Co-administration of Pneumococcal Conjugate Vaccine With DTPa-IPV-Hib Versus Co-administration With DTPa-HBV-IPV/Hib

Non-inferiority of Co-administration of GSK Biologicals'Pneumococcal Conjugate Vaccine GSK1024850A With DTPa-IPV-Hib Versus Co-administration With DTPa-HBV-IPV/Hib.

The purpose of this trial is to evaluate the immunogenicity and safety of a pneumococcal conjugate vaccine when co-administered with DTPa-IPV-Hib or DTPa-HBV-IPV/Hib in infants as a three-dose primary immunisation course during the first 6 months of life and as a booster dose at 11-12 months of age. The impact of the pneumococcal conjugate vaccine on nasopharyngeal carriage of S. pneumoniae and H. influenzae in children in their first two years of life will also be assessed. The Protocol Posting has been updated in order to comply with the FDA Amendment Act, Sep 2007.

Study Overview

• Status: Completed
• Conditions: Infections, Streptococcal
• Intervention / Treatment: Biological: GSK Biologicals´ Pneumococcal Conjugate Vaccine GSK1024850A (Synflorix™); Biological: Infanrix™ hexa.; Biological: Pediacel™; Biological: Prevenar™

• Study Type: Interventional
• Enrollment (Actual): 780
• Phase: Phase 3

Contacts and Locations

Study Locations

• Netherlands
  • Hoofddorp, Netherlands, 2134 TM
    • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 month to 2 months (Child)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Subjects who the investigator believes that their parents/guardian(s) can and will comply with the requirements of the protocol (e.g., completion of the diary cards, return for follow-up visits) should be enrolled in the study.
• A male or female between, and including, 6-12 weeks (42-90 days) of age at the time of the first vaccination.
• Written informed consent obtained from both parents or from the guardian(s) of the subject.
• Free of obvious health problems as established by medical history and clinical examination before entering into the study.
• Born after a gestation period of at least 36 weeks.

Exclusion Criteria:

• Use of any investigational or non-registered product (drug or vaccine) other than the study vaccine(s) within 30 days preceding the first dose of study vaccine, or planned use during the study period.
• Concurrently participating in another clinical study, at any time during the entire study period, in which the subject has been or will be exposed to an investigational or a non-investigational product (pharmaceutical product or device).
• Chronic administration (defined as more than 14 days) of immunosuppressants or other immune-modifying drugs since birth.
• Planned administration/administration of a vaccine not foreseen by the study protocol during the period starting from one month (30 days) before and up to one month (30 days) after each dose of study vaccine.
• Previous vaccination against diphtheria, tetanus, pertussis, polio, hepatitis B, Haemophilus influenzae type b and/or Streptococcus pneumoniae.
• Children for whom hepatitis B vaccination is required according to the local recommendations
• History of or intercurrent diphtheria, tetanus, pertussis, hepatitis B, polio, Haemophilus influenzae type b disease.
• History of allergic disease or reactions likely to be exacerbated by any component of the vaccines.
• History of any neurologic disorders or seizures.
• Acute disease at the time of enrolment.
• Any confirmed or suspected immunosuppressive or immunodeficient condition based on medical history and physical examination
• A family history of congenital or hereditary immunodeficiency.
• Major congenital defects or serious chronic illness.
• Administration of immunoglobulins and/or any blood products since birth or planned administration during the study period.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Synflorix + Infanrix hexa Group; Subjects received 3 doses of SynflorixTM vaccine co-administered with Infanrix hexaTM at 2, 3 and 4 months of age (Study Months 0, 1, 2) and received a booster dose of each vaccine between 11 and 13 months of age (Study Month 9). All vaccines were administered intramuscularly in the right (SynflorixTM) or left (Infanrix hexaTM) thigh or deltoid.	Biological: GSK Biologicals´ Pneumococcal Conjugate Vaccine GSK1024850A (Synflorix™); Intramuscular injection, 3 doses in the primary vaccination and 1 dose in the booster vaccination; Biological: Infanrix™ hexa.; Intramuscular injection, , 3 doses in the primary vaccination and 1 dose in the booster vaccination
Experimental: Synflorix + Pediacel Group; Subjects received 3 doses of SynflorixTM vaccine co-administered with PediacelTM at 2, 3 and 4 months of age (Study Months 0, 1, 2) and received a booster dose of each vaccine between 11 and 13 months of age (Study Month 9). All vaccines were administered intramuscularly in the right (SynflorixTM) or left (PediacelTM) thigh or deltoid.thigh or deltoid.	Biological: GSK Biologicals´ Pneumococcal Conjugate Vaccine GSK1024850A (Synflorix™); Intramuscular injection, 3 doses in the primary vaccination and 1 dose in the booster vaccination; Biological: Pediacel™; Intramuscular injection, , 3 doses in the primary vaccination and 1 dose in the booster vaccination
Active Comparator: Prevenar + Pediacel Group; Subjects received 3 doses of PrevenarTM co-administered with PediacelTM vaccine at 2, 3 and 4 months of age (Study Months 0, 1, 2) and received a booster dose of each vaccine between 11 and 13 months of age (Study Month 9). All vaccines were administered intramuscularly in the right (PrevenarTM) or left (PediacelTM) thigh or deltoid.	Biological: Pediacel™; Intramuscular injection, , 3 doses in the primary vaccination and 1 dose in the booster vaccination; Biological: Prevenar™; Intramuscular injection, , 3 doses in the primary vaccination and 1 dose in the booster vaccination

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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) - Primary Vaccination	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 measured by 22F-inhibition Enzyme-Linked ImmunSorbent Assay (ELISA); presented as geometric mean concentrations (GMCs) and expressed in micrograms per milliliter (μg/mL). The seropositivity cut-off for the assay was greater than or equal to (≥) 0.05 μg/mL.	At Month 3, one month after the administration of the third dose of pneumococcal conjugate vaccine
Antibody Concentration Against Protein D (PD) - Primary Vaccination	Anti-PD antibody concentrations were presented as geometric mean concentrations (GMCs) and expressed in ELISA units per milliliter (EL.U/mL). The seropositivity cut-off for the assay was ≥ 100 EL.U/mL.	At Month 3, one month after the administration of the third dose of pneumococcal conjugate vaccine

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Subjects With 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) ≥ 0.2 μg/mL - Primary Vaccination	Antibody concentrations against the pneumococcal serotypes were assessed by 22F-inhibition ELISA. The reference cut-off value of the assay was an antibody concentration greater than or equal to (≥) 0.02 µg/mL.	At Month 3, one month after the administration of the third vaccine dose
Opsonophagocytic Activity (OPA) Titers Against Pneumococcal Serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F - Primary Vaccination	Titers were presented as geometric mean titers (GMTs), for the seropositivity cut-off value of 8.	At Month 3, one month after the administration of the third vaccine dose
Number of Subjects With Antibody Concentrations Against Pneumococcal Cross-reactive Serotypes 6A and 19A (Anti-6A and 19A) ≥ 0.2 μg/mL - Primary Vaccination.	Antibody concentrations against the cross- reactive pneumococcal serotypes were assessed by 22F-inhibition ELISA. The reference cut-off value of the assay was an antibody concentration greater than or equal to (≥) 0.02 µg/mL.	At Month 3, one month after the administration of the third vaccine dose
Antibody Concentrations Against Pneumococcal Cross-reactive Serotypes 6A and 19A (Anti-6A and 19A) - Primary Vaccination	Anti-pneumococcal cross-reactive serotypes 6A and 19A antibody concentrations (Anti-6A and -19A) were measured by 22F-inhibition ELISA; presented as geometric mean concentrations (GMCs) and expressed in micrograms per milliliter (μg/mL). The seropositivity cut-off for the assay was ≥ 0.05 μg/mL.	At Month 3, one month after the administration of the third vaccine dose
Opsonophagocytic Activity (OPA) Titers Against Pneumococcal Cross-reactive Serotypes 6A and 19A - Primary Vaccination.	Titers were presented as geometric mean titers (GMTs), for the seropositivity cut-off of 8.	At Month 3, one month after the administration of the third vaccine dose
Concentrations of Antibodies Against Diphtheria and Tetanus Toxoids (Anti-D and T) - Primary Vaccination	Anti-D and anti-T antibody concentrations were presented as geometric mean concentrations (GMCs) and expressed in international units per milliliter (IU/mL). The seropositivity cut-off value was greater than or equal to (≥) 0.1 IU/mL.	At Month 3, one month after the administration of the third vaccine dose
Anti-polyribosyl-ribitol Phosphate (Anti-PRP) Antibody Concentrations - Primary Vaccination	Anti-PRP antibody concentrations were presented as geometric mean concentrations (GMCs) and expressed in micrograms per milliliter (µg/mL). The seropositivity cut-off value was ≥ 0.15 µg/mL.	At Month 3, one month after the administration of the third vaccine dose
Anti-pertussis Toxoid (Anti-PT), Anti-filamentous Haemagglutinin (Anti-FHA) and Anti-pertactin (Anti-PRN) Antibody Concentrations - Primary Vaccination	Anti-PT, anti-FHA and anti-PRN antibody concentrations were presented as geometric mean concentrations (GMCs) and expressed in ELISA units per milliliter (EL.U/mL). The seropositivity cut-off value was ≥ 5 EL.U/mL.	At Month 3, one month after the administration of the third vaccine dose
Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentrations - Primary Vaccination.	Antibody concentrations were presented as geometric mean concentrations (GMCs) and expressed in milli-international units per milliliter (mIU/mL). A seroprotected subject was a subject whose antibody ChemiLuminescence ImmunoAssay (CLIA) concentration was greater than or equal to the cut-off value ≥ 10 milli-international units per milliliter (mIU/mL). Note: investigations on the quality of some serology assays revealed that the anti-HBs ELISA overestimated concentration between 10-100 mIU/mL while values > 100 mIU/mL were confirmed valid. Therefore, all available samples at one month post-dose III and one month post-dose IV timepoints for which the anti-HBs antibody concentration was between 10-100 mIU/mL by in-house ELISA, were retested by the commercial assay Centaur™, an FDA-approved and CE-marked CLIA with a cut-off defining seropositivity of 6.2 mIU/mL. Anti-HBs seroprotection was redefined as in-house ELISA concentration > 100 mIU/mL or CLIA concentration > 10 mIU/mL.	At Month 3, one month after the administration of the third vaccine dose
Anti-polio Types 1, 2 and 3 Titers - Primary Vaccination.	Anti-polio 1, -polio 2, -polio 3 antibody titers were presented as geometric mean titers (GMTs), for the seropositivity cut-off value ≥ 8.	At Month 3, one month after the administration of the third vaccine dose
Number of Subjects With 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) ≥ 0.2 μg/mL - Booster Vaccination	Antibody concentrations against the pneumococcal serotypes were assessed by 22F-inhibition ELISA. The reference cut-off value of the assay was an antibody concentration greater than or equal to (≥) 0.02 µg/mL.	Prior to (Month 9) and one month after the administration of the booster dose (Month 10)
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) - Booster Vaccination	Anti-pneumococcal serotype 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F antibody concentrations were assessed by 22F-inhibition ELISA, presented as geometric mean concentrations (GMCs) and expressed in micrograms per milliliter (μg/mL). The seropositivity cut-off value was ≥ 0.05 μg/mL.	Prior (Month 9) to and one month after the administration of the booster dose (Month 10)
Opsonophagocytic Activity (OPA) Titers Against Pneumococcal Serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F - Booster Vaccination	Titers were presented as geometric mean titers (GMTs), for the seropositivity cut-off value of 8.	Prior (Month 9) to and one month after the administration of the booster dose(Month 10)
Number of Subjects With Antibody Concentrations Against Pneumococcal Cross-reactive Serotypes 6A and 19A (Anti-6A and 19A) ≥ 0.2 μg/mL - Booster Vaccination.	Antibody concentrations against the cross-reactive pneumococcal serotypes were assessed by 22F-inhibition ELISA. The reference cut-off value of the assay was an antibody concentration greater than or equal to (≥) 0.02 µg/mL.	Prior (Month 9) to and one month after the administration of the booster dose(Month 10)
Antibody Concentrations Against Pneumococcal Cross-reactive Serotypes 6A and 19A (Anti-6A and 19A) - Booster Vaccination	Anti-pneumococcal cross-reactive serotype 6A and 19A antibody concentrations were assessed by 22F-inhibition ELISA, presented as geometric mean concentrations (GMCs) and expressed in micrograms per milliliter (μg/mL). The seropositivity cut-off value was ≥ 0.05 μg/mL.	Prior (Month 9) to and one month after the administration of the booster dose (Month 10)
Opsonophagocytic Activity (OPA) Titers Against Pneumococcal Cross-reactive Serotypes 6A and 19A - Booster Vaccination.	Titers were presented as geometric mean titers (GMTs), for the seropositivity cut-off value of 8.	Prior to (Month 9) and one month after the administration of the booster dose (Month 10)
Concentrations of Antibodies Against Protein D (Anti-PD) - Booster Vaccination.	Anti-PD antibody concentrations were presented as geometric mean concentrations (GMCs) and expressed in ELISA units per milliliter (EL.U/mL). The seropositivity cut-off for the assay was ≥ 100 EL.U/mL.	Prior (Month 9) to and one month after (Month 10) the administration of the booster dose
Concentrations of Antibodies Against Diphtheria and Tetanus Toxoids (Anti-D and T) - Booster Vaccination.	Anti-D and anti-T antibody concentrations were presented as geometric mean concentrations (GMCs) and expressed in international units per milliliter (IU/mL). The seropositivity cut-off value was greater than or equal to (≥) 0.1 IU/mL.	Prior to (Month 9) and one month after (Month 10) the administration of the booster dose
Anti-polyribosyl-ribitol Phosphate (Anti-PRP) Antibody Concentrations - Booster Vaccination	Anti-PRP antibody concentrations were presented as geometric mean concentrations (GMCs) and expressed in micrograms per milliliter (µg/mL). The seropositivity cut-off value was ≥ 0.15 µg/mL.	Prior to (Month 9) and one month after (Month 10) the administration of the booster dose
Anti-pertussis Toxoid (Anti-PT), Anti-filamentous Haemagglutinin (Anti-FHA) and Anti-pertactin (Anti-PRN) Antibody Concentrations - Booster Vaccination.	Anti-PT, anti-FHA and anti-PRN antibody concentrations were presented as geometric mean concentrations (GMCs) and expressed in ELISA units per milliliter (EL.U/mL). The seropositivity cut-off value was ≥ 5 EL.U/mL.	Prior (Month 9) to and one month after (Month 10) the administration of the booster dose
Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentrations - Booster Vaccination.	Antibody concentrations were presented as geometric mean concentrations (GMCs) and expressed in milli-international units per milliliter (mIU/mL). A seroprotected subject was a subject whose antibody ChemiLuminescence ImmunoAssay (CLIA) concentration was greater than or equal to the cut-off value ≥ 10 milli-international units per milliliter (mIU/mL). Note: investigations on the quality of some serology assays revealed that the anti-HBs ELISA overestimated concentration between 10-100 mIU/mL while values > 100 mIU/mL were confirmed valid. Therefore, all available samples at one month post-dose III and one month post-dose IV timepoints for which the anti-HBs antibody concentration was between 10-100 mIU/mL by in-house ELISA, were retested by the commercial assay Centaur™, an FDA-approved and CE-marked CLIA with a cut-off defining seropositivity of 6.2 mIU/mL. Anti-HBs seroprotection was redefined as in-house ELISA concentration > 100 mIU/mL or CLIA concentration > 10 mIU/mL.	Prior (Month 9) to and one month after (Month 10) the administration of the booster dose
Anti-polio Types 1, 2 and 3 Titers - Booster Vaccination.	Anti-polio 1, -polio 2, -polio 3 antibody titers were presented as geometric mean titers (GMTs), for the seropositivity cut-off value ≥ 8.	Prior (Month 9) to and one month after (Month 10) the administration of the booster dose
Number of Subjects With Booster Vaccine Response Against Pertussis Toxoid (PT), Filamentous Haemagglutinin (FHA) and Pertactin (PRN) Antibodies - Booster Vaccination.	A booster responder to PT/FHA/PRN was defined as a subject with antibodies concentration ≥ 5 EL.U/mL against PT/FHA/PRN in subjects who were initially seronegative for anti-PT/FHA/PRN antibodies (i.e., subjects with anti-PT/FHA/PRN antibody concentrations < 5 EL.U/mL), or antibody concentration ≥ 2 fold the pre-vaccination antibody concentration in subjects who were initially seropositive (i.e., subjects with anti-PT/FHA/PRN antibody concentrations ≥ 5 EL.U/mL).	One month after (Month 10) the administration of the booster dose
Number of Subjects With 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) ≥ 0.2 μg/mL - 12 Months After Booster Dose.	Antibody concentrations against the pneumococcal serotypes were assessed by 22F-inhibition ELISA. The reference cut-off value of the assay was an antibody concentration greater than or equal to (≥) 0.02 µg/mL.	At Month 21, 12 months after the administration of the booster dose (at 23-25 months of age)
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) - 12 Months After Booster Dose.	Anti-pneumococcal serotype 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F antibody concentrations were assessed by 22F-inhibition ELISA, presented as geometric mean concentrations (GMCs) and expressed in micrograms per milliliter (μg/mL). The seropositivity cut-off value was ≥ 0.05 μg/mL.	At Month 21, 12 months after the administration of the booster dose (at 23-25 months of age)
Opsonophagocytic Activity (OPA) Titers Against Pneumococcal Serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F - 12 Months After Booster Dose.	Titers were presented as geometric mean titers (GMTs), for the seropositivity cut-off value of 8.	At Month 21, 12 months after the administration of the booster dose (at 23-25 months of age)
Number of Subjects With Antibody Concentrations Against Pneumococcal Cross-reactive Serotypes 6A and 19A (Anti-6A and 19A) ≥ 0.2 μg/mL - 12 Months After Booster Dose.	Antibody concentrations against the cross-reactive pneumococcal serotypes were assessed by 22F-inhibition ELISA. The reference cut-off value of the assay was an antibody concentration greater than or equal to (≥) 0.02 µg/mL.	At Month 21, 12 months after the administration of the booster dose (at 23-25 months of age)
Antibody Concentrations Against Pneumococcal Cross-reactive Serotypes 6A and 19A (Anti-6A and 19A) - 12 Months After Booster Dose.	Anti-pneumococcal cross-reactive serotype 6A and 19A antibody concentrations were assessed by 22F-inhibition ELISA, presented as geometric mean concentrations (GMCs) and expressed in micrograms per milliliter (μg/mL). The seropositivity cut-off value was ≥ 0.05 μg/mL.	At Month 21, 12 months after the administration of the booster dose (at 23-25 months of age)
Opsonophagocytic Activity (OPA) Titers Against Pneumococcal Cross-reactive Serotypes 6A and 19A - 12 Months After Booster Dose.	Titers were presented as geometric mean titers (GMTs), for the seropositivity cut-off value of 8.	At Month 21, 12 months after the administration of the booster dose (at 23-25 months of age)
Concentrations of Antibodies Against Protein D (Anti-PD) - 12 Months After Booster Dose.	Anti-PD antibody concentrations were presented as geometric mean concentrations (GMCs) and expressed in ELISA units per milliliter (EL.U/mL). The seropositivity cut-off for the assay was ≥ 100 EL.U/mL.	At Month 21, 12 months after the administration of the booster dose (at 23-25 months of age)
Number of Subjects With Positive Cultures of Haemophilus Influenzae and/or Streptococcus Pneumoniae in the Nasopharynx - Primary Vaccination.	Positive cultures of H. influenzae* (HI) and S. pneumoniae (SP) identified in the nasopharynx at each swab time point: one month post-Dose III (M3), M9 (11-13 months of age), M12 (14-16 months of age), M16 (18-20 months of age) and M21 (23-25 months of age). *Data presented only include results from samples confirmed as positive for H. influenzae / Non-typeable H. influenzae after differentiation from H. haemolyticus by Polymerase Chain Reaction (PCR) assay.	One month after the third dose (Month 3), prior to the booster dose (Month 9), 3 months after the booster dose (Month 12), 7 months after the booster dose (Month 16) and 12 months after the booster dose (Month 21)
Number of Subjects With Positive Cultures of Streptococcus Pneumoniae Vaccine Seroptypes (VS), Cross-reactive Serotypes (CRS) or Other Serotypes (OS) in the Nasopharynx - Primary Vaccination.	Positive cultures of S. pneumoniae (SP) identified in the nasopharynx at each swab time point: one month post-Dose III (M3), pre-booster vaccination (11-13 months of age), M12 (14-16 months of age), M16 (18-20 months of age) and M21 (23-25 months of age).	One month after the third dose (Month 3), prior to the booster dose (Month 9), 3 months after the booster dose (Month 12), 7 months after the booster dose (Month 16) and 12 months after the booster dose (Month 21)
Number of Subjects With Acquisition of New Streptococcus Pneumoniae and Haemophilus Influenzae Strains Identified in Nasopharyngeal Swabs - Primary Vaccination.	Acquisition of new H. influenzae* (HI) and S. pneumoniae (SP) strains, identified in the nasopharynx at each swab time point: pre-booster vaccination (11-13 months of age), M12 (14-16 months of age), M16 (18-20 months of age) and M21 (23-25 months of age). *Data presented only include results from samples confirmed as positive for H. influenzae / Non-typeable H. influenzae after differentiation from H. haemolyticus by Polymerase Chain Reaction (PCR) assay.	Prior to the booster dose (Month 9), 3 months after the booster dose (Month 12), 7 months after the booster dose (Month 16) and 12 months after the booster dose (Month 21)
Number of Subjects With Acquisition of New Streptococcus Pneumoniae Vaccine Serotypes (VS), Cross-reactive Serotypes (CRS) or Other Serotypes (OS) Identified in Nasopharyngeal Swabs - Primary Vaccination.	Acquisition of new S. pneumonia (SP) strains, identified in the nasopharynx at each swab time point: pre-booster vaccination (11-13 months of age), M12 (14-16 months of age), M16 (18-20 months of age) and M21 (23-25 months of age).	Prior to the booster dose (Month 9), 3 months after the booster dose (Month 12), 7 months after the booster dose (Month 16) and 12 months after the booster dose (Month 21)
Number of Subjects With Solicited Local Symptoms - Primary Vaccination	Solicited local symptoms assessed were pain, redness and swelling. Any was defined as any occurrence of the specified symptom regardless of intensity. Grade 3 pain was defined as cried when limb was moved/spontaneously painful. Grade 3 redness/swelling was defined as redness/swelling spreading beyond (>) 30 millimeters from injection site.	During the 4-day (Days 0-3) post-vaccination period following each dose and across doses
Number of Subjects With Solicited General Symptoms - Primary Vaccination	Solicited general symptoms assessed include drowsiness, fever (defined as rectal temperature ≥ 38.0°C), irritability, and loss of appetite. Any was defined as incidence of the specified symptom regardless of intensity. 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 activity. Grade 3 loss of appetite was defined as the subject not eating at all. Related symptom was defined as a general symptom assessed by the investigator as causally related to study vaccination.	During the 4-day (Days 0-3) post-vaccination period following each dose and across doses
Number of Subjects With Unsolicited Adverse Events (AEs) - Primary 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. "Any" is defined an incidence of an unsolicited AE regardless of intensity or relationship to study vaccination.	Within the 31-day (Days 0-30) post-primary vaccination
Number of Subjects With 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.	Throughout the entire study period (up to Month 21)
Number of Subjects With Solicited Local Symptoms -Booster Vaccination	Solicited local symptoms assessed were pain, redness and swelling. Any was defined as any occurrence of the specified symptom regardless of intensity. Grade 3 pain was defined as cried when limb was moved/spontaneously painful. Grade 3 redness/swelling was defined as redness/swelling > 30 millimeters from injection site.	During the 4-day (Days 0-3) post-vaccination period following booster dose
Number of Subjects With Solicited General Symptoms - Booster Vaccination.	Solicited general symptoms assessed include drowsiness, fever (defined as rectal temperature ≥ 38.0°C), irritability, and loss of appetite. Any was defined as incidence of the specified symptom regardless of intensity. 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 activity. Grade 3 loss of appetite was defined as the subject not eating at all. Related symptom was defined as a general symptom assessed by the investigator as causally related to study vaccination.	During the 4-day (Days 0-3) post-vaccination period following booster dose
Number of Subjects With Unsolicited Adverse Events (AEs) - Booster 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. "Any" was defined an incidence of an unsolicited AE regardless of intensity or relationship to study vaccination.	Within the 31-day (Days 0-30) after booster vaccination

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Publications and helpful links

General Publications

• van den Bergh MR, Spijkerman J, Francois N, Swinnen K, Borys D, Schuerman L, Veenhoven RH, Sanders EA. Immunogenicity, safety, and reactogenicity of the 10-valent pneumococcal nontypeable Haemophilus influenzae protein D conjugate vaccine and DTPa-IPV-Hib when coadministered as a 3-dose primary vaccination schedule in The Netherlands: a randomized controlled trial. Pediatr Infect Dis J. 2011 Sep;30(9):e170-8. doi: 10.1097/INF.0b013e31821a0614. Erratum In: Pediatr Infect Dis J. 2015 Aug;34(8):918. Dosage error in article text.
• van den Bergh MR, Spijkerman J, Swinnen KM, Francois NA, Pascal TG, Borys D, Schuerman L, Ijzerman EP, Bruin JP, van der Ende A, Veenhoven RH, Sanders EA. Effects of the 10-valent pneumococcal nontypeable Haemophilus influenzae protein D-conjugate vaccine on nasopharyngeal bacterial colonization in young children: a randomized controlled trial. Clin Infect Dis. 2013 Feb;56(3):e30-9. doi: 10.1093/cid/cis922. Epub 2012 Nov 1.
• van den Bergh MR, Spijkerman J, Francois N, Swinnen K, Borys D, Schuerman L, Veenhoven RH, Sanders EA. Immunogenicity, Safety and Reactogenicity of a Booster Dose of the 10-Valent Pneumococcal Nontypeable H. influenzae Protein D Conjugate Vaccine Coadministered With DTPa-IPV-Hib in Dutch Children: A Randomized Controlled Trial. Pediatr Infect Dis J. 2016 Jul;35(7):e206-19. doi: 10.1097/INF.0000000000001170.

Helpful Links

• Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2008
• Primary Completion (Actual): May 12, 2009
• Study Completion (Actual): December 1, 2010

Study Registration Dates

• First Submitted: March 21, 2008
• First Submitted That Met QC Criteria: April 1, 2008
• First Posted (Estimate): April 4, 2008

Study Record Updates

• Last Update Posted (Actual): June 26, 2019
• Last Update Submitted That Met QC Criteria: June 11, 2019
• Last Verified: June 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Streptococcal Infections; Physiological Effects of Drugs; Immunologic Factors; Heptavalent Pneumococcal Conjugate Vaccine
• Other Study ID Numbers: 110142; 111053; 2007-004002-26 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: IPD for this study will be made available via the Clinical Study Data Request site.
• IPD Sharing Time Frame: IPD is available via the Clinical Study Data Request site (click on the link provided below)
• IPD Sharing Access Criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Study Data/Documents

1. Individual Participant Data Set
   Information identifier: 110142
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register. The results of this study 110142 are summarised with study 111053 on GSK Clinical Study Register
2. Clinical Study Report
   Information identifier: 110142
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
3. Informed Consent Form
   Information identifier: 110142
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
4. Annotated Case Report Form
   Information identifier: 110142
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
5. Statistical Analysis Plan
   Information identifier: 110142
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
6. Dataset Specification
   Information identifier: 110142
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
7. Study Protocol
   Information identifier: 110142
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register