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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00466947
Recruitment Status : Completed
First Posted : April 27, 2007
Results First Posted : September 4, 2013
Last Update Posted : July 16, 2019
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Care Provider, Investigator);   Primary Purpose: Prevention
Condition Infections, Streptococcal
Interventions Biological: Pneumococcal conjugate vaccine GSK1024850A
Biological: Havrix
Biological: Engerix-B
Biological: Infanrix hexa
Biological: GSK Biologicals' DTPa-IPV/Hib vaccine
Enrollment 23802
Recruitment Details Analysis on the primary outcome was performed when at least 535 first bacterial CAP episodes were reported from 2 weeks after vaccine Dose 3 (31 August 2010) with 23738 subjects (11875 and 11863 in Synflorix and Control groups) and analysis at study end was performed on 23597 subjects.
Pre-assignment Details  
Arm/Group Title Synflorix Group Control Group
Hide Arm/Group Description 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). 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 vaccine were administered in the right (Engerix, Havrix) or the left (Infanrix-IPV/Hib) thigh.
Period Title: Primary Outcome Analysis Period
Started 11875 11863
Ongoing 11875 11863
Completed 0 [1] 0 [1]
Not Completed 11875 11863
Reason Not Completed
Other: study still ongoing             11875             11863
[1]
No data on study completion and withdrawal were available at first analysis as the study was ongoing
Period Title: Study End Analysis Period
Started 11798 11799
Completed 9302 9265
Not Completed 2496 2534
Reason Not Completed
Adverse Event             35             43
Lost to Follow-up             1137             1167
Physician Decision             29             29
Protocol Violation             9             17
Withdrawal by Subject             1264             1267
Other - Forbidden vaccination             21             10
Other - Subject without a legal guardian             1             0
Other - Unconformity in team's treatment             0             1
Arm/Group Title Synflorix Group Control Group Total
Hide Arm/Group Description 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). 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 vaccine were administered in the right (Engerix, Havrix) or the left (Infanrix-IPV/Hib) thigh. Total of all reporting groups
Overall Number of Baseline Participants 11798 11799 23597
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous   [1] 
Mean (Standard Deviation)
Unit of measure:  Weeks
Number Analyzed 11798 participants 11799 participants 23597 participants
9.2  (1.93) 9.2  (1.92) 9.2  (1.92)
[1]
Measure Description: Baseline measures presented below correspond to those of the subjects whose data were exploited towards analysis of results at the end of the study
Sex: Female, Male   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 11798 participants 11799 participants 23597 participants
Female
5796
  49.1%
5767
  48.9%
11563
  49.0%
Male
6002
  50.9%
6032
  51.1%
12034
  51.0%
[1]
Measure Description: Baseline measures presented below correspond to those of the subjects whose data were exploited towards analysis of results at the end of the study
Region of Enrollment   [1] 
Measure Type: Number
Unit of measure:  Subjects
 Number Analyzed 11798 participants 11799 participants 23597 participants
Argentina 6990 6991 13981
Columbia 1206 1196 2402
Panama 3602 3612 7214
[1]
Measure Description: Baseline measures presented below correspond to those of the subjects whose data were exploited towards analysis of results at the end of the study
1.Primary Outcome
Title Number of Subjects With a First Episode Reported of Bacterial Community Acquired Pneumoniae (B-CAP)
Hide Description 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.
Time Frame Any time from 2 weeks after Dose 3 up to 31 August 2010
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on the Interim ATP cohort for efficacy which included all evaluable vaccinated subjects who had received the 3-dose primary vaccination course, with available contact and efficacy data beyond Day 14 post study vaccine Dose 3, and whose parents/guardians consented to the use of the subject's data as of 31 August 2010.
Arm/Group Title Synflorix Group Control Group
Hide Arm/Group Description:
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).
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.
Overall Number of Participants Analyzed 10295 10201
Measure Type: Number
Unit of Measure: Subjects
240 304
2.Secondary Outcome
Title Number of Subjects With Serious Adverse Events (SAEs)
Hide Description 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.
Time Frame Throughout the study (Month 0 to Month 22-25)
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis was performed on all vaccinated subjects whose data were exploited towards analysis of results at the end of the study.
Arm/Group Title Synflorix Group Control Group
Hide Arm/Group Description:
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).
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.
Overall Number of Participants Analyzed 11798 11799
Measure Type: Number
Unit of Measure: Subjects
2534 2668
3.Secondary Outcome
Title Number of Subjects With Any Unsolicited Adverse Event (AE), in the Panama Subset
Hide Description 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.
Time Frame Throughout the study (Month 0 to Month 22-25)
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis was performed on all vaccinated subjects included in the Panama subset.
Arm/Group Title Synflorix Group Control Group
Hide Arm/Group Description:
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).
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.
Overall Number of Participants Analyzed 3602 3612
Measure Type: Number
Unit of Measure: Subjects
3530 3518
4.Secondary Outcome
Title Number of Subjects With Solicited Local Symptoms Post Primary Vaccination in the Immunogenicity and Tolerability Subset
Hide Description 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.
Time Frame Within the 4-days (Days 0-3) follow-up period across the 3 doses of the primary study vaccine administration
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis was performed on all vaccinated subjects included in the Immunogenicity and Tolerability subset for the primary vaccination course.
Arm/Group Title Synflorix Group
Hide Arm/Group Description:
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).
Overall Number of Participants Analyzed 368
Measure Type: Number
Unit of Measure: Subjects
Pain after vaccination with Synflorix 275
Pain after vaccination with Infanrix Hexa 270
Redness after vaccination with Synflorix 182
Redness after vaccination with Infanrix Hexa 171
Swelling after vaccination with Synflorix 141
Swelling after vaccination with Infanrix Hexa 143
5.Secondary Outcome
Title Number of Subjects With Solicited Local Symptoms Post Booster Vaccination in the Immunogenicity and Tolerability Subset
Hide Description 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.
Time Frame Within the 4-days (Days 0-3) follow-up period following the booster vaccine administration
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis was performed on all vaccinated subjects included in the Immunogenicity and Tolerability subset for the booster vaccination.
Arm/Group Title Synflorix Group
Hide Arm/Group Description:
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).
Overall Number of Participants Analyzed 317
Measure Type: Number
Unit of Measure: Subjects
Pain after vaccination with Synflorix 129
Pain after vaccination with Infanrix-IPV/Hib 131
Redness after vaccination with Synflorix 104
Redness after vaccination with Infanrix-IPV/Hib 98
Swelling after vaccination with Synflorix 74
Swelling after vaccination with Infanrix-IPV/Hib 69
6.Secondary Outcome
Title Number of Subjects With Solicited Local Symptoms Post Primary Vaccination in the Immunogenicity and Tolerability Subset
Hide Description 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.
Time Frame Within the 4-days (Days 0-3) follow-up period across the 3 doses of the primary study vaccine administration
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis was performed on all vaccinated subjects included in the Immunogenicity and Tolerability subset for the primary vaccination course.
Arm/Group Title Control Group
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 357
Measure Type: Number
Unit of Measure: Subjects
Pain after vaccination with Infanrix-IPV/Hib 169
Pain after vaccination with Engerix 165
Redness after vaccination with Infanrix-IPV/Hib 118
Redness after vaccination with Engerix 109
Swelling after vaccination with Infanrix-IPV/Hib 98
Swelling after vaccination with Engerix 91
7.Secondary Outcome
Title Number of Subjects With Solicited Local Symptoms Post Booster Vaccination in the Immunogenicity and Tolerability Subset, for the Control Group
Hide Description 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.
Time Frame Within the 4-days (Days 0-3) follow-up period following the booster vaccine administration.
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis was performed on all vaccinated subjects included in the Immunogenicity and Tolerability subset for the booster vaccination.
Arm/Group Title Control Group
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 303
Measure Type: Number
Unit of Measure: Subjects
Pain after vaccination with Infanrix-IPV/Hib 81
Pain after vaccination with Havrix 89
Redness after vaccination with Infanrix-IPV/Hib 81
Redness after vaccination with Havrix 73
Swelling after vaccination with Infanrix-IPV/Hib 70
Swelling after vaccination with Havrix 55
8.Secondary Outcome
Title Number of Subjects With Solicited General Symptoms Post Primary Vaccination in the Immunogenicity and Tolerability Subset
Hide Description 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.
Time Frame Within the 4-days (Days 0-3) follow-up period across the 3 doses of the primary study vaccine administration
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis was performed on all vaccinated subjects included in the Immunogenicity and Tolerability subset for the primary vaccination course.
Arm/Group Title Synflorix Group Control Group
Hide Arm/Group Description:
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).
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.
Overall Number of Participants Analyzed 368 357
Measure Type: Number
Unit of Measure: Subjects
Drowsiness 236 168
Fever (rectal temperature >= 38°C) 247 125
Irritability 289 206
Loss of appetite 133 80
9.Secondary Outcome
Title Number of Subjects With Solicited General Symptoms Post Booster Vaccination in the Immunogenicity and Tolerability Subset
Hide Description 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.
Time Frame Within the 4-days (Days 0-3) follow-up period following the booster vaccine administration
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis was performed on all vaccinated subjects included in the Immunogenicity and Tolerability subset for the booster vaccination.
Arm/Group Title Synflorix Group Control Group
Hide Arm/Group Description:
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).
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.
Overall Number of Participants Analyzed 317 303
Measure Type: Number
Unit of Measure: Subjects
Drowsiness 74 65
Fever (rectal temperature >= 38°C) 93 73
Irritability 121 95
Loss of appetite 51 46
10.Secondary Outcome
Title Number of Subjects With a First Episode Reported of Clinically Confirmed Acute Otitis Media (AOM) (C-AOM), in the Panama Subset
Hide Description The Panama Subset contained all subjects enrolled in Panama.
Time Frame Any time from 2 weeks after Dose 3 to study end at Month 22-25
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on the Final ATP cohort for efficacy which included all evaluable vaccinated subjects who had received the 3-dose primary vaccination course, with available contact and efficacy data beyond Day 14 post study vaccine Dose 3, and whose parents/guardians consented to the use of the subject's data as of study end.
Arm/Group Title Synflorix Group Control Group
Hide Arm/Group Description:
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).
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.
Overall Number of Participants Analyzed 3010 2979
Measure Type: Number
Unit of Measure: Subjects
204 239
11.Secondary Outcome
Title 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)
Hide Description 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.
Time Frame Any time from 2 weeks post primary vaccination Dose 3 to study end at Month 22-25
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on the Final ATP cohort for efficacy which included all evaluable vaccinated subjects who had received the 3-dose primary vaccination course, with available contact and efficacy data beyond Day 14 post study vaccine Dose 3, and whose parents/guardians consented to the use of the subject's data as of study end.
Arm/Group Title Synflorix Group Control Group
Hide Arm/Group Description:
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).
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.
Overall Number of Participants Analyzed 10211 10140
Measure Type: Number
Unit of Measure: Subjects
181 231
12.Secondary Outcome
Title 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
Hide Description The Panama Subset contained all subjects enrolled in Panama.
Time Frame Any time from 2 weeks post primary vaccination Dose 3 to study end at Month 22-25
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on the Final ATP cohort for efficacy which included all evaluable vaccinated subjects who had received the 3-dose primary vaccination course, with available contact and efficacy data beyond Day 14 post study vaccine Dose 3, and whose parents/guardians consented to the use of the subject's data as of study end.
Arm/Group Title Synflorix Group Control Group
Hide Arm/Group Description:
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).
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.
Overall Number of Participants Analyzed 3010 2979
Measure Type: Number
Unit of Measure: Subjects
32 45
13.Secondary Outcome
Title 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
Hide Description 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.
Time Frame Any time from 2 weeks post primary vaccination Dose 3 to study end at Month 22-25
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on the Final ATP cohort for efficacy which included all evaluable vaccinated subjects who had received the 3-dose primary vaccination course, with available contact and efficacy data beyond Day 14 post study vaccine Dose 3, and whose parents/guardians consented to the use of the subject's data as of study end.
Arm/Group Title Synflorix Group Control Group
Hide Arm/Group Description:
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).
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.
Overall Number of Participants Analyzed 3010 2979
Measure Type: Number
Unit of Measure: Subjects
6 18
14.Secondary Outcome
Title 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.
Hide Description 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.
Time Frame Any time from 2 weeks post primary vaccination Dose 3 to study end at Month 22-25
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on the Final ATP cohort for efficacy which included all evaluable vaccinated subjects who had received the 3-dose primary vaccination course, with available contact and efficacy data beyond Day 14 post study vaccine Dose 3, and whose parents/guardians consented to the use of the subject's data as of study end.
Arm/Group Title Synflorix Group Control Group
Hide Arm/Group Description:
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).
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.
Overall Number of Participants Analyzed 3010 2979
Measure Type: Number
Unit of Measure: Subjects
3 4
15.Secondary Outcome
Title 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.
Hide Description 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.
Time Frame Any time from 2 weeks post primary vaccination Dose 3 to study end at Month 22-25
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on the Final ATP cohort for efficacy which included all evaluable vaccinated subjects who had received the 3-dose primary vaccination course, with available contact and efficacy data beyond Day 14 post study vaccine Dose 3, and whose parents/guardians consented to the use of the subject's data as of study end.
Arm/Group Title Synflorix Group Control Group
Hide Arm/Group Description:
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).
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.
Overall Number of Participants Analyzed 3010 2979
Measure Type: Number
Unit of Measure: Subjects
3 4
16.Secondary Outcome
Title 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
Hide Description The Panama Subset contained all subjects enrolled in Panama.
Time Frame Any time from 2 weeks post primary vaccination Dose 3 to study end at Month 22-25
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on the Final ATP cohort for efficacy which included all evaluable vaccinated subjects who had received the 3-dose primary vaccination course, with available contact and efficacy data beyond Day 14 post study vaccine Dose 3, and whose parents/guardians consented to the use of the subject's data as of study end.
Arm/Group Title Synflorix Group Control Group
Hide Arm/Group Description:
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).
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.
Overall Number of Participants Analyzed 3010 2979
Measure Type: Number
Unit of Measure: Subjects
12 14
17.Secondary Outcome
Title 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
Hide Description The Panama Subset contained all subjects enrolled in Panama
Time Frame Any time from 2 weeks post primary vaccination Dose 3 to study end at Month 22-25
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on the Final ATP cohort for efficacy which included all evaluable vaccinated subjects who had received the 3-dose primary vaccination course, with available contact and efficacy data beyond Day 14 post study vaccine Dose 3, and whose parents/guardians consented to the use of the subject's data as of study end.
Arm/Group Title Synflorix Group Control Group
Hide Arm/Group Description:
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).
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.
Overall Number of Participants Analyzed 3010 2979
Measure Type: Number
Unit of Measure: Subjects
12 14
18.Secondary Outcome
Title 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
Hide Description Other pathogens assessed included among others Moraxella catarrhalis, Group A streptococci, and Staphyloccus aureus. The Panama Subset contained all subjects enrolled in Panama.
Time Frame Any time from 2 weeks post primary vaccination Dose 3 to study end at Month 22-25
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on the Final ATP cohort for efficacy which included all evaluable vaccinated subjects who had received the 3-dose primary vaccination course, with available contact and efficacy data beyond Day 14 post study vaccine Dose 3, and whose parents/guardians consented to the use of the subject's data as of study end.
Arm/Group Title Synflorix Group Control Group
Hide Arm/Group Description:
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).
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.
Overall Number of Participants Analyzed 3010 2979
Measure Type: Number
Unit of Measure: Subjects
8 7
19.Secondary Outcome
Title 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)
Hide Description 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.
Time Frame Any time from 2 weeks post primary vaccination Dose 3 to study end at Month 22-25
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on the Final ATP cohort for efficacy which included all evaluable vaccinated subjects who had received the 3-dose primary vaccination course, with available contact and efficacy data beyond Day 14 post study vaccine Dose 3, and whose parents/guardians consented to the use of the subject's data as of study end.
Arm/Group Title Synflorix Group Control Group
Hide Arm/Group Description:
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).
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.
Overall Number of Participants Analyzed 10211 10140
Measure Type: Number
Unit of Measure: Subjects
21 25
20.Secondary Outcome
Title Number of Subjects With a First Episode Reported of Community Acquired Pneumoniae (CAP) With Any Abnormal CXR With Positive Respiratory Viral Test (RVT)
Hide Description 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.
Time Frame Any time from 2 weeks post primary vaccination Dose 3 to study end at Month 22-25
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on the Final ATP cohort for efficacy which included all evaluable vaccinated subjects who had received the 3-dose primary vaccination course, with available contact and efficacy data beyond Day 14 post study vaccine Dose 3, and whose parents/guardians consented to the use of the subject's data as of study end.
Arm/Group Title Synflorix Group Control Group
Hide Arm/Group Description:
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).
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.
Overall Number of Participants Analyzed 10211 10140
Measure Type: Number
Unit of Measure: Subjects
104 112
21.Secondary Outcome
Title Number of Subjects With a First Episode Reported of Bacterial Community Acquired Pneumoniae (B-CAP) With Positive Respiratory Viral Test (RVT).
Hide Description [Not Specified]
Time Frame Any time from 2 weeks post primary vaccination Dose 3 to study end at Month 22-25
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on the Final ATP cohort for efficacy which included all evaluable vaccinated subjects who had received the 3-dose primary vaccination course, with available contact and efficacy data beyond Day 14 post study vaccine Dose 3, and whose parents/guardians consented to the use of the subject's data as of study end.
Arm/Group Title Synflorix Group Control Group
Hide Arm/Group Description:
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).
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.
Overall Number of Participants Analyzed 10211 10140
Measure Type: Number
Unit of Measure: Subjects
35 39
22.Secondary Outcome
Title Number of Subjects With a First Episode Reported of Suspected Community Acquired Pneumoniae (CAP) (S-CAP)
Hide Description 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.
Time Frame Any time from 2 weeks post primary vaccination Dose 3 to study end at Month 22-25
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on the Final ATP cohort for efficacy which included all evaluable vaccinated subjects who had received the 3-dose primary vaccination course, with available contact and efficacy data beyond Day 14 post study vaccine Dose 3, and whose parents/guardians consented to the use of the subject's data as of study end.
Arm/Group Title Synflorix Group Control Group
Hide Arm/Group Description:
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).
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.
Overall Number of Participants Analyzed 10211 10140
Measure Type: Number
Unit of Measure: Subjects
2108 2237
23.Secondary Outcome
Title Number of Subjects With a First Episode Reported of Community Acquired Pneumoniae (CAP) With Any Abnormal Chest X-ray (CXR)
Hide Description 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.
Time Frame Any time from 2 weeks post primary vaccination Dose 3 to study end at Month 22-25
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on the Final ATP cohort for efficacy which included all evaluable vaccinated subjects who had received the 3-dose primary vaccination course, with available contact and efficacy data beyond Day 14 post study vaccine Dose 3, and whose parents/guardians consented to the use of the subject's data as of study end.
Arm/Group Title Synflorix Group Control Group
Hide Arm/Group Description:
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).
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.
Overall Number of Participants Analyzed 10211 10140
Measure Type: Number
Unit of Measure: Subjects
681 764
24.Secondary Outcome
Title 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
Hide Description 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.
Time Frame Any time from 2 weeks post primary vaccination Dose 3 to study end at Month 22-25
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on the Final ATP cohort for efficacy which included all evaluable vaccinated subjects who had received the 3-dose primary vaccination course, with available contact and efficacy data beyond Day 14 post study vaccine Dose 3, and whose parents/guardians consented to the use of the subject's data as of study end.
Arm/Group Title Synflorix Group Control Group
Hide Arm/Group Description:
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).
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.
Overall Number of Participants Analyzed 10211 10140
Measure Type: Number
Unit of Measure: Subjects
S-CAP with CRP >= 40 mg/L regardless of CXR exam 425 499
S-CAP with CRP >= 80 mg/L regardless of CXR exam 175 237
S-CAP with CRP >= 120 mg/L regardless of CXR exam 85 119
25.Secondary Outcome
Title 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.
Hide Description CRP cut-off values applied for this outcome measure were 80 milligrams per liter (mg/L), and 120 mg/L.
Time Frame Any time from 2 weeks post primary vaccination Dose 3 to study end at Month 22-25
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on the Final ATP cohort for efficacy which included all evaluable vaccinated subjects who had received the 3-dose primary vaccination course, with available contact and efficacy data beyond Day 14 post study vaccine Dose 3, and whose parents/guardians consented to the use of the subject's data as of study end.
Arm/Group Title Synflorix Group Control Group
Hide Arm/Group Description:
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).
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.
Overall Number of Participants Analyzed 10211 10140
Measure Type: Number
Unit of Measure: Subjects
C-CAP or NAI-CAP with CRP >= 80 mg/L 208 256
C-CAP or NAI-CAP with CRP >= 120 mg/L 191 240
26.Secondary Outcome
Title Number of Subjects With a First Episode Reported of Vaccine-type Invasive Pneumococcal Disease (VT-IPD).
Hide Description 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.
Time Frame Any time from 2 weeks post primary vaccination Dose 3 to study end at Month 22-25
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on the Final ATP cohort for efficacy which included all evaluable vaccinated subjects who had received the 3-dose primary vaccination course, with available contact and efficacy data beyond Day 14 post study vaccine Dose 3, and whose parents/guardians consented to the use of the subject's data as of study end.
Arm/Group Title Synflorix Group Control Group
Hide Arm/Group Description:
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).
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.
Overall Number of Participants Analyzed 10211 10140
Measure Type: Number
Unit of Measure: Subjects
0 16
27.Secondary Outcome
Title Number of Subjects With a First Episode Reported of a Bacteriologically Confirmed Invasive Pneumococcal Disease (Bact.-Conf. ID).
Hide Description 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.
Time Frame Any time from 2 weeks post primary vaccination Dose 3 to study end at Month 22-25
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on the Final ATP cohort for efficacy which included all evaluable vaccinated subjects who had received the 3-dose primary vaccination course, with available contact and efficacy data beyond Day 14 post study vaccine Dose 3, and whose parents/guardians consented to the use of the subject's data as of study end.
Arm/Group Title Synflorix Group Control Group
Hide Arm/Group Description:
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).
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.
Overall Number of Participants Analyzed 10211 10140
Measure Type: Number
Unit of Measure: Subjects
6 17
28.Secondary Outcome
Title Number of Subjects With a First Episode Reported of Pneumococcal Invasive Disease (Pneumococcal ID)
Hide Description 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.
Time Frame Any time from 2 weeks post primary vaccination Dose 3 to study end at Month 22-25
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on the Final ATP cohort for efficacy which included all evaluable vaccinated subjects who had received the 3-dose primary vaccination course, with available contact and efficacy data beyond Day 14 post study vaccine Dose 3, and whose parents/guardians consented to the use of the subject's data as of study end.
Arm/Group Title Synflorix Group Control Group
Hide Arm/Group Description:
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).
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.
Overall Number of Participants Analyzed 10211 10140
Measure Type: Number
Unit of Measure: Subjects
6 17
29.Secondary Outcome
Title Number of Subjects With a First Episode Reported of Invasive Pneumococcal Disease (IPD) Due to Streptococcus (S. pn.) Cross-reactive Pneumococcal Serotypes.
Hide Description The S. pn. cross-reactive serotypes assessed for this outcome measure were the serotypes 19A, 6A and 9N.
Time Frame Any time from 2 weeks post primary vaccination Dose 3 to study end at Month 22-25
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on the Final ATP cohort for efficacy which included all evaluable vaccinated subjects who had received the 3-dose primary vaccination course, with available contact and efficacy data beyond Day 14 post study vaccine Dose 3, and whose parents/guardians consented to the use of the subject's data as of study end.
Arm/Group Title Synflorix Group Control Group
Hide Arm/Group Description:
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).
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.
Overall Number of Participants Analyzed 10211 10140
Measure Type: Number
Unit of Measure: Subjects
2 1
30.Secondary Outcome
Title 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.
Hide Description The serotypes assessed for this outcome measure included among others the pneumococcal serotypes 12F, 16F, 24F, 38 and 8.
Time Frame Any time from 2 weeks post primary vaccination Dose 3 to study end at Month 22-25
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on the Final ATP cohort for efficacy which included all evaluable vaccinated subjects who had received the 3-dose primary vaccination course, with available contact and efficacy data beyond Day 14 post study vaccine Dose 3, and whose parents/guardians consented to the use of the subject's data as of study end.
Arm/Group Title Synflorix Group Control Group
Hide Arm/Group Description:
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).
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.
Overall Number of Participants Analyzed 10211 10140
Measure Type: Number
Unit of Measure: Subjects
3 0
31.Secondary Outcome
Title Number of Subjects With a First Episode Reported of Invasive Disease (ID) Due to Haemophilus Influenzae
Hide Description No subject was reported with any case of ID due to Haemophilus influenzae.
Time Frame Any time from 2 weeks post primary vaccination Dose 3 to study end at Month 22-25
Outcome Measure Data Not Reported
32.Secondary Outcome
Title Number of Subjects With Streptococcus Pneumoniae (S. pn.) Vaccine Serotypes Identified in Nasopharyngeal Swabs, in the Carriage Subset.
Hide Description 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.
Time Frame At Months 5, 10-13, 13-16, 14-17, 16-19 and 22-25
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis was performed on all vaccinated subjects included in the carriage subset.
Arm/Group Title Synflorix Group Control Group
Hide Arm/Group Description:
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).
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.
Overall Number of Participants Analyzed 814 814
Measure Type: Number
Unit of Measure: Subjects
Month 5 (N=814; 814) 104 123
Month 10-13 (N=788; 784) 92 123
Month 13-16 (N=758; 762) 88 109
Month 14-17 (N=720; 738) 74 103
Month 16-19 (N=696; 690) 68 98
Month 22-25 (N=627; 639) 61 86
33.Secondary Outcome
Title Number of Subjects With Streptococcus Pneumoniae (S. pn.) Cross-reactive Serotypes Identified in Nasopharyngeal Swabs, in the Carriage Subset.
Hide Description 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.
Time Frame At Months 5, 10-13, 13-16, 14-17, 16-19 and 22-25
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis was performed on all vaccinated subjects included in the carriage subset.
Arm/Group Title Synflorix Group Control Group
Hide Arm/Group Description:
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).
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.
Overall Number of Participants Analyzed 814 814
Measure Type: Number
Unit of Measure: Subjects
Month 5 (N=814; 814) 63 67
Month 10-13 (N=788; 784) 81 63
Month 13-16 (N=758; 762) 57 63
Month 14-17 (N=720; 738) 57 49
Month 16-19 (N=696; 690) 55 57
Month 22-25 (N=627; 639) 38 46
34.Secondary Outcome
Title 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
Hide Description 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.
Time Frame At Months 5, 10-13, 13-16, 14-17, 16-19 and 22-25
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis was performed on all vaccinated subjects included in the carriage subset.
Arm/Group Title Synflorix Group Control Group
Hide Arm/Group Description:
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).
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.
Overall Number of Participants Analyzed 814 814
Measure Type: Number
Unit of Measure: Subjects
Month 5 (N=814; 814) 99 86
Month 10-13 (N=788; 784) 85 85
Month 13-16 (N=758; 762) 83 85
Month 14-17 (N=720; 738) 78 85
Month 16-19 (N=696; 690) 89 69
Month 22-25 (N=627; 639) 74 61
35.Secondary Outcome
Title Number of Subjects With H. Influenzae Strains Identified in Nasopharyngeal Swabs, in the Carriage Subset
Hide Description 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.
Time Frame At Months 5, 10-13, 13-16, 14-17, 16-19 and 22-25
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis was performed on all vaccinated subjects included in the carriage subset.
Arm/Group Title Synflorix Group Control Group
Hide Arm/Group Description:
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).
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.
Overall Number of Participants Analyzed 824 820
Measure Type: Number
Unit of Measure: Subjects
Month 5 (N=824; 820) 36 40
Month 10-13 (N=788;785) 45 44
Month 13-16 (N=757;762) 32 39
Month 14-17 (N=720; 737) 28 34
Month 16-19 (N=696; 690) 28 38
Month 22-25 (N=628; 640) 29 33
36.Secondary Outcome
Title Number of Subjects With Acquisition of New Streptococcus Pneumoniae Strains Identified in Nasopharyngeal Swabs, in the Carriage Subset
Hide Description The Carriage Subset consisted in a subgroup of 2,000 subjects enrolled in Panama.
Time Frame At Months 10-13, 13-16, 14-17, 16-19 and 22-25
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis was performed on all vaccinated subjects included in the carriage subset.
Arm/Group Title Synflorix Group Control Group
Hide Arm/Group Description:
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).
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.
Overall Number of Participants Analyzed 788 784
Measure Type: Number
Unit of Measure: Subjects
Month 10-13 (N=788;784) 171 175
Month 13-16 (N=758;762) 145 165
Month 14-17 (N=720;738) 110 137
Month 16-19 (N=696;690) 126 137
Month 22-25;N=627;639) 123 124
37.Secondary Outcome
Title Number of Subjects With Acquisition of New Haemophilus Influenzae Strains Identified in Nasopharyngeal Swabs, in the Carriage Subset.
Hide Description The Carriage Subset consisted in a subgroup of 2,000 subjects enrolled in Panama.
Time Frame At Months 10-13, 13-16, 14-17, 16-19 and 22-25
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis was performed on all vaccinated subjects included in the carriage subset.
Arm/Group Title Synflorix Group Control Group
Hide Arm/Group Description:
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).
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.
Overall Number of Participants Analyzed 788 785
Measure Type: Number
Unit of Measure: Subjects
Month 10-13 (N=788;785) 39 37
Month 13-16 (N=757;762) 27 33
Month 14-17 (N=720;737) 23 28
Month 16-19 (N=696;690) 22 32
Month 22-25 (N=628;640) 28 31
38.Secondary Outcome
Title Number of Subjects With Any Antibiotic Prescription at Least Once During the Entire Study Period, in the Carriage Subset.
Hide Description The Carriage Subset consisted in a subgroup of 2,000 subjects enrolled in Panama.
Time Frame Throughout the study (Month 0 to Month 22-25)
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis was performed on all vaccinated subjects included in the carriage subset.
Arm/Group Title Synflorix Group Control Group
Hide Arm/Group Description:
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).
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.
Overall Number of Participants Analyzed 955 966
Measure Type: Number
Unit of Measure: Subjects
611 626
39.Secondary Outcome
Title Pneumococcal Antibody Concentrations Against Pneumococcal Vaccine Serotypes, in the Immunogenicity and Tolerability Subset.
Hide Description 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.
Time Frame At Month 5, one month after the third dose of primary vaccination
Hide Outcome Measure Data
Hide Analysis Population Description
Analyses were performed on the Primary According-to-Protocol immunogenicity cohort, including all evaluable subjects in the Immunogenicity and Tolerability Subset (500 subjects in Argentina, 500 in Panama) with post primary vaccination assay results against at least 1 study vaccine antigen component and concerning immunogenicity outcomes available.
Arm/Group Title Synflorix Group Control Group
Hide Arm/Group Description:
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).
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.
Overall Number of Participants Analyzed 334 331
Geometric Mean (95% Confidence Interval)
Unit of Measure: µg/mL
ANTI-1 (N=334;312)
2.51
(2.29 to 2.75)
0.04
(0.03 to 0.04)
ANTI-4 (N=334;328)
3.26
(2.98 to 3.56)
0.03
(0.03 to 0.04)
ANTI-5 (N=334;324)
4.20
(3.86 to 4.57)
0.05
(0.04 to 0.05)
ANITI-6B (N=334;322)
1.34
(1.18 to 1.52)
0.03
(0.03 to 0.03)
ANTI-7F (N=334;330)
3.86
(3.56 to 4.19)
0.04
(0.04 to 0.05)
ANTI-9V (N=334;331)
3.15
(2.84 to 3.50)
0.04
(0.03 to 0.04)
ANTI-14 (N=334;330)
4.55
(4.07 to 5.10)
0.09
(0.08 to 0.11)
ANTI-18C (N=334;328)
5.32
(4.73 to 5.99)
0.04
(0.04 to 0.04)
ANTI-19F (N=334;327)
5.33
(4.70 to 6.06)
0.06
(0.05 to 0.07)
ANTI-23F (N=334;331)
1.99
(1.76 to 2.26)
0.04
(0.03 to 0.04)
40.Secondary Outcome
Title Antibody Concentrations Against Pneumococcal Cross-reactive Serotypes 6A and 19A, in the Immunogenicity and Tolerability Subset
Hide Description 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.
Time Frame At Month 5, one month after the third dose of primary vaccination
Hide Outcome Measure Data
Hide Analysis Population Description
Analyses were performed on the Primary According-to-Protocol immunogenicity cohort, including all evaluable subjects in the Immunogenicity and Tolerability Subset (500 subjects in Argentina, 500 in Panama) with post primary vaccination assay results against at least 1 study vaccine antigen component and concerning immunogenicity outcomes available.
Arm/Group Title Synflorix Group Control Group
Hide Arm/Group Description:
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).
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.
Overall Number of Participants Analyzed 334 326
Geometric Mean (95% Confidence Interval)
Unit of Measure: µg/mL
ANTI-6A (N=334;321)
0.32
(0.27 to 0.37)
0.03
(0.03 to 0.04)
ANTI-19A (N=334;326)
0.29
(0.25 to 0.33)
0.04
(0.04 to 0.05)
41.Secondary Outcome
Title Antibody Concentrations Against Pneumococcal Vaccine Serotypes, in the Immunogenicity and Tolerability Subset.
Hide Description 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.
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)
Hide Outcome Measure Data
Hide Analysis Population Description
Analyses were performed on the Booster According-to-Protocol immunogenicity cohort, including all evaluable subjects in the Immunogenicity and Tolerability Subset (500 subjects in Argentina, 500 in Panama) with post booster assay results against at least 1 study vaccine antigen component and concerning immunogenicity outcomes available.
Arm/Group Title Synflorix Group Control Group
Hide Arm/Group Description:
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).
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.
Overall Number of Participants Analyzed 231 214
Geometric Mean (95% Confidence Interval)
Unit of Measure: µg/mL
ANTI-1, PRE (N=231;203)
0.35
(0.31 to 0.39)
0.05
(0.04 to 0.06)
ANTI-1, M1 POST-BST (N=219;196)
3.58
(3.15 to 4.07)
0.06
(0.05 to 0.06)
ANTI-1, M9 POST-BST (N=206;181)
0.65
(0.56 to 0.75)
0.06
(0.05 to 0.06)
ANTI-4, PRE (N=231;214)
0.48
(0.42 to 0.55)
0.04
(0.04 to 0.05)
ANTI-4, M1 POST-BST (N=217;204)
6.55
(5.81 to 7.38)
0.05
(0.04 to 0.05)
ANTI-4, M9 POST-BST (N=206;183)
0.87
(0.77 to 0.99)
0.04
(0.04 to 0.05)
ANTI-5, PRE (N=231;209)
0.90
(0.80 to 1.01)
0.07
(0.07 to 0.09)
ANTI-5, M1 POST-BST (N=219;199)
5.73
(5.04 to 6.50)
0.07
(0.06 to 0.08)
ANTI-5, M9 POST-BST (N=206;182)
1.19
(1.05 to 1.36)
0.09
(0.08 to 0.10)
ANTI-6B, PRE (N=229;212)
0.55
(0.47 to 0.64)
0.04
(0.03 to 0.04)
ANTI-6B, M1 POST-BST (N=217;198)
3.32
(2.92 to 3.77)
0.04
(0.03 to 0.04)
ANTI-6B, M9 POST-BST (N=206;182)
0.83
(0.71 to 0.96)
0.05
(0.04 to 0.06)
ANTI-7F, PRE (N=231;210)
0.94
(0.84 to 1.04)
0.06
(0.05 to 0.07)
ANTI-7F, M1 POST-BST (N=218;198)
5.77
(5.23 to 6.36)
0.06
(0.05 to 0.07)
ANTI-7F, M9 POST-BST (N=206;182)
1.32
(1.19 to 1.45)
0.07
(0.05 to 0.08)
ANTI-9V, PRE (N=230;214)
1.14
(1.00 to 1.31)
0.04
(0.04 to 0.05)
ANTI-9V, M1 POST-BST (N=218;203)
7.34
(6.51 to 8.27)
0.04
(0.04 to 0.05)
ANTI-9V, M9 POST-BST (N=206;182)
1.80
(1.59 to 2.03)
0.05
(0.04 to 0.06)
ANTI-14, PRE (N=231;214)
1.15
(1.15 to 1.35)
0.11
(0.09 to 0.13)
ANTI-14, M1 POST-BST (N=219;200)
9.31
(8.18 to 10.60)
0.12
(0.10 to 0.14)
ANTI-14, M9 POST-BST (N=206;183)
1.98
(1.74 to 2.26)
0.17
(0.14 to 0.21)
ANTI-18C, PRE (N=231;210)
0.90
(0.79 to 1.03)
0.05
(0.04 to 0.06)
ANTI-18C, M1 POST-BST (N=219;203)
16.38
(14.47 to 18.55)
0.05
(0.04 to 0.05)
ANTI-18C, M9 POST-BST (N=206;181)
2.50
(2.21 to 2.83)
0.05
(0.04 to 0.06)
ANTI-19F, PRE (N=231;206)
1.27
(1.09 to 1.48)
0.06
(0.05 to 0.07)
ANTI-19F, M1 POST-BST (N=219;198)
9.40
(8.40 to 10.52)
0.07
(0.05 to 0.08)
ANTI-19F, M9 POST-BST (N=205;181)
2.47
(2.16 to 2.84)
0.10
(0.08 to 0.12)
ANTI-23F, PRE (N=229;204)
0.62
(0.53 to 0.72)
0.04
(0.03 to 0.05)
ANTI-23F, M1 POST-BST (N=218;201)
4.02
(3.49 to 4.62)
0.04
(0.03 to 0.04)
ANTI-23F, M9 POST-BST (N=206;179)
0.92
(0.80 to 1.06)
0.05
(0.04 to 0.06)
42.Secondary Outcome
Title Antibody Concentrations Against Pneumococcal Cross-reactive Serotypes 6A and 19A, in the Immunogenicity and Tolerability Subset
Hide Description 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.
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)
Hide Outcome Measure Data
Hide Analysis Population Description
Analyses were performed on the Booster According-to-Protocol immunogenicity cohort, including all evaluable subjects in the Immunogenicity and Tolerability Subset (500 subjects in Argentina, 500 in Panama) with post booster assay results against at least 1 study vaccine antigen component and concerning immunogenicity outcomes available.
Arm/Group Title Synflorix Group Control Group
Hide Arm/Group Description:
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).
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.
Overall Number of Participants Analyzed 231 214
Geometric Mean (95% Confidence Interval)
Unit of Measure: µg/mL
ANTI-6A, PRE (N=231;214)
0.22
(0.18 to 0.26)
0.04
(0.04 to 0.05)
ANTI-6A, M1 POST-BST (N=219;204)
1.14
(0.93 to 1.40)
0.04
(0.03 to 0.04)
ANTI-6A, M9 POST-BST (N=206;183)
0.31
(0.26 to 0.37)
0.05
(0.04 to 0.06)
ANTI-19A, PRE (N=229;212)
0.25
(0.21 to 0.30)
0.05
(0.05 to 0.07)
ANTI-19A, M1 POST-BST (N=218;201)
1.34
(1.11 to 1.62)
0.06
(0.05 to 0.07)
ANTI-19A, M9 POST-BST (N=206;181)
0.54
(0.46 to 0.65)
0.09
(0.07 to 0.11)
43.Secondary Outcome
Title Number of Subjects With Antibody Concentrations Against Pneumococcal Vaccine Serotypes >= 0.20 Micrograms Per Milliliter (µg/mL), in the Immunogenicity and Tolerability Subset
Hide Description 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.
Time Frame At Month 5, one month after the third dose of primary vaccination
Hide Outcome Measure Data
Hide Analysis Population Description
Analyses were performed on the Primary According-to-Protocol immunogenicity cohort, including all evaluable subjects in the Immunogenicity and Tolerability Subset (500 subjects in Argentina, 500 in Panama) with post primary vaccination assay results against at least 1 study vaccine antigen component and concerning immunogenicity outcomes available.
Arm/Group Title Synflorix Group Control Group
Hide Arm/Group Description:
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).
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.
Overall Number of Participants Analyzed 334 331
Measure Type: Number
Unit of Measure: Subjects
ANTI-1 (N=334;312) 333 13
ANTI-4 (N=334;328) 332 11
ANTI-5 (N=334;324) 333 22
ANITI-6B (N=334;322) 311 8
ANTI-7F (N=334;330) 333 28
ANTI-9V (N=334;331) 330 19
ANTI-14 (N=334;330) 328 77
ANTI-18C (N=334;328) 330 21
ANTI-19F (N=334;327) 325 40
ANTI-23F (N=334;331) 321 15
44.Secondary Outcome
Title 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
Hide Description 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.
Time Frame At Month 5, one month after the third dose of primary vaccination
Hide Outcome Measure Data
Hide Analysis Population Description
Analyses were performed on the Primary According-to-Protocol immunogenicity cohort, including all evaluable subjects in the Immunogenicity and Tolerability Subset (500 subjects in Argentina, 500 in Panama) with post primary vaccination assay results against at least 1 study vaccine antigen component and concerning immunogenicity outcomes available.
Arm/Group Title Synflorix Group Control Group
Hide Arm/Group Description:
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).
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.
Overall Number of Participants Analyzed 334 326
Measure Type: Number
Unit of Measure: Subjects
ANTI-6A (N=334;321) 215 5
ANTI-19A (N=334;326) 204 18
45.Secondary Outcome
Title Number of Subjects With Antibody Concentrations Against Pneumococcal Vaccine Serotypes >= 0.20 Micrograms Per Milliliter (µg/mL), in the Immunogenicity and Tolerability Subset
Hide Description 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.
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)
Hide Outcome Measure Data
Hide Analysis Population Description
Analyses were performed on the Booster According-to-Protocol immunogenicity cohort, including all evaluable subjects in the Immunogenicity and Tolerability Subset (500 subjects in Argentina, 500 in Panama) with post booster assay results against at least 1 study vaccine antigen component and concerning immunogenicity outcomes available.
Arm/Group Title Synflorix Group Control Group
Hide Arm/Group Description:
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).
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.
Overall Number of Participants Analyzed 231 214
Measure Type: Number
Unit of Measure: Subjects
ANTI-1, PRE (N=231;203) 164 14
ANTI-1, M1 POST-BST (N=219;196) 219 19
ANTI-1, M9 POST-BST (N=206;181) 186 14
ANTI-4, PRE (N=231;214) 190 26
ANTI-4, M1 POST-BST (N=217;204) 217 24
ANTI-4, M9 POST-BST (N=206;183) 198 15
ANTI-5, PRE (N=231;209) 218 27
ANTI-5, M1 POST-BST (N=219;199) 219 30
ANTI-5, M9 POST-BST (N=206;182) 200 34
ANTI-6B, PRE (N=229;212) 182 12
ANTI-6B, M1 POST-BST (N=217;198) 215 13
ANTI-6B, M9 POST-BST (N=206;182) 192 21
ANTI-7F, PRE (N=231;210) 222 34
ANTI-7F, M1 POST-BST (N=218;198) 218 36
ANTI-7F, M9 POST-BST (N=206;182) 205 31
ANTI-9V, PRE (N=230;214) 221 22
ANTI-9V, M1 POST-BST (N=218;203) 218 14
ANTI-9V, M9 POST-BST (N=206;182) 206 26
ANTI-14, PRE (N=231;214) 217 51
ANTI-14, M1 POST-BST (N=219;200) 219 52
ANTI-14, M9 POST-BST (N=206;183) 204 68
ANTI-18C, PRE (N=231;210) 217 22
ANTI-18C, M1 POST-BST (N=219;203) 219 21
ANTI-18C, M9 POST-BST (N=206;181) 205 18
ANTI-19F, PRE (N=231;206) 221 35
ANTI-19F, M1 POST-BST (N=219;198) 218 39
ANTI-19F, M9 POST-BST (N=205;181) 204 52
ANTI-23F, PRE (N=229;204) 198 15
ANTI-23F, M1 POST-BST (N=218;201) 216 14
ANTI-23F, M9 POST-BST (N=206;179) 196 25
46.Secondary Outcome
Title 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
Hide Description 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.
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)
Hide Outcome Measure Data
Hide Analysis Population Description
Analyses were performed on the Booster According-to-Protocol immunogenicity cohort, including all evaluable subjects in the Immunogenicity and Tolerability Subset (500 subjects in Argentina, 500 in Panama) with post booster assay results against at least 1 study vaccine antigen component and concerning immunogenicity outcomes available.
Arm/Group Title Synflorix Group Control Group
Hide Arm/Group Description:
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).
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.
Overall Number of Participants Analyzed 231 214
Measure Type: Number
Unit of Measure: Subjects
ANTI-6A, PRE (N=231;214) 119 14
ANTI-6A, M1 POST-BST (N=219;204) 187 12
ANTI-6A, M9 POST-BST (N=206;183) 129 24
ANTI-19A, PRE (N=229;212) 131 28
ANTI-19A, M1 POST-BST (N=218;201) 197 27
ANTI-19A, M9 POST-BST (N=206;181) 165 47
47.Secondary Outcome
Title 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
Hide Description 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.
Time Frame At Month 5, one month after the third dose of primary vaccination
Hide Outcome Measure Data
Hide Analysis Population Description
Analyses were performed on the Primary According-to-Protocol immunogenicity cohort, including all evaluable subjects in the Immunogenicity and Tolerability Subset (500 subjects in Argentina, 500 in Panama) with post primary vaccination assay results against at least 1 study vaccine antigen component and concerning immunogenicity outcomes available.
Arm/Group Title Synflorix Group Control Group
Hide Arm/Group Description:
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).
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.
Overall Number of Participants Analyzed 334 331
Measure Type: Number
Unit of Measure: Subjects
ANTI-1 (N=334;312) 333 88
ANTI-4 (N=334;328) 333 48
ANTI-5 (N=334;324) 334 153
ANITI-6B (N=334;322) 324 48
ANTI-7F (N=334;330) 333 116
ANTI-9V (N=334;331) 331 68
ANTI-14 (N=334;330) 333 234
ANTI-18C (N=334;328) 333 92
ANTI-19F (N=334;327) 331 176
ANTI-23F (N=334;331) 328 78
48.Secondary Outcome
Title Number of Subjects With Pneumococcal Antibody Concentrations Against Serotypes 6A and 19A >= 0.05 µg/mL, in the Immunogenicity and Tolerability Subset
Hide Description 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.
Time Frame At Month 5, one month after the third dose of primary vaccination
Hide Outcome Measure Data
Hide Analysis Population Description
Analyses were performed on the Primary According-to-Protocol immunogenicity cohort, including all evaluable subjects in the Immunogenicity and Tolerability Subset (500 subjects in Argentina, 500 in Panama) with post primary vaccination assay results against at least 1 study vaccine antigen component and concerning immunogenicity outcomes available.
Arm/Group Title Synflorix Group Control Group
Hide Arm/Group Description:
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).
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.
Overall Number of Participants Analyzed 334 326
Measure Type: Number
Unit of Measure: Subjects
ANTI-6A (N=334;321) 306 77
ANTI-19A (N=334;326) 303 120
49.Secondary Outcome
Title 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
Hide Description 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.
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
Hide Outcome Measure Data
Hide Analysis Population Description
Analyses were performed on the Booster According-to-Protocol immunogenicity cohort, including all evaluable subjects in the Immunogenicity and Tolerability Subset (500 subjects in Argentina, 500 in Panama) with post booster assay results against at least 1 study vaccine antigen component and concerning immunogenicity outcomes available.
Arm/Group Title Synflorix Group Control Group
Hide Arm/Group Description:
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).
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.
Overall Number of Participants Analyzed 231 214
Measure Type: Number
Unit of Measure: Subjects
ANTI-1, PRE (N=231;203) 231 87
ANTI-1, M1 POST-BST (N=219;196) 219 101
ANTI-1, M9 POST-BST (N=206;181) 206 95
ANTI-4, PRE (N=231;214) 231 52
ANTI-4, M1 POST-BST (N=217;204) 217 65
ANTI-4, M9 POST-BST (N=206;183) 206 58
ANTI-5, PRE (N=231;209) 231 150
ANTI-5, M1 POST-BST (N=219;199) 219 142
ANTI-5, M9 POST-BST (N=206;182) 206 133
ANTI-6B, PRE (N=229;212) 226 60
ANTI-6B, M1 POST-BST (N=217;198) 216 54
ANTI-6B, M9 POST-BST (N=206;182) 206 72
ANTI-7F, PRE (N=231;210) 231 79
ANTI-7F, M1 POST-BST (N=218;198) 218 79
ANTI-7F, M9 POST-BST (N=206;182) 206 87
ANTI-9V, PRE (N=230;214) 230 51
ANTI-9V, M1 POST-BST (N=218;203) 218 58
ANTI-9V, M9 POST-BST (N=206;182) 206 68
ANTI-14, PRE (N=231;214) 231 157
ANTI-14, M1 POST-BST (N=219;200) 219 160
ANTI-14, M9 POST-BST (N=206;183) 206 154
ANTI-18C, PRE (N=231;210) 230 72
ANTI-18C, M1 POST-BST (N=219;203) 219 71
ANTI-18C, M9 POST-BST (N=206;181) 206 73
ANTI-19F, PRE (N=231;206) 231 71
ANTI-19F, M1 POST-BST (N=219;198) 219 85
ANTI-19F, M9 POST-BST (N=205;181) 205 93
ANTI-23F, PRE (N=229;204) 223 44
ANTI-23F, M1 POST-BST (N=218;201) 216 44
ANTI-23F, M9 POST-BST (N=206;179) 206 62
50.Secondary Outcome
Title Number of Subjects With Pneumococcal Antibody Concentrations Against Serotypes 6A and 19A >= 0.05 µg/mL, in the Immunogenicity and Tolerability Subset
Hide Description 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.
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) .
Hide Outcome Measure Data
Hide Analysis Population Description
Analyses were performed on the Booster According-to-Protocol immunogenicity cohort, including all evaluable subjects in the Immunogenicity and Tolerability Subset (500 subjects in Argentina, 500 in Panama) with post booster assay results against at least 1 study vaccine antigen component and concerning immunogenicity outcomes available.
Arm/Group Title Synflorix Group Control Group
Hide Arm/Group Description:
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).
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.
Overall Number of Participants Analyzed 231 214
Measure Type: Number
Unit of Measure: Subjects
ANTI-6A, PRE (N=231;214) 210 61
ANTI-6A, M1 POST-BST (N=219;204) 214 61
ANTI-6A, M9 POST-BST (N=206;183) 196 69
ANTI-19A, PRE (N=229;212) 208 76
ANTI-19A, M1 POST-BST (N=218;201) 212 83
ANTI-19A, M9 POST-BST (N=206;181) 201 89
51.Secondary Outcome
Title 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
Hide Description The cut-off of the assay was >= 8. The Immunogenicity and Tolerability Subset included 500 subjects coming from Argentina and Panama respectively.
Time Frame At Month 5, one month after the third dose of primary vaccination,
Hide Outcome Measure Data
Hide Analysis Population Description
Analyses were performed on the Primary According-to-Protocol immunogenicity cohort, including all evaluable subjects in the Immunogenicity and Tolerability Subset (500 subjects in Argentina, 500 in Panama) with post primary vaccination assay results against at least 1 study vaccine antigen component and concerning immunogenicity outcomes available.
Arm/Group Title Synflorix Group Control Group
Hide Arm/Group Description:
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).
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.
Overall Number of Participants Analyzed 317 317
Geometric Mean (95% Confidence Interval)
Unit of Measure: Titers
OPSONO-1 (N=306;305)
139.5
(116.8 to 166.5)
4.8
(4.5 to 5.3)
OPSONO-4 (N=310;299)
771.7
(686.5 to 867.6)
5.1
(4.5 to 5.8)
OPSONO-5 (N=313;314)
224.8
(196.0 to 257.8)
4.5
(4.2 to 4.8)
OPSONO-6B (N=315;309)
689.7
(553.2 to 859.7)
5.4
(4.6 to 6.2)
OPSONO-7F (N=302;266)
4656.7
(4175.6 to 5193.3)
110.4
(78.8 to 154.7)
OPSONO-9V (N=312;302)
1690.4
(1489.4 to 1918.7)
14.6
(11.6 to 18.2)
OPSONO-14 (N=308;273)
908.5
(795.2 to 1038.1)
16.5
(12.9 to 21.1)
OPSONO-18C (N=308;317)
310.9
(259.4 to 372.6)
4.4
(4.1 to 4.7)
OPSONO-19F (N=304;314)
383.0
(308.5 to 475.5)
4.7
(4.3 to 5.2)
OPSONO-23F (N=317;282)
2167.4
(1863.4 to 2521.1)
14.5
(11.0 to 19.1)
52.Secondary Outcome
Title Titers for Opsonophagocytic Activity Against Cross-reactive Pneumococcal Serotypes 6A and 19A, in the Immunogenicity and Tolerability Subset
Hide Description The cut-off of the assay was >= 8. The Immunogenicity and Tolerability Subset included 500 subjects coming from Argentina and Panama respectively.
Time Frame At Month 5, one month after the third dose of primary vaccination
Hide Outcome Measure Data
Hide Analysis Population Description
Analyses were performed on the Primary According-to-Protocol immunogenicity cohort, including all evaluable subjects in the Immunogenicity and Safety Subset (500 subjects in Argentina, 500 in Panama) with post primary vaccination assay results against at least 1 study vaccine antigen component and concerning immunogenicity outcomes available.
Arm/Group Title Synflorix Group Control Group
Hide Arm/Group Description:
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).
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.
Overall Number of Participants Analyzed 302 309
Geometric Mean (95% Confidence Interval)
Unit of Measure: Titers
OPSONO-6A (N=297;305)
156.9
(121.8 to 202.1)
5.0
(4.5 to 5.5)
OPSONO-19A (N=302;309)
18.2
(14.5 to 22.9)
4.1
(4.0 to 4.3)
53.Secondary Outcome
Title 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
Hide Description The cut-off of the assay was >= 8. The Immunogenicity and Tolerability Subset included 500 subjects coming from Argentina and Panama respectively.
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)
Hide Outcome Measure Data
Hide Analysis Population Description
Analyses were performed on the Booster According-to-Protocol immunogenicity cohort, including all evaluable subjects in the Immunogenicity and Tolerability Subset (500 subjects in Argentina, 500 in Panama) with post booster assay results against at least 1 study vaccine antigen component and concerning immunogenicity outcomes available.
Arm/Group Title Synflorix Group Control Group
Hide Arm/Group Description:
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).
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.
Overall Number of Participants Analyzed 221 210
Geometric Mean (95% Confidence Interval)
Unit of Measure: Titers
OPSONO-1, PRE (N=221;210)
9.0
(7.4 to 10.9)
4.6
(4.2 to 5.0)
OPSONO-1, M1 POST-BST (N=209;200)
357.5
(281.8 to 453.5)
4.8
(4.4 to 5.4)
OPSONO-1, M9 POST-BST (N=196;176)
34.4
(26.6 to 44.7)
4.6
(4.2 to 5.1)
OPSONO-4, PRE (N=208;193)
29.2
(21.2 to 40.2)
8.6
(6.4 to 11.5)
OPSONO-4, M1 POST-BST (N=207;193)
2853.5
(2365.5 to 3442.1)
8.3
(6.3 to 10.9)
OPSONO-4, M9 POST-BST (N=192;173)
165.6
(115.3 to 237.9)
8.1
(6.1 to 10.8)
OPSONO-5, PRE (N=205;204)
18.5
(15.4 to 22.3)
4.3
(4.1 to 4.6)
OPSONO-5, M1 POST-BST (N=196;187)
306.1
(252.0 to 371.8)
4.4
(4.1 to 4.7)
OPSONO-5, M9 POST-BST (N=192;173)
44.1
(35.5 to 54.7)
4.2
(4.0 to 4.4)
OPSONO-6B, PRE (N=209;197)
95.5
(70.1 to 130.1)
7.6
(6.0 to 9.8)
OPSONO-6B, M1 POST-BST (N=203;190)
1123.4
(939.2 to 1343.9)
7.1
(5.6 to 8.9)
OPSONO-6B, M9 POST-BST (N=178;165)
128.9
(92.7 to 179.2)
11.4
(8.3 to 15.8)
OPSONO-7F, PRE (N=217;202)
1522.8
(1338.5 to 1732.6)
979.5
(821.2 to 1168.5)
OPSONO-7F, M1 POST-BST (N=205;196)
4336.3
(3607.9 to 5211.8)
746.4
(590.7 to 943.1)
OPSONO-7F, M9 POST-BST (N=192;172)
2598.0
(2232.0 to 3024.1)
1214.3
(1011.4 to 1458.0)
OPSONO-9V, PRE (N=213;188)
709.4
(601.7 to 836.3)
233.7
(175.3 to 311.4)
OPSONO-9V, M1 POST-BST (N=200;189)
3763.0
(3317.5 to 4268.3)
250.9
(186.1 to 338.4)
OPSONO-9V, M9 POST-BST (N=194;168)
1320.3
(1153.1 to 1511.7)
337.4
(252.4 to 451.0)
OPSONO-14, PRE (N=205;192)
121.2
(89.7 to 163.8)
27.0
(18.9 to 38.5)
OPSONO-14, M1 POST-BST (N=209;188)
2659.6
(2266.2 to 3121.3)
21.7
(15.0 to 31.2)
OPSONO-14, M9 POST-BST (N=185;159)
330.6
(242.7 to 450.5)
27.6
(18.3 to 41.8)
OPSONO-18C, PRE (N=204;191)
15.0
(11.5 to 19.6)
4.8
(4.2 to 5.4)
OPSONO-18C, M1 POST-BST (N=188;187)
2426.0
(2041.8 to 2882.5)
5.2
(4.4 to 6.0)
OPSONO-18C, M9 POST-BST (N=170;164)
722.0
(553.6 to 941.6)
5.3
(4.4 to 6.5)
OPSONO-19F, PRE (N=218;205)
24.3
(19.6 to 30.1)
5.0
(4.4 to 5.7)
OPSONO-19F, M1 POST-BST (N=199;200)
657.5
(497.4 to 869.1)
5.0
(4.4 to 5.7)
OPSONO-19F, M9 POST-BST (N=194;170)
118.0
(90.6 to 153.7)
4.8
(4.3 to 5.4)
OPSONO-23F, PRE (N=215;199)
679.3
(494.3 to 933.6)
76.9
(49.0 to 120.6)
OPSONO-23F, M1 POST-BST (N=206;190)
4278.3
(3609.3 to 5071.3)
99.7
(62.7 to 158.6)
OPSONO-23F, M9 POST-BST (N=187;167)
999.6
(711.8 to 1403.9)
109.4
(65.7 to 182.2)
54.Secondary Outcome
Title Titers for Opsonophagocytic Activity Against Pneumococcal Serotypes 6A and 19A in the Immunogenicity and Tolerability Subset
Hide Description The cut-off of the assay was >= 8. The Immunogenicity and Tolerability Subset included 500 subjects coming from Argentina and Panama respectively.
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)
Hide Outcome Measure Data
Hide Analysis Population Description
Analyses were performed on the Booster According-to-Protocol immunogenicity cohort, including all evaluable subjects in the Immunogenicity and Tolerability Subset (500 subjects in Argentina, 500 in Panama) with post booster assay results against at least 1 study vaccine antigen component and concerning immunogenicity outcomes available.
Arm/Group Title Synflorix Group Control Group
Hide Arm/Group Description:
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).
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.
Overall Number of Participants Analyzed 217 204
Geometric Mean (95% Confidence Interval)
Unit of Measure: Titers
OPSONO-6A, PRE (N=189;194)
43.8
(31.0 to 62.0)
7.1
(5.7 to 8.9)
OPSONO-6A, M1 POST BST (N=185;185)
277.2
(198.7 to 386.7)
7.6
(6.0 to 9.7)
OPSONO-6A, M9 POST-BST (N=175;156)
63.9
(44.3 to 92.0)
17.2
(12.1 to 24.4)
OPSONO-19A, PRE (N=217;204)
6.3
(5.3 to 7.4)
5.0
(4.4 to 5.6)
OPSONO-19A, M1 POST-BST (N=200;197)
132.8
(97.5 to 180.8)
5.4
(4.7 to 6.2)
OPSONO-19A, M9 POST-BST (N=187;171)
26.1
(19.5 to 35.1)
6.3
(5.3 to 7.5)
55.Secondary Outcome
Title 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
Hide Description 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.
Time Frame At Month 5, one month after the third dose of primary vaccination
Hide Outcome Measure Data
Hide Analysis Population Description
Analyses were performed on the Primary According-to-Protocol immunogenicity cohort, including all evaluable subjects in the Immunogenicity and Tolerability Subset (500 subjects in Argentina, 500 in Panama) with post primary vaccination assay results against at least 1 study vaccine antigen component and concerning immunogenicity outcomes available.
Arm/Group Title Synflorix Group Control Group
Hide Arm/Group Description:
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).
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.
Overall Number of Participants Analyzed 317 317
Measure Type: Number
Unit of Measure: Subjects
OPSONO-1 (N=306;305) 280 25
OPSONO-4 (N=310;299) 306 15
OPSONO-5 (N=313;314) 303 13
OPSONO-6B (N=315;309) 286 16
OPSONO-7F (N=302;266) 302 162
OPSONO-9V (N=312;302) 311 98
OPSONO-14 (N=308;273) 306 95
OPSONO-18C (N=308;317) 290 8
OPSONO-19F (N=304;314) 277 16
OPSONO-23F (N=317;282) 311 68
56.Secondary Outcome
Title Number of Subjects With Titers for Opsonophagocytic Activity Against Cross-reactive Pneumococcal Serotypes 6A and 19A >= 8, in the Immunogenicity and Tolerability Subset
Hide Description 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.
Time Frame At Month 5, one month after the third dose of primary vaccination
Hide Outcome Measure Data
Hide Analysis Population Description
Analyses were performed on the Primary According-to-Protocol immunogenicity cohort, including all evaluable subjects in the Immunogenicity and Tolerability Subset (500 subjects in Argentina, 500 in Panama) with post primary vaccination assay results against at least 1 study vaccine antigen component and concerning immunogenicity outcomes available.
Arm/Group Title Synflorix Group Control Group
Hide Arm/Group Description:
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).
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.
Overall Number of Participants Analyzed 302 309
Measure Type: Number
Unit of Measure: Subjects
OPSONO-6A (N=297;305) 232 16
OPSONO-19A (N=302;309) 121 5
57.Secondary Outcome
Title 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
Hide Description 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.
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)
Hide Outcome Measure Data
Hide Analysis Population Description
Analyses were performed on the Booster According-to-Protocol immunogenicity cohort, including all evaluable subjects in the Immunogenicity and Tolerability Subset (500 subjects in Argentina, 500 in Panama) with post booster assay results against at least 1 study vaccine antigen component and concerning immunogenicity outcomes available.
Arm/Group Title Synflorix Group Control Group
Hide Arm/Group Description:
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).
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.
Overall Number of Participants Analyzed 221 210
Measure Type: Number
Unit of Measure: Subjects
OPSONO-1, PRE (N=221;210) 58 9
OPSONO-1, M1 POST-BST (N=209;200) 195 14
OPSONO-1, M9 POST-BST (N=196;176) 127 10
OPSONO-4, PRE (N=208;193) 108 25
OPSONO-4, M1 POST-BST (N=207;193) 206 26
OPSONO-4, M9 POST-BST (N=192;173) 147 22
OPSONO-5, PRE (N=205;204) 138 7
OPSONO-5, M1 POST-BST (N=196;187) 194 10
OPSONO-5, M9 POST-BST (N=192;173) 157 3
OPSONO-6B, PRE (N=209;197) 162 27
OPSONO-6B, M1 POST-BST (N=203;190) 200 23
OPSONO-6B, M9 POST-BST (N=178;165) 146 35
OPSONO-7F, PRE (N=217;202) 217 197
OPSONO-7F, M1 POST-BST (N=205;196) 203 185
OPSONO-7F, M9 POST-BST (N=192;172) 192 169
OPSONO-9V, PRE (N=213;188) 212 159
OPSONO-9V, M1 POST-BST (N=200;189) 200 157
OPSONO-9V, M9 POST-BST (N=194;168) 194 148
OPSONO-14, PRE (N=205;192) 158 73
OPSONO-14, M1 POST-BST (N=209;188) 208 61
OPSONO-14, M9 POST-BST (N=185;159) 160 57
OPSONO-18C, PRE (N=204;191) 86 8
OPSONO-18C, M1 POST-BST (N=188;187) 187 11
OPSONO-18C, M9 POST-BST (N=170;164) 165 10
OPSONO-19F, PRE (N=218;205) 150 14
OPSONO-19F, M1 POST-BST (N=199;200) 186 13
OPSONO-19F, M9 POST-BST (N=194;170) 168 11
OPSONO-23F, PRE (N=215;199) 190 94
OPSONO-23F, M1 POST-BST (N=206;190) 205 97
OPSONO-23F, M9 POST-BST (N=187;167) 167 85
58.Secondary Outcome
Title Number of Subjects With Titers for Opsonophagocytic Activity Against Pneumococcal Cross-reactive Serotypes 6A and 19A >= 8, in the Immunogenicity and Tolerability Subset
Hide Description 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.
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).
Hide Outcome Measure Data
Hide Analysis Population Description
Analyses were performed on the Booster According-to-Protocol immunogenicity cohort, including all evaluable subjects in the Immunogenicity and Tolerability Subset (500 subjects in Argentina, 500 in Panama) with post booster assay results against at least 1 study vaccine antigen component and concerning immunogenicity outcomes available.
Arm/Group Title Synflorix Group Control Group
Hide Arm/Group Description:
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).
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.
Overall Number of Participants Analyzed 217 204
Measure Type: Number
Unit of Measure: Subjects
OPSONO-6A, PRE (N=189;194) 99 24
OPSONO-6A, M1 POST BST (N=185;185) 150 26
OPSONO-6A, M9 POST-BST (N=175;156) 104 50
OPSONO-19A, PRE (N=217;204) 32 14
OPSONO-19A, M1 POST-BST (N=200;197) 161 20
OPSONO-19A, M9 POST-BST (N=187;171) 108 32
59.Secondary Outcome
Title Concentrations of Antibodies Against Protein D (ANTI-PD), in the Immunogenicity and Tolerability Subset
Hide Description 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.
Time Frame At Month 5, one month after the third dose of primary vaccination
Hide Outcome Measure Data
Hide Analysis Population Description
Analyses were performed on the Primary According-to-Protocol immunogenicity cohort, including all evaluable subjects in the Immunogenicity and Tolerability Subset (500 subjects in Argentina, 500 in Panama) with post primary vaccination assay results against at least 1 study vaccine antigen component and concerning immunogenicity outcomes available.
Arm/Group Title Synflorix Group Control Group
Hide Arm/Group Description:
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).
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.
Overall Number of Participants Analyzed 334 325
Geometric Mean (95% Confidence Interval)
Unit of Measure: EL.U/mL
2455.2
(2248.3 to 2681.1)
101.2
(91.3 to 112.2)
60.Secondary Outcome
Title Concentrations of Antibodies Against Protein D (ANTI-PD), in the Immunogenicity and Tolerability Subset
Hide Description 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.
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)
Hide Outcome Measure Data
Hide Analysis Population Description
Analyses were performed on the Booster According-to-Protocol immunogenicity cohort, including all evaluable subjects in the Immunogenicity and Tolerability Subset (500 subjects in Argentina, 500 in Panama) with post booster assay results against at least 1 study vaccine antigen component and concerning immunogenicity outcomes available.
Arm/Group Title Synflorix Group Control Group
Hide Arm/Group Description:
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).
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.
Overall Number of Participants Analyzed 230 211
Geometric Mean (95% Confidence Interval)
Unit of Measure: EL.U/mL
ANTI-PD, PRE (N=230;211)
638.6
(556.2 to 733.2)
103.1
(90.5 to 117.5)
ANTI-PD, M1 POST BST (N=218;195)
2787.0
(2435.9 to 3188.7)
92.4
(82.6 to 103.3)
ANTI-PD, M9 POST-BST (N=206;182)
824.1
(704.2 to 964.4)
94.5
(84.4 to 105.8)
61.Secondary Outcome
Title 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
Hide Description 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.
Time Frame At Month 5, one month after the third dose of primary vaccination
Hide Outcome Measure Data
Hide Analysis Population Description
Analyses were performed on the Primary According-to-Protocol immunogenicity cohort, including all evaluable subjects in the Immunogenicity and Tolerability Subset (500 subjects in Argentina, 500 in Panama) with post primary vaccination assay results against at least 1 study vaccine antigen component and concerning immunogenicity outcomes available.
Arm/Group Title Synflorix Group Control Group
Hide Arm/Group Description:
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).
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.
Overall Number of Participants Analyzed 334 325
Measure Type: Number
Unit of Measure: Subjects
333 141
62.Secondary Outcome
Title 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.
Hide Description 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.
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
Hide Outcome Measure Data
Hide Analysis Population Description
Analyses were performed on the Booster According-to-Protocol immunogenicity cohort, including all evaluable subjects in the Immunogenicity and Safety Subset (500 subjects in Argentina, 500 in Panama) with post booster assay results against at least 1 study vaccine antigen component and concerning immunogenicity outcomes available.
Arm/Group Title Synflorix Group Control Group
Hide Arm/Group Description:
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).
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.
Overall Number of Participants Analyzed 230 211
Measure Type: Number
Unit of Measure: Subjects
ANTI-PD, PRE (N=230;211) 223 96
ANTI-PD, M1 POST BST (N=218;195) 218 83
ANTI-PD, M9 POST-BST (N=206;182) 198 84
Time Frame SAEs and unsolicited AEs: throughout the study (Months 0 to 22-25). Solicited symptoms: 4-day follow-up period across the 3 doses of primary study vaccine course/ 4-day follow-up period post booster vaccination. Reports for SAEs were collected from all subjects from the Total Vaccinated cohort (TVC). Reports for unsolicited AEs and for solicited symptoms were collected from subjects from the Panama Subset and from the Immunogenicity and Tolerability Subset, respectively.
Adverse Event Reporting Description For this study, the Total Number (#) of Participants Affected by Other (non-serious) Adverse Events (AEs) was analyzed separately for expected AEs and for unexpected AEs. A consolidated analysis of all expected and unexpected AEs was not technically possible to be performed and the relevant data are no longer available. Therefore, the Total #Participants Affected in Other Adverse Events Table is currently populated by the highest value of #Participants affected within other AE's table.
 
Arm/Group Title Synflorix Group Control Group
Hide Arm/Group Description 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). 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.
All-Cause Mortality
Synflorix Group Control Group
Affected / at Risk (%) Affected / at Risk (%)
Total   19/11798 (0.16%)   26/11799 (0.22%) 
Hide Serious Adverse Events
Synflorix Group Control Group
Affected / at Risk (%) Affected / at Risk (%)
Total   2534/11798 (21.48%)   2668/11799 (22.61%) 
Blood and lymphatic system disorders     
Anaemia * 1  5/11798 (0.04%)  9/11799 (0.08%) 
Coagulopathy * 1  1/11798 (0.01%)  0/11799 (0.00%) 
Febrile neutropenia * 1  4/11798 (0.03%)  4/11799 (0.03%) 
Haemolysis * 1  1/11798 (0.01%)  1/11799 (0.01%) 
Disseminated intravascular coagulation * 1  1/11798 (0.01%)  0/11799 (0.00%) 
Haemolytic anaemia * 1  1/11798 (0.01%)  1/11799 (0.01%) 
Haemolytic uraemic syndrome * 1  2/11798 (0.02%)  1/11799 (0.01%) 
Haemorrhagic disorder * 1  1/11798 (0.01%)  0/11799 (0.00%) 
Hypersplenism * 1  1/11798 (0.01%)  0/11799 (0.00%) 
Hypochromic anaemia * 1  1/11798 (0.01%)  0/11799 (0.00%) 
Idiopathic thrombocytopenic purpura * 1  3/11798 (0.03%)  2/11799 (0.02%) 
Iron deficiency anaemia * 1  1/11798 (0.01%)  0/11799 (0.00%) 
Leukaemoid reaction * 1  0/11798 (0.00%)  1/11799 (0.01%) 
Lymphadenitis * 1  12/11798 (0.10%)  19/11799 (0.16%) 
Lymphadenopathy * 1  2/11798 (0.02%)  2/11799 (0.02%) 
Pancytopenia * 1  1/11798 (0.01%)  0/11799 (0.00%) 
Thrombocytopenia * 1  1/11798 (0.01%)  0/11799 (0.00%) 
Thrombocytopenic purpura * 1  1/11798 (0.01%)  2/11799 (0.02%) 
Neutropenia * 1  0/11798 (0.00%)  1/11799 (0.01%) 
Cardiac disorders     
Cardiac failure * 1  1/11798 (0.01%)  1/11799 (0.01%) 
Cardiac failure congestive * 1  1/11798 (0.01%)  0/11799 (0.00%) 
Cardio-respiratory arrest * 1  2/11798 (0.02%)  0/11799 (0.00%) 
Cyanosis * 1  1/11798 (0.01%)  1/11799 (0.01%) 
Intracardiac mass * 1  1/11798 (0.01%)  0/11799 (0.00%) 
Ventricular arrhythmia * 1  1/11798 (0.01%)  0/11799 (0.00%) 
Congenital, familial and genetic disorders     
Cerebral palsy * 1  0/11798 (0.00%)  1/11799 (0.01%) 
Coarctation of the aorta * 1  0/11798 (0.00%)  1/11799 (0.01%) 
Congenital absence of bile ducts * 1  1/11798 (0.01%)  0/11799 (0.00%) 
Congenital oral malformation * 1  0/11798 (0.00%)  1/11799 (0.01%) 
Congenital syphilis * 1  1/11798 (0.01%)  0/11799 (0.00%) 
Cystic fibrosis * 1  3/11798 (0.03%)  0/11799 (0.00%) 
Dermoid cyst * 1  1/11798 (0.01%)  0/11799 (0.00%) 
Heart disease congenital * 1  0/11798 (0.00%)  1/11799 (0.01%) 
Laryngomalacia * 1  1/11798 (0.01%)  0/11799 (0.00%) 
Meningomyelocele * 1  1/11798 (0.01%)  0/11799 (0.00%) 
Porencephaly * 1  0/11798 (0.00%)  1/11799 (0.01%) 
Pyloric stenosis * 1  1/11798 (0.01%)  1/11799 (0.01%) 
Retinoblastoma * 1  1/11798 (0.01%)  0/11799 (0.00%) 
Sickle cell anaemia * 1  1/11798 (0.01%)  1/11799 (0.01%) 
Sickle cell anaemia with crisis * 1  0/11798 (0.00%)  2/11799 (0.02%) 
Spinal muscular atrophy * 1  1/11798 (0.01%)  0/11799 (0.00%) 
Thalassaemia sickle cell * 1  0/11798 (0.00%)  1/11799 (0.01%) 
Endocrine disorders     
Hyperadrenalism * 1  1/11798 (0.01%)  0/11799 (0.00%) 
Hypothyroidism * 1  1/11798 (0.01%)  0/11799 (0.00%) 
Eye disorders     
Conjunctivitis * 1  1/11798 (0.01%)  1/11799 (0.01%) 
Conjunctivitis allergic * 1  0/11798 (0.00%)  1/11799 (0.01%) 
Ulcerative keratitis * 1  1/11798 (0.01%)  0/11799 (0.00%) 
Gastrointestinal disorders     
Abdominal adhesions * 1  0/11798 (0.00%)  1/11799 (0.01%) 
Abdominal distension * 1  1/11798 (0.01%)  0/11799 (0.00%) 
Abdominal mass * 1  1/11798 (0.01%)  0/11799 (0.00%) 
Abdominal pain * 1  8/11798 (0.07%)  5/11799 (0.04%) 
Acute abdomen * 1  2/11798 (0.02%)  0/11799 (0.00%) 
Appendix disorder * 1  2/11798 (0.02%)  0/11799 (0.00%) 
Constipation * 1  11/11798 (0.09%)  10/11799 (0.08%) 
Diarrhoea * 1  63/11798 (0.53%)  53/11799 (0.45%) 
Diarrhoea haemorrhagic * 1  1/11798 (0.01%)  1/11799 (0.01%) 
Dyspepsia * 1  1/11798 (0.01%)  0/11799 (0.00%) 
Enteritis * 1  15/11798 (0.13%)  20/11799 (0.17%) 
Faecaloma * 1  2/11798 (0.02%)  3/11799 (0.03%) 
Food poisoning * 1  5/11798 (0.04%)  1/11799 (0.01%) 
Gastritis * 1  1/11798 (0.01%)  4/11799 (0.03%) 
Gastritis erosive * 1  0/11798 (0.00%)  1/11799 (0.01%) 
Gastrointestinal disorder * 1  0/11798 (0.00%)  1/11799 (0.01%) 
Gastrointestinal haemorrhage * 1  0/11798 (0.00%)  2/11799 (0.02%) 
Gastrooesophageal reflux disease * 1  6/11798 (0.05%)  3/11799 (0.03%) 
Gingival bleeding * 1  1/11798 (0.01%)  0/11799 (0.00%) 
Haematochezia * 1  1/11798 (0.01%)  0/11799 (0.00%) 
Ileus * 1  4/11798 (0.03%)  3/11799 (0.03%) 
Ileus paralytic * 1  33/11798 (0.28%)  23/11799 (0.19%) 
Infantile colic * 1  0/11798 (0.00%)  1/11799 (0.01%) 
Inguinal hernia * 1  0/11798 (0.00%)  3/11799 (0.03%) 
Inguinal hernia, obstructive * 1  5/11798 (0.04%)  3/11799 (0.03%) 
Intestinal haemorrhage * 1  1/11798 (0.01%)  0/11799 (0.00%) 
Intestinal obstruction * 1  2/11798 (0.02%)  2/11799 (0.02%) 
Intestinal perforation * 1  1/11798 (0.01%)  0/11799 (0.00%) 
Intussusception * 1  14/11798 (0.12%)  11/11799 (0.09%) 
Malabsorption * 1  0/11798 (0.00%)  1/11799 (0.01%) 
Mallory-weiss syndrome * 1  1/11798 (0.01%)  1/11799 (0.01%) 
Rectal haemorrhage * 1  0/11798 (0.00%)  1/11799 (0.01%) 
Stomatitis * 1  3/11798 (0.03%)  6/11799 (0.05%) 
Upper gastrointestinal haemorrhage * 1  2/11798 (0.02%)  1/11799 (0.01%) 
Vomiting * 1  42/11798 (0.36%)  37/11799 (0.31%) 
General disorders     
Crying * 1  1/11798 (0.01%)  1/11799 (0.01%) 
Effusion * 1  1/11798 (0.01%)  0/11799 (0.00%) 
Electrocution * 1  2/11798 (0.02%)  2/11799 (0.02%) 
Hypothermia * 1  1/11798 (0.01%)  1/11799 (0.01%) 
Multi-organ failure * 1  1/11798 (0.01%)  0/11799 (0.00%) 
Pyrexia * 1  24/11798 (0.20%)  31/11799 (0.26%) 
Sudden death * 1  0/11798 (0.00%)  1/11799 (0.01%) 
Sudden infant death syndrome * 1  0/11798 (0.00%)  1/11799 (0.01%) 
Systemic inflammatory response syndrome * 1  1/11798 (0.01%)  0/11799 (0.00%) 
Hepatobiliary disorders     
Cholangitis * 1  1/11798 (0.01%)  0/11799 (0.00%) 
Cholecystitis * 1  0/11798 (0.00%)  1/11799 (0.01%) 
Hepatic failure * 1  1/11798 (0.01%)  1/11799 (0.01%) 
Hepatitis acute * 1  0/11798 (0.00%)  1/11799 (0.01%) 
Immune system disorders     
Drug hypersensitivity * 1  2/11798 (0.02%)  0/11799 (0.00%) 
Food allergy * 1  0/11798 (0.00%)  1/11799 (0.01%) 
Hypersensitivity * 1  5/11798 (0.04%)  6/11799 (0.05%) 
Immunodeficiency * 1  0/11798 (0.00%)  1/11799 (0.01%) 
Milk allergy * 1  0/11798 (0.00%)  1/11799 (0.01%) 
Selective iga immunodeficiency * 1  1/11798 (0.01%)  0/11799 (0.00%) 
Infections and infestations     
Abdominal wall abscess * 1  0/11798 (0.00%)  1/11799 (0.01%) 
Abscess * 1  11/11798 (0.09%)  9/11799 (0.08%) 
Abscess limb * 1  10/11798 (0.08%)  16/11799 (0.14%) 
Abscess neck * 1  4/11798 (0.03%)  8/11799 (0.07%) 
Abscess of eyelid * 1  1/11798 (0.01%)  0/11799 (0.00%) 
Acarodermatitis * 1  0/11798 (0.00%)  1/11799 (0.01%) 
Acquired immunodeficiency syndrome * 1  1/11798 (0.01%)  0/11799 (0.00%) 
Acute sinusitis * 1  2/11798 (0.02%)  3/11799 (0.03%) 
Adenoiditis * 1  1/11798 (0.01%)  4/11799 (0.03%) 
Adenovirus infection * 1  0/11798 (0.00%)  1/11799 (0.01%) 
Amoebiasis * 1  0/11798 (0.00%)  2/11799 (0.02%) 
Amoebic dysentery * 1  0/11798 (0.00%)  3/11799 (0.03%) 
Anal abscess * 1  2/11798 (0.02%)  0/11799 (0.00%) 
Appendicitis * 1  3/11798 (0.03%)  3/11799 (0.03%) 
Appendicitis perforated * 1  1/11798 (0.01%)  0/11799 (0.00%) 
Arthritis bacterial * 1  3/11798 (0.03%)  2/11799 (0.02%) 
Ascariasis * 1  0/11798 (0.00%)  1/11799 (0.01%) 
Atypical pneumonia * 1  14/11798 (0.12%)  12/11799 (0.10%) 
Bacteraemia * 1  4/11798 (0.03%)  6/11799 (0.05%) 
Bacterial diarrhoea * 1  2/11798 (0.02%)  2/11799 (0.02%) 
Bacterial infection * 1  0/11798 (0.00%)  2/11799 (0.02%) 
Breast abscess * 1  0/11798 (0.00%)  1/11799 (0.01%) 
Bronchiolitis * 1  473/11798 (4.01%)  518/11799 (4.39%) 
Bronchitis * 1  124/11798 (1.05%)  129/11799 (1.09%) 
Bronchopneumonia * 1  106/11798 (0.90%)  95/11799 (0.81%) 
Bullous impetigo * 1  1/11798 (0.01%)  0/11799 (0.00%) 
Burn infection * 1  2/11798 (0.02%)  1/11799 (0.01%) 
Cat scratch disease * 1  0/11798 (0.00%)  1/11799 (0.01%) 
Cellulitis * 1  45/11798 (0.38%)  46/11799 (0.39%) 
Cellulitis of male external genital organ * 1  1/11798 (0.01%)  1/11799 (0.01%) 
Cellulitis orbital * 1  1/11798 (0.01%)  1/11799 (0.01%) 
Colostomy infection * 1  1/11798 (0.01%)  0/11799 (0.00%) 
Conjunctivitis bacterial * 1  0/11798 (0.00%)  1/11799 (0.01%) 
Conjunctivitis chlamydial * 1  0/11798 (0.00%)  1/11799 (0.01%) 
Conjunctivitis infective * 1  1/11798 (0.01%)  0/11799 (0.00%) 
Croup infectious * 1  10/11798 (0.08%)  7/11799 (0.06%) 
Cytomegalovirus hepatitis * 1  1/11798 (0.01%)  1/11799 (0.01%) 
Dengue fever * 1  18/11798 (0.15%)  15/11799 (0.13%) 
Diarrhoea infectious * 1  2/11798 (0.02%)  0/11799 (0.00%) 
Dysentery * 1  0/11798 (0.00%)  1/11799 (0.01%) 
Ear infection * 1  1/11798 (0.01%)  2/11799 (0.02%) 
Empyema * 1  2/11798 (0.02%)  2/11799 (0.02%) 
Encephalitis viral * 1  1/11798 (0.01%)  1/11799 (0.01%) 
Enteritis infectious * 1  1/11798 (0.01%)  0/11799 (0.00%) 
Enterococcal sepsis * 1  1/11798 (0.01%)  0/11799 (0.00%) 
Erysipelas * 1  1/11798 (0.01%)  0/11799 (0.00%) 
Escherichia urinary tract infection * 1  4/11798 (0.03%)  2/11799 (0.02%) 
Exanthema subitum * 1  4/11798 (0.03%)  4/11799 (0.03%) 
External ear cellulitis * 1  2/11798 (0.02%)  0/11799 (0.00%) 
Fungal skin infection * 1  1/11798 (0.01%)  0/11799 (0.00%) 
Gastroenteritis * 1  553/11798 (4.69%)  497/11799 (4.21%) 
Gastroenteritis adenovirus * 1  1/11798 (0.01%)  3/11799 (0.03%) 
Gastroenteritis bacterial * 1  8/11798 (0.07%)  9/11799 (0.08%) 
Gastroenteritis rotavirus * 1  38/11798 (0.32%)  49/11799 (0.42%) 
Gastroenteritis shigella * 1  8/11798 (0.07%)  8/11799 (0.07%) 
Gastroenteritis viral * 1  9/11798 (0.08%)  9/11799 (0.08%) 
Giardiasis * 1  1/11798 (0.01%)  3/11799 (0.03%) 
Gingivitis * 1  0/11798 (0.00%)  1/11799 (0.01%) 
Hantaviral infection * 1  1/11798 (0.01%)  0/11799 (0.00%) 
Herpangina * 1  2/11798 (0.02%)  0/11799 (0.00%) 
Herpes simplex * 1  0/11798 (0.00%)  1/11799 (0.01%) 
Herpes virus infection * 1  0/11798 (0.00%)  1/11799 (0.01%) 
Impetigo * 1  10/11798 (0.08%)  4/11799 (0.03%) 
Infected bites * 1  0/11798 (0.00%)  1/11799 (0.01%) 
Infected cyst * 1  2/11798 (0.02%)  0/11799 (0.00%) 
Infected fistula * 1  0/11798 (0.00%)  1/11799 (0.01%) 
Infectious mononucleosis * 1  5/11798 (0.04%)  4/11799 (0.03%) 
Infective pulmonary exacerbation of cystic fibrosis * 1  1/11798 (0.01%)  0/11799 (0.00%) 
Influenza * 1  1/11798 (0.01%)  2/11799 (0.02%) 
Klebsiella bacteraemia * 1  1/11798 (0.01%)  0/11799 (0.00%) 
Klebsiella sepsis * 1  1/11798 (0.01%)  0/11799 (0.00%) 
Laryngitis * 1  9/11798 (0.08%)  14/11799 (0.12%) 
Lobar pneumonia * 1  1/11798 (0.01%)  0/11799 (0.00%) 
Lung infection * 1  1/11798 (0.01%)  0/11799 (0.00%) 
Lymph node abscess * 1  2/11798 (0.02%)  0/11799 (0.00%) 
Mastoiditis * 1  2/11798 (0.02%)  0/11799 (0.00%) 
Meningitis * 1  1/11798 (0.01%)  2/11799 (0.02%) 
Meningitis aseptic * 1  6/11798 (0.05%)  2/11799 (0.02%) 
Meningitis meningococcal * 1  1/11798 (0.01%)  1/11799 (0.01%) 
Meningitis pneumococcal * 1  0/11798 (0.00%)  2/11799 (0.02%) 
Meningitis viral * 1  1/11798 (0.01%)  1/11799 (0.01%) 
Myiasis * 1  1/11798 (0.01%)  4/11799 (0.03%) 
Nasal abscess * 1  0/11798 (0.00%)  1/11799 (0.01%) 
Nasopharyngitis * 1  6/11798 (0.05%)  3/11799 (0.03%) 
Necrotising fasciitis * 1  0/11798 (0.00%)  1/11799 (0.01%) 
Nosocomial infection * 1  1/11798 (0.01%)  3/11799 (0.03%) 
Oral candidiasis * 1  1/11798 (0.01%)  0/11799 (0.00%) 
Oral herpes * 1  11/11798 (0.09%)  2/11799 (0.02%) 
Osteomyelitis * 1  1/11798 (0.01%)  0/11799 (0.00%) 
Otitis externa * 1  1/11798 (0.01%)  0/11799 (0.00%) 
Otitis media * 1  4/11798 (0.03%)  8/11799 (0.07%) 
Otitis media acute * 1  16/11798 (0.14%)  16/11799 (0.14%) 
Paronychia * 1  0/11798 (0.00%)  1/11799 (0.01%) 
Parotitis * 1  1/11798 (0.01%)  0/11799 (0.00%) 
Periorbital cellulitis * 1  12/11798 (0.10%)  16/11799 (0.14%) 
Peritonitis * 1  4/11798 (0.03%)  4/11799 (0.03%) 
Pertussis * 1  19/11798 (0.16%)  16/11799 (0.14%) 
Pharyngeal abscess * 1  1/11798 (0.01%)  0/11799 (0.00%) 
Pharyngitis * 1  5/11798 (0.04%)  13/11799 (0.11%) 
Pharyngotonsillitis * 1  4/11798 (0.03%)  2/11799 (0.02%) 
Pneumococcal sepsis * 1  1/11798 (0.01%)  2/11799 (0.02%) 
Pneumocystis jiroveci infection * 1  1/11798 (0.01%)  0/11799 (0.00%) 
Pneumonia * 1  478/11798 (4.05%)  557/11799 (4.72%) 
Pneumonia adenoviral * 1  0/11798 (0.00%)  1/11799 (0.01%) 
Pneumonia bacterial * 1  1/11798 (0.01%)  0/11799 (0.00%) 
Pneumonia influenzal * 1  1/11798 (0.01%)  1/11799 (0.01%) 
Pneumonia pneumococcal * 1  0/11798 (0.00%)  1/11799 (0.01%) 
Pneumonia respiratory syncytial viral * 1  2/11798 (0.02%)  5/11799 (0.04%) 
Pneumonia viral * 1  8/11798 (0.07%)  9/11799 (0.08%) 
Postoperative wound infection * 1  2/11798 (0.02%)  1/11799 (0.01%) 
Pseudomembranous colitis * 1  1/11798 (0.01%)  0/11799 (0.00%) 
Pulmonary sepsis * 1  1/11798 (0.01%)  0/11799 (0.00%) 
Pyelonephritis * 1  11/11798 (0.09%)  6/11799 (0.05%) 
Pyelonephritis acute * 1  2/11798 (0.02%)  1/11799 (0.01%) 
Pyoderma * 1  4/11798 (0.03%)  8/11799 (0.07%) 
Pyomyositis * 1  1/11798 (0.01%)  0/11799 (0.00%) 
Respiratory syncytial virus bronchiolitis * 1  6/11798 (0.05%)  5/11799 (0.04%) 
Respiratory syncytial virus bronchitis * 1  3/11798 (0.03%)  6/11799 (0.05%) 
Respiratory syncytial virus infection * 1  0/11798 (0.00%)  2/11799 (0.02%) 
Respiratory tract infection * 1  0/11798 (0.00%)  1/11799 (0.01%) 
Respiratory tract infection viral * 1  0/11798 (0.00%)  1/11799 (0.01%) 
Rhinitis * 1  5/11798 (0.04%)  7/11799 (0.06%) 
Roseola * 1  1/11798 (0.01%)  0/11799 (0.00%) 
Salmonellosis * 1  1/11798 (0.01%)  0/11799 (0.00%) 
Scarlet fever * 1  0/11798 (0.00%)  1/11799 (0.01%) 
Sepsis * 1  11/11798 (0.09%)  14/11799 (0.12%) 
Sepsis syndrome * 1  1/11798 (0.01%)  0/11799 (0.00%) 
Septic shock * 1  4/11798 (0.03%)  7/11799 (0.06%) 
Shigella infection * 1  1/11798 (0.01%)  1/11799 (0.01%) 
Sinusitis * 1  9/11798 (0.08%)  5/11799 (0.04%) 
Skin candida * 1  0/11798 (0.00%)  1/11799 (0.01%) 
Skin infection * 1  0/11798 (0.00%)  1/11799 (0.01%) 
Staphylococcal bacteraemia * 1  2/11798 (0.02%)  1/11799 (0.01%) 
Staphylococcal scalded skin syndrome * 1  3/11798 (0.03%)  0/11799 (0.00%) 
Staphylococcal sepsis * 1  1/11798 (0.01%)  1/11799 (0.01%) 
Staphylococcal skin infection * 1  1/11798 (0.01%)  0/11799 (0.00%) 
Streptococcal sepsis * 1  2/11798 (0.02%)  0/11799 (0.00%) 
Subcutaneous abscess * 1  8/11798 (0.07%)  14/11799 (0.12%) 
Systemic candida * 1  2/11798 (0.02%)  1/11799 (0.01%) 
Thyroglossal cyst infection * 1  1/11798 (0.01%)  0/11799 (0.00%) 
Tonsillitis * 1  4/11798 (0.03%)  3/11799 (0.03%) 
Tooth abscess * 1  2/11798 (0.02%)  0/11799 (0.00%) 
Tracheitis * 1  8/11798 (0.07%)  7/11799 (0.06%) 
Typhoid fever * 1  1/11798 (0.01%)  1/11799 (0.01%) 
Upper respiratory tract infection * 1  15/11798 (0.13%)  11/11799 (0.09%) 
Urinary tract infection * 1  76/11798 (0.64%)  93/11799 (0.79%) 
Urosepsis * 1  1/11798 (0.01%)  0/11799 (0.00%) 
Varicella * 1  10/11798 (0.08%)  18/11799 (0.15%) 
Viral infection * 1  12/11798 (0.10%)  11/11799 (0.09%) 
Viral pharyngitis * 1  9/11798 (0.08%)  7/11799 (0.06%) 
Viral rash * 1  3/11798 (0.03%)  4/11799 (0.03%) 
Viral sepsis * 1  0/11798 (0.00%)  1/11799 (0.01%) 
Viral tonsillitis * 1  0/11798 (0.00%)  1/11799 (0.01%) 
Vulvovaginitis * 1  0/11798 (0.00%)  1/11799 (0.01%) 
Wound infection * 1  0/11798 (0.00%)  3/11799 (0.03%) 
Injury, poisoning and procedural complications     
Abdominal injury * 1  0/11798 (0.00%)  1/11799 (0.01%) 
Accidental exposure * 1  10/11798 (0.08%)  8/11799 (0.07%) 
Accidental overdose * 1  1/11798 (0.01%)  0/11799 (0.00%) 
Accidental poisoning * 1  3/11798 (0.03%)  3/11799 (0.03%) 
Animal bite * 1  5/11798 (0.04%)  2/11799 (0.02%) 
Arthropod bite * 1  2/11798 (0.02%)  1/11799 (0.01%) 
Arthropod sting * 1  6/11798 (0.05%)  5/11799 (0.04%) 
Back injury * 1  1/11798 (0.01%)  0/11799 (0.00%) 
Burns first degree * 1  0/11798 (0.00%)  1/11799 (0.01%) 
Burns second degree * 1  6/11798 (0.05%)  8/11799 (0.07%) 
Carbon monoxide poisoning * 1  2/11798 (0.02%)  1/11799 (0.01%) 
Chemical injury * 1  1/11798 (0.01%)  0/11799 (0.00%) 
Chemical poisoning * 1  24/11798 (0.20%)  21/11799 (0.18%) 
Chest injury * 1  1/11798 (0.01%)  1/11799 (0.01%) 
Contusion * 1  1/11798 (0.01%)  0/11799 (0.00%) 
Craniocerebral injury * 1  39/11798 (0.33%)  36/11799 (0.31%) 
Electric shock * 1  4/11798 (0.03%)  1/11799 (0.01%) 
Electrical burn * 1  1/11798 (0.01%)  1/11799 (0.01%) 
Extradural haematoma * 1  0/11798 (0.00%)  1/11799 (0.01%) 
Eye burns * 1  1/11798 (0.01%)  0/11799 (0.00%) 
Eye injury * 1  1/11798 (0.01%)  0/11799 (0.00%) 
Eyelid injury * 1  0/11798 (0.00%)  1/11799 (0.01%) 
Face injury * 1  0/11798 (0.00%)  1/11799 (0.01%) 
Femur fracture * 1  2/11798 (0.02%)  5/11799 (0.04%) 
Foreign body * 1  16/11798 (0.14%)  15/11799 (0.13%) 
Fracture * 1  1/11798 (0.01%)  1/11799 (0.01%) 
Gingival injury * 1  0/11798 (0.00%)  1/11799 (0.01%) 
Hand fracture * 1  2/11798 (0.02%)  3/11799 (0.03%) 
Head injury * 1  75/11798 (0.64%)  74/11799 (0.63%) 
Herbal toxicity * 1  2/11798 (0.02%)  2/11799 (0.02%) 
Humerus fracture * 1  4/11798 (0.03%)  2/11799 (0.02%) 
Injury * 1  0/11798 (0.00%)  1/11799 (0.01%) 
Laceration * 1  2/11798 (0.02%)  0/11799 (0.00%) 
Limb crushing injury * 1  0/11798 (0.00%)  2/11799 (0.02%) 
Limb traumatic amputation * 1  0/11798 (0.00%)  1/11799 (0.01%) 
Lower limb fracture * 1  0/11798 (0.00%)  1/11799 (0.01%) 
Mouth injury * 1  1/11798 (0.01%)  2/11799 (0.02%) 
Multiple injuries * 1  26/11798 (0.22%)  33/11799 (0.28%) 
Near drowning * 1  6/11798 (0.05%)  3/11799 (0.03%) 
Open fracture * 1  0/11798 (0.00%)  2/11799 (0.02%) 
Open wound * 1  1/11798 (0.01%)  0/11799 (0.00%) 
Pneumonitis chemical * 1  1/11798 (0.01%)  3/11799 (0.03%) 
Poisoning * 1  3/11798 (0.03%)  2/11799 (0.02%) 
Postoperative fever * 1  0/11798 (0.00%)  1/11799 (0.01%) 
Procedural haemorrhage * 1  0/11798 (0.00%)  1/11799 (0.01%) 
Road traffic accident * 1  0/11798 (0.00%)  2/11799 (0.02%) 
Skull fracture * 1  6/11798 (0.05%)  5/11799 (0.04%) 
Subdural haematoma * 1  0/11798 (0.00%)  1/11799 (0.01%) 
Tendon injury * 1  0/11798 (0.00%)  1/11799 (0.01%) 
Thermal burn * 1  25/11798 (0.21%)  36/11799 (0.31%) 
Tibia fracture * 1  1/11798 (0.01%)  2/11799 (0.02%) 
Tongue injury * 1  1/11798 (0.01%)  0/11799 (0.00%) 
Tooth fracture * 1  1/11798 (0.01%)  0/11799 (0.00%) 
Toxicity to various agents * 1  12/11798 (0.10%)  12/11799 (0.10%) 
Traumatic haematoma * 1  1/11798 (0.01%)  0/11799 (0.00%) 
Upper limb fracture * 1  3/11798 (0.03%)  4/11799 (0.03%) 
Vulvovaginal injury * 1  1/11798 (0.01%)  0/11799 (0.00%) 
Wound * 1  0/11798 (0.00%)  5/11799 (0.04%) 
Wound dehiscence * 1  1/11798 (0.01%)  0/11799 (0.00%) 
Investigations     
Acid base balance abnormal * 1  1/11798 (0.01%)  0/11799 (0.00%) 
Aspiration bronchial * 1  2/11798 (0.02%)  3/11799 (0.03%) 
Metabolism and nutrition disorders     
Cow's milk intolerance * 1  1/11798 (0.01%)  1/11799 (0.01%) 
Dehydration * 1  463/11798 (3.92%)  438/11799 (3.71%) 
Diabetes mellitus * 1  1/11798 (0.01%)  0/11799 (0.00%) 
Diabetic ketoacidosis * 1  1/11798 (0.01%)  0/11799 (0.00%) 
Electrolyte imbalance * 1  8/11798 (0.07%)  5/11799 (0.04%) 
Failure to thrive * 1  1/11798 (0.01%)  0/11799 (0.00%) 
Feeding disorder neonatal * 1  0/11798 (0.00%)  1/11799 (0.01%) 
Food intolerance * 1  0/11798 (0.00%)  3/11799 (0.03%) 
Hypercalcaemia * 1  1/11798 (0.01%)  0/11799 (0.00%) 
Hyperglycaemia * 1  0/11798 (0.00%)  1/11799 (0.01%) 
Hypoglycaemia * 1  3/11798 (0.03%)  0/11799 (0.00%) 
Hypokalaemia * 1  4/11798 (0.03%)  5/11799 (0.04%) 
Lactose intolerance * 1  0/11798 (0.00%)  1/11799 (0.01%) 
Malnutrition * 1  3/11798 (0.03%)  4/11799 (0.03%) 
Metabolic acidosis * 1  1/11798 (0.01%)  0/11799 (0.00%) 
Type 1 diabetes mellitus * 1  0/11798 (0.00%)  1/11799 (0.01%) 
Musculoskeletal and connective tissue disorders     
Arthritis * 1  0/11798 (0.00%)  1/11799 (0.01%) 
Compartment syndrome * 1  1/11798 (0.01%)  0/11799 (0.00%) 
Connective tissue disorder * 1  0/11798 (0.00%)  1/11799 (0.01%) 
Dactylitis * 1  0/11798 (0.00%)  2/11799 (0.02%) 
Muscular weakness * 1  0/11798 (0.00%)  1/11799 (0.01%) 
Periostitis * 1  0/11798 (0.00%)  1/11799 (0.01%) 
Sacroiliitis * 1  0/11798 (0.00%)  1/11799 (0.01%) 
Synovitis * 1  3/11798 (0.03%)  2/11799 (0.02%) 
Tenosynovitis * 1  0/11798 (0.00%)  1/11799 (0.01%) 
Torticollis * 1  1/11798 (0.01%)  0/11799 (0.00%) 
Trigger finger * 1  1/11798 (0.01%)  0/11799 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Acute lymphocytic leukaemia * 1  1/11798 (0.01%)  2/11799 (0.02%) 
Acute myeloid leukaemia * 1  1/11798 (0.01%)  1/11799 (0.01%) 
Brain neoplasm * 1  1/11798 (0.01%)  0/11799 (0.00%) 
Hepatoblastoma * 1  1/11798 (0.01%)  0/11799 (0.00%) 
Histiocytosis haematophagic * 1  0/11798 (0.00%)  1/11799 (0.01%) 
Nephroblastoma * 1  0/11798 (0.00%)  1/11799 (0.01%) 
Neuroblastoma * 1  0/11798 (0.00%)  2/11799 (0.02%) 
Retinoblastoma bilateral * 1  0/11798 (0.00%)  1/11799 (0.01%) 
Nervous system disorders     
Ataxia * 1  2/11798 (0.02%)  2/11799 (0.02%) 
Brain injury * 1  1/11798 (0.01%)  0/11799 (0.00%) 
Brain oedema * 1  0/11798 (0.00%)  1/11799 (0.01%) 
Cerebrospinal fistula * 1  1/11798 (0.01%)  0/11799 (0.00%) 
Cns ventriculitis * 1  1/11798 (0.01%)  0/11799 (0.00%) 
Convulsion * 1  28/11798 (0.24%)  25/11799 (0.21%) 
Dystonia * 1  0/11798 (0.00%)  1/11799 (0.01%) 
Encephalopathy * 1  0/11798 (0.00%)  1/11799 (0.01%) 
Epilepsy * 1  2/11798 (0.02%)  2/11799 (0.02%) 
Extrapyramidal disorder * 1  2/11798 (0.02%)  0/11799 (0.00%) 
Febrile convulsion * 1  95/11798 (0.81%)  135/11799 (1.14%) 
Grand mal convulsion * 1  0/11798 (0.00%)  1/11799 (0.01%) 
Guillain-barre syndrome * 1  0/11798 (0.00%)  1/11799 (0.01%) 
Hypoxic-ischaemic encephalopathy * 1  1/11798 (0.01%)  0/11799 (0.00%) 
Infantile spasms * 1  0/11798 (0.00%)  1/11799 (0.01%) 
Intracranial pressure increased * 1  0/11798 (0.00%)  1/11799 (0.01%) 
Myoclonic epilepsy * 1  0/11798 (0.00%)  1/11799 (0.01%) 
Post-traumatic epilepsy * 1  1/11798 (0.01%)  0/11799 (0.00%) 
Presyncope * 1  0/11798 (0.00%)  1/11799 (0.01%) 
Status epilepticus * 1  1/11798 (0.01%)  0/11799 (0.00%) 
Syncope * 1  1/11798 (0.01%)  1/11799 (0.01%) 
Viith nerve paralysis * 1  0/11798 (0.00%)  1/11799 (0.01%) 
Pregnancy, puerperium and perinatal conditions     
Cephalhaematoma * 1  1/11798 (0.01%)  1/11799 (0.01%) 
Psychiatric disorders     
Agitation * 1  0/11798 (0.00%)  1/11799 (0.01%) 
Binge eating * 1  1/11798 (0.01%)  0/11799 (0.00%) 
Breath holding * 1  2/11798 (0.02%)  6/11799 (0.05%) 
Psychomotor retardation * 1  0/11798 (0.00%)  1/11799 (0.01%) 
Renal and urinary disorders     
Glomerulonephritis acute * 1  2/11798 (0.02%)  0/11799 (0.00%) 
Haematuria * 1  3/11798 (0.03%)  4/11799 (0.03%) 
Hydronephrosis * 1  0/11798 (0.00%)  1/11799 (0.01%) 
Nephrotic syndrome * 1  2/11798 (0.02%)  3/11799 (0.03%) 
Oliguria * 1  1/11798 (0.01%)  0/11799 (0.00%) 
Prerenal failure * 1  1/11798 (0.01%)  0/11799 (0.00%) 
Pyelocaliectasis * 1  1/11798 (0.01%)  0/11799 (0.00%) 
Renal failure acute * 1  0/11798 (0.00%)  1/11799 (0.01%) 
Reproductive system and breast disorders     
Balanoposthitis * 1  1/11798 (0.01%)  0/11799 (0.00%) 
Genital lesion * 1  1/11798 (0.01%)  0/11799 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
Acute lung injury * 1  1/11798 (0.01%)  0/11799 (0.00%) 
Acute pulmonary oedema * 1  1/11798 (0.01%)  1/11799 (0.01%) 
Acute respiratory failure * 1  0/11798 (0.00%)  2/11799 (0.02%) 
Allergic bronchitis * 1  1/11798 (0.01%)  1/11799 (0.01%) 
Apnoea * 1  3/11798 (0.03%)  1/11799 (0.01%) 
Apnoeic attack * 1  0/11798 (0.00%)  1/11799 (0.01%) 
Apparent life threatening event * 1  4/11798 (0.03%)  3/11799 (0.03%) 
Asphyxia * 1  2/11798 (0.02%)  3/11799 (0.03%) 
Aspiration * 1