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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Infections, Streptococcal

Intervention / Treatment
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* Biological: Pneumococcal conjugate vaccine GSK1024850A
* Biological: Havrix
* Biological: Engerix-B
* Biological: Infanrix hexa
* Biological: GSK Biologicals' DTPa-IPV/Hib vaccine


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 6 Weeks
Maximum Age: 16 Weeks

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Synflorix Group<br>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<br>* Intramuscular injection, 4 doses<br>Biological: Havrix<br>* Intramuscular injection, 2 doses in Synflorix group and 3 doses in Control group<br>* Other names: Hepatitis A vaccine;Biological: Infanrix hexa<br>* Intramuscular injection,3 doses<br>* Other names: DTPa-HBV-IPV/Hib;Biological: GSK Biologicals' DTPa-IPV/Hib vaccine<br>* Intramuscular injection, 1 dose in Synflorix group and 4 doses in Control group<br>|
| Active Comparator: Control Group<br>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<br>* Intramuscular injection, 2 doses in Synflorix group and 3 doses in Control group<br>* Other names: Hepatitis A vaccine;Biological: Engerix-B<br>* Intramuscular injection, 3 doses<br>* Other names: Hepatitis B vaccine;Biological: GSK Biologicals' DTPa-IPV/Hib vaccine<br>* Intramuscular injection, 1 dose in Synflorix group and 4 doses in Control group<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Otitis media, Pneumonia, Community acquired pneumonia (CAP), Pneumococcal disease, Booster vaccination, Immunogenicity, Pneumococcal vaccine, Safety, Efficacy, Carriage