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

Primary Purpose

Infections, Streptococcal

Status

Completed

Phase

Phase 3

Locations

International

Study Type

Interventional

Intervention

Synflorix

Prevenar

Infanrix hexa

About this trial

This is an interventional prevention trial for Infections, Streptococcal focused on measuring Streptococcus pneumonia, pneumococcal conjugate vaccine

Eligibility Criteria

12 Months - 18 Months (Child)All SexesAccepts Healthy Volunteers

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.

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Active Comparator

Experimental

Arm Label

Synflorix-Synflorix Group

Prevenar-Prevenar Group

Prevenar-Synflorix Group

Arm Description

This group consisted of subjects previously vaccinated with the Synflorix™ vaccine as part of a previous study by GSK Biologicals - the 10PN-PD-DIT-001 (105553) study (EuDRA-CT number: 2005-003300-11). As part of the 105553 study, subjects had received a 3-dose primary vaccination of Synflorix™ vaccine at 2, 3 and 4 months of age (injected intramuscularly [IM] in the right thigh) co-administered with Infanrix hexa™ vaccine, except for the second dose in France, which was co-administered with Infanrix™ IPV Hib, injected intramuscularly in the left thigh. As part of this study, at 12-18 months of age, subjects received a booster dose of Synflorix™ vaccine, injected IM in the right thigh or deltoid, co-administered with Infanrix hexa™ vaccine, injected IM in the left thigh or deltoid.

This group consisted of subjects previously vaccinated with the Prevenar™ vaccine as part of a previous study by GSK Biologicals - the 10PN-PD-DIT-001 (105553) study (EuDRA-CT number: 2005-003300-11). As part of the 105553 study, subjects had received a 3-dose primary vaccination of Prevenar™ vaccine at 2, 3 and 4 months of age (injected intramuscularly [IM] in the right thigh) co-administered with Infanrix hexa™ vaccine, except for the second dose in France, which was co-administered with Infanrix™ IPV Hib, injected intramuscularly in the left thigh. As part of this study, at 12-18 months of age, subjects received a booster dose of Prevenar™ vaccine, injected IM in the right thigh or deltoid, co-administered with Infanrix hexa™ vaccine, injected IM in the left thigh or deltoid.

This group consisted of subjects previously vaccinated with the Prevenar™ vaccine as part of a previous study by GSK Biologicals - the 10PN-PD-DIT-001 (105553) study (EuDRA-CT number: 2005-003300-11). As part of the 105553 study, subjects had received a 3-dose primary vaccination of Synflorix vaccine at 2, 3 and 4 months of age (injected intramuscularly [IM] in the right thigh) co-administered with Infanrix hexa™ vaccine, except for the second dose in France, which was co-administered with Infanrix™ IPV Hib, injected intramuscularly in the left thigh. As part of this study, at 12-18 months of age, subjects received a booster dose of Synflorix™, injected IM in the right thigh or deltoid, co-administered with Infanrix hexa™ vaccine, injected IM in the left thigh or deltoid.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.

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.

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.

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.

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.

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.

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.

Opsonophagocytic Activity (OPA) Titers 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. Antibody titers below the cut-off of the assay were given an arbitrary value of half the cut-off for the purpose of GMT 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.

Antibody Concentrations to Protein D (Anti-PD) - by Enzyme-Linked Immunosorbent Assay (ELISA)

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 milli-liter (EL.U/mL) and tabulated. The seropositivity cut-off for the assay was ≥ 100 EL.U/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.

Anti-polyribosyl Ribitol Phosphate (Anti-PRP) Antibody Concentrations

Anti-PRP antibody concentrations were calculated, expressed as geometric mean concentrations (GMCs), in microgram per milliliter (µg/mL), and tabulated. The seroprotection cut-off for the assay for the purpose of this endpoint was ≥ 0.15 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.

Anti-pertussis Toxoid (Anti-PT), Anti- Filamentous Haemagglutinin (Anti-FHA) and Anti-pertactin (Anti-PRN) Antibody Concentrations

Anti-PT, Anti-FHA and Anti-PRN concentrations measured by Enzyme-Linked Immunosorbent Assay (ELISA) were calculated, expressed as geometric mean concentrations (GMCs) in ELISA unit per milli-liter (EL.U/mL) and tabulated. The seropositivity cut-off for the assay was ≥ 5 EL.U/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.

Anti-diphtheria (Anti-D) and Anti-tetanus Toxoids (Anti-TT) Antibody Concentrations

Anti-D and Anti-TT antibody concentrations were calculated, expressed as geometric mean concentrations (GMCs), in International units per milliliter (IU/mL), and tabulated. The seropositivity cut-off for the assay was ≥ 0.1 IU/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.

Anti-hepatitis B Surface Antigen (HBs) Antibody Concentrations

Anti-HBs antibody concentrations were calculated, expressed as geometric mean concentrations (GMCs), in milli-International unit per milliliter (IU/mL), and tabulated. The seropositivity cut-off for the assay was ≥ 10 mIU/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.

Anti-polio Type 1, 2 and 3 (Anti-Polio 1, 2 and 3) Antibody Titers

Anti-Polio 1, 2 and 3 antibody titers were calculated, expressed as geometric mean titers (GMTs) and tabulated. The seroprotection cut-off for the assay was ≥ 8. Antibody titers below the cut-off of the assay were given an arbitrary value of half the cut-off for the purpose of GMT 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.

Number of Subjects Booster (BST) Responder to Pertussis Toxoid (PT), Filamentous Haemagglutinin (FHA) and Pertactin Antigens

A BST responder to PT, FHA and PRN antigens was defined as a subject with the appearance of antibodies in subjects who were seronegative prior to the booster vaccination or at least 2-fold increase of pre-booster vaccination antibody concentrations in subjects who were seropositive prior to the booster vaccination. A seropositive/seronegative subject as regards Anti-PT/-FHA/ -PRN antibodies was defined as a subject with anti-PT/-FHA/ -PRN antibody concentrations ≥ 5 Enzyme-linked Immunosorbent assay (ELISA) unit per milli-liter (EL.U/mL)

Full Information

NCT ID

NCT00370396

First Posted

August 30, 2006

Last Updated

June 6, 2019

Sponsor

GlaxoSmithKline

1. Study Identification

Unique Protocol Identification Number

NCT00370396

Brief Title

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

Official Title

To Assess the Safety, Reactogenicity & Immunogenicity of a 4th Dose of GSK Biologicals' Pneumococcal Vaccine or Prevenar™ in Children (12-18 Months) Previously Vaccinated in the Primary Study NCT00307554 With Either Pneumococcal Vaccine or Prevenar™

Study Type

Interventional

2. Study Status

Record Verification Date

June 2019

Overall Recruitment Status

Completed

Study Start Date

September 25, 2006 (Actual)

Primary Completion Date

June 4, 2007 (Actual)

Study Completion Date

November 6, 2007 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

GlaxoSmithKline

4. Oversight

5. Study Description

Brief Summary

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Infections, Streptococcal

Keywords

Streptococcus pneumonia, pneumococcal conjugate vaccine

7. Study Design

Primary Purpose

Prevention

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Allocation

Randomized

Enrollment

1200 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Synflorix-Synflorix Group

Arm Type

Experimental

Arm Description

Arm Title

Prevenar-Prevenar Group

Arm Type

Active Comparator

Arm Description

Arm Title

Prevenar-Synflorix Group

Arm Type

Experimental

Arm Description

This group consisted of subjects previously vaccinated with the Prevenar™ vaccine as part of a previous study by GSK Biologicals - the 10PN-PD-DIT-001 (105553) study (EuDRA-CT number: 2005-003300-11). As part of the 105553 study, subjects had received a 3-dose primary vaccination of Synflorix vaccine at 2, 3 and 4 months of age (injected intramuscularly [IM] in the right thigh) co-administered with Infanrix hexa™ vaccine, except for the second dose in France, which was co-administered with Infanrix™ IPV Hib, injected intramuscularly in the left thigh. As part of this study, at 12-18 months of age, subjects received a booster dose of Synflorix™, injected IM in the right thigh or deltoid, co-administered with Infanrix hexa™ vaccine, injected IM in the left thigh or deltoid.

Intervention Type

Biological

Intervention Name(s)

Synflorix

Other Intervention Name(s)

10 valent pneumococcal conjugate (vaccine)

Intervention Description

1 dose injected IM in the right thigh or deltoid.

Intervention Type

Biological

Intervention Name(s)

Prevenar

Intervention Description

1 dose injected IM in the right thigh or deltoid.

Intervention Type

Biological

Intervention Name(s)

Infanrix hexa

Intervention Description

1 dose injected IM in the right thigh or deltoid.

Primary Outcome Measure Information:

Title

Number of Subjects With Rectal Temperature Above (>) 39.0 Degrees Celsius (°C) Post Booster Between the Synflorix-Synflorix and Prevenar-Prevenar Groups

Description

Time Frame

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

Secondary Outcome Measure Information:

Title

Number of Subjects With Any and Grade 3 Solicited Local Symptoms

Description

Time Frame

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

Title

Number of Subjects With Any and Any Grade 3 Solicited General Symptoms

Description

Time Frame

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

Title

Number of Subjects With Unsolicited Adverse Events (AEs)

Description

Time Frame

Within 31 days (Day 0-30) after the booster vaccination at Month 0 in this study 10PN-PD-DIT-007

Title

Number of Subjects With Serious Adverse Events (SAEs) During the Active Phase of the Study

Description

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

Title

Number of Subjects With Serious Adverse Events (SAEs) During the Entire Study

Description

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

Title

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)

Description

Time Frame

Prior to (PRE) and one month after (Month 1) booster vaccination

Title

Description

Time Frame