Immunogenicity of GSK Biologicals' Pandemic Influenza Vaccine (GSK1562902A) at Different Boosting Vaccination Schedules

Study Overview
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Brief Summary
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Today, the leading contender for the next influenza pandemic is H5N1, a strain of avian virus found primarily in domestic and wild birds. Experts warn that the next influenza pandemic is imminent and could be severe. 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 best formulation and vaccination schedule. The purpose of this study is to assess the immune response of a candidate pandemic vaccine. The protocol posting deals with objectives & outcome measures of the secondary phase of this study. The objectives and outcome measures of the primary phase are presented in a separate protocol posting (NCT number = 00449670).

Official Title
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Immunogenicity of GSK Biologicals' Pandemic Influenza Vaccine (GSK1562902A) at Different Boosting Vaccination Schedules

Conditions
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Influenza

Intervention / Treatment
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* Biological: Pandemic influenza vaccine GSK1562902A


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects who completed participation in primary phase of this study. Subjects who the investigator believes can and will comply with the requirements of the protocol should be enrolled in the study. 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 be post-menopausal; if of childbearing potential, she must practice adequate contraception for 30 days prior to vaccination, have a negative pregnancy test and continue such precautions for two months after completion of the vaccination series. Exclusion Criteria: Administration of any licensed vaccines within 4 weeks prior to enrolment in this study. Planned administration of a vaccine not foreseen by the study protocol: 4 weeks prior to any visit or within 30 days after vaccination. Chronic administration (defined as more than 14 days) of immunosuppressants or other immune-modifying drugs within six months prior to the first visit or planned use during the study Any confirmed or suspected immunosuppressive or immunodeficient condition, or autoimmune diseases such as Guillain Barre Syndrome, based on medical history and physical examination (no laboratory testing required). History of hypersensitivity to vaccines. History of allergic disease or reactions likely to be exacerbated by any component of the vaccine. History of chronic alcohol consumption and/or drug abuse. Acute 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. Acute disease at the time of enrolment. Administration of immunoglobulins and/or any blood products within the three months preceding the first visit or planned use during the study. Pregnant or 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 visit, or planned use during the study period. Any condition which, in the opinion of the investigator, prevents the subject from participation in the study.

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: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: GSK1562902A M6 Group<br>Healthy male or female adults, primed with 2 doses of adjuvanted investigational H5N1 vaccine (A/Vietnam/1194/04 strain) and boosted 6 months (M6) after primary vaccination with one dose of Pandemic influenza candidate vaccine (GSK1562902A) in study 109630 (NCT00449670), administrated intramuscularly (IM) in the deltoid region of the non-dominant arm. | Biological: Pandemic influenza vaccine GSK1562902A<br>* IM administration<br>|
| Experimental: GSK1562902A M12 Group<br>Healthy male or female adults, primed with 2 doses of adjuvanted investigational H5N1 vaccine (A/Vietnam/1194/04 strain) in study 109630 (NCT00449670) receiving one dose of Pandemic influenza candidate vaccine (GSK1562902A) in this booster study, at 12 Months (M12) after the primary vaccination, administrated intramuscularly (IM) in the deltoid region of the non-dominant arm. | Biological: Pandemic influenza vaccine GSK1562902A<br>* IM administration<br>|
| Experimental: GSK1562902A M36 Group<br>Healthy male or female adults, primed with 2 doses of adjuvanted investigational H5N1 vaccine (A/Vietnam/1194/04 strain) in study 109630 (NCT00449670) receiving one dose of Pandemic influenza candidate vaccine (GSK1562902A) in this booster study, at 36 Months (M36) after the primary vaccination, administrated intramuscularly (IM) in the deltoid region of the non-dominant arm. | Biological: Pandemic influenza vaccine GSK1562902A<br>* IM administration<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects Boosted at Month 12 With Haemagglutinin-inhibition (HI) Antibody Concentrations Above the Cut-off Value | Seropositivity cut-off values assessed were equal to or above (≥) 1:10 in the sera of subjects seronegative before vaccination. The flu strain assessed was Flu A/Indonesia/05/2005. | At Month 12 + 21 days | 
| Titers for Antibodies Against A/Indonesia/05/2005 Strain of Influenza Disease for Subjects Boosted at Month 12 | 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 Flu A/Indonesia/05/2005. | At Month 12 + 21 days | 
| Number of Subjects Boosted at Month 36 With HI Antibody Concentrations Above the Cut-off Value | Seropositivity cut-off values assessed were equal to or above (≥) 1:10 in the sera of subjects seronegative before vaccination. The flu strain assessed was Flu A/Indonesia/05/2005. | At Month 36 + 21 days | 
| Titers for Antibodies Against A/Indonesia/05/2005 Strain of Influenza Disease for Subjects Boosted at Month 36 | 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 Flu A/Indonesia/05/2005. | At Month 36 + 21 days | 
| Booster Vaccine Response for HI Antibodies Against A/Indonesia/05/2005 Strain of Influenza Disease for Subjects Boosted at Month 12 | Booster vaccine response was defined as: antibody titer after booster vaccination ≥ 4-fold the pre-booster antibody titer. The Flu strain assessed was A/Indonesia/05/2005 (H5N1). | At Month 12 + 21 days | 
| Booster Vaccine Response for HI Antibodies Against A/Indonesia/05/2005 Strain of Influenza Disease for Subjects Boosted at Month 36 | Booster vaccine response was defined as: antibody titer after booster vaccination ≥ 4-fold the pre-booster antibody titer. The Flu strain assessed was A/Indonesia/05/2005 (H5N1). | At Month 36 + 21 Days | 
| Geometric Mean Fold Rise (GMFR) for HI Antibodies Against A/Indonesia/05/2005 Strain of Influenza Disease for Subjects Boosted at Month 12 | GMFR, also known as seroconversion factor (SCF), was defined as the geometric mean of the within-subject ratios of the post-vaccination reciprocal HI titer to the pre-vaccination reciprocal HI titer for the vaccine virus. The flu strain assessed was Flu A/Indonesia/05/2005. | At Month 12 + 21 days | 
| Geometric Mean Fold Rise (GMFR) for HI Antibodies Against A/Indonesia/05/2005 Strain of Influenza Disease for Subjects Boosted at Month 36 | GMFR, also known as seroconversion factor (SCF), was defined as the geometric mean of the within-subject ratios of the post-vaccination reciprocal HI titer to the pre-vaccination reciprocal HI titer for the vaccine virus. The flu strain assessed was Flu A/Indonesia/05/2005. | At Month 36 +21 days | 
| Number of Subjects Boosted at Month 12 Seroprotected (SPR) for HI Antibodies Against A/Indonesia/05/2005 Strain of Influenza Disease | Seroprotection (SPR) was defined as the proportion of subjects with H5N1 reciprocal HI titers equal to or above (≥) 1:40 against the tested vaccine virus. The flu strain assessed was Flu A/Indonesia/05/2005. | At Month 12 + 21 days | 
| Number of Subjects Boosted at Month 36 Seroprotected (SPR) for HI Antibodies Against A/Indonesia/05/2005 Strain of Influenza Disease | Seroprotection (SPR) was defined as the proportion of subjects with H5N1 reciprocal HI titers equal to or above (≥) 1:40 against the tested vaccine virus. The flu strain assessed was Flu A/Indonesia/05/2005. | At Month 36 + 21 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Seropositive Subjects for H5N1 HI Antibodies | Seropositivity was defined as the proportion of subjects with H5N1 reciprocal HI titers equal to or above (≥) 1:10 against the tested vaccine virus. The flu strains assessed were A/Indonesia/05/2005 and A/Vietnam/1194/2004. | At Months 18, 24, 30 and 36 | 
| Number of Seropositive Subjects for H5N1 HI Antibodies | Seropositivity was defined as the proportion of subjects with H5N1 reciprocal HI titers equal to or above (≥) 1:10 against the tested vaccine virus. The flu strains assessed were A/Indonesia/05/2005 and A/Vietnam/1194/2004. | At Months 42 and 48 | 
| Booster Vaccine Response for H5N1 HI Antibodies for Subjects Boosted at Month 6 and Month 12 | Booster vaccine response was defined as: antibody titer after booster vaccination ≥ 4 fold the pre-booster antibody titer. The Flu strains assessed were A/Indonesia/05/2005 and A/Vietnam/1194/2004. | At Months 18, 24 and 30 | 
| Number of Subjects Boosted at Month 36 Seroconverted for H5N1 HI Antibodies | Seroconversion 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 strains assessed were A/Indonesia/05/2005 and A/Vietnam/1194/2004. | At Months 18, 24 and 30 | 
| Booster Vaccine Response for H5N1 HI Antibodies | Booster vaccine response was defined as: antibody titer after booster vaccination ≥ 4-fold the pre-booster antibody titer. The Flu strains assessed were A/Indonesia/05/2005 and A/Vietnam/1194/2004. | At Months 36, 42 and 48 | 
| Geometric Mean Fold Rise (GMFR) for H5N1 HI Antibodies | GMFR, also known as seroconversion factor (SCF), was defined as the geometric mean of the within-subject ratios of the post-vaccination reciprocal HI titer to the pre-vaccination reciprocal HI titer for the vaccine virus. The flu strains assessed were A/Indonesia/05/2005 and A/Vietnam/1194/2004. | At Months 18, 24, 30 | 
| Geometric Mean Fold Rise (GMFR) for H5N1 HI Antibodies | GMFR, also known as seroconversion factor (SCF), was defined as the geometric mean of the within-subject ratios of the post-vaccination reciprocal HI titer to the pre-vaccination reciprocal HI titer for the vaccine virus. The flu strains assessed were A/Indonesia/05/2005 and A/Vietnam/1194/2004. | At Months 36, 42 and 48 | 
| Number of Seroprotected (SPR) Subjects for H5N1 HI Antibodies | Seroprotection (SPR) was defined as the proportion of subjects with H5N1 reciprocal HI titers equal to or above (≥) 1:40 against the tested vaccine virus. The flu strains assessed were A/Indonesia/05/2005 and A/Vietnam/1194/2004. | At Months 18, 24 and 30 | 
| Number of Seroprotected (SPR) Subjects for H5N1 HI Antibodies | Seroprotection (SPR) was defined as the proportion of subjects with H5N1 reciprocal HI titers equal to or above (≥) 1:40 against the tested vaccine virus. The flu strains assessed were A/Indonesia/05/2005 and A/Vietnam/1194/2004. | At Months 36, 42 and 48 | 
| Titers for Serum Neutralizing Antibodies | Titers were presented as geometric mean titers (GMTs). The reference seropositivity cut-off value was equal to or above (≥) 1:28. The flu strains assessed were A/Indonesia/05/2005 and A/Vietnam/1194/2004. | At Months 6/12, 6/12 + 21 days, 24, 36 and 48 | 
| Booster Vaccine Response for Neutralizing Antibodies | Booster vaccine response was defined as: for pre-booster antibody titer < 1:28, antibody titer ≥ 1:56 post-booster; for pre-booster, antibody titer ≥ 1:28, post-booster ≥ 4-fold the pre-booster antibody titer. The flu strains assessed were A/Indonesia/05/2005 and A/Vietnam/1194/2004. | At Months 6/12/36 + 21 days, 12, 24, 36 and 48 | 
| Number of Subjects With Neutralizing Antibody Concentrations Above the Cut-off Value | Seropositivity cut-off values assessed were equal to or above (≥) 1:28, ≥ 1:56 and ≥ 1:112 in the sera of subjects seronegative before vaccination. The flu strain assessed was A/Indonesia/05/2005. | At Months 6/12/36 + 21 days, 12, 24, 36 and 48 | 
| Number of Subjects With Neutralizing Antibody Concentrations Above the Cut-off | Seropositivity cut-off values assessed were equal to or above (≥) 1:28, ≥ 1:56 and ≥ 1:112 in the sera of subjects seronegative before vaccination. The flu strain assessed was A/Vietnam/1194/2004. | At Months 6/12/36 + 21 days, 12, 24, 36 and 48 | 
| 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. | During the 7-day (Days 0-6) post-vaccination period - subjects boosted at Month 12 and Month 36 | 
| Number of Subjects With Any, Grade 3 and Related Solicited General Symptom | 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 - subjects boosted at Month 12 and 36 | 
| Number of Subjects With 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. | During the entire study period (From Month 12 to Month 48) | 
| Frequency of Antigen-specific CD4 T-cells (Per 10E6) in Tests Identified as Producing at Least Two Out of Four Different Cytokines (for A/Indonesia/05/2005 Strain) | Among cytokines expressed after background reduction were cluster of differentiation 4 all doubles (CD4 all doubles), cluster of differentiation 40-ligand (CD40-L), interferon-gamma (IFN-γ), interleukin-2 (IL-2) and tumour necrosis factor-alpha (TNF-α). The flu strain assessed was H5N1 A/Indonesia/05/2005. | At Months 6, 12, 18, 24, 30, 36, 42 and 48 and at Months 6/12/36 + 21 days | 
| Frequency of Antigen-specific CD4 T-cells (Per 10E6) in Tests Identified as Producing at Least Two Out of Four Different Cytokines (for A/Vietnam/1194/2004 Strain) | Among cytokines expressed after background reduction were cluster of differentiation 4 all doubles (CD4 all doubles), cluster of differentiation 40-ligand (CD40-L), interferon-gamma (IFN-γ), interleukin-2 (IL-2) and tumour necrosis factor-alpha (TNF-α). The flu strain assessed was H5N1 A/Vietnam/1194/2004. | At Months 6, 12, 18, 24, 30, 36, 42 and 48 and at Months 6/12/36 + 21 days | 
| Frequency of Antigen-specific CD8 T-cells (Per 10E6) in Tests Identified as Producing at Least Two Out of Four Different Cytokines (for A/Indonesia/05/2005 Strain) | Among cytokines expressed after background reduction were cluster of differentiation 8 all doubles (CD8 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 strain assessed was H5N1 A/Indonesia/05/2005. | At Months 6, 12, 18, 24, 30, 36, 42 and 48 and at Months 6/12/36 + 21 days | 
| Frequency of Antigen-specific CD8 T-cells (Per 10E6) in Tests Identified as Producing at Least Two Out of Four Different Cytokines (for A/Vietnam/1194/2004 Strain) | Among cytokines expressed after background reduction were cluster of differentiation 8 all doubles (CD8 all doubles), cluster of differentiation 40-ligand (CD40-L), interferon-gamma (IFN-γ), interleukin-2 (IL-2) and tumour necrosis factor-alpha (TNF-α). The flu strain assessed was H5N1 A/Vietnam/1194/2004. | At Months 6, 12, 18, 24, 30, 36, 42 and 48 and at Months 6/12/36 + 21 days | 
| 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 vaccination | 
| Number of Subjects With Serious Adverse Events (SAEs) | Serious adverse events (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 Month 12 up to Month 48) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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immunogenicity, safety, GSK pandemic candidate vaccine