Safety and Immunogenicity Study of a Booster Dose of GSK Biologicals' 10-valent Pneumococcal Conjugate Vaccine.

Study Overview
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Brief Summary
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This study will evaluate the safety, reactogenicity and immunogenicity of a booster dose of GSK Biologicals' pneumococcal conjugate vaccine compared to Prevenar™ given at 12-18 mo of age to children primed with either pneumococcal vaccine or Prevenar™ in study 105553. Antibody persistence will be evaluated at 8-14 mo after completion of the 3-dose immunization course in study 105553 (NCT00307554). The immune response to a booster dose of GSK Biologicals' pneumococcal conjugate vaccine will also be evaluated when given at 12-18 mo to subjects not primed with GSK Biologicals' vaccine but with Prevenar™. The study has 3 groups. 1 group of children primed with GSK Biologicals' pneumococcal conjugate vaccine will receive a booster dose of the same vaccine. 2nd group of children primed with Prevenar™ will receive a booster dose of Prevenar™ (control group). 3rd group of children primed with Prevenar™ will receive a booster dose of GSK Biologicals' pneumococcal conjugate vaccine. All children will receive concomitantly a booster dose of DTPa-HBV-IPV/Hib vaccine.

Official Title
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To Assess the Safety, Reactogenicity & Immunogenicity of a 4th Dose of GSK Biologicals' Pneumococcal Vaccine or Prevenar™ in Children (12-18 Months) Previously Vaccinated in the Primary Study NCT00307554 With Either Pneumococcal Vaccine or Prevenar™

Conditions
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Infections, Streptococcal

Intervention / Treatment
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* Biological: Synflorix
* Biological: Prevenar
* Biological: Infanrix hexa


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: a healthy male or female, 12 to 18 months of age at the time of vaccination, who received at least one dose of either pneumococcal conjugate vaccine or Prevenar™ during study 105553 and with written informed consent obtained from the parent/guardian of the subject. Exclusion Criteria: use of any investigational or non-registered drug or vaccine other than the study vaccine within 30 days preceding the vaccination, or planned use during the entire study period (active phase and safety follow-up). Planned administration/ administration of a vaccine not foreseen by the study protocol during the period starting one month before vaccination up to Visit 2. Administration of any additional pneumococcal vaccine or DTPa-combined vaccine since end of study 105553. Children with a history of seizures or neurological disease, allergic disease, immunosuppressive or immunodeficient condition.

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Synflorix-Synflorix Group<br>This group consisted of subjects previously vaccinated with the Synflorix™ vaccine as part of a previous study by GSK Biologicals - the 10PN-PD-DIT-001 (105553) study (EuDRA-CT number: 2005-003300-11). As part of the 105553 study, subjects had received a 3-dose primary vaccination of Synflorix™ vaccine at 2, 3 and 4 months of age (injected intramuscularly [IM] in the right thigh) co-administered with Infanrix hexa™ vaccine, except for the second dose in France, which was co-administered with Infanrix™ IPV Hib, injected intramuscularly in the left thigh. As part of this study, at 12-18 months of age, subjects received a booster dose of Synflorix™ vaccine, injected IM in the right thigh or deltoid, co-administered with Infanrix hexa™ vaccine, injected IM in the left thigh or deltoid. | Biological: Synflorix<br>* 1 dose injected IM in the right thigh or deltoid.<br>* Other names: 10 valent pneumococcal conjugate (vaccine);Biological: Infanrix hexa<br>* 1 dose injected IM in the right thigh or deltoid.<br>|
| Active Comparator: Prevenar-Prevenar Group<br>This group consisted of subjects previously vaccinated with the Prevenar™ vaccine as part of a previous study by GSK Biologicals - the 10PN-PD-DIT-001 (105553) study (EuDRA-CT number: 2005-003300-11). As part of the 105553 study, subjects had received a 3-dose primary vaccination of Prevenar™ vaccine at 2, 3 and 4 months of age (injected intramuscularly [IM] in the right thigh) co-administered with Infanrix hexa™ vaccine, except for the second dose in France, which was co-administered with Infanrix™ IPV Hib, injected intramuscularly in the left thigh. As part of this study, at 12-18 months of age, subjects received a booster dose of Prevenar™ vaccine, injected IM in the right thigh or deltoid, co-administered with Infanrix hexa™ vaccine, injected IM in the left thigh or deltoid. | Biological: Prevenar<br>* 1 dose injected IM in the right thigh or deltoid.<br>Biological: Infanrix hexa<br>* 1 dose injected IM in the right thigh or deltoid.<br>|
| Experimental: Prevenar-Synflorix Group<br>This group consisted of subjects previously vaccinated with the Prevenar™ vaccine as part of a previous study by GSK Biologicals - the 10PN-PD-DIT-001 (105553) study (EuDRA-CT number: 2005-003300-11). As part of the 105553 study, subjects had received a 3-dose primary vaccination of Synflorix vaccine at 2, 3 and 4 months of age (injected intramuscularly [IM] in the right thigh) co-administered with Infanrix hexa™ vaccine, except for the second dose in France, which was co-administered with Infanrix™ IPV Hib, injected intramuscularly in the left thigh. As part of this study, at 12-18 months of age, subjects received a booster dose of Synflorix™, injected IM in the right thigh or deltoid, co-administered with Infanrix hexa™ vaccine, injected IM in the left thigh or deltoid. | Biological: Synflorix<br>* 1 dose injected IM in the right thigh or deltoid.<br>* Other names: 10 valent pneumococcal conjugate (vaccine);Biological: Infanrix hexa<br>* 1 dose injected IM in the right thigh or deltoid.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects With Rectal Temperature Above (>) 39.0 Degrees Celsius (°C) Post Booster Between the Synflorix-Synflorix and Prevenar-Prevenar Groups | Fever was measured as rectal temperature. Assessment of occurrences of rectal temperature > 39.0 °C was performed post administration of the booster dose of pneumococcal vaccine (Synflorix™ or Prevenar™ vaccine) in this study. The analysis was performed on the Total vaccinated cohort, which included all subjects vaccinated in this study 10PN-PD-DIT-007, solely on subjects with results available. | Within 4 days (Days 0-3) after the booster vaccination at Month 0 in this study 10PN-PD-DIT-007 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects With Any and Grade 3 Solicited Local Symptoms | Solicited local symptoms assessed include 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 larger than (>) 30 millimeters (mm). Any is defined as incidence of the specified symptom regardless of intensity. The analysis was performed on the Total vaccinated cohort, which included all subjects vaccinated in this study 10PN-PD-DIT-007, solely on subjects with results available. | Within 4 days (Days 0-3) after the booster vaccination at Month 0 in this study 10PN-PD-DIT-007 | 
| Number of Subjects With Any and Any Grade 3 Solicited General Symptoms | Solicited general symptoms assessed include drowsiness, fever (defined as rectal temperature ≥ 38.0°C), irritability, and loss of appetite. Grade 3 drowsiness was defined as drowsiness which prevented normal everyday activities. Grade 3 fever was defined as fever (rectal temperature) above (>) 40.0 degree Celsius (°C). Grade 3 irritability was defined as crying that could not be comforted/preventing normal everyday activities. Grade 3 loss of appetite was defined as the subject not eating at all. Any is defined as incidence of the specified symptom regardless of intensity or relationship to study vaccination. The analysis was performed on the Total vaccinated cohort, which included all subjects vaccinated in this study 10PN-PD-DIT-007, solely on subjects with results available. | Within 4 days (Days 0-3) after the booster vaccination at Month 0 in this study 10PN-PD-DIT-007 | 
| 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 is defined an incidence of an unsolicited AE regardless of intensity or relationship to study vaccination. The analysis was performed on the Total vaccinated cohort, which included all subjects vaccinated in this study 10PN-PD-DIT-007. | Within 31 days (Day 0-30) after the booster vaccination at Month 0 in this study 10PN-PD-DIT-007 | 
| Number of Subjects With Serious Adverse Events (SAEs) During the Active Phase of the Study | An SAE is any untoward medical occurrence that: results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or may evolve into one of the outcomes listed above. Any is defined an incidence of a SAE regardless of intensity/severity . The analysis was performed on the Total vaccinated cohort, which included all subjects vaccinated in this study 10PN-PD-DIT-007. | Throughout the Active Phase of the study, that is, within 31 days (Day 0-30) after the booster vaccination at Month 0 in this study 10PN-PD-DIT-007 | 
| Number of Subjects With Serious Adverse Events (SAEs) During the Entire Study | An SAE is any untoward medical occurrence that: results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or may evolve into one of the outcomes listed above. Any is defined an incidence of a SAE regardless of intensity/severity. The analysis was performed on the Total vaccinated cohort, which included all subjects vaccinated in this study 10PN-PD-DIT-007, solely on subjects enrolled in the ESFU Phase of the study. | Throughout the study period, from Month 0 prior to booster vaccination up to Month 6, end of the ESFU in this study 10PN-PD-DIT-007 | 
| Number of Subjects Seroprotected as Regards Anti-pneumococcal Serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F Antigens - by 22F-inhibition Enzyme-linked Immunosorbent Assay (ELISA) | A seroprotected subject as regards anti-pneumococcal serotype antibody was defined as a subject with anti-pneumococcal serotype antibody concentration above than or equal to (≥) 0.20 microgram per millilitre (μg/mL). Anti-pneumococcal serotypes antibodies assessed were antibodies against 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). Analysis was performed using the 22F-inhibition Enzyme-linked immunosorbent assay (ELISA), using ≥ 0.05 μg/mL as seropositivity cut off. For this endpoint, the analysis was performed on the according-to-protocol cohort for immunogenicity, e. a., evaluable subjects for whom assay results were available for antibodies against at least one study vaccine antigen component after booster vaccination. | Prior to (PRE) and one month after (Month 1) booster vaccination | 
| Antibody Concentrations Against 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) - by 22F-inhibition Enzyme-linked Immunosorbent Assay (ELISA) | Anti-pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F antibody concentrations (Anti-1, -4, -5, -6B, -7F, -9V, -14, -18C, -19F and -23F) were calculated, expressed as geometric mean concentrations (GMCs), in microgram per millilitre (µg/mL). The seropositivity cut-off for the assay was ≥ 0.05 µg/mL. Antibody concentrations below the cut-off of the assay were given an arbitrary value of half the cut-off for the purpose of GMC calculation. For this endpoint, the analysis was performed on the according-to-protocol cohort for immunogenicity, e. a., evaluable subjects for whom assay results were available for antibodies against at least one study vaccine antigen component after booster vaccination. | Prior to (PRE) and one month (Month 1) post booster vaccination | 
| Opsonophagocytic Activity (OPA) Titers Against Pneumococcal Serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F | OPA titers against pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F (Opsono-1, -4, -5, -6B, -7F, -9V, -14, -18C, -19F and -23F) were calculated, expressed as geometric mean titers (GMTs) and tabulated. The seropositivity cut-off for the assay was ≥ 8. Antibody titers below the cut-off of the assay were given an arbitrary value of half the cut-off for the purpose of GMT calculation. For this endpoint, the analysis was performed on the according-to-protocol cohort for immunogenicity, e. a., evaluable subjects for whom assay results were available for antibodies against at least one study vaccine antigen component after booster vaccination. | Prior to (PRE) and one month (Month 1) post booster vaccination | 
| Antibody Concentrations to Protein D (Anti-PD) - by Enzyme-Linked Immunosorbent Assay (ELISA) | 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 below the cut-off of the assay were given an arbitrary value of half the cut-off for the purpose of GMC calculation. For this endpoint, the analysis was performed on the according-to-protocol cohort for immunogenicity, e. a., evaluable subjects for whom assay results were available for antibodies against at least one study vaccine antigen component after booster vaccination. | Prior to (PRE) and one month (Month 1) post booster vaccination | 
| Anti-polyribosyl Ribitol Phosphate (Anti-PRP) Antibody Concentrations | Anti-PRP antibody concentrations were calculated, expressed as geometric mean concentrations (GMCs), in microgram per milliliter (µg/mL), and tabulated. The seroprotection cut-off for the assay for the purpose of this endpoint was ≥ 0.15 µg/mL. Antibody concentrations below the cut-off of the assay were given an arbitrary value of half the cut-off for the purpose of GMC calculation. For this endpoint, the analysis was performed on the according-to-protocol cohort for immunogenicity, e. a., evaluable subjects for whom assay results were available for antibodies against at least one study vaccine antigen component after booster vaccination. | Prior to (PRE) and one month (Month 1) post booster vaccination | 
| Anti-pertussis Toxoid (Anti-PT), Anti- Filamentous Haemagglutinin (Anti-FHA) and Anti-pertactin (Anti-PRN) Antibody Concentrations | Anti-PT, Anti-FHA and Anti-PRN concentrations measured 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 ≥ 5 EL.U/mL. Antibody concentrations below the cut-off of the assay were given an arbitrary value of half the cut-off for the purpose of GMC calculation. For this endpoint, the analysis was performed on the according-to-protocol cohort for immunogenicity, e. a., evaluable subjects for whom assay results were available for antibodies against at least one study vaccine antigen component after booster vaccination. | Prior to (PRE) and one month (Month 1) post booster vaccination | 
| Anti-diphtheria (Anti-D) and Anti-tetanus Toxoids (Anti-TT) Antibody Concentrations | Anti-D and Anti-TT antibody concentrations were calculated, expressed as geometric mean concentrations (GMCs), in International units per milliliter (IU/mL), and tabulated. The seropositivity cut-off for the assay was ≥ 0.1 IU/mL. Antibody concentrations below the cut-off of the assay were given an arbitrary value of half the cut-off for the purpose of GMC calculation. For this endpoint, the analysis was performed on the according-to-protocol cohort for immunogenicity, e. a., evaluable subjects for whom assay results were available for antibodies against at least one study vaccine antigen component after booster vaccination. | Prior to (PRE) and one month (Month 1) post booster vaccination | 
| Anti-hepatitis B Surface Antigen (HBs) Antibody Concentrations | Anti-HBs antibody concentrations were calculated, expressed as geometric mean concentrations (GMCs), in milli-International unit per milliliter (IU/mL), and tabulated. The seropositivity cut-off for the assay was ≥ 10 mIU/mL. Antibody concentrations below the cut-off of the assay were given an arbitrary value of half the cut-off for the purpose of GMC calculation. For this endpoint, the analysis was performed on the according-to-protocol cohort for immunogenicity, e. a., evaluable subjects for whom assay results were available for antibodies against at least one study vaccine antigen component after booster vaccination. | Prior to (PRE) and one month (Month 1) post booster vaccination | 
| Anti-polio Type 1, 2 and 3 (Anti-Polio 1, 2 and 3) Antibody Titers | Anti-Polio 1, 2 and 3 antibody titers were calculated, expressed as geometric mean titers (GMTs) and tabulated. The seroprotection cut-off for the assay was ≥ 8. Antibody titers below the cut-off of the assay were given an arbitrary value of half the cut-off for the purpose of GMT calculation. For this endpoint, the analysis was performed on the according-to-protocol cohort for immunogenicity, e. a., evaluable subjects for whom assay results were available for antibodies against at least one study vaccine antigen component after booster vaccination. | Prior to (PRE) and one month (Month 1) post booster vaccination | 
| Number of Subjects Booster (BST) Responder to Pertussis Toxoid (PT), Filamentous Haemagglutinin (FHA) and Pertactin Antigens | A BST responder to PT, FHA and PRN antigens was defined as a subject with the appearance of antibodies in subjects who were seronegative prior to the booster vaccination or at least 2-fold increase of pre-booster vaccination antibody concentrations in subjects who were seropositive prior to the booster vaccination. A seropositive/seronegative subject as regards Anti-PT/-FHA/ -PRN antibodies was defined as a subject with anti-PT/-FHA/ -PRN antibody concentrations ≥ 5 Enzyme-linked Immunosorbent assay (ELISA) unit per milli-liter (EL.U/mL) | One month (Month 1) post booster vaccination | 

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