COMPAS (Clinical Otitis Media & Pneumonia Study): Pneumonia & Acute Otitis Media (AOM ) Efficacy Study of the Pneumococcal Conjugate Vaccine

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00466947
First received: April 26, 2007
Last updated: June 20, 2013
Last verified: June 2013
  Purpose

This is a study in a large number of healthy children less than 3 years old to measure the efficacy of GlaxoSmithKline (GSK) Biologicals' 10-valent pneumococcal conjugate candidate vaccine (Synflorix vaccine, or GSK1024850A) to prevent cases of pneumonia (lung infection) likely caused by bacteria (Streptococcus pneumoniae and Haemophilus influenzae) or cases of otitis media (ear infection) in children under 3 years old.


Condition Intervention Phase
Pneumonia & AOM Caused by S. Pneumoniae & H. Influenzae
Biological: Pneumococcal conjugate vaccine GSK1024850A
Biological: Havrix
Biological: Engerix-B
Biological: Infanrix hexa
Biological: GSK Biologicals' DTPa-IPV/Hib vaccine
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Caregiver, Investigator)
Primary Purpose: Prevention
Official Title: COMPAS: A Phase III Study to Demonstrate Efficacy of GSK Biologicals' 10-valent Pneumococcal Vaccine (GSK1024850A) Against Community Acquired Pneumonia and Acute Otitis Media

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Number of Subjects With a First Episode Reported of Bacterial Community Acquired Pneumoniae (B-CAP) [ Time Frame: Any time from 2 weeks after Dose 3 up to 31 August 2010 ] [ Designated as safety issue: No ]

    A B-CAP episode was defined as a radiologically confirmed community acquired pneumoniae (CAP) episode with either alveolar consolidation/pleural effusion on the chest X-ray (CXR) or with non-alveolar infiltrates but with C reactive protein (CRP) higher than or equal to (>=) 40 milligrams per liter (mg/L). The results are presented for data lock point for the primary outcome analysis (31 August 2010), which was performed, as per protocol, when at least 535 first B-CAP episodes were reported from 2 weeks after the third vaccination dose.

    After analysis on primary outcome was performed, re-monitoring activities revealed ICF issues for some subjects. Therefore, a sensitivity analysis excluding 144 subjects was performed. This analysis confirmed the validity of the results for primary outcome.



Secondary Outcome Measures:
  • Number of Subjects With Serious Adverse Events (SAEs) [ Time Frame: Throughout the study (Month 0 to Month 22-25) ] [ Designated as safety issue: No ]
    SAEs assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization, result in disability/incapacity or are a congenital anomaly/birth defect in the offspring of a study subject.

  • Number of Subjects With Any Unsolicited Adverse Event (AE), in the Panama Subset [ Time Frame: Throughout the study (Month 0 to Month 22-25) ] [ Designated as safety issue: No ]
    An unsolicited AE is any AE (i.e. any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with use of a medicinal product, whether or not considered related to the medicinal product) reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for solicited symptoms. The Panama Subset included all subjects from Panama.

  • Number of Subjects With Solicited Local Symptoms Post Primary Vaccination in the Immunogenicity and Tolerability Subset [ Time Frame: Within the 4-days (Days 0-3) follow-up period across the 3 doses of the primary study vaccine administration ] [ Designated as safety issue: No ]
    Assessed symptoms were redness, swelling and pain. The Immunogenicity and Tolerability Subset included 500 subjects coming from Argentina and Panama respectively. This outcome measure concerns solely subjects from the Synflorix Group.

  • Number of Subjects With Solicited Local Symptoms Post Booster Vaccination in the Immunogenicity and Tolerability Subset [ Time Frame: Within the 4-days (Days 0-3) follow-up period following the booster vaccine administration ] [ Designated as safety issue: No ]
    Assessed symptoms were redness, swelling and pain. The Immunogenicity and Tolerability Subset included 500 subjects coming from Argentina and Panama respectively. This outcome measure concerns solely subjects from the Synflorix Group.

  • Number of Subjects With Solicited Local Symptoms Post Primary Vaccination in the Immunogenicity and Tolerability Subset [ Time Frame: Within the 4-days (Days 0-3) follow-up period across the 3 doses of the primary study vaccine administration ] [ Designated as safety issue: No ]
    Assessed symptoms were redness, swelling and pain. The Immunogenicity and Tolerability Subset included 500 subjects coming from Argentina and Panama respectively. This outcome measure concerns solely subjects from the Control Group.

  • Number of Subjects With Solicited Local Symptoms Post Booster Vaccination in the Immunogenicity and Tolerability Subset, for the Control Group [ Time Frame: Within the 4-days (Days 0-3) follow-up period following the booster vaccine administration. ] [ Designated as safety issue: No ]
    Assessed symptoms were redness, swelling and pain. The Immunogenicity and Safety Tolerability Subset included 500 subjects coming from Argentina and Panama respectively. This outcome measure concerns solely subjects from the Control Group.

  • Number of Subjects With Solicited General Symptoms Post Primary Vaccination in the Immunogenicity and Tolerability Subset [ Time Frame: Within the 4-days (Days 0-3) follow-up period across the 3 doses of the primary study vaccine administration ] [ Designated as safety issue: No ]
    Assessed symptoms were fever (defined as rectal temperature equal or higher than [>=] 38 degrees Celsius [°C]). irritability/fussiness, drowsiness, and loss of appetite. The Immunogenicity and Tolerability Subset included 500 subjects coming from Argentina and Panama respectively.

  • Number of Subjects With Solicited General Symptoms Post Booster Vaccination in the Immunogenicity and Tolerability Subset [ Time Frame: Within the 4-days (Days 0-3) follow-up period following the booster vaccine administration ] [ Designated as safety issue: No ]
    Assessed symptoms were fever (defined as rectal temperature equal or higher than [>=] 38 degrees Celsius [°C]). irritability/fussiness, drowsiness, and loss of appetite. The Immunogenicity and Tolerability Subset included 500 subjects coming from Argentina and Panama respectively.

  • Number of Subjects With a First Episode Reported of Clinically Confirmed Acute Otitis Media (AOM) (C-AOM), in the Panama Subset [ Time Frame: Any time from 2 weeks after Dose 3 to study end at Month 22-25 ] [ Designated as safety issue: No ]
    The Panama Subset contained all subjects enrolled in Panama.

  • Number of Subjects With a First Episode Reported of Community Acquired Pneumoniae (CAP) With Alveolar Consolidation or Pleural Effusion on the Chest X-ray (CXR) (C-CAP) [ Time Frame: Any time from 2 weeks post primary vaccination Dose 3 to study end at Month 22-25 ] [ Designated as safety issue: No ]
    CXR alveolar consolidation was defined as CXR with a dense, often homogeneous, confluent alveolar infiltrate that could encompass an entire lobe or segment, or a fluffy, mass-like, cloud-like density that erased heart and diaphragm borders (silhouette sign) and that often contained air bronchograms. CXR pleural effusion was defined as a fluid collecting in the pleural space around the lung, seen radiologically as a dense rim (the same density as the chest-wall muscles) interposed between the lung and the ribs.

  • Number of Subjects With a First Episode Reported of Bacteriologically Confirmed Acute Otitis Media (AOM) (B-AOM) Due to Any Bacterial Pathogen, in the Panama Subset [ Time Frame: Any time from 2 weeks post primary vaccination Dose 3 to study end at Month 22-25 ] [ Designated as safety issue: No ]
    The Panama Subset contained all subjects enrolled in Panama.

  • Number of Subjects With a First Episode Reported of Bacteriologically Confirmed Acute Otitis Media (AOM) (B-AOM) Due to Streptococcus Pneumoniae (S. pn.) Vaccine Serotypes, in the Panama Subset [ Time Frame: Any time from 2 weeks post primary vaccination Dose 3 to study end at Month 22-25 ] [ Designated as safety issue: No ]
    The 10 pneumococcal S. pneumoniae vaccine serotypes assessed for this outcome measure were the serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F. The Panama Subset contained all subjects enrolled in Panama.

  • Number of Subjects With a First Episode Reported of Bacteriologically Confirmed Acute Otitis Media (AOM) (B-AOM) Due to Streptococcus Pneumoniae (S. pn.) Cross-reactive Serotypes, in the Panama Subset. [ Time Frame: Any time from 2 weeks post primary vaccination Dose 3 to study end at Month 22-25 ] [ Designated as safety issue: No ]
    The S. pn. cross-reactive serotypes assessed for this outcome measure were the serotypes 6A, 18B, 19A and 23A. The Panama Subset contained all subjects enrolled in Panama.

  • Number of Subjects With a First Episode Reported of Bacteriologically Confirmed Acute Otitis Media (AOM) (B-AOM) Due to Other Pneumococcal Serotypes, in the Panama Subset. [ Time Frame: Any time from 2 weeks post primary vaccination Dose 3 to study end at Month 22-25 ] [ Designated as safety issue: No ]
    Other pneumococcal serotypes were defined for this outcome measures as non-Streptococcus pneumoniae vaccine and cross-reactive serotypes. The Panama Subset contained all subjects enrolled in Panama.

  • Number of Subjects With a First Episode Reported of Bacteriologically Confirmed Acute Otitis Media (AOM) (B-AOM) Due to Haemophilus Influenzae (H. Influenzae), in the Panama Subset [ Time Frame: Any time from 2 weeks post primary vaccination Dose 3 to study end at Month 22-25 ] [ Designated as safety issue: No ]
    The Panama Subset contained all subjects enrolled in Panama.

  • Number of Subjects With a First Episode Reported of Bacteriologically Confirmed Acute Otitis Media (AOM) (B-AOM) Due to Non-typeable Haemophilus Influenzae (H. Influenzae), in the Panama Subset [ Time Frame: Any time from 2 weeks post primary vaccination Dose 3 to study end at Month 22-25 ] [ Designated as safety issue: No ]
    The Panama Subset contained all subjects enrolled in Panama

  • Number of Subjects With a First Episode Reported of Bacteriologically Confirmed Acute Otitis Media (AOM) (B-AOM) Due to Other AOM Pathogens, in the Panama Subset [ Time Frame: Any time from 2 weeks post primary vaccination Dose 3 to study end at Month 22-25 ] [ Designated as safety issue: No ]
    Other pathogens assessed included among others Moraxella catarrhalis, Group A streptococci, and Staphyloccus aureus. The Panama Subset contained all subjects enrolled in Panama.

  • Number of Subjects With a First Episode Reported of Community Acquired Pneumoniae (CAP) With Alveolar Consolidation or Pleural Effusion on the Chest X-ray (CXR) (C-CAP) With Positive Respiratory Viral Test (RVT) [ Time Frame: Any time from 2 weeks post primary vaccination Dose 3 to study end at Month 22-25 ] [ Designated as safety issue: No ]
    A CXR with consolidation was defined as a CXR with a dense, often homogeneous, confluent alveolar infiltrate that could encompass an entire lobe or segment, or a fluffy, mass-like, cloud-like density that erased heart and diaphragm borders (silhouette sign) and that often contained air bronchograms. Pleural effusion was defined as a fluid collecting in the pleural space around the lung, seen radiologically as a dense rim (the same density as the chest-wall muscles) interposed between the lung and the ribs.

  • Number of Subjects With a First Episode Reported of Community Acquired Pneumoniae (CAP) With Any Abnormal CXR With Positive Respiratory Viral Test (RVT) [ Time Frame: Any time from 2 weeks post primary vaccination Dose 3 to study end at Month 22-25 ] [ Designated as safety issue: No ]
    An "abnormal CXR" was defined as a CXR with either consolidation, pleural effusion and/or abnormal pulmonary alveolar or non-alveolar infiltrates on the digital CXR image. CXR with consolidation was defined as a CXR with a dense, often homogeneous, confluent alveolar infiltrate that could encompass an entire lobe or segment, or a fluffy, mass-like, cloud-like density that erased heart and diaphragm borders (silhouette sign) and that often contained air bronchograms. Pleural effusion was defined as a fluid collecting in the pleural space around the lung, seen radiologically as a dense rim (the same density as the chest-wall muscles) interposed between the lung and the ribs.

  • Number of Subjects With a First Episode Reported of Bacterial Community Acquired Pneumoniae (B-CAP) With Positive Respiratory Viral Test (RVT). [ Time Frame: Any time from 2 weeks post primary vaccination Dose 3 to study end at Month 22-25 ] [ Designated as safety issue: No ]
  • Number of Subjects With a First Episode Reported of Suspected Community Acquired Pneumoniae (CAP) (S-CAP) [ Time Frame: Any time from 2 weeks post primary vaccination Dose 3 to study end at Month 22-25 ] [ Designated as safety issue: No ]
    An episode of S-CAP involved either any subject who was referred to have a chest X-ray (CXR) performed as part of the clinical assessment of a febrile syndrome or an acute respiratory infection (ARI), or a hospitalized child who had a CXR performed within 2 days prior to, or within the first 3 days after hospital admission, as part of the clinical assessment of a febrile syndrome or an ARI.

  • Number of Subjects With a First Episode Reported of Community Acquired Pneumoniae (CAP) With Any Abnormal Chest X-ray (CXR) [ Time Frame: Any time from 2 weeks post primary vaccination Dose 3 to study end at Month 22-25 ] [ Designated as safety issue: No ]
    An "abnormal CXR" was defined as a CXR with either consolidation, pleural effusion and/or abnormal pulmonary alveolar or non-alveolar infiltrates on the digital CXR image. CXR with consolidation was defined as a CXR with a dense, often homogeneous, confluent alveolar infiltrate that could encompass an entire lobe or segment, or a fluffy, mass-like, cloud-like density that erased heart and diaphragm borders (silhouette sign) and that often contained air bronchograms. Pleural effusion was defined as a fluid collecting in the pleural space around the lung, seen radiologically as a dense rim (the same density as the chest-wall muscles) interposed between the lung and the ribs.

  • Number of Subjects With a First Episode Reported of Suspected Community Acquired Pneumoniae (CAP) (S-CAP) With C Reactive Protein (CRP) >= Cut-off, Regardless of Chest X-ray (CXR) Reading [ Time Frame: Any time from 2 weeks post primary vaccination Dose 3 to study end at Month 22-25 ] [ Designated as safety issue: No ]
    A case of S-CAP involved either any subject who was referred to have a CXR performed as part of the clinical assessment of a febrile syndrome or an acute respiratory infection (ARI), or a hospitalized child who had a CXR performed within 2 days prior to, or within the first 3 days after hospital admission, as part of the clinical assessment of a febrile syndrome or an ARI. CRP cut-off values applied for this outcome measure were 40 milligrams per liter (mg/L), 80 mg/L, and 120 mg/L.

  • Number of Subjects With a First Episode Reported of CAP With Either Alveolar Consolidation/Pleural Effusion on Chest X-ray (CXR) (C-CAP) or With Non-alveolar Infiltrates (NAI-CAP) But With C Reactive Protein (CRP) >= Cut-off. [ Time Frame: Any time from 2 weeks post primary vaccination Dose 3 to study end at Month 22-25 ] [ Designated as safety issue: No ]
    CRP cut-off values applied for this outcome measure were 80 milligrams per liter (mg/L), and 120 mg/L.

  • Number of Subjects With a First Episode Reported of Vaccine-type Invasive Pneumococcal Disease (VT-IPD). [ Time Frame: Any time from 2 weeks post primary vaccination Dose 3 to study end at Month 22-25 ] [ Designated as safety issue: No ]
    A VT-IPD was defined as a bacteriologically culture confirmed invasive pneumococcal disease case caused by any of the 10 pneumococcal Streptococcus pneumoniae vaccine serotypes. The 10 pneumococcal S. pneumoniae vaccine serotypes assessed for this outcome measure were the serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F.

  • Number of Subjects With a First Episode Reported of a Bacteriologically Confirmed Invasive Pneumococcal Disease (Bact.-Conf. ID). [ Time Frame: Any time from 2 weeks post primary vaccination Dose 3 to study end at Month 22-25 ] [ Designated as safety issue: No ]
    A Bact.-conf. ID was defined as a bacteriologically culture confirmed invasive pneumococcal disease (ID) cases due to any of the 10 Streptococcus pneumoniae vaccine serotypes as identified through positive culture. The 10 pneumococcal S. pneumoniae vaccine serotypes assessed for this outcome measure were the serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F.

  • Number of Subjects With a First Episode Reported of Pneumococcal Invasive Disease (Pneumococcal ID) [ Time Frame: Any time from 2 weeks post primary vaccination Dose 3 to study end at Month 22-25 ] [ Designated as safety issue: No ]
    A Pneumococcal ID was defined as a bacteriologically culture confirmed invasive pneumococcal disease (ID) cases due to any of the 10 Streptococcus pneumoniae vaccine serotypes. The 10 pneumococcal S. pneumoniae vaccine serotypes assessed for this outcome measure were the serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F. Pneumococcal ID cases were identified through non-culture pneumococcal diagnostic tests with additional non-culture vaccine type serotyping. Tests used included rapid in-vitro diagnostic tests or Latex agglutination.

  • Number of Subjects With a First Episode Reported of Invasive Pneumococcal Disease (IPD) Due to Streptococcus (S. pn.) Cross-reactive Pneumococcal Serotypes. [ Time Frame: Any time from 2 weeks post primary vaccination Dose 3 to study end at Month 22-25 ] [ Designated as safety issue: No ]
    The S. pn. cross-reactive serotypes assessed for this outcome measure were the serotypes 19A, 6A and 9N.

  • Number of Subjects With a First Episode Reported of Invasive Pneumococcal Disease (IPD) Due to Pneumococcal Serotypes Other Than Streptococcus (S. pn.) Vaccine and Cross-reactive Serotypes. [ Time Frame: Any time from 2 weeks post primary vaccination Dose 3 to study end at Month 22-25 ] [ Designated as safety issue: No ]
    The serotypes assessed for this outcome measure included among others the pneumococcal serotypes 12F, 16F, 24F, 38 and 8.

  • Number of Subjects With a First Episode Reported of Invasive Disease (ID) Due to Haemophilus Influenzae [ Time Frame: Any time from 2 weeks post primary vaccination Dose 3 to study end at Month 22-25 ] [ Designated as safety issue: No ]
    No subject was reported with any case of ID due to Haemophilus influenzae.

  • Number of Subjects With Streptococcus Pneumoniae (S. pn.) Vaccine Serotypes Identified in Nasopharyngeal Swabs, in the Carriage Subset. [ Time Frame: At Months 5, 10-13, 13-16, 14-17, 16-19 and 22-25 ] [ Designated as safety issue: No ]

    The 10 pneumococcal S. pn. vaccine serotypes assessed for this outcome measure were the serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F. S. pn. serotypes were identified using latex agglutination and by quellung reaction with omni serum.

    The Carriage Subset consisted in a subgroup of 2,000 subjects enrolled in Panama.


  • Number of Subjects With Streptococcus Pneumoniae (S. pn.) Cross-reactive Serotypes Identified in Nasopharyngeal Swabs, in the Carriage Subset. [ Time Frame: At Months 5, 10-13, 13-16, 14-17, 16-19 and 22-25 ] [ Designated as safety issue: No ]
    Any serotype belonging to the same serogroup as the Synflorix vaccine serotypes, but different from the vaccine serotypes, was considered for this analysis of carriage S. pn. cross-reactive serotypes. S. pn. serotypes were identified using latex agglutination and by quellung reaction with omni serum. The Carriage Subset consisted in a subgroup of 2,000 subjects enrolled in Panama.

  • Number of Subjects With Streptococcus Pneumoniae (S. pn.) Serotypes Identified in Nasopharyngeal Swabs Other Than the Synflorix Vaccine and Cross-reactive Serotypes, in the Carriage Subset [ Time Frame: At Months 5, 10-13, 13-16, 14-17, 16-19 and 22-25 ] [ Designated as safety issue: No ]
    S. pn. serotypes were identified using latex agglutination and by quellung reaction with omni serum. The Carriage Subset consisted in a subgroup of 2,000 subjects enrolled in Panama.

  • Number of Subjects With H. Influenzae Strains Identified in Nasopharyngeal Swabs, in the Carriage Subset [ Time Frame: At Months 5, 10-13, 13-16, 14-17, 16-19 and 22-25 ] [ Designated as safety issue: No ]
    Results included samples confirmed as positive for Haemophilus influenzae (H. influenzae) or non-typeable H. influenzae (NTHi) after differentiation from H. haemolyticus by polymerase chain reaction (PCR) assay. The Carriage Subset contained a subgroup of 2,000 subjects enrolled in Panama.

  • Number of Subjects With Acquisition of New Streptococcus Pneumoniae Strains Identified in Nasopharyngeal Swabs, in the Carriage Subset [ Time Frame: At Months 10-13, 13-16, 14-17, 16-19 and 22-25 ] [ Designated as safety issue: No ]
    The Carriage Subset consisted in a subgroup of 2,000 subjects enrolled in Panama.

  • Number of Subjects With Acquisition of New Haemophilus Influenzae Strains Identified in Nasopharyngeal Swabs, in the Carriage Subset. [ Time Frame: At Months 10-13, 13-16, 14-17, 16-19 and 22-25 ] [ Designated as safety issue: No ]
    The Carriage Subset consisted in a subgroup of 2,000 subjects enrolled in Panama.

  • Number of Subjects With Any Antibiotic Prescription at Least Once During the Entire Study Period, in the Carriage Subset. [ Time Frame: Throughout the study (Month 0 to Month 22-25) ] [ Designated as safety issue: No ]
    The Carriage Subset consisted in a subgroup of 2,000 subjects enrolled in Panama.

  • Pneumococcal Antibody Concentrations Against Pneumococcal Vaccine Serotypes, in the Immunogenicity and Tolerability Subset. [ Time Frame: At Month 5, one month after the third dose of primary vaccination ] [ Designated as safety issue: No ]
    Antibody concentrations were measured by 22F enzyme-linked Immunosorbent Assay (ELISA), expressed as geometric mean concentrations (GMCs), in micrograms per milliliter (µg/mL). Serotypes assessed were the pneumococcal vaccine serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F. The cut-off of the assay was >= 0.05 µg/mL. The Immunogenicity and Tolerability Subset included 500 subjects coming from Argentina and Panama respectively.

  • Antibody Concentrations Against Pneumococcal Cross-reactive Serotypes 6A and 19A, in the Immunogenicity and Tolerability Subset [ Time Frame: At Month 5, one month after the third dose of primary vaccination ] [ Designated as safety issue: No ]
    Antibody concentrations were measured by 22F enzyme-linked immunosorbent assay (ELISA), expressed as geometric mean concentrations (GMCs), in micrograms per milliliter (µg/mL). The cut-off of the assay was >= 0.05 µg/mL. The Immunogenicity and Tolerability Subset included 500 subjects coming from Argentina and Panama respectively.

  • Antibody Concentrations Against Pneumococcal Vaccine Serotypes, in the Immunogenicity and Tolerability Subset. [ Time Frame: Before the administration of booster vaccination (PRE), and 1 month and 9 months post booster vaccination (M1 POST-BST and M9 POST-BST) ] [ Designated as safety issue: No ]
    Antibody concentrations were measured by 22F enzyme-linked immunosorbent assay (ELISA), expressed as geometric mean concentrations (GMCs), in micrograms per milliliter (µg/mL). Serotypes assessed were the pneumococcal vaccine serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F. The cut-off of the assay was >= 0.05 µg/mL. The Immunogenicity and Tolerability Subset included 500 subjects coming from Argentina and Panama respectively.

  • Antibody Concentrations Against Pneumococcal Cross-reactive Serotypes 6A and 19A, in the Immunogenicity and Tolerability Subset [ Time Frame: Before the administration of booster vaccination (PRE), and 1 month and 9 months post booster vaccination (M1 POST-BST and M9 POST-BST) ] [ Designated as safety issue: No ]
    Antibody concentrations were measured by 22F enzyme-linked immunosorbent assay (ELISA), expressed as geometric mean concentrations (GMCs), in micrograms per milliliter (µg/mL). The cut-off of the assay was >= 0.05 µg/mL. The Immunogenicity and Tolerability Subset included 500 subjects coming from Argentina and Panama respectively.

  • Number of Subjects With Antibody Concentrations Against Pneumococcal Vaccine Serotypes >= 0.20 Micrograms Per Milliliter (µg/mL), in the Immunogenicity and Tolerability Subset [ Time Frame: At Month 5, one month after the third dose of primary vaccination ] [ Designated as safety issue: No ]
    Antibody concentrations were measured by 22F enzyme-linked immunosorbent assay (ELISA). Serotypes assessed were the pneumococcal vaccine serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F. The Immunogenicity and Tolerability Subset included 500 subjects coming from Argentina and Panama respectively.

  • Number of Subjects With Antibody Concentrations Against Pneumococcal Cross-reactive Serotypes 6A and 19A >= 0.20 Micrograms Per Milliliter (µg/mL), in the Immunogenicity and Tolerability Subset [ Time Frame: At Month 5, one month after the third dose of primary vaccination ] [ Designated as safety issue: No ]
    Antibody concentrations were measured by 22F enzyme-linked immunosorbent assay (ELISA). The Immunogenicity and Tolerability Subset included 500 subjects coming from Argentina and Panama respectively.

  • Number of Subjects With Antibody Concentrations Against Pneumococcal Vaccine Serotypes >= 0.20 Micrograms Per Milliliter (µg/mL), in the Immunogenicity and Tolerability Subset [ Time Frame: Before the administration of booster vaccination (PRE), and 1 month and 9 months post booster vaccination (M1 POST-BST and M9 POST-BST) ] [ Designated as safety issue: No ]
    Antibody concentrations were measured by 22F enzyme-linked immunosorbent assay (ELISA). Serotypes assessed with the pneumococcal vaccine serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F. The Immunogenicity and Tolerability Subset included 500 subjects coming from Argentina and Panama respectively.

  • Number of Subjects With Pneumococcal Antibody Concentrations Against Cross-reactive Serotypes 6A and 19A Higher >= 0.20 Micrograms Per Milliliter (µg/mL), in the Immunogenicity and Tolerability Subset [ Time Frame: Before the administration of booster vaccination (PRE), and 1 month and 9 months post booster vaccination (M1 POST-BST and M9 POST-BST) ] [ Designated as safety issue: No ]
    Antibody concentrations were measured by 22F enzyme-linked immunosorbent assay (ELISA). The Immunogenicity and Tolerability Subset included 500 subjects coming from Argentina and Panama respectively.

  • Number of Subjects With Antibody Concentrations Against Vaccine Pneumococcal Serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F >= 0.05 Microgram Per Milliliter (µg/mL), in the Immunogenicity and Tolerability Subset [ Time Frame: At Month 5, one month after the third dose of primary vaccination ] [ Designated as safety issue: No ]
    A seropositive subject was defined as a subject with antibody concentrations against vaccine pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F => 0.05 µg/mL. The Immunogenicity and Tolerability Subset included 500 subjects coming from Argentina and Panama respectively.

  • Number of Subjects With Pneumococcal Antibody Concentrations Against Serotypes 6A and 19A >= 0.05 µg/mL, in the Immunogenicity and Tolerability Subset [ Time Frame: At Month 5, one month after the third dose of primary vaccination ] [ Designated as safety issue: No ]
    A seropositive subject was defined as a subject with antibody concentrations against cross-reactive pneumococcal serotypes 6A and 19A>= 0.05 µg/mL. The Immunogenicity and Tolerability Subset included 500 subjects coming from Argentina and Panama respectively.

  • Number of Subjects With Antibody Concentrations Against Vaccine Pneumococcal Serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F >= 0.05 Microgram Per Milliliter (µg/mL), in the Immunogenicity and Tolerability Subset [ Time Frame: Before the administration of booster vaccination (PRE), and 1 month and 9 months post booster vaccination (M1 POST-BST and M9 POST-BST ] [ Designated as safety issue: No ]
    A seropositive subject was defined as a subject with antibody concentrations against vaccine pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F => 0.05 µg/mL. The Immunogenicity and Tolerability Subset included 500 subjects coming from Argentina and Panama respectively.

  • Number of Subjects With Pneumococcal Antibody Concentrations Against Serotypes 6A and 19A >= 0.05 µg/mL, in the Immunogenicity and Tolerability Subset [ Time Frame: Before the administration of booster vaccination (PRE), and 1 month and 9 months post booster vaccination (M1 POST-BST and M9 POST-BST) . ] [ Designated as safety issue: No ]
    A seropositive subject was defined as a subject with antibody concentrations against cross-reactive pneumococcal serotypes 6A and 19A>= 0.05 µg/mL. The Immunogenicity and Tolerability Subset included 500 subjects coming from Argentina and Panama respectively.

  • Titers for Opsonophagocytic Activity Against Vaccine Pneumococcal Serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F, in the Immunogenicity and Tolerability Subset [ Time Frame: At Month 5, one month after the third dose of primary vaccination, ] [ Designated as safety issue: No ]
    The cut-off of the assay was >= 8. The Immunogenicity and Tolerability Subset included 500 subjects coming from Argentina and Panama respectively.

  • Titers for Opsonophagocytic Activity Against Cross-reactive Pneumococcal Serotypes 6A and 19A, in the Immunogenicity and Tolerability Subset [ Time Frame: At Month 5, one month after the third dose of primary vaccination ] [ Designated as safety issue: No ]
    The cut-off of the assay was >= 8. The Immunogenicity and Tolerability Subset included 500 subjects coming from Argentina and Panama respectively.

  • Titers for Opsonophagocytic Activity Against Vaccine Pneumococcal Serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F, in the Immunogenicity and Tolerability Subset [ Time Frame: Before the administration of booster vaccination (PRE), and 1 month and 9 months post booster vaccination (M1 POST-BST and M9 POST-BST) ] [ Designated as safety issue: No ]
    The cut-off of the assay was >= 8. The Immunogenicity and Tolerability Subset included 500 subjects coming from Argentina and Panama respectively.

  • Titers for Opsonophagocytic Activity Against Pneumococcal Serotypes 6A and 19A in the Immunogenicity and Tolerability Subset [ Time Frame: Before the administration of booster vaccination (PRE), and 1 month and 9 months post booster vaccination (M1 POST-BST and M9 POST-BST) ] [ Designated as safety issue: No ]
    The cut-off of the assay was >= 8. The Immunogenicity and Tolerability Subset included 500 subjects coming from Argentina and Panama respectively.

  • Number of Subjects With Titers for Opsonophagocytic Activity Against Vaccine Pneumococcal Serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F => 8, in the Immunogenicity and Tolerability Subset [ Time Frame: At Month 5, one month after the third dose of primary vaccination ] [ Designated as safety issue: No ]
    A seropositive subject was defined as a subject with titers for opsonophagocytic activity against vaccine pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F >= 8. The Immunogenicity and Tolerability Subset included 500 subjects coming from Argentina and Panama respectively.

  • Number of Subjects With Titers for Opsonophagocytic Activity Against Cross-reactive Pneumococcal Serotypes 6A and 19A >= 8, in the Immunogenicity and Tolerability Subset [ Time Frame: At Month 5, one month after the third dose of primary vaccination ] [ Designated as safety issue: No ]
    A seropositive subject was defined as a subject with titers for opsonophagocytic activity against cross-reactive pneumococcal serotypes 6A and 19A >= 8. The Immunogenicity and Tolerability Subset included 500 subjects coming from Argentina and Panama respectively.

  • Number of Subjects With Titers for Opsonophagocytic Activity Against Vaccine Pneumococcal Serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F >= 8, in the Immunogenicity and Tolerability Subset [ Time Frame: Before the administration of booster vaccination (PRE), and 1 month and 9 months post booster vaccination (M1 POST-BST and M9 POST-BST) ] [ Designated as safety issue: No ]
    A seropositive subject was defined as a subject with titers for opsonophagocytic activity against vaccine pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F >= 8. The Immunogenicity and Tolerability Subset included 500 subjects coming from Argentina and Panama respectively.

  • Number of Subjects With Titers for Opsonophagocytic Activity Against Pneumococcal Cross-reactive Serotypes 6A and 19A >= 8, in the Immunogenicity and Tolerability Subset [ Time Frame: Before the administration of booster vaccination (PRE), and 1 month and 9 months post booster vaccination (M1 POST-BST and M9 POST-BST). ] [ Designated as safety issue: No ]
    A seropositive subject was a subject with titers for opsonophagocytic activity against pneumococcal cross-reactive serotypes 6A and 19A >= 8. The Immunogenicity and Tolerability Subset included 500 subjects coming from Argentina and Panama respectively.

  • Concentrations of Antibodies Against Protein D (ANTI-PD), in the Immunogenicity and Tolerability Subset [ Time Frame: At Month 5, one month after the third dose of primary vaccination ] [ Designated as safety issue: No ]
    ANTI-PD concentrations are expressed as geometric mean concentrations (GMCs), in enzyme-linked immunosorbent assay (ELISA) unit per milliliter (EL.U/mL). The Immunogenicity and Tolerability Subset included 500 subjects coming from Argentina and Panama respectively.

  • Concentrations of Antibodies Against Protein D (ANTI-PD), in the Immunogenicity and Tolerability Subset [ Time Frame: Before the administration of booster vaccination (PRE), and 1 month and 9 months post booster vaccination (M1 Post-BST and M9 POST-BST) ] [ Designated as safety issue: No ]
    ANTI-PD concentrations are expressed as geometric mean concentrations (GMCs), in enzyme-linked immunosorbent assay (ELISA) unit per milliliter (EL.U/mL). The Immunogenicity and Tolerability Subset included 500 subjects coming from Argentina and Panama respectively.

  • Number of Subjects With Anti-protein D (ANTI-PD) Antibody Concentrations >= 100 Enzyme-linked Immunosorbent Assay Units Per Milliliter ( EL.U/mL), in the Immunogenicity and Tolerability Subset [ Time Frame: At Month 5, one month after the third dose of primary vaccination ] [ Designated as safety issue: No ]
    A seropositive subject was defined as a subject with ANTI-PD antibody concentrations >= 100 EL.U/mL. The Immunogenicity and Tolerability Subset included 500 subjects coming from Argentina and Panama respectively.

  • Number of Subjects With Anti-protein D (ANTI-PD) Antibody Concentrations >= 100 Enzyme-linked Immunosorbent Assay Units Per Milliliter ( EL.U/mL), in the Immunogenicity and Tolerability Subset. [ Time Frame: Before the administration of booster vaccination (PRE), and 1 month and 9 months post booster vaccination (M1 Post-BST and M9 POST-BST ] [ Designated as safety issue: No ]
    A seropositive subject was defined as a subject with ANTI-PD antibody concentrations >= 100 EL.U/mL. The Immunogenicity and Tolerability Subset included 500 subjects coming from Argentina and Panama respectively.


Enrollment: 23802
Study Start Date: June 2007
Study Completion Date: June 2011
Primary Completion Date: June 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Synflorix Group
Subjects received 3 primary doses of Synflorix at 2, 4 and 6 months of age co-administered with Infanrix-hexa and booster dose of Synflorix at 15-18 months of age co-administered with Infanrix-IPV/Hib. All vaccines were administered intramuscularly in the right (Synflorix) or the left (Infanrix-hexa, Infanrix-IPV/Hib) thigh (primary dose) or deltoid (booster dose).
Biological: Pneumococcal conjugate vaccine GSK1024850A
Intramuscular injection, 4 doses
Biological: Havrix
Intramuscular injection, 2 doses in Synflorix group and 3 doses in Control group
Other Name: Hepatitis A vaccine
Biological: Infanrix hexa
Intramuscular injection,3 doses
Other Name: DTPa-HBV-IPV/Hib
Biological: GSK Biologicals' DTPa-IPV/Hib vaccine
Intramuscular injection, 1 dose in Synflorix group and 4 doses in Control group
Active Comparator: Control Group
Subjects received 3 doses of Engerix at 2, 4 and 6 months of age co-administered with Infanrix-IPV/Hib and 1 dose of Havrix co-administered with Infanrix-IPV/Hib at 15-18 months of age. All vaccines were administered in the right (Engerix, Havrix) or the left (Infanrix-IPV/Hib) thigh.
Biological: Havrix
Intramuscular injection, 2 doses in Synflorix group and 3 doses in Control group
Other Name: Hepatitis A vaccine
Biological: Engerix-B
Intramuscular injection, 3 doses
Other Name: Hepatitis B vaccine
Biological: GSK Biologicals' DTPa-IPV/Hib vaccine
Intramuscular injection, 1 dose in Synflorix group and 4 doses in Control group

Detailed Description:

The Protocol Posting has been updated in order to comply with the FDA Amendment Act, Sep 2007. The following vaccines will be offered by the sponsor:

  • Two doses of hepatitis A vaccine will be offered to all subjects to comply with national recommendations.
  • NeisVac-C vaccine against Neisseria meningitis group C will be offered to all subjects in Argentina at 12 months of age.
  • Varicella vaccine will be offered to all subjects in Colombia and Panama at 12 months of age.
  • Two doses of Rotarix vaccine will be offered to all subjects in Colombia within the first six months of life.

In addition, all subjects will receive a dose of Hepatitis B vaccine at birth according to national recommendations and a dose of measles, mumps and rubella (MMR) vaccine at 12 to 15 months of age according to local Extended Program of Immunization (EPI) .

These vaccines will not be provided by the sponsor. The protocol posting has been updated according to the amendment of the protocol dated 25 Nov 2008. The protocol posting has been updated according to the amendment of the protocol dated 14 December 2009. The protocol posting has been updated according to the amendment of the protocol dated 09 September 2010.

  Eligibility

Ages Eligible for Study:   6 Weeks to 16 Weeks
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • A male or female between, and including, 6 and 16 weeks of age at the time of the first vaccination. Pre-term born infants can be included in the study starting from 8 weeks of chronological age at the time of first vaccination and up to 16 weeks of chronological age
  • Subjects should be living in the area covered by the surveillance system for community acquired pneumonia (CAP), invasive disease and acute otitis media (AOM) •Written informed consent obtained from the parent or guardian of the subject.
  • Free of any known or suspected health problems (as established by medical history and clinical examination before entering into the study), that would contraindicate the initiation of routine immunizations outside a clinical trial context.
  • Subjects for whom the investigator believes that their parents/guardians can and will comply with the requirements of the protocol

Exclusion Criteria:

  • Use of any investigational or non-registered drug or planned use during the study period.
  • Use or planned use of any investigational or non-registered vaccine other than the study vaccine(s).
  • Previous vaccination against diphtheria, tetanus, pertussis, Haemophilus influenzae type b, hepatitis A and/or Streptococcus. pneumoniae . Locally recommended EPI vaccines to be given at birth are allowed, but should be administered at least one month before the first dose of the study vaccine .Other locally recommended vaccines are always allowed, even if concomitantly administered with the study vaccines. •Previous or planned vaccination with a registered pneumococcal vaccine such as Prevnar is not allowed. If Prevnar immunization needs to be initiated, due to the presence of a high risk disease for pneumococcal infections for which the Prevnar vaccine is made locally available, the subject can not be enrolled in the study and should be referred to the specific Prevnar immunization program.
  • 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
  • For Colombia: infants with low birth weight ( less than (<) 2.500 grams)
  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: NCT00466947

Locations
Argentina
GSK Investigational Site
Godoy Cruz, Mendoza, Argentina
GSK Investigational Site
Guaymallen, Mendoza, Argentina
GSK Investigational Site
Las Heras, Mendoza, Argentina
GSK Investigational Site
Luján de Cuyo, Mendoza, Argentina
GSK Investigational Site
Villanueva, Mendoza, Argentina
GSK Investigational Site
Albardón, San Juan, Argentina
GSK Investigational Site
Caucete, San Juan, Argentina
GSK Investigational Site
Fernandez, Santiago Del Estero, Argentina, 4200
GSK Investigational Site
La Banda, Santiago Del Estero, Argentina, 4300
GSK Investigational Site
La Banda, Argentina, 4300
GSK Investigational Site
Maipu, Argentina
GSK Investigational Site
Mendoza, Argentina, 5500
GSK Investigational Site
San Juan, Argentina, 5425
GSK Investigational Site
San Juan, Argentina
GSK Investigational Site
San Juan, Argentina, 5400
GSK Investigational Site
san Martín, Argentina
GSK Investigational Site
Santiago del Estero, Argentina, 4300
GSK Investigational Site
Santiago del Estero, Argentina, 4200
GSK Investigational Site
Santiago del Estero, Argentina
Colombia
GSK Investigational Site
Cali, Colombia
Panama
GSK Investigational Site
Panama, Panamá, Panama
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

Publications:
Sáez-Llorens X et al. Impact of 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) nasopharyngeal bacterial carriage in Panamanian children. Abstract presented at the 29th Annual Meeting of the European Society for Paediatric Infectious Diseases (ESPID). 16-19 November 2011.
Tregnaghi M et al. Evaluating the efficacy of 10-valent pneumococcal non-typeable Haemophilus influenzae protein-D conjugate vaccine (PHiD-CV) against community-acquired pneumonia in Latin America. Abstract presented at the 29th annual meeting of the European Society for Paediatric Infectious Diseases (ESPID), The Hague, The Netherlands, 07-11 June, 2011.
Sáez-Llorens X et al. Design/setting of COMPAS: a Latin American trial evaluating the efficacy of 10-valent pneumococcal non-typeable Haemophilus influenzae protein-D conjugate vaccine (PHiD-CV). Abstract presented at the 29th annual meeting of the European Society for Paediatric Infectious Diseases (ESPID), The Hague, The Netherlands, 07-11 June, 2011.
Tregnaghi MW et al. Immunogenicity profile of the 10-valent pneumococcal non-typeable Haemophilus influenzae protein-D conjugate vaccine (PHiD-CV) in Latin American children enrolled in COMPAS. Abstract presented at the 7th World Congress of the World Society for Pediatric Infectious Diseases (WSPID). Melbourne, Australia, 16-19 November 2011 (Abstract 430).
Sáez-Llorens X et al. Impact of 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) on nasopharyngeal bacterial carriage in Panamanian children. Abstract presented at the 7th World Congress of the World Society for Pediatric Infectious Diseases (WSPID). Melbourne, Australia, 16-19 November 2011 (Abstract 854).

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT00466947     History of Changes
Other Study ID Numbers: 109563
Study First Received: April 26, 2007
Results First Received: August 25, 2011
Last Updated: June 20, 2013
Health Authority: Colombia: INVIMA
Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica
Panama: Instituto Conmemorativo Gorgas de Estudios de la Salud. Comité Nacional de Bioética de la Investigación

Keywords provided by GlaxoSmithKline:
Otitis media
Pneumonia
Community acquired pneumonia (CAP)
Pneumococcal disease
Booster vaccination
Immunogenicity
Pneumococcal vaccine
Safety
Efficacy
Carriage

Additional relevant MeSH terms:
Otitis
Otitis Media
Pneumonia
Ear Diseases
Lung Diseases
Otorhinolaryngologic Diseases
Respiratory Tract Diseases
Respiratory Tract Infections

ClinicalTrials.gov processed this record on October 29, 2014