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

Phase 3

Completed

Conditions: Infections, Streptococcal

Interventions: Biological: Synflorix
Biological: Tritanrix-HepB
Biological: Hiberix
Biological: Poliorix
Biological: Prevenar (Wyeth)
Biological: Polio Sabin

Registration Number: NCT00547248

Lead Sponsor: GlaxoSmithKline

Brief Summary: 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: The Protocol Posting has been updated in order to comply with the FDA Amendment Act, Sep 2007

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 756

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Synflorix + Tritanrix -HepB/ Hiberix + Polio Sabin Group	Tritanrix-HepB	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.
Prevenar + Tritanrix - HepB/ Hiberix + Polio Sabin Group	Prevenar (Wyeth)	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.
Synflorix + Tritanrix -HepB/ Hiberix + Polio Sabin Group	Hiberix	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.
Prevenar + Tritanrix -HepB/ Hiberix + Poliorix Group	Poliorix	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.
Synflorix + Tritanrix -HepB/ Hiberix + Polio Sabin Group	Synflorix	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.
Prevenar + Tritanrix - HepB/ Hiberix + Polio Sabin Group	Hiberix	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.
Synflorix + Tritanrix -HepB/ Hiberix + Poliorix Group	Synflorix	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.
Prevenar + Tritanrix -HepB/ Hiberix + Poliorix Group	Hiberix	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.
Synflorix + Tritanrix -HepB/ Hiberix + Polio Sabin Group	Polio Sabin	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.
Synflorix + Tritanrix -HepB/ Hiberix + Poliorix Group	Hiberix	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.
Prevenar + Tritanrix -HepB/ Hiberix + Poliorix Group	Tritanrix-HepB	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.
Prevenar + Tritanrix -HepB/ Hiberix + Poliorix Group	Prevenar (Wyeth)	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.
Prevenar + Tritanrix - HepB/ Hiberix + Polio Sabin Group	Tritanrix-HepB	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.
Prevenar + Tritanrix - HepB/ Hiberix + Polio Sabin Group	Polio Sabin	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.
Synflorix + Tritanrix -HepB/ Hiberix + Poliorix Group	Poliorix	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.
Synflorix + Tritanrix -HepB/ Hiberix + Poliorix Group	Tritanrix-HepB	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.

Primary Outcome Measures

Name	Time	Method
Number of Subjects Reporting Rectal Temperature Greater Than (>) the Cut-off	Within the 4-day (Days 0-3) period after booster vaccination	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.

Secondary Outcome Measures

Name	Time	Method
Number of Subjects With Anti-pneumococcal Serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F Antibody Concentrations ≥ the Cut-off	Prior to (Month 0) and one month after booster vaccination (Month 1)	The cut-off of the assay was 0.05 μg/mL.
Antibody Concentrations to Protein D (Anti-PD)	Prior to (Month 0) and one month after booster vaccination (Month 1)	Seropositivity status, defined as anti-PD antibody concentrations ≥100 enzyme-linked immunosorbent assay (ELISA) units per milliliter (EL.U/mL).
Anti-diphtheria (Anti-DT) and Anti-tetanus Toxoids (Anti-TT) Antibody Concentrations	Prior to (Month 0) and one month after booster vaccination (Month 1)	Seroprotection status, defined as anti-diphtheria toxoid or anti-tetanus toxoid antibody concentrations ≥ 0.1 international units per milliliter (IU/mL).
Anti-Bordetella Pertussis (BPT) Antibody Concentrations	Prior to (Month 0) and one month after booster vaccination (Month 1)	Seropositivity status, defined as anti-BPT antibody concentrations ≥ 15 EL.U/mL.
Number of Subjects With Anti-polyribosyl-ribitol Phosphate (Anti-PRP) Antibody Concentration ≥ the Cut-off	Prior to (Month 0) and one month after booster vaccination (Month 1)	The cut-off for the assay was 0.15 μg/mL.
Number of Subjects With Unsolicited Adverse Events (AEs)	Within the 31-day (Days 0-30) period after booster vaccination	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.
Opsonophagocytic Activity (OPA) Titers Against Pneumococcal Serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F	Prior to (Month 0) and one month after booster vaccination (Month 1)	Seropositivity status, defined as Opsonophagocytic activity against pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F ≥ 8.
Number of Subjects With Antibody Concentrations Against Protein D (Anti-PD) ≥ the Cut-off	Prior to (Month 0) and one month after booster vaccination (Month 1)	The cut-off for the assay was 100 ELISA units per milliliter (EL.U/mL).
Anti-hepatitis B Surface Antigen (HBs) Antibody Concentrations	Prior to (Month 0) and one month after booster vaccination (Month 1)	Seroprotection status, defined as anti-HBs antibody concentrations ≥ 10 milli international units per milliliter (mIU/mL).
Anti-polio Type 1, 2 and 3 Antibody Titers	Prior to (Month 0) and one month after booster vaccination (Month 1)	Seroprotection status, defined as anti-polio type 1, anti-polio type 2 and anti-polio type 3 antibody titers ≥ 8.
Number of Subjects With Anti-polio Type 1, 2 and 3 (Anti-Polio 1, 2 and 3) Antibody Titers ≥ the Cut-off	Prior to (Month 0) and one month after booster vaccination (Month 1)	The cut-off for the assay was 8.
Number of Subjects With Any and Grade 3 Solicited Local Symptoms	Within the 4-day (Days 0-3) period after booster vaccination	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).
Number of Subjects With Serious Adverse Events (SAEs)	Throughout the active phase of the study (Month 0 to Month 1)	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.
Anti-pneumococcal Serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F Antibody Concentrations	Prior to (Month 0) and one month after booster vaccination (Month 1)	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).
Antibody Concentrations Against Pneumococcal Cross-reactive Serotypes 6A and 19A	Prior to (Month 0) and one month after booster vaccination (Month 1)	Seropositivity status, defined as anti-pneumococcal cross-reactive serotypes 6A and 19A antibody concentrations ≥ 0.05 microgram per milliliter (μg/mL).
Number of Subjects With Anti-hepatitis B Surface Antigen (HBs) Antibody Concentrations ≥ the Cut-off	Prior to (Month 0) and one month after booster vaccination (Month 1)	The cut-off for the assay was 10 mIU/mL.
Number of Subjects With Any and Grade 3 Solicited General Symptoms	Within the 4-day (Days 0-3) period after booster vaccination	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.
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	Prior to (Month 0) and one month after booster vaccination (Month 1)	The cut-off for the assay was 8.
Number of Subjects With Concentrations of Antibodies Against Cross-reactive Pneumococcal Serotypes 6A and 19A ≥ the Cut-off	Prior to (Month 0) and one month after booster vaccination (Month 1)	The cut-of for the assay was 0.05 μg/mL.
Number of Subjects With Anti-diphtheria (Anti-DT) and Anti-tetanus Toxoids (Anti-TT) Antibody Concentrations ≥ the Cut-off	Prior to (Month 0) and one month after booster vaccination (Month 1)	The cut-off for the assay was 0.1 milli-international units per milliliter (mIU/mL).
Number of Subjects With Vaccine Response to Anti-Bordetella Pertussis (BPT)	One month after booster vaccination (Month 1)	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.
Opsonophagocytic Activity (OPA) Against Pneumococcal Cross-reactive Serotypes 6A and 19A	Prior to (Month 0) and one month after booster vaccination (Month 1)	Seropositivity status, defined as Opsonophagocytic activity against pneumococcal cross-reactive serotypes 6A and 19A ≥ 8.
Number of Subjects With Opsonophagocytic Activity (OPA) Against Pneumococcal Cross-reactive Serotypes 6A and 19A ≥ the Cut-off	Prior to (Month 0) and one month after booster vaccination (Month 1)	The cut-off for the assay was 8.
Anti-polyribosyl-ribitol-phosphate (Anti-PRP) Antibody Concentrations	Prior to (Month 0) and one month after booster vaccination (Month 1)	Seroprotection status, defined as anti-PRP antibody concentrations ≥ 0.15 μg/mL and ≥ 1.0 μg/mL.
Number of Subjects With Anti-Bordetella Pertussis (BPT) With Concentrations ≥ the Cut-off	Prior to (Month 0) and one month after booster vaccination (Month 1)	The cut-off for the assay was 15 EL.U/mL.
Number of Subjects With Anti-PRP Antibody Concentration ≥ the Cut-off	Prior to (Month 0) and one month after booster vaccination (Month 1)	The cut-off for the assay was 1.0 μg/mL.