Primary and Booster Vaccination Study With Pneumococcal Vaccine GSK1024850A in Healthy Japanese Children

Study Overview
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Brief Summary
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This study will aim to evaluate the immunogenicity, safety and reactogenicity of GlaxoSmithKline Biologicals' 10-valent pneumococcal conjugate vaccine GSK1024850A when co-administered with Japanese DTPa vaccine as a 3-dose primary immunization course in healthy Japanese children at 3, 4 and 5 months of age and as a booster vaccination at 17-19 months of age.

Official Title
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Immunogenicity, Safety and Reactogenicity of GlaxoSmithKline Biologicals' Pneumococcal Vaccine GSK1024850A Following Primary and Booster Vaccination of Healthy Japanese Children

Conditions
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Infections, Streptococcal

Intervention / Treatment
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* Biological: Pneumococcal vaccine GSK1024850A
* Biological: DTPa


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects who the investigator/co-investigator believes that their parent(s)/Legally Acceptable Representative(s) (LAR(s)) can and will comply with the requirements of the protocol. A male or female between, and including, 90 and 118 days of age (3 months) at the time of the first vaccination. Written informed consent obtained from the parent(s)/LAR(s) of the subject. Healthy subjects as established by medical history and clinical examination before entering into the study. Born after a gestation period of 36 to 42 weeks inclusive. 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 study vaccine(s), or planned use during the study period. Chronic administration of immunosuppressants or other immune-modifying drugs since birth. Planned administration/administration of a vaccine not foreseen by the study protocol during the period starting from 30 days before the first dose of study vaccine(s) and ending on the last study visit, with the exception of Haemophilus influenzae type b vaccine, Hepatitis B Vaccine, Bacille Calmette-Guérin vaccine, Oral Polio Vaccine, Japanese encephalitis, measles and rubella, varicella, mumps, and flu vaccines. 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). Administration of any pneumococcal vaccine since birth except for the DTPa group for whom vaccination with a licensed pneumococcal vaccine by catch-up schedule will be allowed only if the 2 vaccine doses are administered between Study Visit 4 and 5, i.e. from the second blood sampling timepoint (Visit 4) onwards and up to 7 days before the booster dose of the DTPa vaccine. Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination (no laboratory testing required). History of, or intercurrent diphtheria, tetanus, pertussis disease. History of any reaction or hypersensitivity likely to be exacerbated by any component of the study vaccines. Major congenital defects or serious chronic illness. History of any seizures or progressive neurological disease. Administration of immunoglobulins and/or any blood products since birth or planned administration during the study period. Child in care. Acute disease and/or fever at the time of enrolment.

Ages Eligible for Study
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Minimum Age: 90 Days
Maximum Age: 118 Days

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: 10Pn Group<br>Healthy male or female subjects, between 90 and 118 days of age who received 3 doses of Synflorix (10Pn) vaccine, administered intramuscularly on alternating (left/right) sides of the anterolateral thigh and DPT KAKETSUKEN Syringe (DTPa) vaccine administered subcutaneously on alternating (left/right) sides of the distal one third of the upper arm. Both vaccines were administered at 3, 4, and 5 months of age, followed by a booster dose at 17-19 months of age. | Biological: Pneumococcal vaccine GSK1024850A<br>* Intramuscular injection, 4 doses<br>* Other names: Synflorix;Biological: DTPa<br>* Subcutaneous injection, 4 doses<br>* Other names: DPT KAKETSUKEN Syringe;|
| Active Comparator: DTPa Group<br>Healthy male or female subjects, between 90 and 118 days of age who received 3 doses of the DPT KAKETSUKEN Syringe (DTPa) vaccine, administered subcutaneously on alternating (left/right) sides of the distal one third of the upper arm at 3, 4, and 5 months of age, followed by a booster dose at 17-19 months of age. | Biological: DTPa<br>* Subcutaneous injection, 4 doses<br>* Other names: DPT KAKETSUKEN Syringe;|

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 (Primary Immunization) | Concentrations were expressed as geometric mean concentrations (GMCs). Antibodies assessed for this outcome measure were those against the vaccine pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F (ANTI-1, -4, -5, -6B, -7F, -9V, -14, -18C, -19F and -23F). The seropositivity cut-off of the assay was an antibody concentration ≥ 0.05 microgram per milliliter (µg/mL). | 1 month following primary immunization (at Month 3) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes (Booster Immunization) | Antibodies assessed for this outcome measure were those against the vaccine pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F (ANTI-1, -4, -5, -6B, -7F, -9V, -14, -18C, -19F and -23F). Antibody concentrations were measured by 22F ELISA, expressed as GMCs, in μg/mL. The seropositivity cut-off of the assay was an antibody concentration ≥ 0.05 μg/mL. Antibody concentrations < 0.05 μg/mL were given an arbitrary value of half the cut-off for the purpose of GMC calculation. Administration of catch-up pneumococcal vaccination with a licensed product other than Synflorix was allowed in the DTPa Group at least 7 days before DTPa vaccine booster dose. Thus, for this booster phase analysis, the DTPa Group was further split in DTPa + Prevenar Group and DTPa - no Prevenar Group. | Prior to (PRE, at Month 14-16 ) and one month after booster (POST, at Month 15-17) immunization | 
| Opsonophagocytic Titers Against Vaccine Pneumococcal Serotypes (Primary Immunization) | Pneumococcal vaccine serotypes assessed were 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F and were calculated, expressed as geometric mean titers (GMTs). The seropositivity cut-off for the assay was ≥ 8. Antibody titers < 8 were given an arbitrary value of half the cut-off for the purpose of GMT calculation. | 1 month following primary immunization (at Month 3) | 
| Opsonophagocytic Titers Against Vaccine Pneumococcal Serotypes (Booster Immunization) | Pneumococcal vaccine serotypes assessed were 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F and were calculated, expressed as geometric mean titers (GMTs). The seropositivity cut-off for the assay was ≥ 8. Antibody titers < 8 were given an arbitrary value of half the cut-off for the purpose of GMT calculation. Administration of catch-up pneumococcal vaccination with a licensed product other than Synflorix was allowed in the DTPa Group at least 7 days before DTPa vaccine booster dose. Thus, for this booster phase analysis, the DTPa Group was further split in DTPa + Prevenar Group and DTPa - no Prevenar Group. | Prior to (PRE, at Month 14-16) and one month after booster (POST, at Month 15-17) immunization | 
| Concentrations of Antibodies Against Cross-reactive Pneumococcal Serotypes 6A and 19A (Primary Immunization) | Concentrations were given in microgram per millilitre (µg/mL) and were expressed in geometric mean antibody concentrations. Cross-reactive pneumococcal vaccine serotypes assessed were 6A and 19A. The seropositivity cut-off of the assay was an antibody concentration ≥ 0.05 µg/mL. Antibody concentrations < 0.05 µg/mL were given an arbitrary value of half the cut-off for the purpose of GMC calculation. | 1 month following primary immunization (at Month 3) | 
| Concentrations of Antibodies Against Cross-reactive Pneumococcal Serotypes 6A and 19A (Booster Immunization) | Concentrations were given in microgram per millilitre (µg/mL) and were expressed in geometric mean antibody concentrations. Cross-reactive pneumococcal vaccine serotypes assessed were 6A and 19A. The seropositivity cut-off of the assay was an antibody concentration ≥ 0.05 µg/mL. Antibody concentrations < 0.05 g/mL were given an arbitrary value of half the cut-off for the purpose of GMC calculation. Administration of catch-up pneumococcal vaccination with a licensed product other than Synflorix was allowed in the DTPa Group at least 7 days before DTPa vaccine booster dose. Thus, for this booster phase analysis, the DTPa Group was further split in DTPa + Prevenar Group and DTPa - no Prevenar Group. | Prior to (PRE, at Month 14-16) and one month after booster (POST, at Month 15-17) immunization | 
| Opsonophagocytic Titers Against Cross-reactive Pneumococcal Serotypes 6A and 19A (Primary Immunization) | Cross-reactive pneumococcal vaccine serotypes assessed were 6A and 19A and were calculated, expressed as geometric mean titers (GMTs). The seropositivity cut-off for the assay was ≥ 8. Antibody titers < 8 were given an arbitrary value of half the cut-off for the purpose of GMT calculation. | 1 month following primary immunization (at Month 3) | 
| Opsonophagocytic Titers Against Cross-reactive Pneumococcal Serotypes 6A and 19A (Booster Immunization) | Cross-reactive pneumococcal vaccine serotypes assessed were 6A and 19A and were calculated, expressed as geometric mean titers (GMTs). The seropositivity cut-off for the assay was ≥ 8. Antibody titers < 8 were given an arbitrary value of half the cut-off for the purpose of GMT calculation. Administration of catch-up pneumococcal vaccination with a licensed product other than Synflorix was allowed in the DTPa Group at least 7 days before DTPa vaccine booster dose. Thus, for this booster phase analysis, the DTPa Group was further split in DTPa + Prevenar Group and DTPa - no Prevenar Group. | Prior to (PRE, at Month 14-16) and one month after booster (POST, at Month 15-17) immunization | 
| Concentrations of Antibodies Against Protein D (PD) (Primary Immunization) | Anti-protein D (Anti-PD) antibody concentrations by Enzyme-Linked Immunosorbent Assay (ELISA) were calculated, expressed as geometric mean concentrations (GMCs) in ELISA unit per milli-liter (EL.U/mL) and tabulated. The seropositivity cut-off for the assay was ≥ 100 EL.U/mL. Antibody concentrations < 100 EL.U/mL were given an arbitrary value of half the cut-off for the purpose of GMC calculation. | 1 month following primary immunization (at Month 3) | 
| Concentrations of Antibodies Against Protein D (PD) (Booster Immunization) | Anti-protein D (Anti-PD) antibody concentrations by Enzyme-Linked Immunosorbent Assay (ELISA) were calculated, expressed as geometric mean concentrations (GMCs) in ELISA unit per milli-liter (EL.U/mL) and tabulated. The seropositivity cut-off for the assay was ≥ 100 EL.U/mL. Antibody concentrations < 100 EL.U/mL were given an arbitrary value of half the cut-off for the purpose of GMC calculation. | Prior to (PRE, at Month 14-16) and one month after booster (POST, at Month 15-17) immunization | 
| Concentrations of Antibodies Against Diphtheria Toxoid (DT) and Tetanus Toxoid (TT)(Primary Immunization) | Concentrations of antibodies are presented as geometric mean concentrations expressed as International units per millilitre (IU/mL). Seroprotection status, defined as Anti-DT or Anti-TT antibody concentration equal to or greater than 0.1 IU/mL. | 1 month following primary immunization (at Month 3) | 
| Concentrations of Antibodies Against Diphtheria Toxoid (DT) and Tetanus Toxoid (TT)(Booster Immunization) | Concentrations of antibodies are presented as geometric mean concentrations expressed as International units per millilitre (IU/mL). Seroprotection status, defined as Anti-DT or Anti-TT antibody concentration equal to or greater than 0.1 IU/mL. | Prior to (PRE, at Month 14-16) and one month after booster (POST, at Month 15-17) immunization | 
| Concentrations of Antibodies Against Pertussis (PT) and Filamentous Haemagglutinin (FHA)(Primary Immunization) | Concentrations of antibodies are presented as geometric mean concentrations expressed as Enzyme-Linked Immuno-Sorbent Assay (ELISA) units per millilitre (EL.U/mL). Seropositivity was defined as an antibody concentration equal to or greater than 5 EL.U/mL | 1 month following primary immunization (at Month 3) | 
| Concentrations of Antibodies Against Pertussis (PT) and Filamentous Haemagglutinin (FHA)(Booster Immunization) | Concentrations of antibodies are presented as geometric mean concentrations expressed as Enzyme-Linked Immuno-Sorbent Assay (ELISA) units per millilitre (EL.U/mL). Seropositivity was defined as an antibody concentration equal to or greater than 5 EL.U/mL | Prior to (PRE, at Month 14-16) and one month after booster (POST, at Month 15-17) immunization | 
| Number of Subjects With Any and Grade 3 Solicited Local Symptoms After Primary Vaccination | Solicited local AEs assessed were pain, redness and swelling. Any = incidence of any local symptom regardless of intensity grade. Grade 3 pain = cried when limb was moved/spontaneously painful. Grade 3 redness/swelling = redness/swelling above 30 millimetre. | During the 8-day (Days 0-7) after each primary vaccine dose | 
| Number of Subjects With Any and Grade 3 Solicited Local Symptoms After Booster Vaccination | Solicited local AEs assessed were pain, redness and swelling. Any = incidence of any local symptom regardless of intensity grade. Grade 3 pain = cried when limb was moved/spontaneously painful. Grade 3 redness/swelling = redness/swelling above 30 millimetre. | During the 8-day (Days 0-7) period following booster vaccination | 
| Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms After Primary Vaccination | General AEs = drowsiness, fever (axillary ≥ 37.5 degrees Celsius), irritabilityand loss of appetite, vomiting. Any= Incidence of any symptom regardless of intensity grade or relationship to vaccination. Grade 3 drowsiness = prevented normal activity. Grade 3 irritability = crying that could not be comforted/ prevented normal activity. Grade 3 loss of appetite = not eating at all. Grade 3 fever = > 39.5°C Related = symptom assessed by the investigator as related to the vaccination. | During the 8-day (Days 0-7) after each primary vaccine dose | 
| Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms After Booster Vaccination | Solicited general AEs = drowsiness, irritability, loss of appetite and fever (axillary ≥ 37.5 degrees Celsius). Any= Incidence of any symptom regardless of intensity grade or relationship to vaccination. Grade 3: drowsiness = prevented normal activity. irritability = crying that could not be comforted/ prevented normal activity. loss of appetite = not eating at all. Fever = temperature > 39.5°C Related = symptom assessed by the investigator as related to the vaccination. | During the 8-day (Days 0-7) period following booster vaccination | 
| Number of Subjects With Unsolicited AEs After Primary Vaccination | An unsolicited adverse event is any adverse event (i.e. any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with use of a medicinal product, whether or not considered related to the medicinal product) reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for solicited symptoms. | Within the 31-day (Days 0-30) post-primary vaccination period, across doses | 
| Number of Subjects With Unsolicited AEs After Booster Vaccination | An unsolicited adverse event is any adverse event (i.e. any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with use of a medicinal product, whether or not considered related to the medicinal product) reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for solicited symptoms. | Within the 31-day (Days 0-30) post booster vaccination period | 
| Number of Subjects With Serious Adverse Events (SAEs) | SAEs assessed include medical occurrences that results in death, are life threatening, require hospitalization or prolongation of hospitalization, results in disability/incapacity or are a congenital anomaly/birth defect in the offspring of a study subjects. | From study start at Month 0 up to study end at Month 15-17 | 

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