Primary Vaccination Course in Children Receiving the Pneumococcal Vaccine GSK 1024850A, Zilbrix™ Hib and Polio Sabin™

Phase 3

Completed

Conditions: Infections, Streptococcal

Interventions: Biological: GSK Biologicals' Synflorix™
Biological: GSK Biologicals' Polio Sabin™
Biological: GSK Biologicals' Zilbrix™ Hib

Registration Number: NCT00678301

Lead Sponsor: GlaxoSmithKline

Brief Summary: The purpose of this study is to assess the immunogenicity in terms of antibody response and the safety/reactogenicity in terms of solicited and unsolicited symptoms and serious adverse events following primary vaccination of African Sub-Saharan infants with pneumococcal conjugate vaccine GSK 1024850A co-administered with a diphtheria, tetanus, whole cell pertussis (DTPw)-combined vaccine and oral polio vaccine in children during the first 4 months of life.

Detailed Description: Vaccination course at 6, 10, 14 weeks of age.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 365

Inclusion Criteria

Male or female subjects between, and including 6-10 weeks of age at the time of the first vaccination.
Subjects for whom the investigator believes that their parent(s)/guardian(s) can and will comply with the requirements of the protocol should be enrolled in the study.
Written or oral, signed or thumb-printed informed consent obtained from the parent(s)/guardian(s) of the child/ward. Where parent(s)/guardian(s) are illiterate, the consent form will be countersigned by a witness.
Free of any known or suspected health problems (as established by medical history and clinical examination before entering into the study), that would contraindicate the initiation of routine immunizations outside a clinical trial context.

Exclusion Criteria

Use of any investigational or non-registered product (drug or vaccine) other than the study vaccines within 30 days preceding the first dose of the study vaccines, 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 of immunosuppressants or other immune-modifying drugs since birth.
A family history of congenital or hereditary immunodeficiency.
Any confirmed or suspected immunosuppressive or immunodeficient condition based on medical history and physical examination.
Administration of immunoglobulins and/or any blood products since birth or planned administration during the study period (Hepatitis B immunoglobulins at birth are allowed).
Previous vaccination against, diphtheria, tetanus, pertussis, Haemophilus influenzae type b and/or Streptococcus pneumoniae.
History of, or intercurrent diphtheria, tetanus, pertussis, hepatitis B, Streptococcus and Haemophilus influenzae type b disease.
History of allergic disease or reactions likely to be exacerbated by any component of the vaccines.
History of any neurological disorders or seizures.
Major congenital defects or serious chronic illness.
Acute disease at the time of enrolment. Study entry should be delayed until the illness has improved.
Babies for which birth weight is < 2 kilogram (if known) at Visit 1

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
SYNFLORIX™ + ZILBRIX™ HIB + POLIO SABIN™	GSK Biologicals' Polio Sabin™	Subjects in this group received 3 doses of Synflorix™ vaccine, according to a 3-dose schedule at 6-10-14 weeks of age co-administered with 3 doses of Expanded Program on Immunization (EPI) vaccines Zilbrix™ Hib and Polio Sabin™ according to the same schedule. The Synflorix™ and Zilbrix™ Hib vaccines were administered by intramuscular injection, in the right and left thigh respectively. The Polio Sabin™ vaccine was administered orally.
ZILBRIX™ HIB + POLIO SABIN™	GSK Biologicals' Zilbrix™ Hib	Subjects in this group received 3 doses of Expanded Program on Immunization (EPI) vaccines Zilbrix™ Hib and Polio Sabin™ according to a 3-dose schedule at 6-10-14 weeks of age. The Zilbrix™ Hib vaccine was administered by intramuscular injection, in the left thigh. The Polio Sabin™ vaccine was administered orally.
SYNFLORIX™ + ZILBRIX™ HIB + POLIO SABIN™	GSK Biologicals' Zilbrix™ Hib	Subjects in this group received 3 doses of Synflorix™ vaccine, according to a 3-dose schedule at 6-10-14 weeks of age co-administered with 3 doses of Expanded Program on Immunization (EPI) vaccines Zilbrix™ Hib and Polio Sabin™ according to the same schedule. The Synflorix™ and Zilbrix™ Hib vaccines were administered by intramuscular injection, in the right and left thigh respectively. The Polio Sabin™ vaccine was administered orally.
SYNFLORIX™ + ZILBRIX™ HIB + POLIO SABIN™	GSK Biologicals' Synflorix™	Subjects in this group received 3 doses of Synflorix™ vaccine, according to a 3-dose schedule at 6-10-14 weeks of age co-administered with 3 doses of Expanded Program on Immunization (EPI) vaccines Zilbrix™ Hib and Polio Sabin™ according to the same schedule. The Synflorix™ and Zilbrix™ Hib vaccines were administered by intramuscular injection, in the right and left thigh respectively. The Polio Sabin™ vaccine was administered orally.
ZILBRIX™ HIB + POLIO SABIN™	GSK Biologicals' Polio Sabin™	Subjects in this group received 3 doses of Expanded Program on Immunization (EPI) vaccines Zilbrix™ Hib and Polio Sabin™ according to a 3-dose schedule at 6-10-14 weeks of age. The Zilbrix™ Hib vaccine was administered by intramuscular injection, in the left thigh. The Polio Sabin™ vaccine was administered orally.

Primary Outcome Measures

Name	Time	Method
Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes	At Month 3, one month after the administration of the third dose of Synflorix vaccine	Pneumococcal serotypes assessed were vaccine pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F. Seropositivity cut-off for the assay was an anti-pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F antibody (Anti-1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F) concentrations greater than or equal to (≥) 0.05 microgram per milliliter (μg/mL).
Antibody Concentrations Against Protein D (Anti-PD Antibodies)	At Month 3, one month after the administration of the third dose of Synflorix vaccine	Anti-PD antibody concentrations were expressed in enzyme-linked immunsorbent assay (ELISA) units per milliliter (EL.U/mL). Seropositivity cut-off for the assay was an anti-PD antibody concentrations ≥ 100 EL.U/mL.

Secondary Outcome Measures

Name	Time	Method
Number of Subjects Seroprotected Against Diphtheria (D) and Tetanus Toxoids (TT) Antigens	At Month 3, one month after the administration of the third dose of Tritanrix -HepB/ Hiberix vaccine	A subject seroprotected against D/TT antigens was defined as a subject with an Anti-D/-TT antibody concentration ≥ 0.1 IU/mL.
Number of Subjects Seroprotected Against Anti-Hepatitis B Surface Antigens (HBs).	At Month 3, one month after the administration of the third dose of Tritanrix HepB/ Hiberix vaccine	The seroprotection cut-off values considered for this endpoint were an anti-HBs antibody concentration ≥ 10 and 100 milli-international units per milliliter (mIU/mL).
Number of Subjects With Any and Any Grade 3 Solicited Local Symptoms	Within the 4-day (Days 0 to 3) follow-up periods after each vaccination, across doses and across vaccines	Solicited local symptoms assessed included pain, redness and swelling. 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). "Any" was defined as incidence of the specified symptom regardless of intensity.
Number of Subjects Seroprotected Against Cross-reactive Pneumococcal Serotypes 6A and 19A (Anti-6A and -19A)	At Month 3, one month after the administration of the third dose of Synflorix vaccine	Serotypes assessed were cross-reactive pneumococcal serotypes 6A and 19 A. Seroprotection cut-off for the assay was an anti-6A/19A antibody concentrations ≥ 0.2 microgram per milliliter (μg/mL).
Number of Subjects Seropositive for Antibodies Against Protein D (Anti-PD Antibodies)	At Month 3, one month after the administration of the third dose of Synflorix vaccine	Seropositivity cut-off for the assay was an anti-PD antibody concentrations ≥ 100 EL.U/mL.
Number of Subjects Seropositive for Opsonophagocytic Activity Against Vaccine Pneumococcal Serotypes	At Month 3, one month after the administration of the third dose of Synflorix vaccine	Pneumococcal serotypes assessed were vaccine pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F. Seropositivity status was defined as an opsonophagocytic activity against vaccine pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F (OPA-1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F) ≥ 8.
Anti-polyribosyl-ribitol-phosphate (Anti-PRP) Antibody Concentrations	At Month 3, one month after the administration of the third dose of Tritanrix -HepB/ Hiberix vaccine	Anti-PRP antibody concentrations were measured and tabulated in microgram per milliliter (μg/mL). Cut-off for the assay was ≥ 0.15 μg/mL.
Number of Subjects Seroprotected Against Polyribosyl-ribitol Phosphate (PRP) Antigens	At Month 3, one month after the administration of the third dose of Tritanrix -HepB/ Hiberix vaccine	Anti-PRP antibody concentrations were expressed in microgram per milliliter (μg/mL). The seroprotection cut-off applied for the assay was ≥ 1 μg/mL.
Anti-hepatitis B Surface Antigen (HBs) Antibody Concentrations	At Month 3, one month after the administration of the third dose of Tritanrix -HepB /Hiberix vaccine	The seroprotection cut-off for the endpoint was an anti-HBs antibody concentration ≥ 10 milli-international units per milliliter (mIU/mL).
Number of Subjects With Unsolicited Adverse Events (AEs)	Within the 31-day (Days 0-30) follow-up periods post vaccination, across doses and across vaccines	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.
Concentrations of Antibodies Against Cross-reactive Pneumococcal Serotypes 6A and 19A (Anti-6A and -19A)	At Month 3, one month after the administration of the third dose of Synflorix vaccine	Seropositivity status was defined as anti-pneumococcal cross-reactive serotypes 6A/19A antibody concentrations (Anti-6A/19A) ≥ 0.05 microgram per milliliter (μg/mL).
Titers for Opsonophagocytic Activity (OPA) Against Vaccine Pneumococcal Serotypes	At Month 3, one month after the administration of the third dose of Synflorix vaccine	Pneumococcal serotypes assessed were vaccine pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F. Seropositivity status was defined as an opsonophagocytic activity against vaccine pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F (OPA-1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F) ≥ 8.
Number of Subjects Seroprotected Against Vaccine Pneumococcal Serotypes	At Month 3, one month after the administration of the third dose of Synflorix vaccine	Pneumococcal serotypes assessed were vaccine pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F. Seroprotection cut-off for the assay was an anti-pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F antibody (Anti-1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F) concentrations ≥ 0.2 microgram per milliliter (μg/mL).
Number of Subjects Seropositive for Antibodies Against Cross-reactive Pneumococcal Serotypes 6A and 19A (Anti-6A and -19A)	At Month 3, one month after the administration of the third dose of Synflorix vaccine	Serotypes assessed were cross-reactive pneumococcal serotypes 6A and 19A. Seropositivity status was defined as anti-pneumococcal cross-reactive serotypes 6A/19A antibody concentrations (Anti-6A/19A) ≥ 0.05 microgram per milliliter (μg/mL).
Titers for Opsonophagocytic Activity (OPA) Against Cross-reactive Pneumococcal Serotypes	At Month 3, one month after the administration of the third dose of Synflorix vaccine	Pneumococcal serotypes assessed were cross-reactive pneumococcal serotypes 6A and 19A. Seropositivity status was defined as an opsonophagocytic activity against cross-reactive pneumococcal serotypes 6A and 19A (OPA-6A and 19A) ≥ 8.
Number of Subjects Seropositive for Antibodies Against Vaccine Pneumococcal Serotypes	At Month 3, one month after the administration of the third dose of Synflorix vaccine	Pneumococcal serotypes assessed were vaccine pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F. Seropositivity cut-off for the assay was an anti-pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F antibody (Anti-1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F) concentrations ≥ 0.05 microgram per milliliter (μg/mL).
Number of Subjects Seropositive for Opsonophagocytic Activity Against Cross-reactive Pneumococcal Serotypes	At Month 3, one month after the administration of the third dose of Synflorix vaccine	Pneumococcal serotypes assessed were cross-reactive pneumococcal serotypes 6A and 19A. Seropositivity status was defined as an opsonophagocytic activity against cross-reactive pneumococcal serotypes 6A and 19A (OPA-6A and 19A) ≥ 8.
Anti-Bordetella Pertussis (Anti-BPT) Antibody Concentrations	At Month 3, one month after the administration of the third dose of Synflorix vaccine	Anti-BPT antibody concentrations were expressed in enzyme-linked immunosorbent assay (ELISA) unit per millilitre (EL.U/mL). Seropositivity cut-off for the assay was defined as an anti-BPT antibody concentrations ≥ 15 EL.U/mL
Number of Subjects Seropositive for Antibodies Against Bordetella Pertussis (Anti-BPT)	At Month 3, one month after the administration of the third dose of DTPw-HBV/Hib vaccine	Seropositivity cut-off for the assay was defined as an anti-BPT antibody concentration ≥ 15 enzyme-linked immunosorbent assay (ELISA) unit per milliliter (EL.U/mL).
Anti-diphtheria (Anti-D) and Anti-tetanus Toxoids (Anti-TT) Antibody Concentrations	At Month 3, one month after the administration of the third dose of Tritanrix -HepB/ Hiberix vaccine	The seroprotection cut-off for the assay was an anti-diphtheria toxoid or anti-tetanus toxoid antibody concentrations ≥ 0.1 international unit per milliliter (IU/mL).
Number of Subjects Seroprotected Against Polyribosyl-ribitol Phosphate (PRP)	At Month 3, one month after the administration of the third dose of Tritanrix -HepB/ Hiberix vaccine	Anti-PRP antibody concentrations were expressed in microgram per milliliter (μg/mL). The seroprotection cut-off applied for the assay was ≥ 0.15 μg/mL.
Number of Subjects With Any and Any Grade 3 and Related Solicited General Symptoms	Within the 4-day (Days 0 to 3) follow-up periods after each vaccination, across doses and across vaccines	Solicited general symptoms assessed include drowsiness, fever (defined as rectal temperature ≥ 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) greater than (\>) 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 Fever (Temperature Measured Rectally) > the Cut-off	Within the 4-day (Days 0 to 3) follow-up periods after each vaccination, across doses and across vaccines	The cut-off for the assay was \> 39.0°C.
Number of Subjects With Serious Adverse Events (SAEs)	Throughout the entire study period, from Month 0 to Month 3	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.