Booster Vaccination Study With a Pneumococcal Vaccine in Children Primed With the Same Vaccine

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to evaluate the reactogenicity, safety and immunogenicity of a booster (fourth) dose of pneumococcal vaccine GSK1024850A when co-administered with Hiberix at 12-18 months of age, in children primed with the same vaccines in primary study NCT00680914.

Official Title
-----------------
Booster Vaccination With Pneumococcal Vaccine GSK1024850A or Prevenar™ Co-administered With Hiberix™ in Children Primed With the Same Vaccines

Conditions
-----------------
Infections, Streptococcal

Intervention / Treatment
-----------------
* Biological: GSK Biologicals' Synflorix™ (Pneumococcal vaccine GSK1024850A)
* Biological: Wyeth-Lederle's Prevenar™
* Biological: GSK Biologicals' Hiberix™


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: A male or female between, and including, 12-18 months of age at the time of booster vaccination. Subjects for whom the investigator believes that their parent(s)/ guardian(s) can and will comply with the requirements of the protocol. Subjects who received three doses of pneumococcal conjugate vaccine in study NCT00680914. Written informed consent obtained from the parent(s)/guardian(s) of the child/ward. 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 (drug or vaccine) within 30 days preceding the vaccination, or planned use during the study period. 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). Chronic administration (defined as more than 14 days) of immunosuppressants or other immune-modifying drugs within six months prior to vaccination. Administration of immunoglobulins and/or any blood products within three months preceding the vaccination or planned administration during the study period. Administration of any pneumococcal and/or Hib vaccine since the end of study NCT00680914. Planned administration/administration of a vaccine not allowed by the study protocol during the period starting 1 month (30 days) before the administration of the booster dose of the study vaccines (Visit 1) and up to the follow-up visit (Visit 2) with the exception of vaccines included in the Korean routine immunization which can be given at least one week before the administration of the study vaccines or after study end. Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination. History of reactions or allergic disease likely to be exacerbated by any component of the study vaccines. Known hypersensitivity to any component of the study vaccines including anaphylactic reactions following the administration of the study vaccines. Major congenital defects or serious chronic illness. History of any neurologic disorders or seizures. Tympanic or axillary/ oral temperature >= 37.5°C or rectal temperature >= 38.0°C. A temperature greater than or equal to these cut-offs warrants deferral of the vaccination pending recovery of the subject. Acute disease at the time of enrolment.

Ages Eligible for Study
-----------------
Minimum Age: 12 Months
Maximum Age: 18 Months

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Synflorix Group<br>Subjects previously primed (NCT00680914) with 3 doses of Synflorix and Hiberix in the first year of life receiving a booster dose of the same vaccines in the second year of life by intramuscular injection into the right and the left thigh or deltoid, respectively. | Biological: GSK Biologicals' Synflorix™ (Pneumococcal vaccine GSK1024850A)<br>* Intramuscular injection, administered as a single dose<br>* Other names: Pneumococcal vaccine GSK1024850A;Biological: GSK Biologicals' Hiberix™<br>* Intramuscular injection, administered as a single dose<br>* Other names: Hib;|
| Active Comparator: Prevenar Group<br>Subjects previously primed (NCT00680914) with 3 doses of Prevenar and Hiberix in the first year of life receiving a booster dose of Prevenar and Hiberix in the second year of life by intramuscular injection into the right and the left thigh or deltoid, respectively. | Biological: Wyeth-Lederle's Prevenar™<br>* Intramuscular injection, administered as a single dose<br>Biological: GSK Biologicals' Hiberix™<br>* Intramuscular injection, administered as a single dose<br>* Other names: Hib;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects Reporting Grade 3 Adverse Events | Grade 3 adverse events are severe symptoms that prevent normal, everyday activities. | Within 31 days (Day 0 - Day 30) after booster vaccination. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects Reporting Solicited Symptoms | Solicited local symptoms assessed include pain, redness and swelling at the injection site. Solicited general symptoms assessed include drowsiness, fever (equal to or above 37.5 degrees Celsius), irritability and loss of appetite. | Within 4 days (Days 0 to 3) after booster vaccination | 
| Number of Subjects Reporting Unsolicited Adverse Events | An unsolicited adverse event is any adverse event (i.e. any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product) reported in addition to those solicited during the clinical study. Also any solicited symptom with onset outside the specified period of follow-up for solicited symptoms will be reported as an unsolicited adverse event. | Within 31 days (Days 0 to 30) after booster vaccination | 
| Number of Subjects Reporting Serious Adverse Events | Serious adverse events are medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization, result in disability/incapacity or are a congenital anomaly/birth defect in the offspring of a study subject. | After booster vaccination up to study end (Month 0 to Month 1) | 
| Concentration of Antibodies Against Vaccine Pneumococcal Serotypes | Concentrations of antibodies are measured by 22F-inhibition enzyme-linked immunosorbent assay (ELISA) and are presented as geometric mean concentrations expressed as microgram per milliliter (ug/mL). Vaccine pneumococcal serotypes included serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F. | One month after booster vaccination (Month 1) | 
| Opsonophagocytic Activity Against Vaccine Pneumococcal Serotypes | Streptococcus pneumoniae opsonophagocytic activity was measured by a killing-assay using a HL 60 cell line. The results are presented as the dilution of serum (opsonic titer) able to sustain 50% killing of live pneumococci under the assay conditions. Vaccine pneumococcal serotypes included serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F. | One month after booster vaccination (Month 1) | 
| Concentration of Antibodies Against Cross-reactive Pneumococcal Serotypes 6A and 19A | Concentrations of antibodies are measured by 22F-inhibition ELISA and are presented as geometric mean concentrations expressed as microgram per milliliter. | One month after booster vaccination (Month 1) | 
| Opsonophagocytic Activity Against Cross-reactive Pneumococcal Serotypes 6A and 19A | Streptococcus pneumoniae opsonophagocytic activity was measured by a killing-assay using a HL 60 cell line. The results are presented as the dilution of serum (opsonic titer) able to sustain 50% killing of live pneumococci under the assay conditions. | One month after booster vaccination (Month 1) | 
| Concentration of Antibodies Against Protein D (PD) | Concentrations of antibodies are presented as geometric mean concentrations expressed as Enzyme-Linked Immuno-Sorbent Assay (ELISA) units per milliliter (EU/mL). | One month after booster vaccination (Month 1) | 
| Concentration of Antibodies Against Polyribosyl-ribitol-phosphate (PRP) | Concentrations of antibodies are presented as geometric mean concentrations expressed as microgram per milliliter. | One month after booster vaccination (Month 1) | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Safety, Pneumococcal vaccine, Immunogenicity, Pneumococcal disease, Booster vaccination