Immunogenicity and Safety Study of GlaxoSmithKline Biologicals' GSK2202083A Vaccine Administered as a Booster Dose

Study Overview
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Brief Summary
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The current trial will evaluate the safety and immunogenicity of GSK Biologicals' GSK2202083A vaccine when administered as a booster dose following priming in the first year of life with the same vaccine. 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 (NCT number = NCT00970307).

Official Title
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Immunogenicity and Safety Study of GlaxoSmithKline Biologicals' GSK2202083A Vaccine Administered as a Booster Dose in 12-18 Months Old Healthy Children

Conditions
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Tetanus, Diphtheria, Haemophilus Influenzae Type b, Hepatitis B, Poliomyelitis, Acellular Pertussis, Diphtheria-Tetanus-aPertussis-Hepatitis B-Poliomyelitis-Haemophilus Influenzae Type b-Neisseria Meni

Intervention / Treatment
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* Biological: GSK2202083A vaccine
* Biological: Infanrix hexa™
* Biological: Menjugate™
* Biological: NeisVac-C™
* Biological: Synflorix™


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects who the investigator believes that parent(s)/ legally acceptable representative(s) can and will comply with the requirements of the protocol. Subjects who have completed the full three-dose primary vaccination course according to their group allocation in the primary study DTPa-HBV-IPV=Hib-MenC-TT-002 (112157). A male or female between, and including, 12 and 18 months of age at the time of booster vaccination. Written informed consent obtained from the parent(s)/ legally acceptable representative(s) of the subject. Healthy subjects as established by medical history and clinical examination before entering into the study. Exclusion Criteria: Child in care. Use of any investigational or non-registered product other than the study vaccines within 30 days preceding the 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 booster vaccination. Planned administration/administration of immunoglobulins and/or any blood products within three months before the booster dose, or during the study period. Planned administration/administration of any vaccine not foreseen by the study protocol during the period starting 30 days before and ending 30 days after the booster dose. Participation in another clinical study since the primary study DTPa-HBV-IPV/Hib-MenC-TT-002 in which the subject has been or will be exposed to an investigational or a non-investigational product. Evidence of previous diphtheria, tetanus, pertussis, hepatitis B, poliomyelitis, Hib, pneumococcal and MenC vaccination or disease since the conclusion visit of study DTPa-HBV-IPV/Hib-MenC-TT-002. Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination. History of any reaction or hypersensitivity likely to be exacerbated by any component of the vaccines. The following adverse event having occurred after previous administration of DTP vaccine: Encephalopathy. Temperature of >= 40.5°C (rectal temperature) within 48 hours of vaccination, not due to another identifiable cause. Collapse or shock-like state within 48 hours of vaccination. Persistent, inconsolable crying occurring within 48 hours of vaccination and lasting >= 3 hours. Seizures with or without fever occurring within 3 days of vaccination. The following condition is temporary or self-limiting, and a subject may be vaccinated once the condition has resolved if no other exclusion criteria is met: • Acute disease and/or fever at the time of enrolment. Fever is defined as temperature ≥ 37.5°C on oral, axillary or tympanic setting, or ≥ 38.0°C on rectal setting. Subjects with a minor illness without fever may be enrolled at the discretion of the investigator.

Ages Eligible for Study
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Minimum Age: 12 Months
Maximum Age: 18 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
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: GSK2202083A + SYNFLORIX GROUP<br>Healthy male and female subjects between, and including, 12 to 18 months of age at the time of booster vaccination, who were primed with 3 doses of GSK2202083A and Synflorix™ vaccines in the primary study DTPa-HBV-IPV=HIB-MenC-TT-002 (112157), additionally received a booster dose of GSK2202083A vaccine at Day 0 and of Synflorix™ vaccine at Month 1. Both vaccines were administered intramuscularly in the anterolateral side of the thigh. | Biological: GSK2202083A vaccine<br>* Intramuscular, one dose.<br>Biological: Synflorix™<br>* Intramuscular, one dose.<br>|
| Active Comparator: INFANRIX HEXA/MENJUGATE GROUP<br>Healthy male and female subjects between, and including, 12 to 18 months of age at the time of booster vaccination, who were primed with 3 doses of Infanrix hexa™ vaccine and 2 doses of Menjugate® vaccine in the primary study DTPa-HBV-IPV=HIB-MenC-TT-002 (112157), additionally received a booster dose of Infanrix hexa™ vaccine co-administered with Menjugate® vaccine at Day 0. Both vaccines were administered intramuscularly in the anterolateral side of the thigh. | Biological: Infanrix hexa™<br>* Intramuscular, one dose.<br>Biological: Menjugate™<br>* Intramuscular, one dose.<br>|
| Active Comparator: INFANRIX HEXA/NEISVAC-C + SYNFLORIX GROUP<br>Healthy male and female subjects between, and including, 12 to 18 months of age at the time of booster vaccination, who were primed with 3 doses of Infanrix hexa™ vaccine and Synflorix™ vaccines in the primary study DTPa-HBV-IPV=HIB-MenC-TT-002 (112157), additionally received a booster dose of Infanrix hexa™ vaccine co-administered with NeisVac-C® vaccine at Day 0 and 1 dose of Synflorix™ vaccine at Month 1. Both vaccines were administered intramuscularly in the anterolateral side of the thigh. | Biological: Infanrix hexa™<br>* Intramuscular, one dose.<br>Biological: NeisVac-C™<br>* Intramuscular, one dose.<br>Biological: Synflorix™<br>* Intramuscular, one dose.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Seroprotected Subjects Against Polyribosyl-Ribitol-Phosphate (PRP) | A seroprotected subject was defined as a subject with anti-PRP antibody concentrations greater than or equal to (≥) 0.15 micrograms per milliliter (μg/mL). | At Month 1, post-booster dose | 
| Number of Seroprotected Subjects Against Neisseria Meningitidis Serogroup C Using Baby Rabbit Completent (rSBA-MenC) | A seroprotected subject was defined as a subject with anti-rSBA-MenC titers greater than or equal to (≥) 1:8. | At Month 1, post-booster dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Seropositive Subjects for Anti-PRP | A seropositive subject was defined as a subject with anti-PRP antibody concentrations ≥ 0.15 μg/mL. | At Month 0, before the booster dose | 
| Number of Subjects With Anti-PRP Antibody Concentrations ≥ the Cut-off | The cut-off value of the assay was an anti-PRP antibody concentration ≥ 1 μg/mL. | At Month 0 and Month 1, before and one month after booster dose | 
| Anti-PRP Antibody Concentrations | Concentrations were expressed as geometric mean concentrations (GMCs) for the cut-off value of ≥ 0.15 μg/mL. | At Month 0 and Month 1, before and one month after booster dose | 
| Number of Seroprotected Subjects Against rSBA-MenC | A seroprotected subject was defined as a subject with anti-rSBA-MenC antibody titers ≥ 1:8. | At Month 0, before the booster dose | 
| Number of Seropositive Subjects for Anti-rSBA-MenC | A seropositive subject for anti-rSBA-MenC was defined as a subject with antibody titers greater than or equal to (≥) 1:128. | At Month 0 and Month 1, before and one month after booster dose | 
| Anti-rSBA-MenC Antibody Titres | Antibody titers were expressed as geometric mean titers (GMTs) for the seroprotection cut-off value of ≥ 1:8. | At Month 0 and Month 1, before and one month after booster dose | 
| Number of Subjects With Polysaccharide N. Meningitidis Serogroup C (PSC) Antibody Concentrations ≥ Cut-off Values | The cut-off values assessed were ≥ 0.3 μg/mL and ≥ 2 μg/mL. | At Month 0 and Month 1, before and one month after booster dose | 
| Anti-PSC Antibody Concentrations | Concentrations were expressed as geometric mean concentrations (GMCs) for the seropositivity cut-off value of ≥ 0.3 μg/mL. | At Month 0 and Month 1, before and one month after booster dose | 
| Number of Seropositive Subjects for Anti-diphteria (Anti-D) and Anti-tetanus (Anti-T) | A seropositive subject was defined as a subject with anti-D and anti-T antibody concentrations ≥ 0.1 international units per milliliter (IU/mL). | At Month 0 and Month 1, before and one month after booster dose | 
| Anti-D and Anti-T Antibody Concentrations | Concentrations were expressed as geometric mean concentrations (GMCs) for the seropositivity cut-off value of ≥ 0.1 IU/mL. | At Month 0 and Month 1, before and one month after booster dose | 
| Number of Subjects With Anti-hepatitis B (Anti-HBs) Antibody Concentrations ≥ Cut-off Values | The cut-off values assessed were 3.3 milli-international units per milliliter (mIU/mL), 10 mIU/mL and 100 mIU/mL. | At Month 0 and Month 1, before and one month after booster dose | 
| Anti-HBs Antibody Concentrations | Concentrations were presented as geometric mean concentrations (GMCs), expressed in mIU/mL. | At Month 0 and Month 1, before and after booster dose | 
| Number of Seropositive Subjects for Anti-poliovirus Types 1, 2 and 3 | A seropositive subject was defined as a subject with anti-polio type 1, 2 or 3 ≥ 1:8. | At Month 0 and Month 1, before and one month after booster dose | 
| Anti-poliovirus Types 1, 2 and 3 Antibody Titres | Titers were expressed as geometric mean titters (GMTs) for the seropositivity cut-off value of ≥ 1:8. | At Month 0 and Month 1, before and one month after booster dose | 
| Number of Seropositive Subjects for Anti-pertussis Toxoid (Anti-PT), Anti-filamentous Haemagglutinin (Anti-FHA) and Anti-pertactin (Anti-PRN) | A seropositive subject was defined as a subject with anti-PT, anti-FHA and anti-PRN antibody concentrations ≥ 5 enzyme-linked immunosorbent assay (ELISA) units per milliliter (EL.U/mL). | At Month 0 and Month 1, before and one month after booster dose | 
| Anti-PT, Anti-FHA and Anti-PRN Antibody Concentrations | Concentrations were expressed as geometric mean concentrations (GMCs) for the seropositivity cut-off value ≥ 5 EL.U/mL. | At Month 0 and Month 1, before and one month after booster dose | 
| Number of Subjects With Any Solicited Local Symptoms | Solicited local symptoms assessed included pain, redness and swelling. Any= all reports of the speecified symptom irrespective of intensity grade. | During the 8-day (Days 0-7) post-booster period | 
| Number of Subjects With Any Solicited General Symptoms | Solicited general symptoms assessed included drowsiness, irritability, loss of appetite and fever (defined as axillary temperature ≥ 37.5º C). Any= all reports of the specified symptom irrespective of intensity grade and relationship to vaccination. | During the 8-day (Days 0-7) post-booster period | 
| Number of Subjects With Unsolicited Adverse Events (AEs) | An unsolicited AE was any AE (i.e. any 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) 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 31-day (Days 0-30) post-booster period | 
| Number of Subjects With Serious Adverse Events (SAEs) | SAEs were defined as medical occurrences that resulted in death, were life threatening, required hospitalization or prolongation of hospitalization or resulted in disability/incapacity. | After the booster dose of the study vaccine up to the study end (from Month 0 to Month 1) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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booster vaccination, combined vaccine