Immunological Persistence After Priming With GSK1024850A Vaccine and Safety& Immunogenicity After Booster Dose

Study Overview
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Brief Summary
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This primary purpose of this study is the evaluation of the immunological persistence following completion of the 3-dose primary vaccination course with either a clinical or a commercial lot of pneumococcal conjugate vaccine GSK1024850A in study NCT00808444. In addition, the study will also assess the safety, reactogenicity and immunogenicity of a fourth dose of pneumococcal conjugate vaccine GSK1024850A (commercial lot) when co-administered with Infanrix-IPV/Hib at 18-21 months of age in children primed in study NCT00808444. The primary vaccination study was conducted in Malaysia and Singapore. The booster vaccination study will not be performed in Malaysia since the pneumococcal conjugate vaccine GSK1024850A has been registered in September 2009. However, subjects in Malaysia will be offered a booster dose of the commercial pneumococcal conjugate vaccine licensed in Malaysia and Infanrix-IPV/Hib vaccine during the second year of life according to the nationally recommended regimen. Administration of the booster dose will be outside the set-up of a clinical trial. Hence no data will be collected, no blood samples will be taken in Malaysia.

Official Title
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Evaluation of Immunological Persistence Following 3-dose Priming With GSK Biologicals' 10-valent Pneumococcal Conjugate Vaccine in Study NCT00808444 and Safety and Immunogenicity Following a Booster Dose of the Same Vaccine

Conditions
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Infections, Streptococcal

Intervention / Treatment
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* Biological: Pneumococcal vaccine GSK1024850A
* Biological: Infanrix-IPV/Hib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects who the investigator believes that their parent(s)/Legally Acceptable Representative(s) (LAR) can and will comply with the requirements of the protocol Male or female between, and including, 18 and 21 months of age at the time of booster vaccination. Subjects who received three doses of pneumococcal conjugate vaccine in study NCT00808444 Written informed consent obtained from the parents/LAR(s) of the subject. Healthy subjects as established by medical history and clinical examination before entering into the study. Exclusion Criteria: Use of any investigational or non-registered product other than the study vaccine(s) within 30 days preceding vaccination, 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. Chronic administration of immunosuppressants or other immune-modifying drugs within six months prior to vaccination. A family history of congenital or hereditary immunodeficiency. Administration of immunoglobulins and/ or any blood products within the 3 months preceding vaccination or planned use during the study period. Administration of any pneumococcal and/or vaccine containing diphtheria, tetanus, pertussis, poliomyelitis or Haemophilus influenzae type b antigens since the end of study NCT00808444. Planned administration/administration of a vaccine not foreseen by the study protocol during the study period starting from 30 days before vaccination and ending 30 days after vaccination. Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination (no laboratory testing required). History of any reaction or allergic disease likely to be exacerbated by any component of the study vaccines. Known hypersensitivity to any component of the study vaccines including anaphylactic reactions following the administration of the study vaccines. Major congenital defects or serious chronic illness. History of any neurologic disorders or seizures. (Subjects who have had a single uncomplicated febrile convulsion in the past can be included) Fever at the time of vaccination. Fever is defined as rectal temperature >= 38.0°C or tympanic/axillary/ oral temperature >= 37.5°C. Acute disease at the time of enrolment. Subjects with a minor illness without fever may be enrolled at the discretion of the investigator. Child in care.

Ages Eligible for Study
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Minimum Age: 18 Months
Maximum Age: 21 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
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Synflorix™ Commercial-Commercial + Infanrix™-IPV/Hib Group<br>children primed with 3 doses of commercial lot of Synflorix™ co-administered with Rotarix™ and Infanrix™-hexa in the primary phase of the study (NCT00808444) and boosted with commercial lot of Synflorix™ co-administered with Infanrix™-IPV/Hib. The Synflorix™ vaccine (commercial lots) was administered intramuscularly in the right deltoid or anterolateral thigh and the Infanrix™-IPV/Hib vaccine was administered intramuscularly in the left deltoid or anterolateral thigh. | Biological: Pneumococcal vaccine GSK1024850A<br>* Intramuscular injection, one dose<br>Biological: Infanrix-IPV/Hib<br>* Intramuscular injection, one dose<br>|
| Active Comparator: Synflorix™ Clinical-Commercial + Infanrix™-IPV/Hib Group<br>children primed with 3 doses of clinical lot of Synflorix™ + Rotarix™ co-administered with Infanrix™-hexa in the primary phase of the study (NCT00808444) and boosted with commercial lot of Synflorix™ co-administered with Infanrix™-IPV/Hib. The Synflorix™ vaccine (clinical and commercial lots) was administered intramuscularly in the right deltoid or anterolateral thigh and the Infanrix™-IPV/Hib vaccine was administered intramuscularly in the left deltoid or anterolateral thigh. | Biological: Pneumococcal vaccine GSK1024850A<br>* Intramuscular injection, one dose<br>Biological: Infanrix-IPV/Hib<br>* Intramuscular injection, one dose<br>|

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. | Vaccine pneumococcal serotypes assessed were serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F. Concentrations were expressed as geometric mean concentrations (GMCs) in microgram per millilitre (µg/mL). Pneumococcal serotype specific total imunoglobuline G (IgG) antibodies were measured by 22F-inhibition Enzyme-linked immunosorbent assay (ELISA). The cut-off of the assay was 0.05 µg/mL. | Before booster vaccination at Month 0 | 
| Concentrations of Antibodies Against Protein D (PD). | Anti-PD antibodies were determined using an ELISA assay. Concentration of specific PD antibodies was determined, using a standard reference serum. The cut-off of the assay is 100 ELISA units per millilitre (EU/mL). | Before booster vaccination at Month 0 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects Reporting Any and Grade 3 Solicited Local Adverse Events (AEs). | Solicited AEs = AEs to be recorded as endpoints in the clinical study. The presence/occurrence/intensity of these events is actively solicited from the subject or an observer during a specified post-vaccination follow-up period. Solicited local symptoms assessed were pain, redness and swelling. Any = occurrence 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 (mm). | Within 4 days (Days 0-3) after booster vaccination. | 
| Number of Subjects Reporting Any, Grade 3 and Related Solicited General Adverse Events (AEs). | Solicited general symptoms assessed were drowsiness, irritability, loss of appetite and fever (= axillary temperature equal to or above 37.5 degrees Celsius (°C)). Any= occurrence of any general symptom regardless of intensity grade or relationship to vaccination Grade 3 drowsiness = drowsiness which 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 = temperature >39.5°C. Related = solicited symptom assessed by the investigator as causally related to study vaccination. | Within 4 days (Days 0-3) after booster vaccination. | 
| Number of Subjects Reporting Unsolicited Adverse Events (AEs). | Unsolicited AEs = Any AE (i.e. any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product) reported in addition to those solicited during the clinical study. Also any solicited symptom with onset outside the specified period of follow-up for solicited symptoms was reported as an unsolicited adverse event. | Within 31 days (Days 0-30) after booster vaccination | 
| Number of Subjects Reporting 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. | During the entire study period, from the booster vaccination, at Month 0, up to the study end, at Month 1 | 
| Opsonophagocytic Activity Against Vaccine Pneumococcal Serotypes. | Opsonophagocytic activity (OPA) testing was not performed. | Before and one month after booster vaccination (at Month 0 and Month 1) | 
| Opsonophagocytic Activity Against Cross-reactive Pneumococcal Serotypes 6A and 19A. | Opsonophagocytic activity (OPA) testing was not performed. | Before and one month after booster vaccination (at Month 0 and Month 1) | 
| Concentrations of Antibodies Against Cross-reactive Pneumococcal Serotypes. | Cross-reactive pneumococcal serotypes assessed were serotypes 6A and 19A. Concentrations were expressed as geometric mean concentrations (GMCs) in microgram per millilitre (µg/mL). The antibody concentrations against the cross-reactive pneumococcal serotypes 6A and 19A were determined by 22F-inhibition Enzyme-linked immunosorbent assay (ELISA). The cut-off of the assay was 0.05 µg/mL. | Before booster vaccination at Month 0 | 
| Concentrations of Antibodies Against Diphtheria and Tetanus. | Concentrations were expressed as geometric mean concentrations (GMCs) in International units per millilitre (IU/mL). The cut-off of the assay was 0.1 IU/mL. | Before booster vaccination at Month 0 | 
| Concentrations of Antibodies Against Pertussis Toxoid (PT), Filamentous Haemagglutinin (FHA) and Pertactin (PRN). | Concentrations were expressed as geometric mean concentrations (GMCs) in ELISA units per millilitre (EU/mL). The cut-off of the assay was 5 EU/mL. | Before booster vaccination at Month 0 | 
| Concentrations of Antibodies Against Polyribosyl-ribitol Phosphate (PRP). | Concentrations were expressed as geometric mean concentrations (GMCs) in microgram per millilitre (µg/mL). The cut-off of the assay was 0.15 µg/mL. | Before booster vaccination at Month 0 | 
| Titers of Antibodies Against Poliovirus Types 1, 2 and 3. | Titers were expresses as geometric mean titers (GMTs). The cut-off of the assay was 8. | Before booster vaccination at Month 0 | 
| Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes. | Vaccine pneumococcal serotypes assessed were serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F. Concentrations were expressed as geometric mean concentrations (GMCs) in microgram per millilitre (µg/mL). Pneumococcal serotype specific total imunoglobuline G (IgG) antibodies were measured by 22F-inhibition Enzyme-linked immunosorbent assay (ELISA). The cut-off of the assay was 0.05 µg/mL. | Before and one month after booster vaccination (at Month 0 and Month 1) | 
| Concentrations of Antibodies Against Cross-reactive Pneumococcal Serotypes. | Cross-reactive pneumococcal serotypes assessed were serotypes 6A and 19A. Concentrations were expressed as geometric mean concentrations (GMCs) in microgram per millilitre (µg/mL). The antibody concentrations against the cross-reactive pneumococcal serotypes 6A and 19A were determined by 22F-inhibition Enzyme-linked immunosorbent assay (ELISA). The cut-off of the assay was 0.05 µg/mL. | Before and one month after booster vaccination (at Month 0 and Month 1) | 
| Concentrations of Antibodies Against Protein D (PD). | Anti-PD antibodies were determined using an ELISA assay. Concentration of specific PD antibodies was determined, using a standard reference serum. The cut-off of the assay is 100 ELISA units per millilitre (EU/mL). | Before and one month after booster vaccination (at Month 0 and Month 1) | 
| Concentrations of Antibodies Against Diphtheria and Tetanus. | Concentrations were expressed as geometric mean concentrations (GMCs) in International units per millilitre (IU/mL). The cut-off of the assay was 0.1 IU/mL. | Before and one month after booster vaccination (at Month 0 and Month 1) | 
| Concentrations of Antibodies Against Pertussis Toxoid (PT), Filamentous Haemagglutinin (FHA) and Pertactin (PRN). | Concentrations were expressed as geometric mean concentrations (GMCs) in ELISA units per millilitre (EU/mL). The cut-off of the assay was 5 EU/mL. | Before and one month after booster vaccination (at Month 0 and Month 1) | 
| Concentrations of Antibodies Against Polyribosyl-ribitol Phosphate (PRP). | Concentrations were expressed as geometric mean concentrations (GMCs) in microgram per millilitre (µg/mL). The cut-off of the assay was 0.15 µg/mL. | Before and one month after booster vaccination (at Month 0 and Month 1) | 
| Titers of Antibodies Against Poliovirus Types 1, 2 and 3. | Titers were expresses as geometric mean titers (GMTs). The cut-off of the assay was 8. | Before and one month after booster vaccination (at Month 0 and Month 1) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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safety, Streptococcus pneumoniae, immunogenicity, Pneumococcal conjugate vaccine, Haemophilus influenzae