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

• ClinicalTrials.gov Identifier: NCT00652951
• Recruitment Status: Completed
• First Posted: April 4, 2008
• Results First Posted: December 14, 2018
• Last Update Posted: June 26, 2019
• Sponsor: GlaxoSmithKline
• Information provided by (Responsible Party): GlaxoSmithKline

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Infections, Streptococcal	Biological: GSK Biologicals´ Pneumococcal Conjugate Vaccine GSK1024850A (Synflorix™); Biological: Infanrix™ hexa.; Biological: Pediacel™; Biological: Prevenar™	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 780 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Participant)
• Primary Purpose: Prevention
• Official Title: Non-inferiority of Co-administration of GSK Biologicals'Pneumococcal Conjugate Vaccine GSK1024850A With DTPa-IPV-Hib Versus Co-administration With DTPa-HBV-IPV/Hib.
• Actual Study Start Date: April 1, 2008
• Actual Primary Completion Date: May 12, 2009
• Actual Study Completion Date: December 1, 2010

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. 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 [ Time Frame: At Month 3, one month after the administration of the third dose of pneumococcal conjugate vaccine ]
   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.
2. Antibody Concentration Against Protein D (PD) - Primary Vaccination [ Time Frame: At Month 3, one month after the administration of the third dose of pneumococcal conjugate vaccine ]
   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.

Secondary Outcome Measures :

1. 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 [ Time Frame: At Month 3, one month after the administration of the third vaccine 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.
2. Opsonophagocytic Activity (OPA) Titers Against Pneumococcal Serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F - Primary Vaccination [ Time Frame: At Month 3, one month after the administration of the third vaccine dose ]
   Titers were presented as geometric mean titers (GMTs), for the seropositivity cut-off value of 8.
3. Number of Subjects With Antibody Concentrations Against Pneumococcal Cross-reactive Serotypes 6A and 19A (Anti-6A and 19A) ≥ 0.2 μg/mL - Primary Vaccination. [ Time Frame: At Month 3, one month after the administration of the third vaccine 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.
4. Antibody Concentrations Against Pneumococcal Cross-reactive Serotypes 6A and 19A (Anti-6A and 19A) - Primary Vaccination [ Time Frame: At Month 3, one month after the administration of the third vaccine dose ]
   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.
5. Opsonophagocytic Activity (OPA) Titers Against Pneumococcal Cross-reactive Serotypes 6A and 19A - Primary Vaccination. [ Time Frame: At Month 3, one month after the administration of the third vaccine dose ]
   Titers were presented as geometric mean titers (GMTs), for the seropositivity cut-off of 8.
6. Concentrations of Antibodies Against Diphtheria and Tetanus Toxoids (Anti-D and T) - Primary Vaccination [ Time Frame: At Month 3, one month after the administration of the third vaccine dose ]
   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.
7. Anti-polyribosyl-ribitol Phosphate (Anti-PRP) Antibody Concentrations - Primary Vaccination [ Time Frame: At Month 3, one month after the administration of the third vaccine dose ]
   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.
8. Anti-pertussis Toxoid (Anti-PT), Anti-filamentous Haemagglutinin (Anti-FHA) and Anti-pertactin (Anti-PRN) Antibody Concentrations - Primary Vaccination [ Time Frame: At Month 3, one month after the administration of the third vaccine dose ]
   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.
9. Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentrations - Primary Vaccination. [ Time Frame: At Month 3, one month after the administration of the third vaccine dose ]
   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.
10. Anti-polio Types 1, 2 and 3 Titers - Primary Vaccination. [ Time Frame: At Month 3, one month after the administration of the third vaccine dose ]
    Anti-polio 1, -polio 2, -polio 3 antibody titers were presented as geometric mean titers (GMTs), for the seropositivity cut-off value ≥ 8.
11. 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 [ Time Frame: Prior to (Month 9) and one month after the administration of the booster dose (Month 10) ]
    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.
12. 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 [ Time Frame: Prior (Month 9) to and one month after the administration of the booster dose (Month 10) ]
    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.
13. Opsonophagocytic Activity (OPA) Titers Against Pneumococcal Serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F - Booster Vaccination [ Time Frame: Prior (Month 9) to and one month after the administration of the booster dose(Month 10) ]
    Titers were presented as geometric mean titers (GMTs), for the seropositivity cut-off value of 8.
14. Number of Subjects With Antibody Concentrations Against Pneumococcal Cross-reactive Serotypes 6A and 19A (Anti-6A and 19A) ≥ 0.2 μg/mL - Booster Vaccination. [ Time Frame: Prior (Month 9) to and one month after the administration of the booster dose(Month 10) ]
    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.
15. Antibody Concentrations Against Pneumococcal Cross-reactive Serotypes 6A and 19A (Anti-6A and 19A) - Booster Vaccination [ Time Frame: Prior (Month 9) to and one month after the administration of the booster dose (Month 10) ]
    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.
16. Opsonophagocytic Activity (OPA) Titers Against Pneumococcal Cross-reactive Serotypes 6A and 19A - Booster Vaccination. [ Time Frame: Prior to (Month 9) and one month after the administration of the booster dose (Month 10) ]
    Titers were presented as geometric mean titers (GMTs), for the seropositivity cut-off value of 8.
17. Concentrations of Antibodies Against Protein D (Anti-PD) - Booster Vaccination. [ Time Frame: Prior (Month 9) to and one month after (Month 10) the administration of the 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.
18. Concentrations of Antibodies Against Diphtheria and Tetanus Toxoids (Anti-D and T) - Booster Vaccination. [ Time Frame: Prior to (Month 9) and one month after (Month 10) the administration of the booster dose ]
    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.
19. Anti-polyribosyl-ribitol Phosphate (Anti-PRP) Antibody Concentrations - Booster Vaccination [ Time Frame: Prior to (Month 9) and one month after (Month 10) the administration of the booster dose ]
    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.
20. Anti-pertussis Toxoid (Anti-PT), Anti-filamentous Haemagglutinin (Anti-FHA) and Anti-pertactin (Anti-PRN) Antibody Concentrations - Booster Vaccination. [ Time Frame: Prior (Month 9) to and one month after (Month 10) the administration of the booster dose ]
    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.
21. Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentrations - Booster Vaccination. [ Time Frame: Prior (Month 9) to and one month after (Month 10) the administration of the booster dose ]
    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.
22. Anti-polio Types 1, 2 and 3 Titers - Booster Vaccination. [ Time Frame: Prior (Month 9) to and one month after (Month 10) the administration of the booster dose ]
    Anti-polio 1, -polio 2, -polio 3 antibody titers were presented as geometric mean titers (GMTs), for the seropositivity cut-off value ≥ 8.
23. Number of Subjects With Booster Vaccine Response Against Pertussis Toxoid (PT), Filamentous Haemagglutinin (FHA) and Pertactin (PRN) Antibodies - Booster Vaccination. [ Time Frame: One month after (Month 10) the administration of the booster dose ]
    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).
24. 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. [ Time Frame: At Month 21, 12 months after the administration of the booster dose (at 23-25 months of age) ]
    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.
25. 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. [ Time Frame: At Month 21, 12 months after the administration of the booster dose (at 23-25 months of age) ]
    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.
26. Opsonophagocytic Activity (OPA) Titers Against Pneumococcal Serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F - 12 Months After Booster Dose. [ Time Frame: At Month 21, 12 months after the administration of the booster dose (at 23-25 months of age) ]
    Titers were presented as geometric mean titers (GMTs), for the seropositivity cut-off value of 8.
27. 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. [ Time Frame: At Month 21, 12 months after the administration of the booster dose (at 23-25 months of age) ]
    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.
28. Antibody Concentrations Against Pneumococcal Cross-reactive Serotypes 6A and 19A (Anti-6A and 19A) - 12 Months After Booster Dose. [ Time Frame: At Month 21, 12 months after the administration of the booster dose (at 23-25 months of age) ]
    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.
29. Opsonophagocytic Activity (OPA) Titers Against Pneumococcal Cross-reactive Serotypes 6A and 19A - 12 Months After Booster Dose. [ Time Frame: At Month 21, 12 months after the administration of the booster dose (at 23-25 months of age) ]
    Titers were presented as geometric mean titers (GMTs), for the seropositivity cut-off value of 8.
30. Concentrations of Antibodies Against Protein D (Anti-PD) - 12 Months After Booster Dose. [ Time Frame: At Month 21, 12 months after the administration of the booster dose (at 23-25 months of age) ]
    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.
31. Number of Subjects With Positive Cultures of Haemophilus Influenzae and/or Streptococcus Pneumoniae in the Nasopharynx - Primary Vaccination. [ Time Frame: 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) ]
    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.
32. 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. [ Time Frame: 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) ]
    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).
33. Number of Subjects With Acquisition of New Streptococcus Pneumoniae and Haemophilus Influenzae Strains Identified in Nasopharyngeal Swabs - Primary Vaccination. [ Time Frame: 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) ]
    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.
34. 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. [ Time Frame: 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) ]
    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).
35. Number of Subjects With Solicited Local Symptoms - Primary Vaccination [ Time Frame: During the 4-day (Days 0-3) post-vaccination period following each dose and across doses ]
    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.
36. Number of Subjects With Solicited General Symptoms - Primary Vaccination [ Time Frame: During the 4-day (Days 0-3) post-vaccination period following each dose and across doses ]
    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.
37. Number of Subjects With Unsolicited Adverse Events (AEs) - Primary Vaccination. [ Time Frame: Within the 31-day (Days 0-30) post-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.
38. Number of Subjects With Serious Adverse Events (SAEs) [ Time Frame: Throughout the entire study period (up to Month 21) ]
    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.
39. Number of Subjects With Solicited Local Symptoms -Booster Vaccination [ Time Frame: During the 4-day (Days 0-3) post-vaccination period following booster dose ]
    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.
40. Number of Subjects With Solicited General Symptoms - Booster Vaccination. [ Time Frame: During the 4-day (Days 0-3) post-vaccination period following booster dose ]
    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.
41. Number of Subjects With Unsolicited Adverse Events (AEs) - Booster Vaccination. [ Time Frame: Within the 31-day (Days 0-30) after 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.

Eligibility Criteria

• Ages Eligible for Study: 6 Weeks to 12 Weeks (Child)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

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.

Contacts and Locations

Locations

Netherlands

GSK Investigational Site

Hoofddorp, Netherlands, 2134 TM

Sponsors and Collaborators

GlaxoSmithKline

Investigators

• Study Director: GSK Clinical Trials; GlaxoSmithKline

More Information

Additional Information:

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Study Data/Documents: Individual Participant Data Set 

Identifier: 110142
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

Clinical Study Report 

Identifier: 110142
For additional information about this study please refer to the GSK Clinical Study Register

Informed Consent Form 

Identifier: 110142
For additional information about this study please refer to the GSK Clinical Study Register

Annotated Case Report Form 

Identifier: 110142
For additional information about this study please refer to the GSK Clinical Study Register

Statistical Analysis Plan 

Identifier: 110142
For additional information about this study please refer to the GSK Clinical Study Register

Dataset Specification 

Identifier: 110142
For additional information about this study please refer to the GSK Clinical Study Register

Study Protocol 

Identifier: 110142
For additional information about this study please refer to the GSK Clinical Study Register

Publications:

van den Bergh MR, Spijkerman J, François 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, François 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, François 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.

• Responsible Party: GlaxoSmithKline
• ClinicalTrials.gov Identifier: NCT00652951
• Other Study ID Numbers: 110142; 111053; 2007-004002-26 ( EudraCT Number )
• First Posted: April 4, 2008
• Results First Posted: December 14, 2018
• Last Update Posted: June 26, 2019
• Last Verified: June 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: IPD for this study will be made available via the Clinical Study Data Request site.
• Supporting Materials: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (CSR)
• Time Frame: IPD is available via the Clinical Study Data Request site (click on the link provided below)
• 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.
• URL: http://clinicalstudydatarequest.com

Additional relevant MeSH terms:

Streptococcal Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Heptavalent Pneumococcal Conjugate Vaccine; Immunologic Factors; Physiological Effects of Drugs