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

COMPAS: A Phase III Study to Demonstrate Efficacy of GSK Biologicals' 10-valent Pneumococcal Vaccine (GSK1024850A) Against Community Acquired Pneumonia and Acute Otitis Media

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.

Study Overview

• Status: Completed
• Conditions: Infections, Streptococcal
• Intervention / Treatment: Biological: Pneumococcal conjugate vaccine GSK1024850A; Biological: Havrix; Biological: Infanrix hexa; Biological: GSK Biologicals' DTPa-IPV/Hib vaccine; Biological: Engerix-B

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.

• Study Type: Interventional
• Enrollment (Actual): 23802
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Cordoba, Argentina, 5000
    • GSK Investigational Site
  • La Banda, Argentina, 4300
    • GSK Investigational Site
  • Maipu, Argentina
    • GSK Investigational Site
  • Mendoza, Argentina, 5500
    • GSK Investigational Site
  • San Juan, Argentina, 5400
    • GSK Investigational Site
  • San Juan, Argentina, 5425
    • GSK Investigational Site
  • San Juan, Argentina
    • GSK Investigational Site
  • Santiago del Estero, Argentina, 4200
    • GSK Investigational Site
  • Santiago del Estero, Argentina, 4300
    • GSK Investigational Site
  • Santiago del Estero, Argentina
    • GSK Investigational Site
  • san Martín, Argentina
    • GSK Investigational Site
  • Mendoza
    • 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
  • San Juan
    • Albardón, San Juan, Argentina
      • GSK Investigational Site
    • Caucete, San Juan, Argentina
      • GSK Investigational Site
  • Santiago Del Estero
    • Fernandez, Santiago Del Estero, Argentina, 4200
      • GSK Investigational Site
    • La Banda, Santiago Del Estero, Argentina, 4300
      • GSK Investigational Site
• Colombia
  • Cali, Colombia
    • GSK Investigational Site
• Panama
  • Panama, Panama
    • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 month to 3 months (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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)

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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 Names: Hepatitis A vaccine; Biological: Infanrix hexa; Intramuscular injection,3 doses; Other Names: 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 Names: Hepatitis A vaccine; Biological: GSK Biologicals' DTPa-IPV/Hib vaccine; Intramuscular injection, 1 dose in Synflorix group and 4 doses in Control group; Biological: Engerix-B; Intramuscular injection, 3 doses; Other Names: Hepatitis B vaccine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Subjects With a First Episode Reported of Bacterial Community Acquired Pneumoniae (B-CAP)	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 Informed Consent Form issues for some subjects. Therefore, a sensitivity analysis excluding 144 subjects was performed. This analysis confirmed the validity of the results for primary outcome.	Any time from 2 weeks after Dose 3 up to 31 August 2010

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Subjects With Serious Adverse Events (SAEs)	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.	Throughout the study (Month 0 to Month 22-25)
Number of Subjects With Any Unsolicited Adverse Event (AE), in the Panama Subset	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.	Throughout the study (Month 0 to Month 22-25)
Number of Subjects With Solicited Local Symptoms Post Primary Vaccination in the Immunogenicity and Tolerability Subset	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.	Within the 4-days (Days 0-3) follow-up period across the 3 doses of the primary study vaccine administration
Number of Subjects With Solicited Local Symptoms Post Booster Vaccination in the Immunogenicity and Tolerability Subset	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.	Within the 4-days (Days 0-3) follow-up period following the booster vaccine administration
Number of Subjects With Solicited Local Symptoms Post Primary Vaccination in the Immunogenicity and Tolerability Subset	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.	Within the 4-days (Days 0-3) follow-up period across the 3 doses of the primary study vaccine administration
Number of Subjects With Solicited Local Symptoms Post Booster Vaccination in the Immunogenicity and Tolerability Subset, for the Control Group	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.	Within the 4-days (Days 0-3) follow-up period following the booster vaccine administration.
Number of Subjects With Solicited General Symptoms Post Primary Vaccination in the Immunogenicity and Tolerability Subset	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.	Within the 4-days (Days 0-3) follow-up period across the 3 doses of the primary study vaccine administration
Number of Subjects With Solicited General Symptoms Post Booster Vaccination in the Immunogenicity and Tolerability Subset	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.	Within the 4-days (Days 0-3) follow-up period following the booster vaccine administration
Number of Subjects With a First Episode Reported of Clinically Confirmed Acute Otitis Media (AOM) (C-AOM), in the Panama Subset	The Panama Subset contained all subjects enrolled in Panama.	Any time from 2 weeks after Dose 3 to study end at Month 22-25
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)	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.	Any time from 2 weeks post primary vaccination Dose 3 to study end at Month 22-25
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	The Panama Subset contained all subjects enrolled in Panama.	Any time from 2 weeks post primary vaccination Dose 3 to study end at Month 22-25
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	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.	Any time from 2 weeks post primary vaccination Dose 3 to study end at Month 22-25
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.	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.	Any time from 2 weeks post primary vaccination Dose 3 to study end at Month 22-25
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.	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.	Any time from 2 weeks post primary vaccination Dose 3 to study end at Month 22-25
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	The Panama Subset contained all subjects enrolled in Panama.	Any time from 2 weeks post primary vaccination Dose 3 to study end at Month 22-25
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	The Panama Subset contained all subjects enrolled in Panama	Any time from 2 weeks post primary vaccination Dose 3 to study end at Month 22-25
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	Other pathogens assessed included among others Moraxella catarrhalis, Group A streptococci, and Staphyloccus aureus. The Panama Subset contained all subjects enrolled in Panama.	Any time from 2 weeks post primary vaccination Dose 3 to study end at Month 22-25
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)	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.	Any time from 2 weeks post primary vaccination Dose 3 to study end at Month 22-25
Number of Subjects With a First Episode Reported of Community Acquired Pneumoniae (CAP) With Any Abnormal CXR With Positive Respiratory Viral Test (RVT)	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.	Any time from 2 weeks post primary vaccination Dose 3 to study end at Month 22-25
Number of Subjects With a First Episode Reported of Bacterial Community Acquired Pneumoniae (B-CAP) With Positive Respiratory Viral Test (RVT).		Any time from 2 weeks post primary vaccination Dose 3 to study end at Month 22-25
Number of Subjects With a First Episode Reported of Suspected Community Acquired Pneumoniae (CAP) (S-CAP)	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.	Any time from 2 weeks post primary vaccination Dose 3 to study end at Month 22-25
Number of Subjects With a First Episode Reported of Community Acquired Pneumoniae (CAP) With Any Abnormal Chest X-ray (CXR)	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.	Any time from 2 weeks post primary vaccination Dose 3 to study end at Month 22-25
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	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.	Any time from 2 weeks post primary vaccination Dose 3 to study end at Month 22-25
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.	CRP cut-off values applied for this outcome measure were 80 milligrams per liter (mg/L), and 120 mg/L.	Any time from 2 weeks post primary vaccination Dose 3 to study end at Month 22-25
Number of Subjects With a First Episode Reported of Vaccine-type Invasive Pneumococcal Disease (VT-IPD).	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.	Any time from 2 weeks post primary vaccination Dose 3 to study end at Month 22-25
Number of Subjects With a First Episode Reported of a Bacteriologically Confirmed Invasive Pneumococcal Disease (Bact.-Conf. ID).	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.	Any time from 2 weeks post primary vaccination Dose 3 to study end at Month 22-25
Number of Subjects With a First Episode Reported of Pneumococcal Invasive Disease (Pneumococcal ID)	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.	Any time from 2 weeks post primary vaccination Dose 3 to study end at Month 22-25
Number of Subjects With a First Episode Reported of Invasive Pneumococcal Disease (IPD) Due to Streptococcus (S. pn.) Cross-reactive Pneumococcal Serotypes.	The S. pn. cross-reactive serotypes assessed for this outcome measure were the serotypes 19A, 6A and 9N.	Any time from 2 weeks post primary vaccination Dose 3 to study end at Month 22-25
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.	The serotypes assessed for this outcome measure included among others the pneumococcal serotypes 12F, 16F, 24F, 38 and 8.	Any time from 2 weeks post primary vaccination Dose 3 to study end at Month 22-25
Number of Subjects With a First Episode Reported of Invasive Disease (ID) Due to Haemophilus Influenzae	No subject was reported with any case of ID due to Haemophilus influenzae.	Any time from 2 weeks post primary vaccination Dose 3 to study end at Month 22-25
Number of Subjects With Streptococcus Pneumoniae (S. pn.) Vaccine Serotypes Identified in Nasopharyngeal Swabs, in the Carriage Subset.	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.	At Months 5, 10-13, 13-16, 14-17, 16-19 and 22-25
Number of Subjects With Streptococcus Pneumoniae (S. pn.) Cross-reactive Serotypes Identified in Nasopharyngeal Swabs, in the Carriage Subset.	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.	At Months 5, 10-13, 13-16, 14-17, 16-19 and 22-25
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	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.	At Months 5, 10-13, 13-16, 14-17, 16-19 and 22-25
Number of Subjects With H. Influenzae Strains Identified in Nasopharyngeal Swabs, in the Carriage Subset	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.	At Months 5, 10-13, 13-16, 14-17, 16-19 and 22-25
Number of Subjects With Acquisition of New Streptococcus Pneumoniae Strains Identified in Nasopharyngeal Swabs, in the Carriage Subset	The Carriage Subset consisted in a subgroup of 2,000 subjects enrolled in Panama.	At Months 10-13, 13-16, 14-17, 16-19 and 22-25
Number of Subjects With Acquisition of New Haemophilus Influenzae Strains Identified in Nasopharyngeal Swabs, in the Carriage Subset.	The Carriage Subset consisted in a subgroup of 2,000 subjects enrolled in Panama.	At Months 10-13, 13-16, 14-17, 16-19 and 22-25
Number of Subjects With Any Antibiotic Prescription at Least Once During the Entire Study Period, in the Carriage Subset.	The Carriage Subset consisted in a subgroup of 2,000 subjects enrolled in Panama.	Throughout the study (Month 0 to Month 22-25)
Pneumococcal Antibody Concentrations Against Pneumococcal Vaccine Serotypes, in the Immunogenicity and Tolerability Subset.	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.	At Month 5, one month after the third dose of primary vaccination
Antibody Concentrations Against Pneumococcal Cross-reactive Serotypes 6A and 19A, in the Immunogenicity and Tolerability Subset	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.	At Month 5, one month after the third dose of primary vaccination
Antibody Concentrations Against Pneumococcal Vaccine Serotypes, in the Immunogenicity and Tolerability Subset.	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.	Before the administration of booster vaccination (PRE), and 1 month and 9 months post booster vaccination (M1 POST-BST and M9 POST-BST)
Antibody Concentrations Against Pneumococcal Cross-reactive Serotypes 6A and 19A, in the Immunogenicity and Tolerability Subset	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.	Before the administration of booster vaccination (PRE), and 1 month and 9 months post booster vaccination (M1 POST-BST and M9 POST-BST)
Number of Subjects With Antibody Concentrations Against Pneumococcal Vaccine Serotypes >= 0.20 Micrograms Per Milliliter (µg/mL), in the Immunogenicity and Tolerability Subset	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.	At Month 5, one month after the third dose of primary vaccination
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	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.	At Month 5, one month after the third dose of primary vaccination
Number of Subjects With Antibody Concentrations Against Pneumococcal Vaccine Serotypes >= 0.20 Micrograms Per Milliliter (µg/mL), in the Immunogenicity and Tolerability Subset	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.	Before the administration of booster vaccination (PRE), and 1 month and 9 months post booster vaccination (M1 POST-BST and M9 POST-BST)
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	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.	Before the administration of booster vaccination (PRE), and 1 month and 9 months post booster vaccination (M1 POST-BST and M9 POST-BST)
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	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.	At Month 5, one month after the third dose of primary vaccination
Number of Subjects With Pneumococcal Antibody Concentrations Against Serotypes 6A and 19A >= 0.05 µg/mL, in the Immunogenicity and Tolerability Subset	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.	At Month 5, one month after the third dose of primary vaccination
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	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.	Before the administration of booster vaccination (PRE), and 1 month and 9 months post booster vaccination (M1 POST-BST and M9 POST-BST
Number of Subjects With Pneumococcal Antibody Concentrations Against Serotypes 6A and 19A >= 0.05 µg/mL, in the Immunogenicity and Tolerability Subset	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.	Before the administration of booster vaccination (PRE), and 1 month and 9 months post booster vaccination (M1 POST-BST and M9 POST-BST) .
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	The cut-off of the assay was >= 8. The Immunogenicity and Tolerability Subset included 500 subjects coming from Argentina and Panama respectively.	At Month 5, one month after the third dose of primary vaccination,
Titers for Opsonophagocytic Activity Against Cross-reactive Pneumococcal Serotypes 6A and 19A, in the Immunogenicity and Tolerability Subset	The cut-off of the assay was >= 8. The Immunogenicity and Tolerability Subset included 500 subjects coming from Argentina and Panama respectively.	At Month 5, one month after the third dose of primary vaccination
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	The cut-off of the assay was >= 8. The Immunogenicity and Tolerability Subset included 500 subjects coming from Argentina and Panama respectively.	Before the administration of booster vaccination (PRE), and 1 month and 9 months post booster vaccination (M1 POST-BST and M9 POST-BST)
Titers for Opsonophagocytic Activity Against Pneumococcal Serotypes 6A and 19A in the Immunogenicity and Tolerability Subset	The cut-off of the assay was >= 8. The Immunogenicity and Tolerability Subset included 500 subjects coming from Argentina and Panama respectively.	Before the administration of booster vaccination (PRE), and 1 month and 9 months post booster vaccination (M1 POST-BST and M9 POST-BST)
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	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.	At Month 5, one month after the third dose of primary vaccination
Number of Subjects With Titers for Opsonophagocytic Activity Against Cross-reactive Pneumococcal Serotypes 6A and 19A >= 8, in the Immunogenicity and Tolerability Subset	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.	At Month 5, one month after the third dose of primary vaccination
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	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.	Before the administration of booster vaccination (PRE), and 1 month and 9 months post booster vaccination (M1 POST-BST and M9 POST-BST)
Number of Subjects With Titers for Opsonophagocytic Activity Against Pneumococcal Cross-reactive Serotypes 6A and 19A >= 8, in the Immunogenicity and Tolerability Subset	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.	Before the administration of booster vaccination (PRE), and 1 month and 9 months post booster vaccination (M1 POST-BST and M9 POST-BST).
Concentrations of Antibodies Against Protein D (ANTI-PD), in the Immunogenicity and Tolerability Subset	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.	At Month 5, one month after the third dose of primary vaccination
Concentrations of Antibodies Against Protein D (ANTI-PD), in the Immunogenicity and Tolerability Subset	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.	Before the administration of booster vaccination (PRE), and 1 month and 9 months post booster vaccination (M1 Post-BST and M9 POST-BST)
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	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.	At Month 5, one month after the third dose of primary vaccination
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.	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.	Before the administration of booster vaccination (PRE), and 1 month and 9 months post booster vaccination (M1 Post-BST and M9 POST-BST

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Publications and helpful links

General Publications

• Silfverdal SA, Coremans V, Francois N, Borys D, Cleerbout J. Safety profile of the 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV). Expert Rev Vaccines. 2017 Feb;16(2):109-121. doi: 10.1586/14760584.2016.1164044. Epub 2016 Sep 30.
• Saez-Llorens X, Rowley S, Wong D, Rodriguez M, Calvo A, Troitino M, Salas A, Vega V, Castrejon MM, Lommel P, Pascal TG, Hausdorff WP, Borys D, Ruiz-Guinazu J, Ortega-Barria E, Yarzabal JP, Schuerman L. Efficacy of 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine against acute otitis media and nasopharyngeal carriage in Panamanian children - A randomized controlled trial. Hum Vaccin Immunother. 2017 Jun 3;13(6):1-16. doi: 10.1080/21645515.2017.1287640. Epub 2017 Feb 25. Erratum In: Hum Vaccin Immunother. 2021 Mar 4;17(3):928-930.
• Tregnaghi MW, Saez-Llorens X, Lopez P, Abate H, Smith E, Posleman A, Calvo A, Wong D, Cortes-Barbosa C, Ceballos A, Tregnaghi M, Sierra A, Rodriguez M, Troitino M, Carabajal C, Falaschi A, Leandro A, Castrejon MM, Lepetic A, Lommel P, Hausdorff WP, Borys D, Ruiz Guinazu J, Ortega-Barria E, Yarzabal JP, Schuerman L; COMPAS Group. Efficacy of pneumococcal nontypable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) in young Latin American children: A double-blind randomized controlled trial. PLoS Med. 2014 Jun 3;11(6):e1001657. doi: 10.1371/journal.pmed.1001657. eCollection 2014 Jun. Erratum In: PLoS Med. 2015 Jun;12(6):e1001850.

Helpful Links

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

Study record dates

Study Major Dates

• Study Start (Actual): June 28, 2007
• Primary Completion (Actual): August 31, 2010
• Study Completion (Actual): July 28, 2011

Study Registration Dates

• First Submitted: April 26, 2007
• First Submitted That Met QC Criteria: April 26, 2007
• First Posted (Estimate): April 27, 2007

Study Record Updates

• Last Update Posted (Actual): July 16, 2019
• Last Update Submitted That Met QC Criteria: July 2, 2019
• Last Verified: July 1, 2019

More Information

Terms related to this study

• Keywords: Safety; Efficacy; Pneumonia; Immunogenicity; Pneumococcal vaccine; Otitis media; Booster vaccination; Pneumococcal disease; Carriage; Community acquired pneumonia (CAP)
• Additional Relevant MeSH Terms: Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Lung Diseases; Otorhinolaryngologic Diseases; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Ear Diseases; Pneumonia; Otitis; Otitis Media; Streptococcal Infections; Physiological Effects of Drugs; Immunologic Factors; Vaccines; Heptavalent Pneumococcal Conjugate Vaccine
• Other Study ID Numbers: 109563; 2011-002076-16 (EudraCT Number)

Plan for Individual participant data (IPD)

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

Study Data/Documents

1. Clinical Study Report
   Information identifier: 109563
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
2. Individual Participant Data Set
   Information identifier: 109563
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
3. Study Protocol
   Information identifier: 109563
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
4. Informed Consent Form
   Information identifier: 109563
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
5. Dataset Specification
   Information identifier: 109563
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
6. Statistical Analysis Plan
   Information identifier: 109563
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register