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

Study Overview
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Brief Summary
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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
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Vaccination course at 6, 10, 14 weeks of age.

Official Title
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Primary Vaccination Course in Children Receiving the Pneumococcal Vaccine GSK 1024850A Co-administered With Zilbrix™ Hib and Polio Sabin™

Conditions
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Infections, Streptococcal

Intervention / Treatment
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* Biological: GSK Biologicals' Synflorix™
* Biological: GSK Biologicals' Polio Sabin™
* Biological: GSK Biologicals' Zilbrix™ Hib


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 6 Weeks
Maximum Age: 10 Weeks

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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SYNFLORIX™ + ZILBRIX™ HIB + POLIO SABIN™<br>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. | Biological: GSK Biologicals' Synflorix™<br>* 3 IM doses.<br>* Other names: 10Pn;Biological: GSK Biologicals' Polio Sabin™<br>* 3 oral doses<br>* Other names: OPV;Biological: GSK Biologicals' Zilbrix™ Hib<br>* 3 IM doses.<br>* Other names: DTPw-HBV/Hib vaccine;|
| Experimental: ZILBRIX™ HIB + POLIO SABIN™<br>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. | Biological: GSK Biologicals' Polio Sabin™<br>* 3 oral doses<br>* Other names: OPV;Biological: GSK Biologicals' Zilbrix™ Hib<br>* 3 IM doses.<br>* Other names: DTPw-HBV/Hib vaccine;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes | 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). | At Month 3, one month after the administration of the third dose of Synflorix vaccine | 
| Antibody Concentrations Against Protein D (Anti-PD Antibodies) | 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. | At Month 3, one month after the administration of the third dose of Synflorix vaccine | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Concentrations of Antibodies Against Cross-reactive Pneumococcal Serotypes 6A and 19A (Anti-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). | At Month 3, one month after the administration of the third dose of Synflorix vaccine | 
| Titers for Opsonophagocytic Activity (OPA) Against Vaccine Pneumococcal Serotypes | 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. | At Month 3, one month after the administration of the third dose of Synflorix vaccine | 
| Titers for Opsonophagocytic Activity (OPA) Against Cross-reactive Pneumococcal Serotypes | 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. | At Month 3, one month after the administration of the third dose of Synflorix vaccine | 
| Number of Subjects Seropositive for Antibodies Against Vaccine Pneumococcal Serotypes | 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). | At Month 3, one month after the administration of the third dose of Synflorix vaccine | 
| Number of Subjects Seroprotected Against Vaccine Pneumococcal Serotypes | 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). | At Month 3, one month after the administration of the third dose of Synflorix vaccine | 
| Number of Subjects Seropositive for Antibodies Against Cross-reactive Pneumococcal Serotypes 6A and 19A (Anti-6A and -19A) | 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). | At Month 3, one month after the administration of the third dose of Synflorix vaccine | 
| Number of Subjects Seroprotected Against Cross-reactive Pneumococcal Serotypes 6A and 19A (Anti-6A and -19A) | 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). | At Month 3, one month after the administration of the third dose of Synflorix vaccine | 
| Number of Subjects Seropositive for Antibodies Against Protein D (Anti-PD Antibodies) | Seropositivity cut-off for the assay was an anti-PD antibody concentrations ≥ 100 EL.U/mL. | At Month 3, one month after the administration of the third dose of Synflorix vaccine | 
| Number of Subjects Seropositive for Opsonophagocytic Activity Against Vaccine Pneumococcal Serotypes | 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. | At Month 3, one month after the administration of the third dose of Synflorix vaccine | 
| Number of Subjects Seropositive for Opsonophagocytic Activity Against Cross-reactive Pneumococcal Serotypes | 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. | At Month 3, one month after the administration of the third dose of Synflorix vaccine | 
| Anti-Bordetella Pertussis (Anti-BPT) Antibody Concentrations | 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 | At Month 3, one month after the administration of the third dose of Synflorix vaccine | 
| Number of Subjects Seropositive for Antibodies Against Bordetella Pertussis (Anti-BPT) | 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). | At Month 3, one month after the administration of the third dose of DTPw-HBV/Hib vaccine | 
| Anti-diphtheria (Anti-D) and Anti-tetanus Toxoids (Anti-TT) Antibody Concentrations | 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). | At Month 3, one month after the administration of the third dose of Tritanrix -HepB/ Hiberix vaccine | 
| Number of Subjects Seroprotected Against Diphtheria (D) and Tetanus Toxoids (TT) Antigens | A subject seroprotected against D/TT antigens was defined as a subject with an Anti-D/-TT antibody concentration ≥ 0.1 IU/mL. | At Month 3, one month after the administration of the third dose of Tritanrix -HepB/ Hiberix vaccine | 
| Anti-polyribosyl-ribitol-phosphate (Anti-PRP) Antibody Concentrations | Anti-PRP antibody concentrations were measured and tabulated in microgram per milliliter (μg/mL). Cut-off for the assay was ≥ 0.15 μg/mL. | At Month 3, one month after the administration of the third dose of Tritanrix -HepB/ Hiberix vaccine | 
| Number of Subjects Seroprotected Against Polyribosyl-ribitol Phosphate (PRP) | 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. | At Month 3, one month after the administration of the third dose of Tritanrix -HepB/ Hiberix vaccine | 
| Number of Subjects Seroprotected Against Polyribosyl-ribitol Phosphate (PRP) Antigens | Anti-PRP antibody concentrations were expressed in microgram per milliliter (μg/mL). The seroprotection cut-off applied for the assay was ≥ 1 μg/mL. | At Month 3, one month after the administration of the third dose of Tritanrix -HepB/ Hiberix vaccine | 
| Anti-hepatitis B Surface Antigen (HBs) Antibody Concentrations | The seroprotection cut-off for the endpoint was an anti-HBs antibody concentration ≥ 10 milli-international units per milliliter (mIU/mL). | At Month 3, one month after the administration of the third dose of Tritanrix -HepB /Hiberix vaccine | 
| Number of Subjects Seroprotected Against Anti-Hepatitis B Surface Antigens (HBs). | 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). | At Month 3, one month after the administration of the third dose of Tritanrix HepB/ Hiberix vaccine | 
| Number of Subjects With Any and Any Grade 3 Solicited Local Symptoms | 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. | Within the 4-day (Days 0 to 3) follow-up periods after each vaccination, across doses and across vaccines | 
| Number of Subjects With Any and Any Grade 3 and Related Solicited General Symptoms | 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. | Within the 4-day (Days 0 to 3) follow-up periods after each vaccination, across doses and across vaccines | 
| Number of Subjects With Fever (Temperature Measured Rectally) > the Cut-off | The cut-off for the assay was > 39.0°C. | Within the 4-day (Days 0 to 3) follow-up periods after each vaccination, across doses and across vaccines | 
| 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) follow-up periods post vaccination, across doses and across vaccines | 
| 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 entire study period, from Month 0 to Month 3 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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pneumococcal conjugate vaccine, Streptococcus pneumoniae