Study to Evaluate the Immunogenicity and Reactogenicity of a Booster Dose of GSK2036874A Vaccine in Healthy Toddlers

Study Overview
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Brief Summary
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The purpose of the study is to assess the immunogenicity and safety of three formulations of GSK Biologicals' GSK2036874A vaccine compared to Zilbrix™/Hib and Poliorix™ vaccines administered concomitantly, when administered as a single booster dose to healthy poliovirus-primed toddlers aged 12-24 months.

Detailed Description
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The study will be conducted in a partially double-blinded manner. The study will be double-blinded with respect to the three GSK2036874A formulation groups and open-label with respect to the Control Group.

Official Title
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Immunogenicity and Reactogenicity of a Booster Dose of GlaxoSmithKline Biologicals' GSK2036874A Vaccine in Healthy Toddlers

Conditions
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Haemophilus Influenzae Type b, Tetanus, Hepatitis B, Whole Cell Pertussis, Diphtheria, Poliomyelitis Vaccines

Intervention / Treatment
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* Biological: GSK2036874A vaccine
* Biological: Zilbrix™/Hib vaccine
* Biological: Poliorix™


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: A male or female subject, between and including 12 and 24 months of age at the time of booster vaccination. Subjects who have received three doses of polio vaccine as primary vaccination along with the routine vaccinations indicated during the first year of life. Subjects who the investigator believes that their parent(s)/Legally Acceptable Representative (s) can and will comply with the requirements of the protocol. 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: Use of any investigational or non-registered product other than the study vaccine(s) within 30 days preceding the booster 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 dose. Administration of a vaccine not foreseen by the study protocol within 30 days prior to booster vaccination, or planned administration during the active study period (up to Visit 2). 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. History of diphtheria, tetanus, pertussis, hepatitis B, poliomyelitis and/or Haemophilus influenza type b diseases. Previous booster vaccination against diphtheria, tetanus, pertussis, poliomyelitis, hepatitis B or H. influenzae diseases. Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination (no laboratory testing required). A family history of congenital or hereditary immunodeficiency. Major congenital defects or serious chronic illness. History of neurologic disorders or seizures. History of any reaction or hypersensitivity likely to be exacerbated by any component of the vaccines. Administration of immunoglobulins and/or any blood products within the three months preceding the booster dose or planned administration during the study period. Occurrence of transient thrombocytopenia or neurological complications following an earlier immunisation against diphtheria and/or tetanus. Child in care. Occurrence of any of the following adverse events after a previous administration of a diphtheria-tetanus-pertussis vaccine: encephalopathy of unknown aetiology occurring within seven days following previous vaccination with pertussis-containing vaccine, fever >= 40 °C within 48 hours of vaccination not due to another identifiable cause, collapse or shock-like state within 48 hours of vaccination, convulsions with or without fever, occurring within 3 days of vaccination. 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. Other conditions which, in the opinion of the investigator, may potentially interfere with interpretation of study results.

Ages Eligible for Study
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Minimum Age: 12 Months
Maximum Age: 24 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: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: GSK2036874A GROUP 1<br>Healthy male or female children between and including 12 and 24 months of age at the time of the booster vaccination, who were primed with a three-dose vaccination course of polio vaccine, additionally received 1 dose of GSK2036874A vaccine (Formulation 1) intramuscularly into the anterolateral region of the left thigh, at Day 0. | Biological: GSK2036874A vaccine<br>* Intramuscular, single dose<br>|
| Experimental: GSK2036874A GROUP 2<br>Healthy male or female children between and including 12 and 24 months of age at the time of the booster vaccination, who were primed with a three-dose vaccination course of polio vaccine, additionally received 1 dose of GSK2036874A vaccine (Formulation 2) intramuscularly into the anterolateral region of the left thigh, at Day 0. | Biological: GSK2036874A vaccine<br>* Intramuscular, single dose<br>|
| Experimental: GSK2036874A GROUP 3<br>Healthy male or female children between and including 12 and 24 months of age at the time of the booster vaccination, who were primed with a three-dose vaccination course of polio vaccine, additionally received 1 dose of GSK2036874A vaccine (Formulation 3) intramuscularly into the anterolateral region of the left thigh, at Day 0. | Biological: GSK2036874A vaccine<br>* Intramuscular, single dose<br>|
| Active Comparator: ZILBRIX/HIB/POLIORIX GROUP<br>Healthy male or female children between and including 12 and 24 months of age at the time of the booster vaccination, who were primed with a three-dose vaccination course of polio vaccine, additionally received 1 dose of Zilbrix/Hib™ and Poliorix™ vaccines at Day 0, administered intramuscularly into the anterolateral regions of the left and right thighs, respectively. | Biological: Zilbrix™/Hib vaccine<br>* Intramuscular, single dose<br>Biological: Poliorix™<br>* Intramuscular, single 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 Poliovirus Types 1, 2 and 3 | Seroprotection was defined as anti-polio types 1, 2 and 3 antibody titres ≥ 8 effective dose (ED50), for 50% of vaccinated subjects. | One month after booster vaccination (At Month 1) | 
| Anti-polio Types 1, 2 and 3 Antibody Titers | Antibody titers were presented as geometric mean titers (GMTs). | Prior to booster vaccination (At Month 0) | 
| Anti-polio Types 1, 2 and 3 Antibody Titers | Antibody titers were presented as geometric mean titers (GMTs). | One month after booster vaccination (At Month 1) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Seroconverted Subjects for Anti-polio Types 1, 2 and 3 | Seroconversion was defined as: For initially seronegative subjects, antibody titer ≥ 8 ED50 one month after the booster dose. For initially seropositive subjects: antibody titer one month after the booster dose ≥ 4 fold the pre-booster antibody titer. For subjects with pre-booster antibody titer below the highest dilution tested (reciprocal < 8192 ED50): highest dilution tested one month after the booster dose (reciprocal > 8192 ED50). | One month after booster vaccination (At Month 1) | 
| Number of Seroprotected Subjects Against Poliovirus Types 1, 2 and 3 | Seroprotection was defined as anti-polio types 1, 2 and 3 antibody titres ≥ 8 effective dose (ED50), for 50% of vaccinated subjects. | Prior to booster vaccination (At Month 0) | 
| Number of Seroprotected Subjects Against Diphteria (D) and Tetanus (T) | Seroprotection was defined as anti-D and anti-T antibody concentration ≥ 0.1 international units per milliliter (IU/mL). | Prior to (At Month 0) and one month after booster vaccination (At Month 1) | 
| Anti-D and Anti-T Antibody Concentrations | Antibody concentrations were presented as geometric mean concentrations (GMCs), expressed in IU/mL. | Prior to (At Month 0) and one month after booster vaccination (At Month 1) | 
| Number of Seroprotected and Seropositive Subjects for Anti-hepatitis B (Anti-HBs) | Seropositivity was defined as anti-HBs antibody concentration ≥ 3.3 milli-international units per milliliter (mIU/mL). Seprotection was defined as anti-HBs antibody concentration ≥ 10 mIU/mL. Note that percentage of subjects with concentration ≥ 10 mIU/mL was over-estimated due to the use of in-house assay overestimating concentrations between 10-100 mIU/mL. Accordingly GMCs were also overestimated. A decrease in the specificity of the anti-HB ELISA assay had been observed in some studies for low levels of antibody (10-100 mIU/mL). The table shows updated results following partial or complete retesting/reanalysis. Some of the available blood samples initially tested with ELISA were re-tested using the new assay, CLIA. | Prior to (At Month 0) and one month after the booster vaccination (At Month 1) | 
| Anti-HBs Antibody Concentrations | Antibody concentrations were presented as geometric mean concentrations (GMCs), expressed in mIU/mL. | Prior to (At Month 0) and one month after the booster vaccination (At Month 1) | 
| Number of Seroprotected Subjects Against Polyribosil-ribitol-phosphate (PRP) | Seprotection was defined as anti-PRP antibody concentration ≥ 0.15 micrograms per milliliter (μg/mL). | Prior to (At Month 0) and one month after booster vaccination (At Month 1) | 
| Anti-PRP Antibody Concentrations | Antibody concentrations were presented as geometric mean concentrations (GMCs), expressed in μg/mL. | Prior to (At Month 0) and one month after booster vaccination (At Month 1) | 
| Number of Seropositive Subjects for Anti-Bordetella Pertussis (Anti-BPT) | Seropositivity was defined as anti-BPT antibody concentration ≥ 15 enzyme-linked immunosorbent assay (ELISA) units per milliliter (EL.U/mL). | Prior to (At Month 0) and one month after the booster vaccination (At Month 1) | 
| Anti-BPT Antibody Concentrations | Antibody concentrations were presented as geometric mean concentrations (GMCs), expressed in EL.U/mL. | Prior to (At Month 0) and one month after booster vaccination (At Month 1) | 
| Number of Subjects With a Booster Response for Anti-BPT | Booster response was defined as: For initially seronegative subjects, antibody concentration ≥ 15 EL.U/mL one month after the booster dose. For initially seropositive subjects: antibody concentration one month after the booster dose ≥ 2 fold the pre-booster antibody concentration. | One month after booster vaccination (At Month 1) | 
| Number of Subjects With Any Solicited Local Symptoms | Assessed solicited local symptoms were pain, redness and swelling. Any = occurrence of the symptom regardless of intensity grade. | During the 8-day (Days 0-7) post-vaccination period | 
| Number of Subjects With Any Solicited General Symptoms | Assessed solicited general symptoms were drowsiness, irritability, loss of appetite and fever [defined as axillary temperature equal to or above (≥) 37.5 degrees Celsius (°C)]. Any = occurrence of the symptom regardless of intensity grade. | During the 8-day (Days 0-7) post-vaccination period | 
| Number of Subjects With Any 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. | During the 31-day (Day 0-Day 30) post-vaccination period | 
| 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 0 to Month 1) |