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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00652951
First received: March 21, 2008
Last updated: October 11, 2016
Last verified: October 2016
  Purpose
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 Intervention Phase
Infections, Streptococcal
Biological: GSK Biologicals´ Pneumococcal Conjugate Vaccine (GSK1024850A)
Biological: Infanrix™ hexa.
Biological: Pediacel™
Biological: Prevenar™
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single Blind (Subject)
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.

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • 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, aka 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) Assay; calculated, expressed as geometric mean concentrations (GMCs) and tabulated. The seropositivity cut-off for the assay was >= 0.05 microgram per millilitre (microg/mL).

  • Antibody concentration against protein D (PD) - Primary vaccination [ Time Frame: At Month 3, aka one month after the administration of the third dose of pneumococcal conjugate vaccine ]
    Anti-PD antibody concentrations were calculated, expressed as geometric mean concentrations (GMCs) and tabulated. The seropositivity cut-off for the assay was >= 100 Enzyme-Linked ImmunoSobent Assay (ELISA) units per millilitre (EL.U/mL).


Secondary Outcome Measures:
  • 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: One month after the administration of the third vaccine dose ]
    A seropositive subject was a subject whose antibody concentration was greater than or equal to the cut-off value >= 0.05 µg/mL

  • Opsonophagocytic activity (OPA) titers against pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F - Primary vaccination [ Time Frame: One month after the administration of the third vaccine dose ]
    A seropositive subject was a subject whose antibody titers were greater than or equal to the cut-off value >= 8

  • 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: One month after the administration of the third vaccine dose ]
    A seropositive subject was a subject whose antibody concentration was greater than or equal to the cut-off value >=0.05 µg/mL.

  • Antibody concentrations against pneumococcal cross-reactive serotypes 6A and 19A (Anti-6A and 19A) - Primary vaccination [ Time Frame: One month after the administration of the third vaccine dose ]
    A seropositive subject was a subject whose antibody concentration was greater than or equal to the cut-off value >=0.05 µg/mL.

  • Opsonophagocytic activity (OPA) titers against pneumococcal cross-reactive serotypes 6A and 19A - Primary vaccination. [ Time Frame: One month after the administration of the third vaccine dose ]
    A seropositive subject was a subject whose antibody titers were greater than or equal to the cut-off value >= 8

  • Concentrations of antibodies against diphtheria and tetanus toxoids (anti-D and T) - Primary vaccination [ Time Frame: One month after the administration of the third vaccine dose ]
    A seroprotected subject was a subject whose antibody concentration was greater than or equal to the cut-off value >= 0.1 IU/mL

  • Anti-polyribosyl-ribitol phosphate (anti-PRP) antibody concentrations - Primary vaccination [ Time Frame: One month after the administration of the third vaccine dose ]
    A seroprotected subject was a subject whose antibody concentration was greater than or equal to the cut-off value >= 0.15 µg/mL and >= 1.0 µg/mL

  • Anti-pertussis toxoid (anti-PT), anti-filamentous haemagglutinin (anti-FHA) and anti-pertactin (anti-PRN) antibody concentrations - Primary vaccination [ Time Frame: One month after the administration of the third vaccine dose ]
    A seropositive subject was a subject whose antibody concentration was greater than or equal to the cut-off value >=5 EL.U/mL.

  • Anti-hepatitis B surface antigen (anti-HBs) antibody concentrations - Primary vaccination. [ Time Frame: One month after the administration of the third vaccine dose ]
    A seroprotected subject was a subject whose antibody ChemiLuminescence ImmunoAssay (CLIA) concentration was greater than or equal to the cut-off value >=10 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.

  • Anti-polio types 1, 2 and 3 titers - Primary vaccination. [ Time Frame: Prior to, 1 and 12 montOne month after the administration of the third vaccine dose ]
    A seroprotected subject was a subject whose antibody titers were greater than or equal to the cut-off value >= 8.

  • 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 (PRE) to and one month after (POST) the administration of the booster dose ]
    A seropositive subject was a subject whose antibody concentration was greater than or equal to the cut-off value >= 0.05 µg/mL.

  • 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 (PRE) to and one month after (POST) the administration of the booster dose ]
    A seropositive subject was a subject whose antibody concentration was greater than or equal to the cut-off value >= 0.05 µg/mL

  • Opsonophagocytic activity (OPA) titers against pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F - Booster vaccination [ Time Frame: Prior (PRE) to and one month after (POST) the administration of the booster dose ]
    A seropositive subject was a subject whose antibody titers were greater than or equal to the cut-off value >= 8

  • 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 (PRE) to and one month after (POST) the administration of the booster dose ]
    A seropositive subject was a subject whose antibody concentration was greater than or equal to the cut-off value >= 0.05 µg/mL.

  • Antibody concentrations against pneumococcal cross-reactive serotypes 6A and 19A (Anti-6A and 19A) - Booster vaccination [ Time Frame: Prior (PRE) to and one month after (POST) the administration of the booster dose ]
    A seropositive subject was a subject whose antibody concentration was greater than or equal to the cut-off value >= 0.05 µg/mL.

  • Opsonophagocytic activity (OPA) titers against pneumococcal cross-reactive serotypes 6A and 19A - Booster vaccination. [ Time Frame: A seropositive subject was a subject whose antibody titers were greater than or equal to the cut-off value >= 8 ]
    Prior (PRE) to and one month after (POST) the administration of the booster dose

  • Concentrations of antibodies against protein D (Anti-PD) - Booster vaccination. [ Time Frame: Prior (PRE) to and one month after (POST) the administration of the booster dose ]
    A seropositive subject was a subject whose antibody concentration was greater than or equal to the cut-off value >= 100 EL.U/mL.

  • Concentrations of antibodies against diphtheria and tetanus toxoids (anti-D and T) - Booster vaccination. [ Time Frame: Prior (PRE) to and one month after (POST) the administration of the booster dose ]
    A seroprotected subject was a subject whose antibody concentration was greater than or equal to the cut-off value >= 0.1 IU/mL.

  • Anti-polyribosyl-ribitol phosphate (anti-PRP) antibody concentrations - Booster vaccination [ Time Frame: Prior (PRE) to and one month after (POST) the administration of the booster dose ]
    A seroprotected subject was a subject whose antibody concentration was greater than or equal to the cut-off value >= 0.15 µg/mL and >= 1.0 µg/mL.

  • Anti-pertussis toxoid (anti-PT), anti-filamentous haemagglutinin (anti-FHA) and anti-pertactin (anti-PRN) antibody concentrations - Booster vaccination. [ Time Frame: Prior (PRE) to and one month after (POST) the administration of the booster dose ]
    A seropositive subject was a subject whose antibody concentration was greater than or equal to the cut-off value >=5 EL.U/mL.

  • Anti-hepatitis B surface antigen (anti-HBs) antibody concentrations - Booster vaccination. [ Time Frame: Prior (PRE) to and one month after (POST) the administration of the booster dose ]
    A seroprotected subject was a subject whose antibody ChemiLuminescence ImmunoAssay (CLIA) concentration was greater than or equal to the cut-off value >= 10 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.

  • Anti-polio types 1, 2 and 3 titers - Booster vaccination. [ Time Frame: Prior (PRE) to and one month after (POST) the administration of the booster dose ]
    A seroprotected subject was a subject whose antibody titers were greater than or equal to the cut-off value >= 8.

  • 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 (POST) 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).

  • 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: 12 months after the administration of the booster dose (at 23-25 months of age, M12) ]
    A seropositive subject was a subject whose antibody concentration was greater than or equal to the cut-off value >= 0.05 µg/mL.

  • 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: 12 months after the administration of the booster dose (at 23-25 months of age, M12) ]
    A seropositive subject was a subject whose antibody concentration was greater than or equal to the cut-off value >= 0.05 µg/mL.

  • 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: 12 months after the administration of the booster dose (at 23-25 months of age, M12) ]
    A seropositive subject was a subject whose antibody titers were greater than or equal to the cut-off value >= 8.

  • Occurrence of serious adverse events [ Time Frame: Throughout the entire study period. ]

Enrollment: 780
Study Start Date: April 2008
Study Completion Date: May 2009
Primary Completion Date: May 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Group A Biological: GSK Biologicals´ Pneumococcal Conjugate Vaccine (GSK1024850A)
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: Group B Biological: GSK Biologicals´ Pneumococcal Conjugate Vaccine (GSK1024850A)
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: Group C 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

  Eligibility

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00652951

Locations
Netherlands
GSK Investigational Site
Hoofddorp, Netherlands, 2134 TM
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

Additional Information:
Publications:
Study Data/Documents: Individual Participant Data Set  This link exits the ClinicalTrials.gov site
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  This link exits the ClinicalTrials.gov site
Identifier: 110142
For additional information about this study please refer to the GSK Clinical Study Register
Informed Consent Form  This link exits the ClinicalTrials.gov site
Identifier: 110142
For additional information about this study please refer to the GSK Clinical Study Register
Annotated Case Report Form  This link exits the ClinicalTrials.gov site
Identifier: 110142
For additional information about this study please refer to the GSK Clinical Study Register
Statistical Analysis Plan  This link exits the ClinicalTrials.gov site
Identifier: 110142
For additional information about this study please refer to the GSK Clinical Study Register
Dataset Specification  This link exits the ClinicalTrials.gov site
Identifier: 110142
For additional information about this study please refer to the GSK Clinical Study Register
Study Protocol  This link exits the ClinicalTrials.gov site
Identifier: 110142
For additional information about this study please refer to the GSK Clinical Study Register

Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT00652951     History of Changes
Other Study ID Numbers: 110142  111053 
Study First Received: March 21, 2008
Last Updated: October 11, 2016
Individual Participant Data  
Plan to Share IPD: Yes
Plan Description: Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.

Additional relevant MeSH terms:
Streptococcal Infections
Gram-Positive Bacterial Infections
Bacterial Infections
Vaccines
Heptavalent Pneumococcal Conjugate Vaccine
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on February 24, 2017