Immunization of Children Previously Primed With GSK Pneumococcal Vaccine GSK1024850A and of Unprimed Children in Nigeria

Study Overview
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Brief Summary
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The purpose of this trial is to assess the safety, reactogenicity and immunogenicity of GSK Biologicals' pneumococcal conjugate vaccine GSK1024850A when administered either as a booster dose or as a two dose catch-up vaccination in the second year of life to the Nigerian subjects previously enrolled in the primary vaccination study NCT00678301. This protocol posting deals with objectives & outcome measures of the booster phase. The objectives & outcome measures of the primary phase are presented in a separate protocol posting (NCT number = NCT00678301).

Official Title
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Safety, Reactogenicity and Immunogenicity Study of GSK Biologicals' Pneumococcal Vaccine GSK1024850A, Given Either as a Booster Dose or as a 2-dose Catch-up Immunization in Healthy Nigerian Children

Conditions
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Infections, Streptococcal

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


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(s)) can and will comply with the requirements of the protocol. A male or female, between and including 15-21 months of age at the time of visit 1. For the Pn-Pn group, subjects who completed the full vaccination course in study NCT00678301. For the Zil-Pn group, subjects who were previously enrolled in the control group of study NCT00678301. Written informed consent, signed or thumb printed, obtained from the parent(s)/LAR(s) of the subject. Where parent(s)/LAR(s) are illiterate, the consent form will be countersigned by a witness. 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)/product(s) within 30 days preceding the first dose of vaccine, or planned use during the study period. Chronic administration of immunosuppressants or other immune-modifying drugs within six months prior to vaccination. Planned administration/administration of a vaccine not foreseen by the study protocol during the period starting from 30 days before each dose of study vaccine and ending 30 days after. Locally recommended vaccines for example Oral Polio Vaccine or influenza vaccine are always allowed, even if concomitantly administered with the study vaccines, but should be documented in the CRF. 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. Administration of any pneumococcal vaccine since the end of study NCT00678301. Any confirmed or suspected immunosuppressive or immunodeficient condition, since the end of study NCT00678301, based on medical history and physical examination. Major congenital defects or serious chronic illness. History of any progressive neurological disorders or seizures. Acute disease and/or fever at the time of enrolment. History of any reaction or hypersensitivity likely to be exacerbated by any component of the vaccines. Administration of immunoglobulins and/or any blood products less than 3 months prior to visit 1 or planned use during the study. Child in care.

Ages Eligible for Study
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Minimum Age: 15 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: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Synflorix/Infanrix primed Group<br>Subjects previously primed with the Synflorix™ vaccine in the primary study 110521 (NCT00678301) received a booster dose of the Synflorix™ vaccine co-administered with a booster dose of the Infanrix™ vaccine at 15-21 months of age. Synflorix™ vaccine was administered intramuscularly in the right thigh or deltoid muscle of the arm. Infanrix™ vaccine was administered intramuscularly in the left thigh or deltoid muscle of the arm. | Biological: Pneumococcal vaccine GSK1024850A<br>* Intramuscular injection, 1 or 2 doses<br>Biological: InfanrixTM<br>* Intramuscular injection, 1dose<br>* Other names: DTPa;|
| Experimental: Synflorix/Infanrix unprimed Group<br>Unprimed subjects from the primary study 110521 (NCT00678301), not previously vaccinated with any pneumococcal vaccine, received a 2-dose catch-up vaccination of Synflorix™ vaccine at 15-21 and 17-23 months of age and a booster dose of Infanrix™ vaccine co-administered with the first dose of Synflorix™ vaccine at 15-21 months of age. Synflorix™ vaccine was administered intramuscularly in the right thigh or deltoid muscle of the arm. Infanrix™ vaccine was administered intramuscularly in the left thigh or deltoid muscle of the arm. | Biological: Pneumococcal vaccine GSK1024850A<br>* Intramuscular injection, 1 or 2 doses<br>Biological: InfanrixTM<br>* Intramuscular injection, 1dose<br>* Other names: DTPa;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects Reporting Grade 3 Symptoms (Solicited and Unsolicited). | Grade 3 symptom = severe symptom that prevented normal activity. Solicited local symptoms assessed were pain, redness and swelling. Solicited general symptoms assessed were drowsiness, fever, irritability and loss of appetite. Unsolicited AEs = Any AE 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 (Day 0 to Day 30) after administration of a booster dose of Synflorix vaccine in the Synflorix/Infanrix primed Group. | 

Secondary 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. | Prior to and one month after the booster immunisation for the Synflorix/Infanrix primed Group and prior to the first dose and one month after Dose 2 in the Synflorix/Infanrix unprimed Group | 
| 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. | Prior to and one month after the booster immunisation for the Synflorix/Infanrix primed Group and prior to the first dose and one month after Dose 2 in the Synflorix/Infanrix unprimed Group | 
| Opsonophagocytic Activity Against Vaccine Pneumococcal Serotypes. | Vaccine pneumococcal serotypes assessed were serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F. Streptococcus pneumoniae opsonophagocytic activity was measured by a killing-assay using a HL 60 cell line. The results were presented as the dilution of serum (opsonic titre) able to sustain 50% killing of live pneumococci under the assay conditions. The cut-off of the assay is an opsonic titre of 8. | One month after the booster immunisation for the Synflorix/Infanrix primed Group and one month after Dose 2 in the Synflorix/Infanrix unprimed Group | 
| Opsonophagocytic Activity Against Cross-reactive Pneumococcal Serotypes. | Cross-reactive pneumococcal serotypes assessed were serotypes 6A and 19A. Streptococcus pneumoniae opsonophagocytic activity was measured by a killing-assay using a HL 60 cell line. The results were presented as the dilution of serum (opsonic titre) able to sustain 50% killing of live pneumococci under the assay conditions. The cut-off of the assay is an opsonic titre of 8. | One month after the booster immunisation for the Synflorix/Infanrix primed Group and one month after Dose 2 in the Synflorix/Infanrix unprimed Group | 
| Concentration of Antibodies Against Protein D (PD). | Anti-PD antibodies were determined using an ELISA assay. Concentrations were expressed as geometric mean concentrations (GMCs) in ELISA units per millilitre (EL.U/mL). Concentration of specific PD antibodies was determined, using a standard reference serum. The cut-off of the assay is 100 ELISA units per millilitre (EL.U/mL). | Prior to and one month after the booster immunisation for the Synflorix/Infanrix primed Group and prior to the first dose and one month after Dose 2 in the Synflorix/Infanrix unprimed Group | 
| Number of Subjects Reporting Any and Grade 3 Solicited Local AEs. | Solicited AEs = AEs to be recorded as endpoints in the clinical study. The presence/occurrence/intensity of these events was 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 vaccination. | 
| Number of Subjects Reporting Any, Grade 3 and Related Solicited General 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 vaccination. | 
| Number of Subjects Reporting Unsolicited 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 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 vaccination visit at Day 0 up to the end of the follow-up visit at Month 1 for the Synflorix/Infanrix primed Group and up to Month 3 for the Synflorix/Infanrix unprimed Group. | 

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