Booster and Catch-up Vaccination With Vaccine GSK1024850A

Phase 3

Completed

Conditions: Infections, Streptococcal

Interventions: Biological: Pneumococcal vaccine GSK1024850A

Registration Number: NCT01030822

Lead Sponsor: GlaxoSmithKline

Brief Summary: The purpose of this study is to evaluate the immunogenicity, safety and reactogenicity of a booster dose of pneumococcal vaccine GSK1024850A administered either at 9-18 months or 15-18 months of age in children primed in primary study NCT00814710.

This study also aims to assess the persistence of antibodies induced following primary vaccination with pneumococcal vaccine GSK1024850A in primary study NCT00814710 prior to booster vaccination and following vaccination in the present study at approximately 24 months of age.

The study is also designed to evaluate the immunogenicity, safety and reactogenicity of pneumococcal vaccine GSK1024850A when administered as a catch-up vaccination (2+1) in the second year of life in children unprimed with vaccine GSK1024850A in study NCT00814710.

Detailed Description: The study is randomized for primed subjects and non-randomized for unprimed subjects.

The protocol posting has been updated according to the amendment of the protocol dated 16 April 2010. The age range at the time of randomization of subjects primed in study NCT00814710 and the age range for booster vaccination of one of the groups has been extended.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 282

Inclusion Criteria

Male or female subjects for whom the investigator believes that their parent(s)/ guardian(s) can and will comply with the requirements of the protocol.
Written, signed or thumb-printed informed consent obtained from the parent(s)/guardian(s) of the child/ward. Where parent(s)/guardian(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.

For primed subjects:

Completion of the full vaccination course in study NCT00814710.
9-18 months of age at the time of randomization.
Group A: 9-18 months of age at the time of booster vaccination.
Group B: 15-18 months of age at the time of booster vaccination.

For unprimed subjects (Group C):

Enrolled in study NCT00814710.
12-18 months of age at the time of first vaccination.

Exclusion Criteria

Use of any investigational or non-registered product within 30 days preceding the 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.
Administration of immunoglobulins and/or any blood products within three months preceding the vaccination or planned administration during the study period.
Administration of any pneumococcal vaccine since the end of study NCT00814710.
Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination.
History of reactions or allergic disease likely to be exacerbated by any component of the vaccine.
Major congenital defects or serious chronic illness.
History of any neurologic disorders or seizures.
Acute disease at the time of enrolment.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Group C	Pneumococcal vaccine GSK1024850A	Unprimed subjects receiving a catch-up vaccination (2+1 schedule) in the second year of life.
Group A	Pneumococcal vaccine GSK1024850A	Subjects previously primed with pneumococcal vaccine GSK1024850A in the first year of life and receiving a booster dose of GSK1024850A at 9-18 months of age.
Group B	Pneumococcal vaccine GSK1024850A	Subjects previously primed with pneumococcal vaccine GSK1024850A in the first year of life and receiving a booster dose of GSK1024850A at 15-18 months of age.

Primary Outcome Measures

Name	Time	Method
Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes	Prior to booster vaccination (PRE), one month after booster vaccination (Month 1) and at approximately 24 months of age: at Month 15 for Synflorix 1 Group and at Month 9 for Synflorix 2 Group (24 months of age)	Antibodies assessed for this outcome measure were those against the vaccine 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). Antibody concentrations were measured by 22F enzyme-linked immunosorbent assay (ELISA), expressed as geometric mean concentrations (GMCs), in micrograms per milliliter (µg/mL). The seropositivity cut-off of the assay was an antibody concentration ≥ 0.05 µg/mL. Antibody concentrations \< 0.05 µg/mL were given an arbitrary value of half the cut-off for the purpose of GMC calculation.

Secondary Outcome Measures

Name	Time	Method
Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes	Prior to vaccination (PRE), one month post-Dose 2 (Month 3), prior to (Month 6) and one month after the third (booster) vaccine dose (Month 7)	Antibodies assessed for this outcome measure were those against the vaccine 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). Antibody concentrations were measured by 22F enzyme-linked immunosorbent assay (ELISA), expressed as geometric mean concentrations (GMCs), in micrograms per milliliter (µg/mL). The seropositivity cut-off of the assay was an antibody concentration ≥ 0.05 µg/mL. Antibody concentrations \< 0.05 µg/mL were given an arbitrary value of half the cut-off for the purpose of GMC calculation.
Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes (Persistence)	Prior to booster vaccination (PRE) for the Synflorix 1 and Synflorix 2 Groups and prior to catch-up vaccination (PRE) for the Tritanrix-HepB+Hiberix Group	Antibodies assessed for this outcome measure were those against the vaccine 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). Antibody concentrations were measured by 22F enzyme-linked immunosorbent assay (ELISA), expressed as geometric mean concentrations (GMCs), in micrograms per milliliter (µg/mL). The seropositivity cut-off of the assay was an antibody concentration ≥ 0.05 µg/mL. Antibody concentrations \< 0.05 µg/mL were given an arbitrary value of half the cut-off for the purpose of GMC calculation.
Opsonophagocytic Activity (OPA) Titers Against Pneumococcal Serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F (Persistence)	Prior to booster vaccination (PRE) for the Synflorix 1 and Synflorix 2 Groups and prior to catch-up vaccination (PRE) for the Tritanrix-HepB + Hiberix Group	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 \< 8 were given an arbitrary value of half the cut-off for the purpose of GMT calculation.
Opsonophagocytic Activity (OPA) Titers Against Cross-reactive Pneumococcal Serotypes 6A and 19A (Persistence)	Prior to booster vaccination (PRE) for the Synflorix 1 and Synflorix 2 Groups and prior to catch-up vaccination (PRE) for the Tritanrix-HepB + Hiberix Group	OPA titers against cross-reactive pneumococcal serotypes 6A and 19A (Opsono-6A and -19A) were calculated, expressed as geometric mean titers (GMTs) and tabulated. The seropositivity cut-off for the assay was ≥ 8. Antibody titers \< 8 were given an arbitrary value of half the cut-off for the purpose of GMT calculation.
Opsonophagocytic Activity (OPA) Titers Against Pneumococcal Serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F	Prior to vaccination (PRE), one month post-Dose 2 (Month 3), prior to (Month 6) and one month after the third (booster) vaccine dose (Month 7)	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 \< 8 were given an arbitrary value of half the cut-off for the purpose of GMT calculation.
Concentrations of Antibodies Against Cross-reactive Pneumococcal Serotypes 6A and 19A (Persistence)	Prior to booster vaccination (PRE) for the Synflorix 1 and Synflorix 2 Groups and prior to catch-up vaccination (PRE) for the Tritanrix-HepB + Hiberix Group	Antibodies assessed for this outcome measure were those against cross-reactive pneumococcal serotypes 6A and 19A (ANTI-6A and -19A). Antibody concentrations were measured by 22F enzyme-linked immunosorbent assay (ELISA), expressed as geometric mean concentrations (GMCs), in micrograms per milliliter (µg/mL). The seropositivity cut-off of the assay was an antibody concentration ≥ 0.05 µg/mL. Antibody concentrations \< 0.05 µg/mL were given an arbitrary value of half the cut-off for the purpose of GMC calculation.
Concentrations of Antibodies Against Cross-reactive Pneumococcal Serotypes 6A and 19A	Prior to vaccination (PRE), one month post-Dose 2 (Month 3), prior to (Month 6) and one month after the third (booster) vaccine dose (Month 7)	Antibodies assessed for this outcome measure were those against cross-reactive pneumococcal serotypes 6A and 19A (ANTI-6A and -19A). Antibody concentrations were measured by 22F enzyme-linked immunosorbent assay (ELISA), expressed as geometric mean concentrations (GMCs), in micrograms per milliliter (µg/mL). The seropositivity cut-off of the assay was an antibody concentration ≥ 0.05 µg/mL. Antibody concentrations \< 0.05 µg/mL were given an arbitrary value of half the cut-off for the purpose of GMC calculation.
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms	Within the 4-day follow-up period (Days 0-3) after the booster dose for the Synflorix 1 and Synflorix 2 Groups and across doses for the Tritanrix-HepB + Hiberix Group	Assessed solicited general symptoms were Drowsiness, Irritability/Fussiness (Irr./Fuss.), Loss of appetite (Loss Appet.) and Fever (rectal temperature higher than \[≥\] 38.0 degrees Celsius \[°C\]),. Any = Occurrence of the specified solicited general symptom, regardless of intensity or relationship to vaccination. Related = Occurrence of the specified symptom assessed by the investigators as causally related to vaccination. Grade 3 Drowsiness = Drowsiness that prevented normal everyday activities. Grade 3 Irr./Fuss. = Crying that could not be comforted/prevented normal everyday activities. Grade 3 Loss of appetite = Subject did not eat at all. Grade 3 Fever = Rectal temperature higher than (\>) 40.0°C.
Number of Subjects With Serious Adverse Events (SAEs)	After the first vaccination up to study end (from Month 0 to Month 15)	SAEs assessed include medical occurrences that result in death, are life- threatening, require hospitalization or prolongation of hospitalization, result in disability/incapacity.
Opsonophagocytic Activity (OPA) Titers Against Cross-reactive Pneumococcal Serotypes 6A and 19A	Prior to vaccination (PRE), one month post-Dose 2 (Month 3), prior to (Month 6) and one month after the third (booster) vaccine dose (Month 7)	OPA titers against cross-reactive pneumococcal serotypes 6A and 19A (Opsono-6A and -19A) were calculated, expressed as geometric mean titers (GMTs) and tabulated. The seropositivity cut-off for the assay was ≥ 8. Antibody titers \< 8 were given an arbitrary value of half the cut-off for the purpose of GMT calculation.
Concentrations of Antibodies Against Protein D (Anti-PD) (Persistence)	Prior to booster vaccination (PRE) for the Synflorix 1 and Synflorix 2 Groups and prior to catch-up vaccination (PRE) for the Tritanrix-HepB + Hiberix Group	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 milliliter (EL.U/mL) and tabulated. The seropositivity cut-off for the assay was ≥ 100 EL.U/mL. Antibody concentrations \< 100 EL.U/mL were given an arbitrary value of half the cut-off for the purpose of GMC calculation.
Concentrations of Antibodies Against Protein D (Anti-PD)	Prior to vaccination (PRE), one month post-Dose 2 (Month 3), prior to (Month 6) and one month after the third (booster) vaccine dose (Month 7)	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 milliliter (EL.U/mL) and tabulated. The seropositivity cut-off for the assay was ≥ 100 EL.U/mL. Antibody concentrations \< 100 EL.U/mL were given an arbitrary value of half the cut-off for the purpose of GMC calculation.
Number of Subjects With Any and Grade 3 Solicited Local Symptoms	Within the 4-day follow-up period (Days 0-3) after the booster dose for the Synflorix 1 and Synflorix 2 Groups and across doses for the Tritanrix-HepB + Hiberix Group	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.
Number of Subjects With Unsolicited Adverse Events (AEs)	Within 31-day follow-up period (Days 0-30) after vaccination	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. Unsolicited AE covers any AE 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.