Pneumococcal Vaccine Booster Study in Healthy Children 12-18 Mths Old Previously Primed With the Same Vaccines

Study Overview
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Brief Summary
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The purpose of this observer blind study is to assess the safety in terms of fever >39°C (rectal temperature) and the immunogenicity in terms of antibody response following a booster vaccination with pneumococcal vaccine GSK 1024850A at 12 to 18 months of age in children previously primed with the same vaccines including a pneumococcal conjugate vaccine co-administered with a diphtheria, tetanus, whole cell pertussis (DTPw)-combined vaccine and OPV or IPV vaccines. Subjects participating in this study should have received three doses of pneumococcal conjugate vaccine in the primary study. 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 = NCT00344318)

Detailed Description
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The Protocol Posting has been updated in order to comply with the FDA Amendment Act, Sep 2007

Official Title
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Booster Vaccination Course With the Pneumococcal Vaccine GSK 1024850A, DTPw-HBV/Hib and OPV or IPV in Children Who Completed the Primary Vaccination Course in Study 107007

Conditions
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Infections, Streptococcal

Intervention / Treatment
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* Biological: Synflorix
* Biological: Tritanrix-HepB
* Biological: Hiberix
* Biological: Polio Sabin
* Biological: Poliorix
* Biological: Prevenar (Wyeth)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects for whom the investigator believes that their parents/guardians can and will comply with the requirements of the protocol. A male or female between, and including, 12-18 months of age at the time of the booster vaccination and who previously participated in study 107007 and received three doses of pneumococcal conjugate vaccine. Written informed consent obtained from the parent or guardian of the subject. Free of obvious health problems as established by medical history and clinical examination before entering into the study. Exclusion Criteria: Concurrently participating in another clinical study, at any time during the study period (active phase and extended safety follow-up), in which the subject has been or will be exposed to an investigational or a non-investigational product (pharmaceutical product or device). Use of any investigational or non-registered product (drug or vaccine) other than the study vaccines within one month preceding the booster dose of study vaccines, or planned use during the entire study period Chronic administration (defined as more than 14 days) of immunosuppressants or other immune-modifying drugs within 6 months prior to the booster dose of study vaccines. Planned administration/administration of a vaccine not foreseen by the study protocol, during the period starting one month before the booster dose of study vaccines and up to the follow-up visit. Administration of any pneumococcal, diphtheria, tetanus, pertussis, polio, hepatitis B, Haemophilus influenzae type b vaccine other than the study vaccines from study 107007. History of, or intercurrent diphtheria, tetanus, pertussis, polio, hepatitis B, Haemophilus influenzae type b diseases. History of allergic disease or reactions likely to be exacerbated by any component of the vaccines. History of seizures (this criterion does not apply to subjects who have had a single, uncomplicated febrile convulsion in the past) or progressive neurological disease. Acute disease at the time of enrolment. Any confirmed or suspected immunosuppressive or immunodeficient condition based on medical history and physical examination A family history of congenital or hereditary immunodeficiency. Major congenital defects or serious chronic illness. Administration of immunoglobulins and/or any blood products within three months preceding the booster dose of study vaccines or planned administration during the active phase of the study.

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: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Synflorix + Tritanrix -HepB/ Hiberix + Polio Sabin Group<br>Subjects in the Philippines, primary vaccinated at 6-10-14 weeks of age, receiving booster dose of Synflorix™ vaccine, co-administered with Tritanrix™-HepB/ Hiberix™ and Polio Sabin™ vaccines at 12-18 months of age. | Biological: Synflorix<br>* Intramuscular injection, 1 dose<br>* Other names: Pneumococcal conjugate vaccine GSK1024850A;Biological: Tritanrix-HepB<br>* Intramuscular injection, 1 dose<br>* Other names: DTPw-HBV vaccine;Biological: Hiberix<br>* Reconstituted with Tritanrix-Hep B before injection<br>* Other names: Hib vaccine;Biological: Polio Sabin<br>* Oral, 1 dose<br>* Other names: OPV;|
| Active Comparator: Prevenar + Tritanrix - HepB/ Hiberix + Polio Sabin Group<br>Subjects in the Philippines, primary vaccinated at 6-10-14 weeks of age, receiving booster dose of the Prevenar™ vaccine, co-administered with Tritanrix™-HepB/ Hiberix™ and Polio Sabin™ at 12-18 months of age. | Biological: Tritanrix-HepB<br>* Intramuscular injection, 1 dose<br>* Other names: DTPw-HBV vaccine;Biological: Hiberix<br>* Reconstituted with Tritanrix-Hep B before injection<br>* Other names: Hib vaccine;Biological: Polio Sabin<br>* Oral, 1 dose<br>* Other names: OPV;Biological: Prevenar (Wyeth)<br>* Intramuscular injection, 1 dose<br>* Other names: Pneumococcal conjugate vaccine;|
| Experimental: Synflorix + Tritanrix -HepB/ Hiberix + Poliorix Group<br>Subjects in Poland, primary vaccinated at 2-4-6 months of age, receiving booster dose of Synflorix™ vaccine co-administered with Tritanrix™-HepB/Hiberix™ and Poliorix™ vaccines at 12-18 months of age. | Biological: Synflorix<br>* Intramuscular injection, 1 dose<br>* Other names: Pneumococcal conjugate vaccine GSK1024850A;Biological: Tritanrix-HepB<br>* Intramuscular injection, 1 dose<br>* Other names: DTPw-HBV vaccine;Biological: Hiberix<br>* Reconstituted with Tritanrix-Hep B before injection<br>* Other names: Hib vaccine;Biological: Poliorix<br>* Intramuscular injection, 1 dose<br>* Other names: IPV;|
| Active Comparator: Prevenar + Tritanrix -HepB/ Hiberix + Poliorix Group<br>Subjects in Poland, primary vaccinated at 2-4-6 months of age, receiving booster dose of the Prevenar™ vaccine, co-administered with Tritanrix -HepB/ Hiberix and Poliorix™ at 12-18 months of age. | Biological: Tritanrix-HepB<br>* Intramuscular injection, 1 dose<br>* Other names: DTPw-HBV vaccine;Biological: Hiberix<br>* Reconstituted with Tritanrix-Hep B before injection<br>* Other names: Hib vaccine;Biological: Poliorix<br>* Intramuscular injection, 1 dose<br>* Other names: IPV;Biological: Prevenar (Wyeth)<br>* Intramuscular injection, 1 dose<br>* Other names: Pneumococcal conjugate vaccine;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects Reporting Rectal Temperature Greater Than (>) the Cut-off | Fever was measured as rectal temperature. The cut-off was 39.0 degree Celsius (°C). Assessment of occurrences of fever > 39.0 (°C) was performed after booster vaccination with Synflorix™ or Prevenar™ vaccines. | Within the 4-day (Days 0-3) period after booster vaccination | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects With Any and Grade 3 Solicited Local Symptoms | Solicited local symptoms assessed included pain, redness and swelling. Any was defined as incidence of the specified symptom regardless of intensity. Grade 3 pain was defined as crying when limb was moved/ spontaneously painful. Grade 3 swelling/ redness was defined as swelling/ redness greater than (>) 30 millimeters (mm). | Within the 4-day (Days 0-3) period after booster vaccination | 
| Number of Subjects With Any and Grade 3 Solicited General Symptoms | Solicited general symptoms assessed include drowsiness, fever (defined as rectal temperature greater than or equal to (≥) 38.0°C), irritability, and loss of appetite.Any was defined as incidence of the specified symptom regardless of intensity or relationship to study vaccination. Grade 3 drowsiness was defined as drowsiness which prevented normal everyday activities. Grade 3 fever was defined as fever (rectal temperature) >40.0 degree Celsius (°C). Grade 3 irritability was defined as crying that could not be comforted/ preventing normal activity. Grade 3 loss of appetite was defined as the subject not eating at all. | Within the 4-day (Days 0-3) period after booster vaccination | 
| 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 an incidence of an unsolicited AE regardless of intensity or relationship to study vaccination. | Within the 31-day (Days 0-30) period after booster 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. | Throughout the active phase of the study (Month 0 to Month 1) | 
| Number of Subjects With Anti-pneumococcal Serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F Antibody Concentrations ≥ the Cut-off | The cut-off was 0.20 microgram per milliliter (μg/mL). | Prior to (Month 0) and one month after booster vaccination (Month 1) | 
| Anti-pneumococcal Serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F Antibody Concentrations | Seropositivity status, defined as anti-pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F antibody concentrations ≥ 0.05 microgram per milliliter (μg/mL). | Prior to (Month 0) and one month after booster vaccination (Month 1) | 
| Opsonophagocytic Activity (OPA) Titers Against Pneumococcal Serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F | Seropositivity status, defined as Opsonophagocytic activity against pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F ≥ 8. | Prior to (Month 0) and one month after booster vaccination (Month 1) | 
| Antibody Concentrations to Protein D (Anti-PD) | Seropositivity status, defined as anti-PD antibody concentrations ≥100 enzyme-linked immunosorbent assay (ELISA) units per milliliter (EL.U/mL). | Prior to (Month 0) and one month after booster vaccination (Month 1) | 
| Antibody Concentrations Against Pneumococcal Cross-reactive Serotypes 6A and 19A | Seropositivity status, defined as anti-pneumococcal cross-reactive serotypes 6A and 19A antibody concentrations ≥ 0.05 microgram per milliliter (μg/mL). | Prior to (Month 0) and one month after booster vaccination (Month 1) | 
| Opsonophagocytic Activity (OPA) Against Pneumococcal Cross-reactive Serotypes 6A and 19A | Seropositivity status, defined as Opsonophagocytic activity against pneumococcal cross-reactive serotypes 6A and 19A ≥ 8. | Prior to (Month 0) and one month after booster vaccination (Month 1) | 
| Number of Subjects With Anti-pneumococcal Serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F Antibody Concentrations ≥ the Cut-off | The cut-off of the assay was 0.05 μg/mL. | Prior to (Month 0) and one month after booster vaccination (Month 1) | 
| Number of Subjects With Opsonophagocytic Activity (OPA) Titers Against Pneumococcal Serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F ≥ the Cut-off | The cut-off for the assay was 8. | Prior to (Month 0) and one month after booster vaccination (Month 1) | 
| Number of Subjects With Concentrations of Antibodies Against Cross-reactive Pneumococcal Serotypes 6A and 19A ≥ the Cut-off | The cut-of for the assay was 0.05 μg/mL. | Prior to (Month 0) and one month after booster vaccination (Month 1) | 
| Number of Subjects With Opsonophagocytic Activity (OPA) Against Pneumococcal Cross-reactive Serotypes 6A and 19A ≥ the Cut-off | The cut-off for the assay was 8. | Prior to (Month 0) and one month after booster vaccination (Month 1) | 
| Number of Subjects With Antibody Concentrations Against Protein D (Anti-PD) ≥ the Cut-off | The cut-off for the assay was 100 ELISA units per milliliter (EL.U/mL). | Prior to (Month 0) and one month after booster vaccination (Month 1) | 
| Anti-diphtheria (Anti-DT) and Anti-tetanus Toxoids (Anti-TT) Antibody Concentrations | Seroprotection status, defined as anti-diphtheria toxoid or anti-tetanus toxoid antibody concentrations ≥ 0.1 international units per milliliter (IU/mL). | Prior to (Month 0) and one month after booster vaccination (Month 1) | 
| Anti-polyribosyl-ribitol-phosphate (Anti-PRP) Antibody Concentrations | Seroprotection status, defined as anti-PRP antibody concentrations ≥ 0.15 μg/mL and ≥ 1.0 μg/mL. | Prior to (Month 0) and one month after booster vaccination (Month 1) | 
| Anti-Bordetella Pertussis (BPT) Antibody Concentrations | Seropositivity status, defined as anti-BPT antibody concentrations ≥ 15 EL.U/mL. | Prior to (Month 0) and one month after booster vaccination (Month 1) | 
| Anti-hepatitis B Surface Antigen (HBs) Antibody Concentrations | Seroprotection status, defined as anti-HBs antibody concentrations ≥ 10 milli international units per milliliter (mIU/mL). | Prior to (Month 0) and one month after booster vaccination (Month 1) | 
| Anti-polio Type 1, 2 and 3 Antibody Titers | Seroprotection status, defined as anti-polio type 1, anti-polio type 2 and anti-polio type 3 antibody titers ≥ 8. | Prior to (Month 0) and one month after booster vaccination (Month 1) | 
| Number of Subjects With Anti-Bordetella Pertussis (BPT) With Concentrations ≥ the Cut-off | The cut-off for the assay was 15 EL.U/mL. | Prior to (Month 0) and one month after booster vaccination (Month 1) | 
| Number of Subjects With Anti-diphtheria (Anti-DT) and Anti-tetanus Toxoids (Anti-TT) Antibody Concentrations ≥ the Cut-off | The cut-off for the assay was 0.1 milli-international units per milliliter (mIU/mL). | Prior to (Month 0) and one month after booster vaccination (Month 1) | 
| Number of Subjects With Anti-polyribosyl-ribitol Phosphate (Anti-PRP) Antibody Concentration ≥ the Cut-off | The cut-off for the assay was 0.15 μg/mL. | Prior to (Month 0) and one month after booster vaccination (Month 1) | 
| Number of Subjects With Anti-PRP Antibody Concentration ≥ the Cut-off | The cut-off for the assay was 1.0 μg/mL. | Prior to (Month 0) and one month after booster vaccination (Month 1) | 
| Number of Subjects With Anti-hepatitis B Surface Antigen (HBs) Antibody Concentrations ≥ the Cut-off | The cut-off for the assay was 10 mIU/mL. | Prior to (Month 0) and one month after booster vaccination (Month 1) | 
| Number of Subjects With Anti-polio Type 1, 2 and 3 (Anti-Polio 1, 2 and 3) Antibody Titers ≥ the Cut-off | The cut-off for the assay was 8. | Prior to (Month 0) and one month after booster vaccination (Month 1) | 
| Number of Subjects With Vaccine Response to Anti-Bordetella Pertussis (BPT) | Vaccine response for anti-BPT, defined as the appearance of antibodies in subjects seronegative at pre-vaccination, or at least 2-fold increase of pre-vaccination antibody concentrations in those who were initially seropositive at pre-vaccination. | One month after booster vaccination (Month 1) | 

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