Study to Evaluate the Immunogenicity and Safety of an Investigational Pandemic Influenza Vaccine in Children

Study Overview
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Brief Summary
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The objective of the study is to evaluate the immunogenicity and safety of prime-boost vaccination schedule of GSK Biologicals' investigational vaccine GSK1562902A.

Detailed Description
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This protocol posting was modified according to the protocol amendment 2 (dated 16-June-2011). The impacted section is eligibility criteria.

Official Title
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Safety and Immunogenicity of GSK Biologicals' (Pre-) Pandemic Influenza Candidate Vaccine (GSK1562902A) in Children Aged 6 to 35 Months

Conditions
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Influenza

Intervention / Treatment
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* Biological: GSK Biologicals' investigational vaccine GSK1562902A


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects who the investigator believes that parents/Legally Acceptable Representatives (LARs) can and will comply with the requirements of the protocol. Children, male or female between, and including, 6 and 35 months of age at the time of first study vaccination. Written informed consent obtained from the parent(s)/LAR(s) of the subject. Healthy children as established by medical history and clinical examination before entering the study. Parent/LAR access to a consistent means of telephone contact, land line or mobile, but NOT a pay phone or other multiple-user device. Subjects who are likely to reside in the vicinity of the study centre for the duration of the study. In studies using the home-based model for vaccination and follow-up, subjects who are likely to remain in the vicinity of the area where they were recruited. Exclusion Criteria: Use of any investigational or non-registered product other than the study vaccine(s) within 30 days preceding the first dose of study vaccine, or planned use during the study period. Chronic administration of immunosuppressants or other immune-modifying drugs within six months prior to the first vaccine dose. Planned administration of any vaccine 30 days prior and 21 days after any study vaccine administration. History of any reaction or hypersensitivity likely to be exacerbated by any component of the vaccines such as egg protein or thiomersal. Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination. 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 tests. Administration of immunoglobulins and/or any blood products within the three months prior to the enrolment in this study, or planned administration during the study period. Any condition which, in the opinion of the investigator, renders the subject unfit for participation in the study. Child in care. Previous vaccination at any time with an H5N1 vaccine. Medical history of physician-confirmed infection with a H5N1 virus.

Ages Eligible for Study
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Minimum Age: 6 Months
Maximum Age: 35 Months

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
Interventional Model Description: Subjects were to be stratified into three age strata (6 to 11 months, 12 to 23 months and 24 to 35 months) in the ratio of 2:1:1.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: GSK1562902A 6 to 12 M Group<br>Subjects between 6 and 12 months of age (6 to 12 M), who received 2 primary doses of A/Indonesia/05/2005 GSK1562902A vaccine on Days 0 and 21 and 1 booster dose of the A/turkey/Turkey/1/2005 GSK1562902A vaccine on Day 182. | Biological: GSK Biologicals' investigational vaccine GSK1562902A<br>* Three intramuscular injections<br>|
| Experimental: GSK1562902A 12 to 24 M Group<br>Subjects between 12 and 24 months of age (12 to 24 M), who received 2 primary doses of A/Indonesia/05/2005 GSK1562902A vaccine on Days 0 and 21 and 1 booster dose of the A/turkey/Turkey/1/2005 GSK1562902A vaccine on Day 182. | Biological: GSK Biologicals' investigational vaccine GSK1562902A<br>* Three intramuscular injections<br>|
| Experimental: GSK1562902A 24 to 36 M Group<br>Subjects between 24 and 36 months of age (24 to 36 M), who received 2 primary doses of A/Indonesia/05/2005 GSK1562902A vaccine on Days 0 and 21 and 1 booster dose of the A/turkey/Turkey/1/2005 GSK1562902A vaccine on Day 182. | Biological: GSK Biologicals' investigational vaccine GSK1562902A<br>* Three intramuscular injections<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Seroconverted Subjects in Terms of H5N1 Hemagglutination Inhibition (HI) Antibodies Against A/Turkey/Turkey/1/2005 H5N1 Virus Strain | A seroconverted subject is defined as a subject that had either a pre-vaccination (Day 0) 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 on Day 192. | At Day 192 | 
| Mean Geometric Change in Terms of H5N1 HI Antibodies Against A/Turkey/Turkey/01/2005 H5N1 Virus Strain | Mean Geometric Change is defined as the geometric mean of the within-subject ratios of the post vaccination (Day 192) reciprocal HI titer to the pre-vaccination (Day 0) reciprocal HI titer (i.e. post-vaccination divided by pre-vaccination titer). | At Day 192 | 
| Number of Seroprotected Subjects in Terms of H5N1 HI Antibodies Against A/Turkey/Turkey/01/2005 H5N1 Virus Strain | A seroprotected subject is defined as a subject with a serum H5N1 HI antibody titer ≥1:40. | At Day 192 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hemagglutination Inhibition (HI) Antibody Titers Against the A/Indonesia/05/2005 H5N1 Virus Strain | Titers were presented as geometric mean titers (GMTs). Analyses were done by age stratum and overall. | At Day 0, Day 42, Day 182, Day 192 and Day 364 | 
| Hemagglutination Inhibition (HI) Antibody Titers Against the A/Turkey/Turkey/01/2005 H5N1 Virus Strain | Titers were presented as geometric mean titers (GMTs). Analyses were done by age stratum and overall. | At Day 0, Day 182, Day 192 and Day 364 | 
| Number of Seropositive Subjects in Terms of H5N1 HI Antibodies Against A/Indonesia/05/2005 | A seropositive subject is defined as a subject with a serum H5N1 HI antibody titer ≥ 1:10. | At Day 0, Day 42, Day 182, Day 192 and Day 364 | 
| Number of Seropositive Subjects in Terms of H5N1 HI Antibodies Against A/Turkey/Turkey/1/2005 H5N1 Virus Strain | A seropositive subject is defined as a subject with a serum H5N1 HI antibody titer ≥ 1:10. | At Day 0, Day 182, Day 192 and Day 364 | 
| Number of Seroconverted Subjects in Terms of H5N1 HI Antibodies Against A/Indonesia/05/2005 H5N1 Virus Strain | A seroconverted subjects is defined as a subject who had either a pre vaccination (Day 0) 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 42, Day 182, Day 192 and Day 364 | 
| Number of Seroconverted Subjects in Terms of H5N1 HI Antibodies Against A/Turkey/Turkey/1/2005 H5N1 Virus Strain | A seroconverted subjects is defined as a subject who had either a pre vaccination (Day 0) 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. Data for Day 192 are presented under Primary Outcome Measures. | At Day 182 and Day 364 | 
| Number of Seroprotected Subjects in Terms of H5N1 HI Antibodies Against A/Indonesia/05/2005 Virus Strain | A seroprotected subject is defined as a subject with a serum H5N1 HI antibody titer ≥1:40. | At Day 0, Day 42, Day 182, Day 192 and Day 364 | 
| Number of Seroprotected Subjects in Terms of H5N1 HI Antibodies Against A/Turkey/Turkey/1/2005 H5N1 Virus Strain | A seroprotected subject is defined as a subject with a serum H5N1 HI antibody titer ≥1:40. Data for Day 192 are presented under Primary Outcome Measures. | Day 0, Day 182 and Day 364 | 
| Mean Geometric Change in Terms of H5N1 HI Antibodies Against A/Indonesia/05/2005 H5N1 Virus Strain | Mean Geometric Change is defined as the geometric mean of the within-subject ratios of the post-vaccination reciprocal HI titer to the pre-vaccination (Day 0) reciprocal HI titer (i.e. post-vaccination divided by pre-vaccination titer). | At Day 42, Day 182, Day 192 and Day 364 | 
| Mean Geometric Change in Terms of H5N1 HI Antibodies Against A/Turkey/Turkey/01/2005 H5N1 Virus Strain | Mean Geometric Change is defined as the geometric mean of the within-subject ratios of the post vaccination reciprocal HI titer to the pre-vaccination (Day 0) reciprocal HI titer (i.e. post-vaccination divided by pre-vaccination titer). Data for Day 192 are presented under Primary Outcome Measures. | Day 182 and Day 364 | 
| Number of Booster Seroconverted Subjects in Terms of H5N1 HI Antibodies Against A/Turkey/Turkey/1/2005 H5N1 Virus Strain | Booster seroconversion is defined as follows: For seronegative subjects at pre-booster (Day 182), antibody titer ≥1:40 at post-booster time point(s). For seropositive subjects at pre-booster (Day 182), antibody titer at post-booster time point(s) ≥4-fold the pre-booster antibody titer. | At Day 192 and Day 364 | 
| Booster Factor in Terms of Neutralizing Antibodies Against A/Turkey/Turkey/1/2005 H5N1 Virus Strain | Booster Factor was defined as the geometric mean of the within-subject ratios of the post-booster vaccination reciprocal HI titer to the pre-booster (Day 182) reciprocal titer. | At Day 192 and Day 364 | 
| Number of Seropositive Subjects in Terms of Serum Neutralizing Antibodies Against A/Indonesia/05/2005 H5N1 Virus Strain | A seropositive subject is defined as a subject with serum neutralizing antibody titers ≥ 1:28 | Day 0, Day 42, Day 182, Day 192 and Day 364 | 
| Number of Seropositive Subjects in Terms of Serum Neutralizing Antibodies Against A/Turkey/Turkey/1/2005 H5N1 Virus Strain | A seropositive subject is defined as a subject with serum neutralizing antibody titers ≥ 1:28. | Day 0, Day 182, Day 192 and Day 364 | 
| Serum Neutralizing Antibody Titers in Terms of Neutralizing Antibodies Against A/Indonesia/05/2005 H5N1 Virus Strain | Titers were presented as geometric mean titers (GMTs). | Day 0, Day 42, Day 182, Day 192 and Day 364 | 
| Serum Neutralizing Antibody Titers in Terms of Neutralizing Antibodies Against A/Turkey/Turkey/1/2005 H5N1 Virus Strain | Titers were presented as geometric mean titers (GMTs). | Day 0, Day 182, Day 192 and Day 364 | 
| Number of Subjects With a Vaccine Response in Terms of Serum Neutralizing Antibodies Against A/Indonesia/05/2005 H5N1 Virus Strain | Vaccine response is defined as: For initially seronegative subjects, neutralizing antibody titer ≥ 1:56 at the considered time point after vaccination For initially seropositive subjects, neutralizing antibody titer ≥ 4 fold from pre-vaccination (Day 0) | At Day 42, Day 182, Day 192 and Day 364 | 
| Number of Subjects With a Vaccine Response in Terms of Serum Neutralizing Antibodies Against A/Turkey/Turkey/1/2005 H5N1 Virus Strain | Vaccine response is defined as: For initially seronegative subjects, neutralizing antibody titer ≥ 1:56 at the considered time point after vaccination For initially seropositive subjects, neutralizing antibody titer ≥ 4 fold from pre-vaccination (Day 0) | At Day 182, Day 192 and Day 364 | 
| Number of Subjects With a Booster Vaccine Response in Terms of Serum Neutralizing Antibodies Against A/Turkey/Turkey/1/2005 H5N1 Virus Strain | Booster vaccine response is defined as: For seronegative subjects at Day 182, neutralizing antibody titers ≥ 1:56 at the considered time point after vaccination For seropositive subjects at Day 182, neutralizing antibody titers ≥ 4 fold from pre-vaccination (Day 182) | At Day 192 and Day 364 | 
| Number of Subjects With Any and Grade 3 Solicited Local Symptoms | Solicited local symptoms assigned were pain, swelling and redness. Any was defined as occurrence of any local symptom regardless of intensity grade; Grade 3 pain was defined as cried when limb was moved spontaneously painful. | During the 7-day post-vaccination period following each dose and across doses (Day 0 - Day 7, Day 21 - Day 28, Day 182 - Day 189) | 
| Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Solicited general symptoms assessed were diarrhoea/ vomiting, drowsiness, irritability/ fussiness, loss of appetite, fever (axillary). Any= occurrence of any general symptom regardless of intensity grade and relationship to the vaccine. Irritability/ fussiness grade 3=crying that could not be comforted/ prevented normal activity; Drowsiness grade 3= drowsiness that prevented normal activity; Loss of appetite grade 3= did not eat at all; Diarrhoea/ vomiting grade 3= diarrhoea/ vomiting that prevented normal activity; Related= general symptom assessed by the investigator as causally related to the study vaccination. | During the 7-day post-vaccination period following each dose and across doses (Day 0 - Day 7, Day 21 - Day 28, Day 182 - Day 189) | 
| Number of Subjects With Medically-attended Events (MAEs) | MAEs were defined as events for which the subject received medical attention defined as hospitalization, an emergency room visit, or a visit to or from medical personnel (medical doctor) for any reason. Any MAE(s) = Occurrence of any MAE(s) regardless of intensity grade or relation to vaccination. Analysis of intensity and relationship to vaccination of MAEs was not performed. | During the entire study period (from Day 0 to Day 364) | 
| Number of Subjects With Potential Immune-mediated Disease (pIMDs) | Potential immune-mediated diseases (pIMDs) are a subset of AEs that include autoimmune diseases and other inflammatory and/or neurologic disorders of interest which may or may not have an autoimmune aetiology. | During the entire study period (from day 0 to Day 364) | 
| Number of Subjects With Unsolicited Adverse Events (AEs) | An AE is 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. Any was defined as an incidence of an unsolicited AE regardless of intensity or relationship to study vaccination. Grade 3 was defined as an AE which prevented normal, everyday activities. Related was defined as an AE assessed by the investigator as causally related to the study vaccination. | During a 21 day follow-up period after each vaccination (Day 0 - Day 21, Day 21 - Day 42, Day 182 - Day 203) | 
| Number of Subjects With Unsolicited Adverse Events (AEs) | An AE is 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. Any was defined as an incidence of an unsolicited AE regardless of intensity or relationship to study vaccination. Grade 3 was defined as an AE which prevented normal, everyday activities. Related was defined as an AE assessed by the investigator as causally related to the study vaccination. | During an 84 day follow-up period after each vaccination (Day 0 - Day 84, Day 21 - Day 105, Day 182 - Day 266) | 
| Number of Subjects With Serious Adverse Events (SAEs) | Serious adverse events (SAEs) assessed included 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 to 364) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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H5N1, influenza infection, Influenza vaccine GSK1562902A