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

GlaxoSmithKline1,200 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

PREVENTION

Enrollment

1,200

Conditions

Infections, Streptococcal

Interventions

Eligibility

Sex: ALLMin age: 12 MonthsMax age: 18 MonthsHealthy volunteers:

Medical Language ↔ Plain English

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.

Locations (35)

GSK Investigational Site

Espoo, Finland

GSK Investigational Site

Helsinki, Finland

GSK Investigational Site

Helsinki, Finland

GSK Investigational Site

Jarvenpaa, Finland

GSK Investigational Site

Jyväskylä, Finland

GSK Investigational Site

Outcomes

Primary Outcomes

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.

Time frame: Within 4 days (Days 0-3) after the booster vaccination at Month 0 in this study 10PN-PD-DIT-007

Secondary Outcomes

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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.