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

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 Malian 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 Malian Children

Conditions
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Infections, Streptococcal

Intervention / Treatment
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* Biological: Pneumococcal vaccine GSK1024850A


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 (drug or vaccine) 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 (pharmaceutical product or device). 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: Pn-Pn group<br>subjects from the Pn-Pn group, previously vaccinated with pneumococcal conjugate vaccine GSK1024850A in the Malian centre of study NCT00678301, receiving a booster dose of pneumococcal conjugate vaccine GSK1024850A | Biological: Pneumococcal vaccine GSK1024850A<br>* Intramuscular injection, 1 or 2 doses<br>|
| Experimental: Zil-Pn group<br>subjects from the unprimed group of the NCT00678301 Malian study centre, not previously vaccinated with any pneumococcal vaccine, receiving two doses of pneumococcal conjugate vaccine GSK1024850A | Biological: Pneumococcal vaccine GSK1024850A<br>* Intramuscular injection, 1 or 2 doses<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects With Grade 3 Adverse Events (Solicited and Unsolicited) | The incidence and nature of Grade 3 symptoms (solicited and unsolicited), reported during the 31-day (Days 0-30) post-vaccination are presented. | Within 31 days (Day 0-Day 30) after booster vaccination | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects With Any and Grade 3 Solicited Local Symptoms | Assessed solicited local symptoms were pain, redness and swelling. Any = occurrence of the symptom regardless of intensity grade. Grade 3 pain = pain that prevented normal activity. Grade 3 redness/swelling = redness/swelling spreading beyond 30 millimeters (mm) of injection site. | Within 4 days (Day 0-Day 3) after the booster dose | 
| Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Assessed solicited general symptoms were drowsiness, fatigue, fever [defined as axillary temperature equal to or above 37.5 degrees Celsius (°C)], irritability and loss of appetite. Any = occurrence of the symptom regardless of intensity grade. Grade 3 Drowsiness and Irritability = symptom that prevented normal activity. Grade 3 Loss of appetite = not eating at all. Grade 3 fever = fever > 39.5 °C. Related = symptom assessed by the investigator as related to the vaccination. | Within 4 days (Day 0-Day 3) after the booster dose | 
| Number of Subjects With Any and Grade 3 Solicited Local Symptoms | Assessed solicited local symptoms were pain, redness and swelling. Any = occurrence of the symptom regardless of intensity grade. Grade 3 pain = pain that prevented normal activity. Grade 3 redness/swelling = redness/swelling spreading beyond 30 millimeters (mm) of injection site. | Within 4 days (Day 0-Day 3) after each vaccine dose | 
| Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Assessed solicited general symptoms were drowsiness, fatigue, fever [defined as axillary temperature equal to or above 37.5 degrees Celsius (°C)], irritability and loss of appetite. Any = occurrence of the symptom regardless of intensity grade. Grade 3 Drowsiness and Irritability = symptom that prevented normal activity. Grade 3 Loss of appetite = not eating at all. Grade 3 fever = fever > 39.5 °C. Related = symptom assessed by the investigator as related to the vaccination. | Within 4 days (Day 0-Day 3) after each vaccine dose | 
| Number of Subjects With Any Unsolicited Adverse Events (AEs) | An unsolicited AE covers 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 and 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. Any was defined as the occurrence of any unsolicited AE regardless of intensity grade or relation to vaccination. | Within 31 days (Day 0-Day 30) after each vaccine dose | 
| 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. | From the first vaccination up to one month (31 days) after the last vaccination for each subject | 
| Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F | 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 milliliter (μg/mL). Pneumococcal serotype specific total immunoglobuline 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 (PRE) and one month after (POST) the booster immunization in the Synflorix Primed Group and prior to (PRE) the first dose and one month after (POST) the second dose of the catch-up vaccination in the Synflorix Unprimed Group | 
| Opsonophagocytic Activity 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. | Prior to (PRE) and one month after (POST) the booster immunization in the Synflorix Primed Group and prior to (PRE) the first dose and one month after (POST) the second dose of the catch-up vaccination in the Synflorix Unprimed Group | 
| Concentrations of Antibodies Against Cross-reactive Pneumococcal Serotypes 6A and 19A | Cross-reactive pneumococcal serotypes assessed were serotypes 6A and 19A. Concentrations were expressed as geometric mean concentrations (GMCs) in microgram per milliliter (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 (PRE) and one month after (POST) the booster immunization in the Synflorix Primed Group and prior to (PRE) the first dose and one month after (POST) the second dose of the catch-up vaccination in the Synflorix Unprimed Group | 
| Opsonophagocytic Activity Against Cross-reactive Pneumococcal Serotypes 6A and 19A | OPA titers against pneumococcal serotypes 6A and 19A (Opsono-6A and Opsono-19A) were calculated, expressed as geometric mean titers (GMTs) and tabulated. The seropositivity cut-off for the assay was ≥ 8. | Prior to (PRE) and one month after (POST) the booster immunization in the Synflorix Primed Group and prior to (PRE) the first dose and one month after (POST) the second dose of the catch-up vaccination in the Synflorix Unprimed Group | 
| Concentrations of Antibodies Against Protein D (PD) | Concentrations of antibodies against protein D (PD) were determined by ELISA assay. Concentrations were expressed as geometric mean concentrations (GMCs) in ELISA units per milliliter (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 milliliter (EL.U/mL). | Prior to (PRE) and one month after (POST) the booster immunization in the Synflorix Primed Group and prior to (PRE) the first dose and one month after (POST) the second dose of the catch-up vaccination in the Synflorix Unprimed Group | 

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