:40 or a pre-vaccination titer ≥ 1:10 and at least a 4-fold increase in post-vaccination titer. | At Day 21 | 
| Seroconversion Factor (SCF) for H5N1 HI Antibodies Against the A/Indonesia/05/2005 Strain | Seroconversion factor (SCF) was defined as the fold increase in H5N1 HI antibody GMTs post-vaccination compared to Day 0. The flu strain assessed was A/Indonesia/05/2005. | At Day 21 | 
| Number of Seroprotected Subjects for H5N1 HI Antibodies Against the A/Indonesia/05/2005 Strain | A seroprotected subject was defined as a vaccinated subject with a serum HI titer equal to or above (≥) 1:40. The flu strain assessed was A/Indonesia/05/2005. | At Day 0 | 
| Number of Seroprotected Subjects for H5N1 HI Antibodies Against the A/Indonesia/05/2005 Strain | A seroprotected subject was defined as a vaccinated subject with a serum HI titer equal to or above (≥) 1:40. The flu strain assessed was A/Indonesia/05/2005. | At Day 21 | 
| Number of Subjects With Any and Grade 3 Solicited Local Symptoms | Assessed solicited local symptoms were ecchymosis, induration, pain, redness and swelling. Any = occurrence of the symptom regardless of intensity grade. Grade 3 pain = pain that prevented normal activity. Grade 3 ecchymosis/induration/redness/swelling = redness/swelling spreading beyond 100 millimeters (mm) of injection site. No subject from GSK1562902A AD F1 Primed Group has received Dose 2. | 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. No subject from GSK1562902A AD F1 Primed Group has received Dose 2. | 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 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 (Days 0-20) follow-up period after the first vaccination and 30-day (Days 0-29) 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 30-day (Days 0-29) follow-up period after the first vaccination | 
| 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. | During the entire study period (From Day 0 up to Month 24) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Titers for Serum Neutralizing HI Antibodies Against A/Indonesia/05/2005 Strain | Titers were 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/Indonesia/05/2005. No subject from GSK1562902A AD F1 Primed Group has received a second vaccination. | At Days 0, 21 (post-vaccination one) and 42 (post-vaccination two) | 
| Titers for Serum Neutralizing HI Antibodies Against A/Indonesia/05/2005 Stain | Titers were 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/Indonesia/05/2005. | At Months 6, 12, 18 and 24 | 
| Titers for Serum H5N1 Haemaglutinin-inhibition (HI) Antibodies Against the A/Indonesia/05/2005 Strain | Titers were 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 Days 0, 7, 14, 21, 28, 35 and 42 | 
| Titers for Serum H5N1 HI Antibodies Against the A/Indonesia/05/2005 Strain | Titers were 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 Months 6, 12, 18 and 24 | 
| Number of Seroconverted (SCR) Subjects for HI Antibodies Against the A/Indonesia/05/2005 Strain | Seroconversion (SCR) was defined as the proportion of subjects who had either a pre-vaccination reciprocal HI titer < 10 and a post-vaccination reciprocal titer ≥ 40, or a pre-vaccination reciprocal HI titer ≥ 10 and at least a 4-fold increase in post-vaccination reciprocal titer against the vaccine virus. The flu strain assessed was Flu A/Indonesia/05/2005. | At Days 7,14, 21, 35 and 42 | 
| Number of Seroconverted (SCR) Subjects for HI Antibodies Against the A/Indonesia/05/2005 Strain | SCR was defined as the proportion of subjects who had either a pre-vaccination reciprocal HI titer< 10 and a post-vaccination reciprocal titer ≥ 40, or a pre-vaccination reciprocal HI titer ≥ 10 and at least a 4-fold increase in post-vaccination reciprocal titer against the vaccine virus. The flu strain assessed was Flu A/Indonesia/05/2005. | At Months 6, 12, 18 and 24 | 
| Number of Seroconverted (SCR) Subjects for Neutralizing HI Antibodies Against the A/Indonesia/05/2005 Strain | Seroconversion rate for anti-HA antibody response was defined as the percentage of vaccines who have either a pre-vaccination titer < 1:40 and a post-vaccination titer ≥ 1:56 or a pre-vaccination titer ≥ 1:56 and at least a 4-fold increase in post-vaccination titer. | At Days 21 (post-vaccination one) and 42 (post-vaccination two) | 
| Number of Seroconverted (SCR) Subjects for Neutralizing HI Antibodies Against the A/Indonesia/05/2005 Strain | Seroconversion rate for neutralizing antibody response was defined as the percentage of vaccines who have either a pre-vaccination titer < 1:40 and a post-vaccination titer ≥ 1:56 or a pre-vaccination titer ≥ 1:56 and at least a 4-fold increase in post-vaccination titer. | At Months 6, 12, 18 and 24 | 
| Seroconversion Factor (SCF) for H5N1 Haemagglutinin-inhibition (HI) Antibodies Against the A/Indonesia/05/2005 Strain | Seroconversion factor (SCF) was defined as the fold increase in H5N1 HI antibody GMTs post-vaccination compared to Day 0. The flu strain assessed was A/Indonesia/05/2005. | At Days 7, 14, 21, 35 and 42 | 
| Seroconversion Factor (SCF) for H5N1 Haemagglutinin-inhibition (HI) Antibodies Against the A/Indonesia/05/2005 Strain | 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. | At Months 6, 12, 18 and 24 | 
| Number of Seroprotected (SPR) Subjects for HI Antibodies Against the A/Indonesia/05/2005 Strain | Seroprotection rate was defined as the percentage of vaccines with a serum HI antibody titer ≥ 1:40 that usually is accepted as indicating protection. The flu strain assessed was A/Indonesia/05/2005 (H5N1). | At Days 0, 7, 14, 21, 28, 35 and 42 | 
| Number of Seroprotected (SPR) Subjects for HI Antibodies Against the A/Indonesia/05/2005 Strain | Seroprotection rate was defined as the percentage of vaccines with a serum HI antibody titer ≥ 1:40 that usually is accepted as indicating protection. The flu strain assessed was A/Indonesia/05/2005 (H5N1). | At Months 6, 12, 18 and 24 | 
| Frequency of Antigen-specific CD4/CD8 T-cells (Per 10E6) in Tests Identified as Producing at Least Two Out of Four Different Cytokines | Among cytokines expressed after background reduction were cluster of differentiation 4 all doubles (CD4 all doubles), cluster of differentiation 40-ligand (CD40-L), interleukin-2 (IL-2), interferon-gamma (IFN-γ) and tumour necrosis factor-alpha (TNF-α). The flu strains assessed wwere H5N1 A/Indonesia and H5N1 A/Vietnam. | At Days 0 and 21 | 
| Frequency of Antigen-specific CD4/CD8 T-cells (Per 10E6) in Tests Identified as Producing at Least Two Out of Four Different Cytokines | Among cytokines expressed after background reduction were cluster of differentiation 4 all doubles (CD4 all doubles), cluster of differentiation 40-ligand (CD40-L), interleukin-2 (IL-2), interferon-gamma (IFN-γ) and tumour necrosis factor-alpha (TNF-α). The flu strains assessed were H5N1 A/Indonesia and H5N1 A/Vietnam. | At Months 6, 12, 18 and 24 |