Trial Outcomes & Findings for Persistence of Antibodies at 3, 4 and 6 Years of Age After Vaccination With Meningococcal, Pneumococcal and Hib Vaccines (NCT NCT00891176)

NCT ID: NCT00891176

Last Updated: 2018-02-15

Results Overview

rSBA-MenC antibody cut-off value assessed was equal to or above 1:8. The rSBA-MenC assay was performed at the Public Health England (PHE) laboratory at 6 years of age while the GSK laboratory was used for testing at 3 and 4 years of age.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 582 participants
• Primary outcome timeframe: At 3 years of age
• Results posted on: 2018-02-15

Participant Flow

At 3 years of age, 582 subjects were enrolled. One subject who did not participate in the primary study was enrolled by mistake and was therefore withdrawn from the study. Therefore the total number of subjects participating at the 36 months of age time point was 581.

Participant milestones

Measure	Synflorix-Meningitec Group Subjects who received concomitantly in the primary study (NCT00334334): 3 primary doses of Synflorix intramuscularly into the right thigh at 2, 4 and 6 months of age 2 primary doses of Meningitec intramuscularly into the lower left thigh at 2 and 4 months of age. 3 primary doses of Infanrix hexa intramuscularly into the upper left thigh at 2, 4 and 6 months of age. (In Poland subjects were offered a third dose of Meningitec at 7 months of age to comply with national recommendations). During the booster study (NCT00463437) subjects received the same vaccines as during the primary study at 11-18 months of age, with the exception of Spain, where Infanrix IPV/Hib was given instead of Infanrix hexa.	Synflorix-NeisVac-C Group Subjects who received concomitantly in the primary study (NCT00334334): 3 primary doses of Synflorix intramuscularly into the right thigh at 2, 4 and 6 months of age, 2 primary doses of Neis-Vac-C intramuscularly into the lower left thigh at 2 and 4 months of age and 3 primary doses of Infanrix hexa intramuscularly into the upper left thigh at 2, 4 and 6 months of age. (In Poland subjects were offered a third dose of Neis-Vac-C at 7 months of age to comply with national recommendations). During the booster study (NCT00463437) subjects received the same vaccines as during the primary study at 11-18 months of age, with the exception of Spain, where Infanrix IPV/Hib was given instead of Infanrix hexa.	Synflorix-Menitorix Group Subjects who received concomitantly in the primary study (NCT00334334): 3 primary doses of Synflorix intramuscularly into the right thigh at 2, 4 and 6 months of age, 3 primary doses of Menitorix intramuscularly into the lower left thigh at 2, 4 and 6 months of age and 3 primary doses of Infanrix penta intramuscularly into the upper left thigh at 2, 4 and 6 months of age. During the booster study (NCT00463437) subjects received the same vaccines as during the primary study at 11-18 months of age, with the exception of Spain, where Infanrix IPV was given instead of Infanrix penta.	Prevenar-Menitorix Group Subjects who received concomitantly in the primary study (NCT00334334): 3 primary doses of Prevenar intramuscularly into the right thigh at 2, 4 and 6 months of age, 3 primary doses of Menitorix intramuscularly into the lower left thigh at 2, 4 and 6 months of age and 3 primary doses of Infanrix penta intramuscularly into the upper left thigh at 2, 4 and 6 months of age. During the booster study (NCT00463437) subjects received the same vaccines as during the primary study at 11-18 months of age, with the exception of Spain, where Infanrix IPV was given instead of Infanrix penta.
At 3 Years of Age STARTED	144	147	149	141
At 3 Years of Age COMPLETED	144	147	149	141
At 3 Years of Age NOT COMPLETED	0	0	0	0
At 4 Years of Age STARTED	140	142	142	137
At 4 Years of Age COMPLETED	140	142	142	137
At 4 Years of Age NOT COMPLETED	0	0	0	0
At 6 Years of Age STARTED	131	138	135	135
At 6 Years of Age COMPLETED	131	138	135	135
At 6 Years of Age NOT COMPLETED	0	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Persistence of Antibodies at 3, 4 and 6 Years of Age After Vaccination With Meningococcal, Pneumococcal and Hib Vaccines

Baseline characteristics by cohort

Measure	Synflorix-Meningitec Group n=144 Participants Subjects who received concomitantly in the primary study (NCT00334334): 3 primary doses of Synflorix intramuscularly into the right thigh at 2, 4 and 6 months of age 2 primary doses of Meningitec intramuscularly into the lower left thigh at 2 and 4 months of age and 3 primary doses of Infanrix hexa intramuscularly into the upper left thigh at 2, 4 and 6 months of age. (In Poland subjects were offered a third dose of Meningitec at 7 months of age to comply with national recommendations). During the booster study (NCT00463437) subjects received the same vaccines as during the primary study at 11-18 months of age, with the exception of Spain, where Infanrix IPV/Hib was given instead of Infanrix hexa.	Synflorix-NeisVac-C Group n=147 Participants Subjects who received concomitantly in the primary study (NCT00334334): 3 primary doses of Synflorix intramuscularly into the right thigh at 2, 4 and 6 months of age, 2 primary doses of Neis-Vac-C intramuscularly into the lower left thigh at 2 and 4 months of age and 3 primary doses of Infanrix hexa intramuscularly into the upper left thigh at 2, 4 and 6 months of age. (In Poland subjects were offered a third dose of Neis-Vac-C at 7 months of age to comply with national recommendations). During the booster study (NCT00463437) subjects received the same vaccines as during the primary study at 11-18 months of age, with the exception of Spain, where Infanrix IPV/Hib was given instead of Infanrix hexa.	Synflorix-Menitorix Group n=149 Participants Subjects who received concomitantly in the primary study (NCT00334334): 3 primary doses of Synflorix intramuscularly into the right thigh at 2, 4 and 6 months of age, 3 primary doses of Menitorix intramuscularly into the lower left thigh at 2, 4 and 6 months of age and 3 primary doses of Infanrix penta intramuscularly into the upper left thigh at 2, 4 and 6 months of age. During the booster study (NCT00463437) subjects received the same vaccines as during the primary study at 11-18 months of age, with the exception of Spain, where Infanrix IPV was given instead of Infanrix penta.	Prevenar-Menitorix Group n=141 Participants Subjects who received concomitantly in the primary study (NCT00334334): 3 primary doses of Prevenar intramuscularly into the right thigh at 2, 4 and 6 months of age, 3 primary doses of Menitorix intramuscularly into the lower left thigh at 2, 4 and 6 months of age and 3 primary doses of Infanrix penta intramuscularly into the upper left thigh at 2, 4 and 6 months of age. During the booster study (NCT00463437) subjects received the same vaccines as during the primary study at 11-18 months of age, with the exception of Spain, where Infanrix IPV was given instead of Infanrix penta.	Total n=581 Participants Total of all reporting groups
Age, Continuous	37.1 Months STANDARD_DEVIATION 1.17 • n=5 Participants	37.2 Months STANDARD_DEVIATION 1.20 • n=7 Participants	37.3 Months STANDARD_DEVIATION 1.18 • n=5 Participants	37.3 Months STANDARD_DEVIATION 1.28 • n=4 Participants	37.2 Months STANDARD_DEVIATION 1.21 • n=21 Participants
Sex: Female, Male Female	71 Participants n=5 Participants	65 Participants n=7 Participants	86 Participants n=5 Participants	71 Participants n=4 Participants	293 Participants n=21 Participants
Sex: Female, Male Male	73 Participants n=5 Participants	82 Participants n=7 Participants	63 Participants n=5 Participants	70 Participants n=4 Participants	288 Participants n=21 Participants

PRIMARY outcome

Timeframe: At 3 years of age

Population: Analysis was performed on the According-to-Protocol cohort for antibody persistence at 3 years of age, which included all evaluable subjects who had received the full vaccination course in the primary study (NCT00334334) and in the booster study (NCT00463437) and had available results at 3 years of age.

rSBA-MenC antibody cut-off value assessed was equal to or above 1:8. The rSBA-MenC assay was performed at the Public Health England (PHE) laboratory at 6 years of age while the GSK laboratory was used for testing at 3 and 4 years of age.

Outcome measures

Measure	Synflorix-Meningitec Group n=139 Participants Subjects who received concomitantly in the primary study (NCT00334334): 3 primary doses of Synflorix intramuscularly into the right thigh at 2, 4 and 6 months of age 2 primary doses of Meningitec intramuscularly into the lower left thigh at 2 and 4 months of age and 3 primary doses of Infanrix hexa intramuscularly into the upper left thigh at 2, 4 and 6 months of age. (In Poland subjects were offered a third dose of Meningitec at 7 months of age to comply with national recommendations). During the booster study (NCT00463437) subjects received the same vaccines as during the primary study at 11-18 months of age, with the exception of Spain, where Infanrix IPV/Hib was given instead of Infanrix hexa.	Synflorix-NeisVac-C Group n=146 Participants Subjects who received concomitantly in the primary study (NCT00334334): 3 primary doses of Synflorix intramuscularly into the right thigh at 2, 4 and 6 months of age, 2 primary doses of Neis-Vac-C intramuscularly into the lower left thigh at 2 and 4 months of age and 3 primary doses of Infanrix hexa intramuscularly into the upper left thigh at 2, 4 and 6 months of age. (In Poland subjects were offered a third dose of Neis-Vac-C at 7 months of age to comply with national recommendations). During the booster study (NCT00463437) subjects received the same vaccines as during the primary study at 11-18 months of age, with the exception of Spain, where Infanrix IPV/Hib was given instead of Infanrix hexa.	Synflorix-Menitorix Group n=143 Participants Subjects who received concomitantly in the primary study (NCT00334334): 3 primary doses of Synflorix intramuscularly into the right thigh at 2, 4 and 6 months of age, 3 primary doses of Menitorix intramuscularly into the lower left thigh at 2, 4 and 6 months of age and 3 primary doses of Infanrix penta intramuscularly into the upper left thigh at 2, 4 and 6 months of age. During the booster study (NCT00463437) subjects received the same vaccines as during the primary study at 11-18 months of age, with the exception of Spain, where Infanrix IPV was given instead of Infanrix penta.	Prevenar-Menitorix Group n=137 Participants Subjects who received concomitantly in the primary study (NCT00334334): 3 primary doses of Prevenar intramuscularly into the right thigh at 2, 4 and 6 months of age, 3 primary doses of Menitorix intramuscularly into the lower left thigh at 2, 4 and 6 months of age and 3 primary doses of Infanrix penta intramuscularly into the upper left thigh at 2, 4 and 6 months of age. During the booster study (NCT00463437) subjects received the same vaccines as during the primary study at 11-18 months of age, with the exception of Spain, where Infanrix IPV was given instead of Infanrix penta.
Number of Subjects With Meningococcal Serogroup C Serum Bactericidal Titers Using Rabbit Complement (rSBA-MenC) Equal to or Above Cut-off Value	120 subjects	144 subjects	127 subjects	113 subjects

PRIMARY outcome

Timeframe: At 6 years of age

Population: Analysis was performed on the According-to-Protocol cohort for antibody persistence at 6 years of age, which included all evaluable subjects who had received the full vaccination course in the primary study (NCT00334334) and in the booster study (NCT00463437) and had available results at 6 years of age.

rSBA-MenC antibody cut-off value assessed was equal to or above 1:8. The rSBA-MenC assay was performed at the Public Health England (PHE) laboratory at 6 years of age while the GSK laboratory was used for testing at 3 and 4 years of age.

Outcome measures

Measure	Synflorix-Meningitec Group n=128 Participants Subjects who received concomitantly in the primary study (NCT00334334): 3 primary doses of Synflorix intramuscularly into the right thigh at 2, 4 and 6 months of age 2 primary doses of Meningitec intramuscularly into the lower left thigh at 2 and 4 months of age and 3 primary doses of Infanrix hexa intramuscularly into the upper left thigh at 2, 4 and 6 months of age. (In Poland subjects were offered a third dose of Meningitec at 7 months of age to comply with national recommendations). During the booster study (NCT00463437) subjects received the same vaccines as during the primary study at 11-18 months of age, with the exception of Spain, where Infanrix IPV/Hib was given instead of Infanrix hexa.	Synflorix-NeisVac-C Group n=137 Participants Subjects who received concomitantly in the primary study (NCT00334334): 3 primary doses of Synflorix intramuscularly into the right thigh at 2, 4 and 6 months of age, 2 primary doses of Neis-Vac-C intramuscularly into the lower left thigh at 2 and 4 months of age and 3 primary doses of Infanrix hexa intramuscularly into the upper left thigh at 2, 4 and 6 months of age. (In Poland subjects were offered a third dose of Neis-Vac-C at 7 months of age to comply with national recommendations). During the booster study (NCT00463437) subjects received the same vaccines as during the primary study at 11-18 months of age, with the exception of Spain, where Infanrix IPV/Hib was given instead of Infanrix hexa.	Synflorix-Menitorix Group n=130 Participants Subjects who received concomitantly in the primary study (NCT00334334): 3 primary doses of Synflorix intramuscularly into the right thigh at 2, 4 and 6 months of age, 3 primary doses of Menitorix intramuscularly into the lower left thigh at 2, 4 and 6 months of age and 3 primary doses of Infanrix penta intramuscularly into the upper left thigh at 2, 4 and 6 months of age. During the booster study (NCT00463437) subjects received the same vaccines as during the primary study at 11-18 months of age, with the exception of Spain, where Infanrix IPV was given instead of Infanrix penta.	Prevenar-Menitorix Group n=134 Participants Subjects who received concomitantly in the primary study (NCT00334334): 3 primary doses of Prevenar intramuscularly into the right thigh at 2, 4 and 6 months of age, 3 primary doses of Menitorix intramuscularly into the lower left thigh at 2, 4 and 6 months of age and 3 primary doses of Infanrix penta intramuscularly into the upper left thigh at 2, 4 and 6 months of age. During the booster study (NCT00463437) subjects received the same vaccines as during the primary study at 11-18 months of age, with the exception of Spain, where Infanrix IPV was given instead of Infanrix penta.
Number of Subjects With Meningococcal Serogroup C Serum Bactericidal Titers Using Rabbit Complement (rSBA-MenC) Equal to or Above Cut-off Value	31 Subjects	55 Subjects	50 Subjects	34 Subjects

PRIMARY outcome

Timeframe: At 4 years of age

Population: Analysis was performed on the According-to-Protocol cohort for antibody persistence at 4 years of age, which included all evaluable subjects who had received the full vaccination course in the primary study (NCT00334334) and in the booster study (NCT00463437) and had available results at 4 years of age.

rSBA-MenC antibody cut-off value assessed was equal to or above 1:8. The rSBA-MenC assay was performed at the Public Health England (PHE) laboratory at 6 years of age while the GSK laboratory was used for testing at 3 and 4 years of age.

Outcome measures

Measure	Synflorix-Meningitec Group n=134 Participants Subjects who received concomitantly in the primary study (NCT00334334): 3 primary doses of Synflorix intramuscularly into the right thigh at 2, 4 and 6 months of age 2 primary doses of Meningitec intramuscularly into the lower left thigh at 2 and 4 months of age and 3 primary doses of Infanrix hexa intramuscularly into the upper left thigh at 2, 4 and 6 months of age. (In Poland subjects were offered a third dose of Meningitec at 7 months of age to comply with national recommendations). During the booster study (NCT00463437) subjects received the same vaccines as during the primary study at 11-18 months of age, with the exception of Spain, where Infanrix IPV/Hib was given instead of Infanrix hexa.	Synflorix-NeisVac-C Group n=137 Participants Subjects who received concomitantly in the primary study (NCT00334334): 3 primary doses of Synflorix intramuscularly into the right thigh at 2, 4 and 6 months of age, 2 primary doses of Neis-Vac-C intramuscularly into the lower left thigh at 2 and 4 months of age and 3 primary doses of Infanrix hexa intramuscularly into the upper left thigh at 2, 4 and 6 months of age. (In Poland subjects were offered a third dose of Neis-Vac-C at 7 months of age to comply with national recommendations). During the booster study (NCT00463437) subjects received the same vaccines as during the primary study at 11-18 months of age, with the exception of Spain, where Infanrix IPV/Hib was given instead of Infanrix hexa.	Synflorix-Menitorix Group n=128 Participants Subjects who received concomitantly in the primary study (NCT00334334): 3 primary doses of Synflorix intramuscularly into the right thigh at 2, 4 and 6 months of age, 3 primary doses of Menitorix intramuscularly into the lower left thigh at 2, 4 and 6 months of age and 3 primary doses of Infanrix penta intramuscularly into the upper left thigh at 2, 4 and 6 months of age. During the booster study (NCT00463437) subjects received the same vaccines as during the primary study at 11-18 months of age, with the exception of Spain, where Infanrix IPV was given instead of Infanrix penta.	Prevenar-Menitorix Group n=128 Participants Subjects who received concomitantly in the primary study (NCT00334334): 3 primary doses of Prevenar intramuscularly into the right thigh at 2, 4 and 6 months of age, 3 primary doses of Menitorix intramuscularly into the lower left thigh at 2, 4 and 6 months of age and 3 primary doses of Infanrix penta intramuscularly into the upper left thigh at 2, 4 and 6 months of age. During the booster study (NCT00463437) subjects received the same vaccines as during the primary study at 11-18 months of age, with the exception of Spain, where Infanrix IPV was given instead of Infanrix penta.
Number of Subjects With Meningococcal Serogroup C Serum Bactericidal Titers Using Rabbit Complement (rSBA-MenC) Equal to or Above Cut-off Value	97 Subjects	132 Subjects	108 Subjects	98 Subjects

SECONDARY outcome

Timeframe: At 3 years of age

Population: Analysis was performed on the According-to-Protocol cohort for antibody persistence at 3 years of age, which included all evaluable subjects who had received the full vaccination course in the primary study (NCT00334334) and in the booster study (NCT00463437) and had available results at 3 years of age.

The cut-off value was defined as a titer equal to or above 1:128.

Outcome measures

Measure	Synflorix-Meningitec Group n=139 Participants Subjects who received concomitantly in the primary study (NCT00334334): 3 primary doses of Synflorix intramuscularly into the right thigh at 2, 4 and 6 months of age 2 primary doses of Meningitec intramuscularly into the lower left thigh at 2 and 4 months of age and 3 primary doses of Infanrix hexa intramuscularly into the upper left thigh at 2, 4 and 6 months of age. (In Poland subjects were offered a third dose of Meningitec at 7 months of age to comply with national recommendations). During the booster study (NCT00463437) subjects received the same vaccines as during the primary study at 11-18 months of age, with the exception of Spain, where Infanrix IPV/Hib was given instead of Infanrix hexa.	Synflorix-NeisVac-C Group n=146 Participants Subjects who received concomitantly in the primary study (NCT00334334): 3 primary doses of Synflorix intramuscularly into the right thigh at 2, 4 and 6 months of age, 2 primary doses of Neis-Vac-C intramuscularly into the lower left thigh at 2 and 4 months of age and 3 primary doses of Infanrix hexa intramuscularly into the upper left thigh at 2, 4 and 6 months of age. (In Poland subjects were offered a third dose of Neis-Vac-C at 7 months of age to comply with national recommendations). During the booster study (NCT00463437) subjects received the same vaccines as during the primary study at 11-18 months of age, with the exception of Spain, where Infanrix IPV/Hib was given instead of Infanrix hexa.	Synflorix-Menitorix Group n=143 Participants Subjects who received concomitantly in the primary study (NCT00334334): 3 primary doses of Synflorix intramuscularly into the right thigh at 2, 4 and 6 months of age, 3 primary doses of Menitorix intramuscularly into the lower left thigh at 2, 4 and 6 months of age and 3 primary doses of Infanrix penta intramuscularly into the upper left thigh at 2, 4 and 6 months of age. During the booster study (NCT00463437) subjects received the same vaccines as during the primary study at 11-18 months of age, with the exception of Spain, where Infanrix IPV was given instead of Infanrix penta.	Prevenar-Menitorix Group n=137 Participants Subjects who received concomitantly in the primary study (NCT00334334): 3 primary doses of Prevenar intramuscularly into the right thigh at 2, 4 and 6 months of age, 3 primary doses of Menitorix intramuscularly into the lower left thigh at 2, 4 and 6 months of age and 3 primary doses of Infanrix penta intramuscularly into the upper left thigh at 2, 4 and 6 months of age. During the booster study (NCT00463437) subjects received the same vaccines as during the primary study at 11-18 months of age, with the exception of Spain, where Infanrix IPV was given instead of Infanrix penta.
Number of Subjects With an rSBA-MenC Titer Equal to or Above Cut-off Value	69 subjects	109 subjects	98 subjects	68 subjects

SECONDARY outcome

Timeframe: At 3 years of age

Population: Analysis was performed on the According-to-Protocol cohort for antibody persistence at 3 years of age, which included all evaluable subjects who had received the full vaccination course in the primary study (NCT00334334) and in the booster study (NCT00463437) and had available results at 3 years of age.

Titers are given as Geometric Mean Titers (GMTs).

Outcome measures

Measure	Synflorix-Meningitec Group n=139 Participants Subjects who received concomitantly in the primary study (NCT00334334): 3 primary doses of Synflorix intramuscularly into the right thigh at 2, 4 and 6 months of age 2 primary doses of Meningitec intramuscularly into the lower left thigh at 2 and 4 months of age and 3 primary doses of Infanrix hexa intramuscularly into the upper left thigh at 2, 4 and 6 months of age. (In Poland subjects were offered a third dose of Meningitec at 7 months of age to comply with national recommendations). During the booster study (NCT00463437) subjects received the same vaccines as during the primary study at 11-18 months of age, with the exception of Spain, where Infanrix IPV/Hib was given instead of Infanrix hexa.	Synflorix-NeisVac-C Group n=146 Participants Subjects who received concomitantly in the primary study (NCT00334334): 3 primary doses of Synflorix intramuscularly into the right thigh at 2, 4 and 6 months of age, 2 primary doses of Neis-Vac-C intramuscularly into the lower left thigh at 2 and 4 months of age and 3 primary doses of Infanrix hexa intramuscularly into the upper left thigh at 2, 4 and 6 months of age. (In Poland subjects were offered a third dose of Neis-Vac-C at 7 months of age to comply with national recommendations). During the booster study (NCT00463437) subjects received the same vaccines as during the primary study at 11-18 months of age, with the exception of Spain, where Infanrix IPV/Hib was given instead of Infanrix hexa.	Synflorix-Menitorix Group n=143 Participants Subjects who received concomitantly in the primary study (NCT00334334): 3 primary doses of Synflorix intramuscularly into the right thigh at 2, 4 and 6 months of age, 3 primary doses of Menitorix intramuscularly into the lower left thigh at 2, 4 and 6 months of age and 3 primary doses of Infanrix penta intramuscularly into the upper left thigh at 2, 4 and 6 months of age. During the booster study (NCT00463437) subjects received the same vaccines as during the primary study at 11-18 months of age, with the exception of Spain, where Infanrix IPV was given instead of Infanrix penta.	Prevenar-Menitorix Group n=137 Participants Subjects who received concomitantly in the primary study (NCT00334334): 3 primary doses of Prevenar intramuscularly into the right thigh at 2, 4 and 6 months of age, 3 primary doses of Menitorix intramuscularly into the lower left thigh at 2, 4 and 6 months of age and 3 primary doses of Infanrix penta intramuscularly into the upper left thigh at 2, 4 and 6 months of age. During the booster study (NCT00463437) subjects received the same vaccines as during the primary study at 11-18 months of age, with the exception of Spain, where Infanrix IPV was given instead of Infanrix penta.
rSBA-MenC Titers	100.5 Titer Interval 75.6 to 133.8	235.3 Titer Interval 189.1 to 292.7	167.5 Titer Interval 126.0 to 222.7	84.0 Titer Interval 61.6 to 114.6

SECONDARY outcome

Timeframe: At 3 years of age

Population: Analysis was performed on the According-to-Protocol cohort for antibody persistence at 3 years of age, which included all evaluable subjects who had received the full vaccination course in the primary study (NCT00334334) and in the booster study (NCT00463437) and had available results at 3 years of age.

The cut-off values were defined as a concentration equal to or above 0.15 microgram per milliliter (μg/mL) and equal to or above 1.0 μg/mL.

Outcome measures

Measure	Synflorix-Meningitec Group n=132 Participants Subjects who received concomitantly in the primary study (NCT00334334): 3 primary doses of Synflorix intramuscularly into the right thigh at 2, 4 and 6 months of age 2 primary doses of Meningitec intramuscularly into the lower left thigh at 2 and 4 months of age and 3 primary doses of Infanrix hexa intramuscularly into the upper left thigh at 2, 4 and 6 months of age. (In Poland subjects were offered a third dose of Meningitec at 7 months of age to comply with national recommendations). During the booster study (NCT00463437) subjects received the same vaccines as during the primary study at 11-18 months of age, with the exception of Spain, where Infanrix IPV/Hib was given instead of Infanrix hexa.	Synflorix-NeisVac-C Group n=139 Participants Subjects who received concomitantly in the primary study (NCT00334334): 3 primary doses of Synflorix intramuscularly into the right thigh at 2, 4 and 6 months of age, 2 primary doses of Neis-Vac-C intramuscularly into the lower left thigh at 2 and 4 months of age and 3 primary doses of Infanrix hexa intramuscularly into the upper left thigh at 2, 4 and 6 months of age. (In Poland subjects were offered a third dose of Neis-Vac-C at 7 months of age to comply with national recommendations). During the booster study (NCT00463437) subjects received the same vaccines as during the primary study at 11-18 months of age, with the exception of Spain, where Infanrix IPV/Hib was given instead of Infanrix hexa.	Synflorix-Menitorix Group n=137 Participants Subjects who received concomitantly in the primary study (NCT00334334): 3 primary doses of Synflorix intramuscularly into the right thigh at 2, 4 and 6 months of age, 3 primary doses of Menitorix intramuscularly into the lower left thigh at 2, 4 and 6 months of age and 3 primary doses of Infanrix penta intramuscularly into the upper left thigh at 2, 4 and 6 months of age. During the booster study (NCT00463437) subjects received the same vaccines as during the primary study at 11-18 months of age, with the exception of Spain, where Infanrix IPV was given instead of Infanrix penta.	Prevenar-Menitorix Group n=138 Participants Subjects who received concomitantly in the primary study (NCT00334334): 3 primary doses of Prevenar intramuscularly into the right thigh at 2, 4 and 6 months of age, 3 primary doses of Menitorix intramuscularly into the lower left thigh at 2, 4 and 6 months of age and 3 primary doses of Infanrix penta intramuscularly into the upper left thigh at 2, 4 and 6 months of age. During the booster study (NCT00463437) subjects received the same vaccines as during the primary study at 11-18 months of age, with the exception of Spain, where Infanrix IPV was given instead of Infanrix penta.
Number of Subjects With Anti-polyribosyl-ribitol Phosphate (Anti-PRP) Antibody Concentrations Equal to or Above Cut-off Values ≥ 0.15 µg/mL	132 subjects	139 subjects	137 subjects	138 subjects
Number of Subjects With Anti-polyribosyl-ribitol Phosphate (Anti-PRP) Antibody Concentrations Equal to or Above Cut-off Values ≥ 1.0 µg/mL	101 subjects	105 subjects	127 subjects	115 subjects

SECONDARY outcome

Timeframe: At 3 years of age

Population: Analysis was performed on the According-to-Protocol cohort for antibody persistence at 3 years of age, which included all evaluable subjects who had received the full vaccination course in the primary study (NCT00334334) and in the booster study (NCT00463437) and had available results at 3 years of age.

Concentrations were defined as Geometric Mean Concentrations (GMCs) in μg/mL,

Outcome measures

Measure	Synflorix-Meningitec Group n=132 Participants Subjects who received concomitantly in the primary study (NCT00334334): 3 primary doses of Synflorix intramuscularly into the right thigh at 2, 4 and 6 months of age 2 primary doses of Meningitec intramuscularly into the lower left thigh at 2 and 4 months of age and 3 primary doses of Infanrix hexa intramuscularly into the upper left thigh at 2, 4 and 6 months of age. (In Poland subjects were offered a third dose of Meningitec at 7 months of age to comply with national recommendations). During the booster study (NCT00463437) subjects received the same vaccines as during the primary study at 11-18 months of age, with the exception of Spain, where Infanrix IPV/Hib was given instead of Infanrix hexa.	Synflorix-NeisVac-C Group n=139 Participants Subjects who received concomitantly in the primary study (NCT00334334): 3 primary doses of Synflorix intramuscularly into the right thigh at 2, 4 and 6 months of age, 2 primary doses of Neis-Vac-C intramuscularly into the lower left thigh at 2 and 4 months of age and 3 primary doses of Infanrix hexa intramuscularly into the upper left thigh at 2, 4 and 6 months of age. (In Poland subjects were offered a third dose of Neis-Vac-C at 7 months of age to comply with national recommendations). During the booster study (NCT00463437) subjects received the same vaccines as during the primary study at 11-18 months of age, with the exception of Spain, where Infanrix IPV/Hib was given instead of Infanrix hexa.	Synflorix-Menitorix Group n=137 Participants Subjects who received concomitantly in the primary study (NCT00334334): 3 primary doses of Synflorix intramuscularly into the right thigh at 2, 4 and 6 months of age, 3 primary doses of Menitorix intramuscularly into the lower left thigh at 2, 4 and 6 months of age and 3 primary doses of Infanrix penta intramuscularly into the upper left thigh at 2, 4 and 6 months of age. During the booster study (NCT00463437) subjects received the same vaccines as during the primary study at 11-18 months of age, with the exception of Spain, where Infanrix IPV was given instead of Infanrix penta.	Prevenar-Menitorix Group n=138 Participants Subjects who received concomitantly in the primary study (NCT00334334): 3 primary doses of Prevenar intramuscularly into the right thigh at 2, 4 and 6 months of age, 3 primary doses of Menitorix intramuscularly into the lower left thigh at 2, 4 and 6 months of age and 3 primary doses of Infanrix penta intramuscularly into the upper left thigh at 2, 4 and 6 months of age. During the booster study (NCT00463437) subjects received the same vaccines as during the primary study at 11-18 months of age, with the exception of Spain, where Infanrix IPV was given instead of Infanrix penta.
Anti-PRP Concentrations	2.293 μg/mL Interval 1.87 to 2.812	2.222 μg/mL Interval 1.794 to 2.752	4.177 μg/mL Interval 3.427 to 5.092	3.636 μg/mL Interval 2.957 to 4.471

SECONDARY outcome

Timeframe: At 3 years of age

Population: Analysis was performed on the According-to-Protocol cohort for antibody persistence at 3 years of age, which included all evaluable subjects who had received the full vaccination course in the primary study (NCT00334334) and in the booster study (NCT00463437) and had available results at 3 years of age.

Antibody concentrations were expressed as GMCs in μg/mL.

Vaccine pneumococcal serotypes assessed included 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F.

Outcome measures

Measure	Synflorix-Meningitec Group n=141 Participants Subjects who received concomitantly in the primary study (NCT00334334): 3 primary doses of Synflorix intramuscularly into the right thigh at 2, 4 and 6 months of age 2 primary doses of Meningitec intramuscularly into the lower left thigh at 2 and 4 months of age and 3 primary doses of Infanrix hexa intramuscularly into the upper left thigh at 2, 4 and 6 months of age. (In Poland subjects were offered a third dose of Meningitec at 7 months of age to comply with national recommendations). During the booster study (NCT00463437) subjects received the same vaccines as during the primary study at 11-18 months of age, with the exception of Spain, where Infanrix IPV/Hib was given instead of Infanrix hexa.	Synflorix-NeisVac-C Group n=146 Participants Subjects who received concomitantly in the primary study (NCT00334334): 3 primary doses of Synflorix intramuscularly into the right thigh at 2, 4 and 6 months of age, 2 primary doses of Neis-Vac-C intramuscularly into the lower left thigh at 2 and 4 months of age and 3 primary doses of Infanrix hexa intramuscularly into the upper left thigh at 2, 4 and 6 months of age. (In Poland subjects were offered a third dose of Neis-Vac-C at 7 months of age to comply with national recommendations). During the booster study (NCT00463437) subjects received the same vaccines as during the primary study at 11-18 months of age, with the exception of Spain, where Infanrix IPV/Hib was given instead of Infanrix hexa.	Synflorix-Menitorix Group n=144 Participants Subjects who received concomitantly in the primary study (NCT00334334): 3 primary doses of Synflorix intramuscularly into the right thigh at 2, 4 and 6 months of age, 3 primary doses of Menitorix intramuscularly into the lower left thigh at 2, 4 and 6 months of age and 3 primary doses of Infanrix penta intramuscularly into the upper left thigh at 2, 4 and 6 months of age. During the booster study (NCT00463437) subjects received the same vaccines as during the primary study at 11-18 months of age, with the exception of Spain, where Infanrix IPV was given instead of Infanrix penta.	Prevenar-Menitorix Group n=140 Participants Subjects who received concomitantly in the primary study (NCT00334334): 3 primary doses of Prevenar intramuscularly into the right thigh at 2, 4 and 6 months of age, 3 primary doses of Menitorix intramuscularly into the lower left thigh at 2, 4 and 6 months of age and 3 primary doses of Infanrix penta intramuscularly into the upper left thigh at 2, 4 and 6 months of age. During the booster study (NCT00463437) subjects received the same vaccines as during the primary study at 11-18 months of age, with the exception of Spain, where Infanrix IPV was given instead of Infanrix penta.
Antibody Concentrations Against Vaccine Pneumococcal Serotypes Anti-1 (N= 139; 146; 142; 139)	0.26 μg/mL Interval 0.22 to 0.3	0.23 μg/mL Interval 0.19 to 0.26	0.21 μg/mL Interval 0.18 to 0.25	0.07 μg/mL Interval 0.06 to 0.09
Antibody Concentrations Against Vaccine Pneumococcal Serotypes Anti-4 (N= 141; 146; 144; 139)	0.27 μg/mL Interval 0.23 to 0.32	0.23 μg/mL Interval 0.2 to 0.27	0.23 μg/mL Interval 0.2 to 0.27	0.35 μg/mL Interval 0.29 to 0.42
Antibody Concentrations Against Vaccine Pneumococcal Serotypes Anti-5 (N= 140; 145; 144; 140)	0.46 μg/mL Interval 0.39 to 0.54	0.39 μg/mL Interval 0.33 to 0.46	0.41 μg/mL Interval 0.35 to 0.5	0.09 μg/mL Interval 0.07 to 0.1
Antibody Concentrations Against Vaccine Pneumococcal Serotypes Anti-6B (N= 139; 146; 144; 138)	0.59 μg/mL Interval 0.45 to 0.76	0.56 μg/mL Interval 0.45 to 0.71	0.63 μg/mL Interval 0.47 to 0.84	0.95 μg/mL Interval 0.77 to 1.18
Antibody Concentrations Against Vaccine Pneumococcal Serotypes Anti-7F (N= 141; 146; 144; 140)	0.58 μg/mL Interval 0.5 to 0.67	0.51 μg/mL Interval 0.43 to 0.59	0.54 μg/mL Interval 0.45 to 0.66	0.07 μg/mL Interval 0.05 to 0.09
Antibody Concentrations Against Vaccine Pneumococcal Serotypes Anti-9V (N= 141; 146; 144; 140)	0.60 μg/mL Interval 0.49 to 0.73	0.54 μg/mL Interval 0.44 to 0.66	0.47 μg/mL Interval 0.39 to 0.57	0.70 μg/mL Interval 0.57 to 0.85
Antibody Concentrations Against Vaccine Pneumococcal Serotypes Anti-14 (N= 141; 146; 144; 140)	1.33 μg/mL Interval 1.04 to 1.7	1.09 μg/mL Interval 0.88 to 1.35	1.00 μg/mL Interval 0.8 to 1.25	1.48 μg/mL Interval 1.23 to 1.78
Antibody Concentrations Against Vaccine Pneumococcal Serotypes Anti-18C (N= 141; 146; 143; 139)	0.60 μg/mL Interval 0.5 to 0.71	0.84 μg/mL Interval 0.73 to 0.97	0.59 μg/mL Interval 0.48 to 0.71	0.59 μg/mL Interval 0.5 to 0.7
Antibody Concentrations Against Vaccine Pneumococcal Serotypes Anti-19F (N= 141; 146; 144; 139)	2.06 μg/mL Interval 1.58 to 2.69	1.63 μg/mL Interval 1.27 to 2.09	1.35 μg/mL Interval 1.05 to 1.72	1.48 μg/mL Interval 1.07 to 2.05
Antibody Concentrations Against Vaccine Pneumococcal Serotypes Anti-23F (N= 140; 146; 144; 140)	0.73 μg/mL Interval 0.58 to 0.92	0.69 μg/mL Interval 0.55 to 0.88	0.62 μg/mL Interval 0.46 to 0.82	1.36 μg/mL Interval 1.07 to 1.73

SECONDARY outcome

Timeframe: At 3 years of age

Population: Analysis was performed on the According-to-Protocol cohort for antibody persistence at 3 years of age, which included all evaluable subjects who had received the full vaccination course in the primary study (NCT00334334) and in the booster study (NCT00463437) and had available results at 3 years of age

Opsonophagocytic activity was measured by a killing-assay. The results were presented as the dilution of serum (opsonic titer) able to sustain 50% killing of live pneumococci under the assay conditions. The cut-off of the assay was an opsonic titre of 8.

Outcome measures

Measure	Synflorix-Meningitec Group n=131 Participants Subjects who received concomitantly in the primary study (NCT00334334): 3 primary doses of Synflorix intramuscularly into the right thigh at 2, 4 and 6 months of age 2 primary doses of Meningitec intramuscularly into the lower left thigh at 2 and 4 months of age and 3 primary doses of Infanrix hexa intramuscularly into the upper left thigh at 2, 4 and 6 months of age. (In Poland subjects were offered a third dose of Meningitec at 7 months of age to comply with national recommendations). During the booster study (NCT00463437) subjects received the same vaccines as during the primary study at 11-18 months of age, with the exception of Spain, where Infanrix IPV/Hib was given instead of Infanrix hexa.	Synflorix-NeisVac-C Group n=131 Participants Subjects who received concomitantly in the primary study (NCT00334334): 3 primary doses of Synflorix intramuscularly into the right thigh at 2, 4 and 6 months of age, 2 primary doses of Neis-Vac-C intramuscularly into the lower left thigh at 2 and 4 months of age and 3 primary doses of Infanrix hexa intramuscularly into the upper left thigh at 2, 4 and 6 months of age. (In Poland subjects were offered a third dose of Neis-Vac-C at 7 months of age to comply with national recommendations). During the booster study (NCT00463437) subjects received the same vaccines as during the primary study at 11-18 months of age, with the exception of Spain, where Infanrix IPV/Hib was given instead of Infanrix hexa.	Synflorix-Menitorix Group n=131 Participants Subjects who received concomitantly in the primary study (NCT00334334): 3 primary doses of Synflorix intramuscularly into the right thigh at 2, 4 and 6 months of age, 3 primary doses of Menitorix intramuscularly into the lower left thigh at 2, 4 and 6 months of age and 3 primary doses of Infanrix penta intramuscularly into the upper left thigh at 2, 4 and 6 months of age. During the booster study (NCT00463437) subjects received the same vaccines as during the primary study at 11-18 months of age, with the exception of Spain, where Infanrix IPV was given instead of Infanrix penta.	Prevenar-Menitorix Group n=132 Participants Subjects who received concomitantly in the primary study (NCT00334334): 3 primary doses of Prevenar intramuscularly into the right thigh at 2, 4 and 6 months of age, 3 primary doses of Menitorix intramuscularly into the lower left thigh at 2, 4 and 6 months of age and 3 primary doses of Infanrix penta intramuscularly into the upper left thigh at 2, 4 and 6 months of age. During the booster study (NCT00463437) subjects received the same vaccines as during the primary study at 11-18 months of age, with the exception of Spain, where Infanrix IPV was given instead of Infanrix penta.
Number of Subjects With Opsonophagocytic Activity Opsono-1 (N= 131; 131; 131; 131)	30 Subjects	32 Subjects	29 Subjects	14 Subjects
Number of Subjects With Opsonophagocytic Activity Opsono-4 (N= 126; 127; 129; 128)	54 Subjects	48 Subjects	43 Subjects	77 Subjects
Number of Subjects With Opsonophagocytic Activity Opsono-5 (N= 130; 130; 129; 132)	73 Subjects	47 Subjects	55 Subjects	5 Subjects
Number of Subjects With Opsonophagocytic Activity Opsono-6B (N= 128; 127; 124; 131)	84 Subjects	81 Subjects	78 Subjects	115 Subjects
Number of Subjects With Opsonophagocytic Activity Opsono-7F (N= 131; 130; 131; 130)	128 Subjects	130 Subjects	131 Subjects	126 Subjects
Number of Subjects With Opsonophagocytic Activity Opsono-9V (N= 131; 131; 129; 132)	127 Subjects	131 Subjects	127 Subjects	124 Subjects
Number of Subjects With Opsonophagocytic Activity Opsono-14 (N= 129; 128; 128; 131)	110 Subjects	118 Subjects	106 Subjects	112 Subjects
Number of Subjects With Opsonophagocytic Activity Opsono-18C (N= 126; 121; 123; 122)	51 Subjects	68 Subjects	44 Subjects	48 Subjects
Number of Subjects With Opsonophagocytic Activity Opsono-19F (N= 130; 130; 131; 132)	105 Subjects	108 Subjects	89 Subjects	91 Subjects
Number of Subjects With Opsonophagocytic Activity Opsono-23F (N= 125; 124; 125; 132)	106 Subjects	112 Subjects	113 Subjects	129 Subjects

SECONDARY outcome

Timeframe: At 3 years of age

Population: Analysis was performed on the According-to-Protocol cohort for antibody persistence at 3 years of age, which included all evaluable subjects who had received the full vaccination course in the primary study (NCT00334334) and in the booster study (NCT00463437) and had available results at 3 years of age

Concentrations were expressed as GMCs in enzyme-linked immunosorbent-assay (ELISA) units per milliliter (EL.U/mL).

Outcome measures

Measure	Synflorix-Meningitec Group n=140 Participants Subjects who received concomitantly in the primary study (NCT00334334): 3 primary doses of Synflorix intramuscularly into the right thigh at 2, 4 and 6 months of age 2 primary doses of Meningitec intramuscularly into the lower left thigh at 2 and 4 months of age and 3 primary doses of Infanrix hexa intramuscularly into the upper left thigh at 2, 4 and 6 months of age. (In Poland subjects were offered a third dose of Meningitec at 7 months of age to comply with national recommendations). During the booster study (NCT00463437) subjects received the same vaccines as during the primary study at 11-18 months of age, with the exception of Spain, where Infanrix IPV/Hib was given instead of Infanrix hexa.	Synflorix-NeisVac-C Group n=145 Participants Subjects who received concomitantly in the primary study (NCT00334334): 3 primary doses of Synflorix intramuscularly into the right thigh at 2, 4 and 6 months of age, 2 primary doses of Neis-Vac-C intramuscularly into the lower left thigh at 2 and 4 months of age and 3 primary doses of Infanrix hexa intramuscularly into the upper left thigh at 2, 4 and 6 months of age. (In Poland subjects were offered a third dose of Neis-Vac-C at 7 months of age to comply with national recommendations). During the booster study (NCT00463437) subjects received the same vaccines as during the primary study at 11-18 months of age, with the exception of Spain, where Infanrix IPV/Hib was given instead of Infanrix hexa.	Synflorix-Menitorix Group n=144 Participants Subjects who received concomitantly in the primary study (NCT00334334): 3 primary doses of Synflorix intramuscularly into the right thigh at 2, 4 and 6 months of age, 3 primary doses of Menitorix intramuscularly into the lower left thigh at 2, 4 and 6 months of age and 3 primary doses of Infanrix penta intramuscularly into the upper left thigh at 2, 4 and 6 months of age. During the booster study (NCT00463437) subjects received the same vaccines as during the primary study at 11-18 months of age, with the exception of Spain, where Infanrix IPV was given instead of Infanrix penta.	Prevenar-Menitorix Group n=139 Participants Subjects who received concomitantly in the primary study (NCT00334334): 3 primary doses of Prevenar intramuscularly into the right thigh at 2, 4 and 6 months of age, 3 primary doses of Menitorix intramuscularly into the lower left thigh at 2, 4 and 6 months of age and 3 primary doses of Infanrix penta intramuscularly into the upper left thigh at 2, 4 and 6 months of age. During the booster study (NCT00463437) subjects received the same vaccines as during the primary study at 11-18 months of age, with the exception of Spain, where Infanrix IPV was given instead of Infanrix penta.
Concentration of Antibodies Against Protein D	494.6 EL.U/mL Interval 414.0 to 591.0	444.8 EL.U/mL Interval 373.2 to 530.1	439.8 EL.U/mL Interval 366.4 to 527.9	100.3 EL.U/mL Interval 87.6 to 114.9

SECONDARY outcome

Timeframe: At 3 years of age

Population: Analysis was performed on the According-to-Protocol cohort for antibody persistence at 3 years of age, which included all evaluable subjects who had received the full vaccination course in the primary study (NCT00334334) and in the booster study (NCT00463437) and had available results at 3 years of age

Cut-off values assessed were defined as equal to or above 10 milli-international units per milliliter (mIU/mL) or equal to or above 100 mIU/mL.

Outcome measures

Measure	Synflorix-Meningitec Group n=107 Participants Subjects who received concomitantly in the primary study (NCT00334334): 3 primary doses of Synflorix intramuscularly into the right thigh at 2, 4 and 6 months of age 2 primary doses of Meningitec intramuscularly into the lower left thigh at 2 and 4 months of age and 3 primary doses of Infanrix hexa intramuscularly into the upper left thigh at 2, 4 and 6 months of age. (In Poland subjects were offered a third dose of Meningitec at 7 months of age to comply with national recommendations). During the booster study (NCT00463437) subjects received the same vaccines as during the primary study at 11-18 months of age, with the exception of Spain, where Infanrix IPV/Hib was given instead of Infanrix hexa.	Synflorix-NeisVac-C Group n=102 Participants Subjects who received concomitantly in the primary study (NCT00334334): 3 primary doses of Synflorix intramuscularly into the right thigh at 2, 4 and 6 months of age, 2 primary doses of Neis-Vac-C intramuscularly into the lower left thigh at 2 and 4 months of age and 3 primary doses of Infanrix hexa intramuscularly into the upper left thigh at 2, 4 and 6 months of age. (In Poland subjects were offered a third dose of Neis-Vac-C at 7 months of age to comply with national recommendations). During the booster study (NCT00463437) subjects received the same vaccines as during the primary study at 11-18 months of age, with the exception of Spain, where Infanrix IPV/Hib was given instead of Infanrix hexa.	Synflorix-Menitorix Group n=105 Participants Subjects who received concomitantly in the primary study (NCT00334334): 3 primary doses of Synflorix intramuscularly into the right thigh at 2, 4 and 6 months of age, 3 primary doses of Menitorix intramuscularly into the lower left thigh at 2, 4 and 6 months of age and 3 primary doses of Infanrix penta intramuscularly into the upper left thigh at 2, 4 and 6 months of age. During the booster study (NCT00463437) subjects received the same vaccines as during the primary study at 11-18 months of age, with the exception of Spain, where Infanrix IPV was given instead of Infanrix penta.	Prevenar-Menitorix Group n=102 Participants Subjects who received concomitantly in the primary study (NCT00334334): 3 primary doses of Prevenar intramuscularly into the right thigh at 2, 4 and 6 months of age, 3 primary doses of Menitorix intramuscularly into the lower left thigh at 2, 4 and 6 months of age and 3 primary doses of Infanrix penta intramuscularly into the upper left thigh at 2, 4 and 6 months of age. During the booster study (NCT00463437) subjects received the same vaccines as during the primary study at 11-18 months of age, with the exception of Spain, where Infanrix IPV was given instead of Infanrix penta.
Number of Subjects With Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentrations Equal to or Above Cut-off Values ≥ 10 mIU/mL	105 subjects	96 subjects	102 subjects	99 subjects
Number of Subjects With Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentrations Equal to or Above Cut-off Values ≥ 100 mIU/mL	77 subjects	81 subjects	74 subjects	74 subjects

SECONDARY outcome

Timeframe: At 3 years of age

Population: Analysis was performed on the According-to-Protocol cohort for antibody persistence at 3 years of age, which included all evaluable subjects who had received the full vaccination course in the primary study (NCT00334334) and in the booster study (NCT00463437) and had available results at 3 years of age

Concentrations were expressed as GMCs in mIU/mL.

Outcome measures

Measure	Synflorix-Meningitec Group n=107 Participants Subjects who received concomitantly in the primary study (NCT00334334): 3 primary doses of Synflorix intramuscularly into the right thigh at 2, 4 and 6 months of age 2 primary doses of Meningitec intramuscularly into the lower left thigh at 2 and 4 months of age and 3 primary doses of Infanrix hexa intramuscularly into the upper left thigh at 2, 4 and 6 months of age. (In Poland subjects were offered a third dose of Meningitec at 7 months of age to comply with national recommendations). During the booster study (NCT00463437) subjects received the same vaccines as during the primary study at 11-18 months of age, with the exception of Spain, where Infanrix IPV/Hib was given instead of Infanrix hexa.	Synflorix-NeisVac-C Group n=102 Participants Subjects who received concomitantly in the primary study (NCT00334334): 3 primary doses of Synflorix intramuscularly into the right thigh at 2, 4 and 6 months of age, 2 primary doses of Neis-Vac-C intramuscularly into the lower left thigh at 2 and 4 months of age and 3 primary doses of Infanrix hexa intramuscularly into the upper left thigh at 2, 4 and 6 months of age. (In Poland subjects were offered a third dose of Neis-Vac-C at 7 months of age to comply with national recommendations). During the booster study (NCT00463437) subjects received the same vaccines as during the primary study at 11-18 months of age, with the exception of Spain, where Infanrix IPV/Hib was given instead of Infanrix hexa.	Synflorix-Menitorix Group n=105 Participants Subjects who received concomitantly in the primary study (NCT00334334): 3 primary doses of Synflorix intramuscularly into the right thigh at 2, 4 and 6 months of age, 3 primary doses of Menitorix intramuscularly into the lower left thigh at 2, 4 and 6 months of age and 3 primary doses of Infanrix penta intramuscularly into the upper left thigh at 2, 4 and 6 months of age. During the booster study (NCT00463437) subjects received the same vaccines as during the primary study at 11-18 months of age, with the exception of Spain, where Infanrix IPV was given instead of Infanrix penta.	Prevenar-Menitorix Group n=102 Participants Subjects who received concomitantly in the primary study (NCT00334334): 3 primary doses of Prevenar intramuscularly into the right thigh at 2, 4 and 6 months of age, 3 primary doses of Menitorix intramuscularly into the lower left thigh at 2, 4 and 6 months of age and 3 primary doses of Infanrix penta intramuscularly into the upper left thigh at 2, 4 and 6 months of age. During the booster study (NCT00463437) subjects received the same vaccines as during the primary study at 11-18 months of age, with the exception of Spain, where Infanrix IPV was given instead of Infanrix penta.
Anti-HBs Antibody Concentrations	367.5 mIU/mL Interval 256.8 to 525.9	325.7 mIU/mL Interval 228.3 to 464.7	288.1 mIU/mL Interval 198.7 to 417.9	371.4 mIU/mL Interval 254.1 to 542.8

SECONDARY outcome

Timeframe: From last study contact of the study (NCT00463437) at 17-24 months of age until 3 years of age

Population: Analysis was performed on the Total Enrolled cohort at 3 years of age, which included all subjects vaccinated in the booster study (NCT00463437) and who were part of the blood sample subset.

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. Related = SAE assessed by the investigator as being related to the study procedures.

Outcome measures

Measure	Synflorix-Meningitec Group n=144 Participants Subjects who received concomitantly in the primary study (NCT00334334): 3 primary doses of Synflorix intramuscularly into the right thigh at 2, 4 and 6 months of age 2 primary doses of Meningitec intramuscularly into the lower left thigh at 2 and 4 months of age and 3 primary doses of Infanrix hexa intramuscularly into the upper left thigh at 2, 4 and 6 months of age. (In Poland subjects were offered a third dose of Meningitec at 7 months of age to comply with national recommendations). During the booster study (NCT00463437) subjects received the same vaccines as during the primary study at 11-18 months of age, with the exception of Spain, where Infanrix IPV/Hib was given instead of Infanrix hexa.	Synflorix-NeisVac-C Group n=147 Participants Subjects who received concomitantly in the primary study (NCT00334334): 3 primary doses of Synflorix intramuscularly into the right thigh at 2, 4 and 6 months of age, 2 primary doses of Neis-Vac-C intramuscularly into the lower left thigh at 2 and 4 months of age and 3 primary doses of Infanrix hexa intramuscularly into the upper left thigh at 2, 4 and 6 months of age. (In Poland subjects were offered a third dose of Neis-Vac-C at 7 months of age to comply with national recommendations). During the booster study (NCT00463437) subjects received the same vaccines as during the primary study at 11-18 months of age, with the exception of Spain, where Infanrix IPV/Hib was given instead of Infanrix hexa.	Synflorix-Menitorix Group n=149 Participants Subjects who received concomitantly in the primary study (NCT00334334): 3 primary doses of Synflorix intramuscularly into the right thigh at 2, 4 and 6 months of age, 3 primary doses of Menitorix intramuscularly into the lower left thigh at 2, 4 and 6 months of age and 3 primary doses of Infanrix penta intramuscularly into the upper left thigh at 2, 4 and 6 months of age. During the booster study (NCT00463437) subjects received the same vaccines as during the primary study at 11-18 months of age, with the exception of Spain, where Infanrix IPV was given instead of Infanrix penta.	Prevenar-Menitorix Group n=141 Participants Subjects who received concomitantly in the primary study (NCT00334334): 3 primary doses of Prevenar intramuscularly into the right thigh at 2, 4 and 6 months of age, 3 primary doses of Menitorix intramuscularly into the lower left thigh at 2, 4 and 6 months of age and 3 primary doses of Infanrix penta intramuscularly into the upper left thigh at 2, 4 and 6 months of age. During the booster study (NCT00463437) subjects received the same vaccines as during the primary study at 11-18 months of age, with the exception of Spain, where Infanrix IPV was given instead of Infanrix penta.
Number of Subjects With Serious Adverse Events (SAEs) SAE(s)	0 subjects	0 subjects	0 subjects	0 subjects
Number of Subjects With Serious Adverse Events (SAEs) Related SAE(s)	0 subjects	0 subjects	0 subjects	0 subjects

SECONDARY outcome

Timeframe: At 4 years of age

Population: Analysis was performed on the According-to-Protocol cohort for antibody persistence at 4 years of age, which included all evaluable subjects who had received the full vaccination course in the primary study (NCT00334334) and in the booster study (NCT00463437) and had available results at 4 years of age

Titers are given as Geometric Mean Titers (GMTs).

Outcome measures

Measure	Synflorix-Meningitec Group n=134 Participants Subjects who received concomitantly in the primary study (NCT00334334): 3 primary doses of Synflorix intramuscularly into the right thigh at 2, 4 and 6 months of age 2 primary doses of Meningitec intramuscularly into the lower left thigh at 2 and 4 months of age and 3 primary doses of Infanrix hexa intramuscularly into the upper left thigh at 2, 4 and 6 months of age. (In Poland subjects were offered a third dose of Meningitec at 7 months of age to comply with national recommendations). During the booster study (NCT00463437) subjects received the same vaccines as during the primary study at 11-18 months of age, with the exception of Spain, where Infanrix IPV/Hib was given instead of Infanrix hexa.	Synflorix-NeisVac-C Group n=137 Participants Subjects who received concomitantly in the primary study (NCT00334334): 3 primary doses of Synflorix intramuscularly into the right thigh at 2, 4 and 6 months of age, 2 primary doses of Neis-Vac-C intramuscularly into the lower left thigh at 2 and 4 months of age and 3 primary doses of Infanrix hexa intramuscularly into the upper left thigh at 2, 4 and 6 months of age. (In Poland subjects were offered a third dose of Neis-Vac-C at 7 months of age to comply with national recommendations). During the booster study (NCT00463437) subjects received the same vaccines as during the primary study at 11-18 months of age, with the exception of Spain, where Infanrix IPV/Hib was given instead of Infanrix hexa.	Synflorix-Menitorix Group n=128 Participants Subjects who received concomitantly in the primary study (NCT00334334): 3 primary doses of Synflorix intramuscularly into the right thigh at 2, 4 and 6 months of age, 3 primary doses of Menitorix intramuscularly into the lower left thigh at 2, 4 and 6 months of age and 3 primary doses of Infanrix penta intramuscularly into the upper left thigh at 2, 4 and 6 months of age. During the booster study (NCT00463437) subjects received the same vaccines as during the primary study at 11-18 months of age, with the exception of Spain, where Infanrix IPV was given instead of Infanrix penta.	Prevenar-Menitorix Group n=128 Participants Subjects who received concomitantly in the primary study (NCT00334334): 3 primary doses of Prevenar intramuscularly into the right thigh at 2, 4 and 6 months of age, 3 primary doses of Menitorix intramuscularly into the lower left thigh at 2, 4 and 6 months of age and 3 primary doses of Infanrix penta intramuscularly into the upper left thigh at 2, 4 and 6 months of age. During the booster study (NCT00463437) subjects received the same vaccines as during the primary study at 11-18 months of age, with the exception of Spain, where Infanrix IPV was given instead of Infanrix penta.
rSBA-MenC Titers	45.3 Titers Interval 33.2 to 61.8	146.8 Titers Interval 116.2 to 185.4	112.4 Titers Interval 81.8 to 154.6	68.1 Titers Interval 48.4 to 95.9

SECONDARY outcome

Timeframe: At 4 years of age

Population: Analysis was performed on the According-to-Protocol cohort for antibody persistence at 4 years of age, which included all evaluable subjects who had received the full vaccination course in the primary study (NCT00334334) and in the booster study (NCT00463437) and had available results at 4 years of age

rSBA-MenC antibody cut-off value assessed was equal to or above 1:128.

Outcome measures

Measure	Synflorix-Meningitec Group n=134 Participants Subjects who received concomitantly in the primary study (NCT00334334): 3 primary doses of Synflorix intramuscularly into the right thigh at 2, 4 and 6 months of age 2 primary doses of Meningitec intramuscularly into the lower left thigh at 2 and 4 months of age and 3 primary doses of Infanrix hexa intramuscularly into the upper left thigh at 2, 4 and 6 months of age. (In Poland subjects were offered a third dose of Meningitec at 7 months of age to comply with national recommendations). During the booster study (NCT00463437) subjects received the same vaccines as during the primary study at 11-18 months of age, with the exception of Spain, where Infanrix IPV/Hib was given instead of Infanrix hexa.	Synflorix-NeisVac-C Group n=137 Participants Subjects who received concomitantly in the primary study (NCT00334334): 3 primary doses of Synflorix intramuscularly into the right thigh at 2, 4 and 6 months of age, 2 primary doses of Neis-Vac-C intramuscularly into the lower left thigh at 2 and 4 months of age and 3 primary doses of Infanrix hexa intramuscularly into the upper left thigh at 2, 4 and 6 months of age. (In Poland subjects were offered a third dose of Neis-Vac-C at 7 months of age to comply with national recommendations). During the booster study (NCT00463437) subjects received the same vaccines as during the primary study at 11-18 months of age, with the exception of Spain, where Infanrix IPV/Hib was given instead of Infanrix hexa.	Synflorix-Menitorix Group n=128 Participants Subjects who received concomitantly in the primary study (NCT00334334): 3 primary doses of Synflorix intramuscularly into the right thigh at 2, 4 and 6 months of age, 3 primary doses of Menitorix intramuscularly into the lower left thigh at 2, 4 and 6 months of age and 3 primary doses of Infanrix penta intramuscularly into the upper left thigh at 2, 4 and 6 months of age. During the booster study (NCT00463437) subjects received the same vaccines as during the primary study at 11-18 months of age, with the exception of Spain, where Infanrix IPV was given instead of Infanrix penta.	Prevenar-Menitorix Group n=128 Participants Subjects who received concomitantly in the primary study (NCT00334334): 3 primary doses of Prevenar intramuscularly into the right thigh at 2, 4 and 6 months of age, 3 primary doses of Menitorix intramuscularly into the lower left thigh at 2, 4 and 6 months of age and 3 primary doses of Infanrix penta intramuscularly into the upper left thigh at 2, 4 and 6 months of age. During the booster study (NCT00463437) subjects received the same vaccines as during the primary study at 11-18 months of age, with the exception of Spain, where Infanrix IPV was given instead of Infanrix penta.
Number of Subjects With an rSBA-MenC Titer Equal to or Above Cut-off Value	49 Subjects	79 Subjects	75 Subjects	58 Subjects

SECONDARY outcome

Timeframe: At 4 years of age

Population: Analysis was performed on the According-to-Protocol cohort for antibody persistence at 4 years of age, which included all evaluable subjects who had received the full vaccination course in the primary study (NCT00334334) and in the booster study (NCT00463437) and had available results at 4 years of age

The cut-off values were defined as a concentration equal to or above 0.15 microgram per milliliter (μg/mL) and equal to or above 1.0 μg/mL.

Outcome measures

Measure	Synflorix-Meningitec Group n=134 Participants Subjects who received concomitantly in the primary study (NCT00334334): 3 primary doses of Synflorix intramuscularly into the right thigh at 2, 4 and 6 months of age 2 primary doses of Meningitec intramuscularly into the lower left thigh at 2 and 4 months of age and 3 primary doses of Infanrix hexa intramuscularly into the upper left thigh at 2, 4 and 6 months of age. (In Poland subjects were offered a third dose of Meningitec at 7 months of age to comply with national recommendations). During the booster study (NCT00463437) subjects received the same vaccines as during the primary study at 11-18 months of age, with the exception of Spain, where Infanrix IPV/Hib was given instead of Infanrix hexa.	Synflorix-NeisVac-C Group n=136 Participants Subjects who received concomitantly in the primary study (NCT00334334): 3 primary doses of Synflorix intramuscularly into the right thigh at 2, 4 and 6 months of age, 2 primary doses of Neis-Vac-C intramuscularly into the lower left thigh at 2 and 4 months of age and 3 primary doses of Infanrix hexa intramuscularly into the upper left thigh at 2, 4 and 6 months of age. (In Poland subjects were offered a third dose of Neis-Vac-C at 7 months of age to comply with national recommendations). During the booster study (NCT00463437) subjects received the same vaccines as during the primary study at 11-18 months of age, with the exception of Spain, where Infanrix IPV/Hib was given instead of Infanrix hexa.	Synflorix-Menitorix Group n=130 Participants Subjects who received concomitantly in the primary study (NCT00334334): 3 primary doses of Synflorix intramuscularly into the right thigh at 2, 4 and 6 months of age, 3 primary doses of Menitorix intramuscularly into the lower left thigh at 2, 4 and 6 months of age and 3 primary doses of Infanrix penta intramuscularly into the upper left thigh at 2, 4 and 6 months of age. During the booster study (NCT00463437) subjects received the same vaccines as during the primary study at 11-18 months of age, with the exception of Spain, where Infanrix IPV was given instead of Infanrix penta.	Prevenar-Menitorix Group n=133 Participants Subjects who received concomitantly in the primary study (NCT00334334): 3 primary doses of Prevenar intramuscularly into the right thigh at 2, 4 and 6 months of age, 3 primary doses of Menitorix intramuscularly into the lower left thigh at 2, 4 and 6 months of age and 3 primary doses of Infanrix penta intramuscularly into the upper left thigh at 2, 4 and 6 months of age. During the booster study (NCT00463437) subjects received the same vaccines as during the primary study at 11-18 months of age, with the exception of Spain, where Infanrix IPV was given instead of Infanrix penta.
Number of Subjects With Anti-polyribosyl-ribitol Phosphate (Anti-PRP) Antibody Concentrations Equal to or Above Cut-off Values ≥ 0.15 µg/mL	133 Subjects	134 Subjects	130 Subjects	132 Subjects
Number of Subjects With Anti-polyribosyl-ribitol Phosphate (Anti-PRP) Antibody Concentrations Equal to or Above Cut-off Values ≥ 1.0 µg/mL	88 Subjects	85 Subjects	117 Subjects	106 Subjects

SECONDARY outcome

Timeframe: At 4 years of age

Population: Analysis was performed on the According-to-Protocol cohort for antibody persistence at 4 years of age, which included all evaluable subjects who had received the full vaccination course in the primary study (NCT00334334) and in the booster study (NCT00463437) and had available results at 4 years of age

Concentrations were defined as Geometric Mean Concentrations (GMCs) in μg/mL

Outcome measures

Measure	Synflorix-Meningitec Group n=134 Participants Subjects who received concomitantly in the primary study (NCT00334334): 3 primary doses of Synflorix intramuscularly into the right thigh at 2, 4 and 6 months of age 2 primary doses of Meningitec intramuscularly into the lower left thigh at 2 and 4 months of age and 3 primary doses of Infanrix hexa intramuscularly into the upper left thigh at 2, 4 and 6 months of age. (In Poland subjects were offered a third dose of Meningitec at 7 months of age to comply with national recommendations). During the booster study (NCT00463437) subjects received the same vaccines as during the primary study at 11-18 months of age, with the exception of Spain, where Infanrix IPV/Hib was given instead of Infanrix hexa.	Synflorix-NeisVac-C Group n=136 Participants Subjects who received concomitantly in the primary study (NCT00334334): 3 primary doses of Synflorix intramuscularly into the right thigh at 2, 4 and 6 months of age, 2 primary doses of Neis-Vac-C intramuscularly into the lower left thigh at 2 and 4 months of age and 3 primary doses of Infanrix hexa intramuscularly into the upper left thigh at 2, 4 and 6 months of age. (In Poland subjects were offered a third dose of Neis-Vac-C at 7 months of age to comply with national recommendations). During the booster study (NCT00463437) subjects received the same vaccines as during the primary study at 11-18 months of age, with the exception of Spain, where Infanrix IPV/Hib was given instead of Infanrix hexa.	Synflorix-Menitorix Group n=130 Participants Subjects who received concomitantly in the primary study (NCT00334334): 3 primary doses of Synflorix intramuscularly into the right thigh at 2, 4 and 6 months of age, 3 primary doses of Menitorix intramuscularly into the lower left thigh at 2, 4 and 6 months of age and 3 primary doses of Infanrix penta intramuscularly into the upper left thigh at 2, 4 and 6 months of age. During the booster study (NCT00463437) subjects received the same vaccines as during the primary study at 11-18 months of age, with the exception of Spain, where Infanrix IPV was given instead of Infanrix penta.	Prevenar-Menitorix Group n=133 Participants Subjects who received concomitantly in the primary study (NCT00334334): 3 primary doses of Prevenar intramuscularly into the right thigh at 2, 4 and 6 months of age, 3 primary doses of Menitorix intramuscularly into the lower left thigh at 2, 4 and 6 months of age and 3 primary doses of Infanrix penta intramuscularly into the upper left thigh at 2, 4 and 6 months of age. During the booster study (NCT00463437) subjects received the same vaccines as during the primary study at 11-18 months of age, with the exception of Spain, where Infanrix IPV was given instead of Infanrix penta.
Anti-PRP Concentrations	1.767 μg/mL Interval 1.454 to 2.146	1.738 μg/mL Interval 1.386 to 2.178	3.804 μg/mL Interval 3.092 to 4.679	2.805 μg/mL Interval 2.297 to 3.425

SECONDARY outcome

Timeframe: At 4 years of age

Population: Analysis was performed on the According-to-Protocol cohort for antibody persistence at 4 years of age, which included all evaluable subjects who had received the full vaccination course in the primary study (NCT00334334) and in the booster study (NCT00463437) and had available results at 4 years of age

Antibody concentrations were expressed as GMCs in μg/mL. Vaccine pneumococcal serotypes assessed included 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F.

Outcome measures

Measure	Synflorix-Meningitec Group n=136 Participants Subjects who received concomitantly in the primary study (NCT00334334): 3 primary doses of Synflorix intramuscularly into the right thigh at 2, 4 and 6 months of age 2 primary doses of Meningitec intramuscularly into the lower left thigh at 2 and 4 months of age and 3 primary doses of Infanrix hexa intramuscularly into the upper left thigh at 2, 4 and 6 months of age. (In Poland subjects were offered a third dose of Meningitec at 7 months of age to comply with national recommendations). During the booster study (NCT00463437) subjects received the same vaccines as during the primary study at 11-18 months of age, with the exception of Spain, where Infanrix IPV/Hib was given instead of Infanrix hexa.	Synflorix-NeisVac-C Group n=138 Participants Subjects who received concomitantly in the primary study (NCT00334334): 3 primary doses of Synflorix intramuscularly into the right thigh at 2, 4 and 6 months of age, 2 primary doses of Neis-Vac-C intramuscularly into the lower left thigh at 2 and 4 months of age and 3 primary doses of Infanrix hexa intramuscularly into the upper left thigh at 2, 4 and 6 months of age. (In Poland subjects were offered a third dose of Neis-Vac-C at 7 months of age to comply with national recommendations). During the booster study (NCT00463437) subjects received the same vaccines as during the primary study at 11-18 months of age, with the exception of Spain, where Infanrix IPV/Hib was given instead of Infanrix hexa.	Synflorix-Menitorix Group n=133 Participants Subjects who received concomitantly in the primary study (NCT00334334): 3 primary doses of Synflorix intramuscularly into the right thigh at 2, 4 and 6 months of age, 3 primary doses of Menitorix intramuscularly into the lower left thigh at 2, 4 and 6 months of age and 3 primary doses of Infanrix penta intramuscularly into the upper left thigh at 2, 4 and 6 months of age. During the booster study (NCT00463437) subjects received the same vaccines as during the primary study at 11-18 months of age, with the exception of Spain, where Infanrix IPV was given instead of Infanrix penta.	Prevenar-Menitorix Group n=136 Participants Subjects who received concomitantly in the primary study (NCT00334334): 3 primary doses of Prevenar intramuscularly into the right thigh at 2, 4 and 6 months of age, 3 primary doses of Menitorix intramuscularly into the lower left thigh at 2, 4 and 6 months of age and 3 primary doses of Infanrix penta intramuscularly into the upper left thigh at 2, 4 and 6 months of age. During the booster study (NCT00463437) subjects received the same vaccines as during the primary study at 11-18 months of age, with the exception of Spain, where Infanrix IPV was given instead of Infanrix penta.
Antibody Concentrations Against Vaccine Pneumococcal Serotypes Anti-1 (N=136;138;131;135)	0.22 μg/mL Interval 0.19 to 0.27	0.21 μg/mL Interval 0.17 to 0.26	0.18 μg/mL Interval 0.15 to 0.21	0.08 μg/mL Interval 0.07 to 0.1
Antibody Concentrations Against Vaccine Pneumococcal Serotypes Anti-4 (N=136;138;131;136)	0.22 μg/mL Interval 0.19 to 0.26	0.21 μg/mL Interval 0.18 to 0.25	0.20 μg/mL Interval 0.17 to 0.24	0.32 μg/mL Interval 0.27 to 0.39
Antibody Concentrations Against Vaccine Pneumococcal Serotypes Anti-5 (N=136;138;131;136)	0.47 μg/mL Interval 0.37 to 0.59	0.36 μg/mL Interval 0.3 to 0.42	0.34 μg/mL Interval 0.28 to 0.42	0.10 μg/mL Interval 0.08 to 0.11
Antibody Concentrations Against Vaccine Pneumococcal Serotypes Anti-6B (N=136;138;133;135)	0.74 μg/mL Interval 0.53 to 1.01	0.65 μg/mL Interval 0.49 to 0.86	0.78 μg/mL Interval 0.57 to 1.06	0.99 μg/mL Interval 0.76 to 1.29
Antibody Concentrations Against Vaccine Pneumococcal Serotypes Anti-7F (N=136;138;131;136)	0.51 μg/mL Interval 0.41 to 0.63	0.44 μg/mL Interval 0.37 to 0.52	0.46 μg/mL Interval 0.37 to 0.58	0.09 μg/mL Interval 0.07 to 0.12
Antibody Concentrations Against Vaccine Pneumococcal Serotypes Anti-9V (N=136;137;131;136)	0.52 μg/mL Interval 0.42 to 0.65	0.61 μg/mL Interval 0.46 to 0.81	0.54 μg/mL Interval 0.4 to 0.72	0.72 μg/mL Interval 0.57 to 0.91
Antibody Concentrations Against Vaccine Pneumococcal Serotypes Anti-14 (N=136;138;132;136)	1.51 μg/mL Interval 1.18 to 1.92	1.57 μg/mL Interval 1.25 to 1.97	1.41 μg/mL Interval 1.1 to 1.82	1.71 μg/mL Interval 1.38 to 2.12
Antibody Concentrations Against Vaccine Pneumococcal Serotypes Anti-18C (N=136;138;132;136)	0.49 μg/mL Interval 0.41 to 0.59	0.81 μg/mL Interval 0.67 to 0.98	0.60 μg/mL Interval 0.48 to 0.75	0.49 μg/mL Interval 0.4 to 0.59
Antibody Concentrations Against Vaccine Pneumococcal Serotypes Anti-19F (N=136;138;133;136)	2.66 μg/mL Interval 1.92 to 3.67	2.36 μg/mL Interval 1.7 to 3.29	2.50 μg/mL Interval 1.8 to 3.48	2.41 μg/mL Interval 1.78 to 3.25
Antibody Concentrations Against Vaccine Pneumococcal Serotypes Anti-23F (N=136;138;133;136)	0.98 μg/mL Interval 0.71 to 1.35	0.84 μg/mL Interval 0.65 to 1.1	0.98 μg/mL Interval 0.69 to 1.39	1.56 μg/mL Interval 1.16 to 2.09

SECONDARY outcome

Timeframe: At 4 years of age

Population: Analysis was performed on the According-to-Protocol cohort for antibody persistence at 4 years of age, which included all evaluable subjects who had received the full vaccination course in the primary study (NCT00334334) and in the booster study (NCT00463437) and had available results at 4 years of age

Opsonophagocytic activity was measured by a killing-assay. The results were presented as the dilution of serum (opsonic titer) able to sustain 50% killing of live pneumococci under the assay conditions. The cut-off of the assay was an opsonic titer of 8.

Outcome measures

Measure	Synflorix-Meningitec Group n=131 Participants Subjects who received concomitantly in the primary study (NCT00334334): 3 primary doses of Synflorix intramuscularly into the right thigh at 2, 4 and 6 months of age 2 primary doses of Meningitec intramuscularly into the lower left thigh at 2 and 4 months of age and 3 primary doses of Infanrix hexa intramuscularly into the upper left thigh at 2, 4 and 6 months of age. (In Poland subjects were offered a third dose of Meningitec at 7 months of age to comply with national recommendations). During the booster study (NCT00463437) subjects received the same vaccines as during the primary study at 11-18 months of age, with the exception of Spain, where Infanrix IPV/Hib was given instead of Infanrix hexa.	Synflorix-NeisVac-C Group n=134 Participants Subjects who received concomitantly in the primary study (NCT00334334): 3 primary doses of Synflorix intramuscularly into the right thigh at 2, 4 and 6 months of age, 2 primary doses of Neis-Vac-C intramuscularly into the lower left thigh at 2 and 4 months of age and 3 primary doses of Infanrix hexa intramuscularly into the upper left thigh at 2, 4 and 6 months of age. (In Poland subjects were offered a third dose of Neis-Vac-C at 7 months of age to comply with national recommendations). During the booster study (NCT00463437) subjects received the same vaccines as during the primary study at 11-18 months of age, with the exception of Spain, where Infanrix IPV/Hib was given instead of Infanrix hexa.	Synflorix-Menitorix Group n=123 Participants Subjects who received concomitantly in the primary study (NCT00334334): 3 primary doses of Synflorix intramuscularly into the right thigh at 2, 4 and 6 months of age, 3 primary doses of Menitorix intramuscularly into the lower left thigh at 2, 4 and 6 months of age and 3 primary doses of Infanrix penta intramuscularly into the upper left thigh at 2, 4 and 6 months of age. During the booster study (NCT00463437) subjects received the same vaccines as during the primary study at 11-18 months of age, with the exception of Spain, where Infanrix IPV was given instead of Infanrix penta.	Prevenar-Menitorix Group n=128 Participants Subjects who received concomitantly in the primary study (NCT00334334): 3 primary doses of Prevenar intramuscularly into the right thigh at 2, 4 and 6 months of age, 3 primary doses of Menitorix intramuscularly into the lower left thigh at 2, 4 and 6 months of age and 3 primary doses of Infanrix penta intramuscularly into the upper left thigh at 2, 4 and 6 months of age. During the booster study (NCT00463437) subjects received the same vaccines as during the primary study at 11-18 months of age, with the exception of Spain, where Infanrix IPV was given instead of Infanrix penta.
Number of Subjects With Opsonophagocytic Activity Opsono-1 (n=131;134;123;128)	33 Subjects	32 Subjects	20 Subjects	12 Subjects
Number of Subjects With Opsonophagocytic Activity Opsono-4 (N=127;132;118;126)	49 Subjects	50 Subjects	36 Subjects	72 Subjects
Number of Subjects With Opsonophagocytic Activity Opsono-5 (N=129;132;122;128)	65 Subjects	46 Subjects	40 Subjects	5 Subjects
Number of Subjects With Opsonophagocytic Activity Opsono-6B (N=128;129;122;126)	93 Subjects	97 Subjects	101 Subjects	111 Subjects
Number of Subjects With Opsonophagocytic Activity Opsono-7F (N=131;134;123;128)	131 Subjects	134 Subjects	123 Subjects	126 Subjects
Number of Subjects With Opsonophagocytic Activity Opsono-9V (N=130;132;120;126)	125 Subjects	130 Subjects	118 Subjects	122 Subjects
Number of Subjects With Opsonophagocytic Activity Opsono-14 (N=126;128;114;121)	96 Subjects	105 Subjects	95 Subjects	110 Subjects
Number of Subjects With Opsonophagocytic Activity Opsono-18C (N=113;118;113;118)	34 Subjects	56 Subjects	46 Subjects	45 Subjects
Number of Subjects With Opsonophagocytic Activity Opsono-19F (N=131;133;123;128)	87 Subjects	88 Subjects	80 Subjects	89 Subjects
Number of Subjects With Opsonophagocytic Activity Opsono-23F (N=129133;119;121)	98 Subjects	108 Subjects	86 Subjects	111 Subjects

SECONDARY outcome

Timeframe: At 4 years of age

Population: Analysis was performed on the According-to-Protocol cohort for antibody persistence at 4 years of age, which included all evaluable subjects who had received the full vaccination course in the primary study (NCT00334334) and in the booster study (NCT00463437) and had available results at 4 years of age

Concentrations were expressed as GMCs in enzyme-linked immunosorbent-assay (ELISA) units per milliliter (EL.U/mL).

Outcome measures

Measure	Synflorix-Meningitec Group n=136 Participants Subjects who received concomitantly in the primary study (NCT00334334): 3 primary doses of Synflorix intramuscularly into the right thigh at 2, 4 and 6 months of age 2 primary doses of Meningitec intramuscularly into the lower left thigh at 2 and 4 months of age and 3 primary doses of Infanrix hexa intramuscularly into the upper left thigh at 2, 4 and 6 months of age. (In Poland subjects were offered a third dose of Meningitec at 7 months of age to comply with national recommendations). During the booster study (NCT00463437) subjects received the same vaccines as during the primary study at 11-18 months of age, with the exception of Spain, where Infanrix IPV/Hib was given instead of Infanrix hexa.	Synflorix-NeisVac-C Group n=138 Participants Subjects who received concomitantly in the primary study (NCT00334334): 3 primary doses of Synflorix intramuscularly into the right thigh at 2, 4 and 6 months of age, 2 primary doses of Neis-Vac-C intramuscularly into the lower left thigh at 2 and 4 months of age and 3 primary doses of Infanrix hexa intramuscularly into the upper left thigh at 2, 4 and 6 months of age. (In Poland subjects were offered a third dose of Neis-Vac-C at 7 months of age to comply with national recommendations). During the booster study (NCT00463437) subjects received the same vaccines as during the primary study at 11-18 months of age, with the exception of Spain, where Infanrix IPV/Hib was given instead of Infanrix hexa.	Synflorix-Menitorix Group n=129 Participants Subjects who received concomitantly in the primary study (NCT00334334): 3 primary doses of Synflorix intramuscularly into the right thigh at 2, 4 and 6 months of age, 3 primary doses of Menitorix intramuscularly into the lower left thigh at 2, 4 and 6 months of age and 3 primary doses of Infanrix penta intramuscularly into the upper left thigh at 2, 4 and 6 months of age. During the booster study (NCT00463437) subjects received the same vaccines as during the primary study at 11-18 months of age, with the exception of Spain, where Infanrix IPV was given instead of Infanrix penta.	Prevenar-Menitorix Group n=132 Participants Subjects who received concomitantly in the primary study (NCT00334334): 3 primary doses of Prevenar intramuscularly into the right thigh at 2, 4 and 6 months of age, 3 primary doses of Menitorix intramuscularly into the lower left thigh at 2, 4 and 6 months of age and 3 primary doses of Infanrix penta intramuscularly into the upper left thigh at 2, 4 and 6 months of age. During the booster study (NCT00463437) subjects received the same vaccines as during the primary study at 11-18 months of age, with the exception of Spain, where Infanrix IPV was given instead of Infanrix penta.
Concentration of Antibodies Against Protein D	401.1 EL.U/mL Interval 338.3 to 475.6	387.2 EL.U/mL Interval 326.7 to 458.9	334.8 EL.U/mL Interval 277.7 to 403.7	107.9 EL.U/mL Interval 94.6 to 123.1

SECONDARY outcome

Timeframe: At 4 years of age

Population: Analysis was performed on the According-to-Protocol cohort for antibody persistence at 4 years of age, which included all evaluable subjects who had received the full vaccination course in the primary study (NCT00334334) and in the booster study (NCT00463437) and had available results at 4 years of age

Cut-off values assessed were defined as equal to or above 10 milli-international units per milliliter (mIU/mL) or equal to or above 100 mIU/mL.

Outcome measures

Measure	Synflorix-Meningitec Group n=95 Participants Subjects who received concomitantly in the primary study (NCT00334334): 3 primary doses of Synflorix intramuscularly into the right thigh at 2, 4 and 6 months of age 2 primary doses of Meningitec intramuscularly into the lower left thigh at 2 and 4 months of age and 3 primary doses of Infanrix hexa intramuscularly into the upper left thigh at 2, 4 and 6 months of age. (In Poland subjects were offered a third dose of Meningitec at 7 months of age to comply with national recommendations). During the booster study (NCT00463437) subjects received the same vaccines as during the primary study at 11-18 months of age, with the exception of Spain, where Infanrix IPV/Hib was given instead of Infanrix hexa.	Synflorix-NeisVac-C Group n=102 Participants Subjects who received concomitantly in the primary study (NCT00334334): 3 primary doses of Synflorix intramuscularly into the right thigh at 2, 4 and 6 months of age, 2 primary doses of Neis-Vac-C intramuscularly into the lower left thigh at 2 and 4 months of age and 3 primary doses of Infanrix hexa intramuscularly into the upper left thigh at 2, 4 and 6 months of age. (In Poland subjects were offered a third dose of Neis-Vac-C at 7 months of age to comply with national recommendations). During the booster study (NCT00463437) subjects received the same vaccines as during the primary study at 11-18 months of age, with the exception of Spain, where Infanrix IPV/Hib was given instead of Infanrix hexa.	Synflorix-Menitorix Group n=98 Participants Subjects who received concomitantly in the primary study (NCT00334334): 3 primary doses of Synflorix intramuscularly into the right thigh at 2, 4 and 6 months of age, 3 primary doses of Menitorix intramuscularly into the lower left thigh at 2, 4 and 6 months of age and 3 primary doses of Infanrix penta intramuscularly into the upper left thigh at 2, 4 and 6 months of age. During the booster study (NCT00463437) subjects received the same vaccines as during the primary study at 11-18 months of age, with the exception of Spain, where Infanrix IPV was given instead of Infanrix penta.	Prevenar-Menitorix Group n=98 Participants Subjects who received concomitantly in the primary study (NCT00334334): 3 primary doses of Prevenar intramuscularly into the right thigh at 2, 4 and 6 months of age, 3 primary doses of Menitorix intramuscularly into the lower left thigh at 2, 4 and 6 months of age and 3 primary doses of Infanrix penta intramuscularly into the upper left thigh at 2, 4 and 6 months of age. During the booster study (NCT00463437) subjects received the same vaccines as during the primary study at 11-18 months of age, with the exception of Spain, where Infanrix IPV was given instead of Infanrix penta.
Number of Subjects With Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentrations Equal to or Above Cut-off Values ≥ 10 mIU/mL	86 Subjects	93 Subjects	86 Subjects	90 Subjects
Number of Subjects With Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentrations Equal to or Above Cut-off Values ≥ 100 mIU/mL	67 Subjects	72 Subjects	62 Subjects	72 Subjects

SECONDARY outcome

Timeframe: At 4 years of age

Population: Analysis was performed on the According-to-Protocol cohort for antibody persistence at 4 years of age, which included all evaluable subjects who had received the full vaccination course in the primary study (NCT00334334) and in the booster study (NCT00463437) and had available results at 4 years of age

Concentrations were expressed as GMCs in mIU/mL.

Outcome measures

Measure	Synflorix-Meningitec Group n=95 Participants Subjects who received concomitantly in the primary study (NCT00334334): 3 primary doses of Synflorix intramuscularly into the right thigh at 2, 4 and 6 months of age 2 primary doses of Meningitec intramuscularly into the lower left thigh at 2 and 4 months of age and 3 primary doses of Infanrix hexa intramuscularly into the upper left thigh at 2, 4 and 6 months of age. (In Poland subjects were offered a third dose of Meningitec at 7 months of age to comply with national recommendations). During the booster study (NCT00463437) subjects received the same vaccines as during the primary study at 11-18 months of age, with the exception of Spain, where Infanrix IPV/Hib was given instead of Infanrix hexa.	Synflorix-NeisVac-C Group n=102 Participants Subjects who received concomitantly in the primary study (NCT00334334): 3 primary doses of Synflorix intramuscularly into the right thigh at 2, 4 and 6 months of age, 2 primary doses of Neis-Vac-C intramuscularly into the lower left thigh at 2 and 4 months of age and 3 primary doses of Infanrix hexa intramuscularly into the upper left thigh at 2, 4 and 6 months of age. (In Poland subjects were offered a third dose of Neis-Vac-C at 7 months of age to comply with national recommendations). During the booster study (NCT00463437) subjects received the same vaccines as during the primary study at 11-18 months of age, with the exception of Spain, where Infanrix IPV/Hib was given instead of Infanrix hexa.	Synflorix-Menitorix Group n=98 Participants Subjects who received concomitantly in the primary study (NCT00334334): 3 primary doses of Synflorix intramuscularly into the right thigh at 2, 4 and 6 months of age, 3 primary doses of Menitorix intramuscularly into the lower left thigh at 2, 4 and 6 months of age and 3 primary doses of Infanrix penta intramuscularly into the upper left thigh at 2, 4 and 6 months of age. During the booster study (NCT00463437) subjects received the same vaccines as during the primary study at 11-18 months of age, with the exception of Spain, where Infanrix IPV was given instead of Infanrix penta.	Prevenar-Menitorix Group n=98 Participants Subjects who received concomitantly in the primary study (NCT00334334): 3 primary doses of Prevenar intramuscularly into the right thigh at 2, 4 and 6 months of age, 3 primary doses of Menitorix intramuscularly into the lower left thigh at 2, 4 and 6 months of age and 3 primary doses of Infanrix penta intramuscularly into the upper left thigh at 2, 4 and 6 months of age. During the booster study (NCT00463437) subjects received the same vaccines as during the primary study at 11-18 months of age, with the exception of Spain, where Infanrix IPV was given instead of Infanrix penta.
Anti-HBs Antibody Concentrations	273.5 mIU/mL Interval 183.2 to 408.3	238.8 mIU/mL Interval 165.6 to 344.3	174.6 mIU/mL Interval 114.5 to 266.4	284.7 mIU/mL Interval 190.7 to 425.1

SECONDARY outcome

Timeframe: From last study contact of the study (NCT00463437) at 17-24 months of age until 4 years of age

Population: Analysis was performed on the Total Enrolled cohort at 4 years of age, which included all subjects vaccinated in the booster study (NCT00463437) and who were part of the blood sample subset.

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. Related = SAE assessed by the investigator as being related to the study procedures.

Outcome measures

Measure	Synflorix-Meningitec Group n=140 Participants Subjects who received concomitantly in the primary study (NCT00334334): 3 primary doses of Synflorix intramuscularly into the right thigh at 2, 4 and 6 months of age 2 primary doses of Meningitec intramuscularly into the lower left thigh at 2 and 4 months of age and 3 primary doses of Infanrix hexa intramuscularly into the upper left thigh at 2, 4 and 6 months of age. (In Poland subjects were offered a third dose of Meningitec at 7 months of age to comply with national recommendations). During the booster study (NCT00463437) subjects received the same vaccines as during the primary study at 11-18 months of age, with the exception of Spain, where Infanrix IPV/Hib was given instead of Infanrix hexa.	Synflorix-NeisVac-C Group n=142 Participants Subjects who received concomitantly in the primary study (NCT00334334): 3 primary doses of Synflorix intramuscularly into the right thigh at 2, 4 and 6 months of age, 2 primary doses of Neis-Vac-C intramuscularly into the lower left thigh at 2 and 4 months of age and 3 primary doses of Infanrix hexa intramuscularly into the upper left thigh at 2, 4 and 6 months of age. (In Poland subjects were offered a third dose of Neis-Vac-C at 7 months of age to comply with national recommendations). During the booster study (NCT00463437) subjects received the same vaccines as during the primary study at 11-18 months of age, with the exception of Spain, where Infanrix IPV/Hib was given instead of Infanrix hexa.	Synflorix-Menitorix Group n=142 Participants Subjects who received concomitantly in the primary study (NCT00334334): 3 primary doses of Synflorix intramuscularly into the right thigh at 2, 4 and 6 months of age, 3 primary doses of Menitorix intramuscularly into the lower left thigh at 2, 4 and 6 months of age and 3 primary doses of Infanrix penta intramuscularly into the upper left thigh at 2, 4 and 6 months of age. During the booster study (NCT00463437) subjects received the same vaccines as during the primary study at 11-18 months of age, with the exception of Spain, where Infanrix IPV was given instead of Infanrix penta.	Prevenar-Menitorix Group n=137 Participants Subjects who received concomitantly in the primary study (NCT00334334): 3 primary doses of Prevenar intramuscularly into the right thigh at 2, 4 and 6 months of age, 3 primary doses of Menitorix intramuscularly into the lower left thigh at 2, 4 and 6 months of age and 3 primary doses of Infanrix penta intramuscularly into the upper left thigh at 2, 4 and 6 months of age. During the booster study (NCT00463437) subjects received the same vaccines as during the primary study at 11-18 months of age, with the exception of Spain, where Infanrix IPV was given instead of Infanrix penta.
Number of Subjects With Serious Adverse Events (SAEs) SAE(s)	0 Subjects	0 Subjects	0 Subjects	0 Subjects
Number of Subjects With Serious Adverse Events (SAEs) Related SAE(s)	0 Subjects	0 Subjects	0 Subjects	0 Subjects

SECONDARY outcome

Timeframe: At 6 years of age

Population: Analysis was performed on the According-to-Protocol cohort for antibody persistence at 6 years of age, which included all evaluable subjects who had received the full vaccination course in the primary study (NCT00334334) and in the booster study (NCT00463437) and had available results at 6 years of age.

rSBA-MenC antibody cut-off value assessed was equal to or above 1:128.

Outcome measures

Measure	Synflorix-Meningitec Group n=128 Participants Subjects who received concomitantly in the primary study (NCT00334334): 3 primary doses of Synflorix intramuscularly into the right thigh at 2, 4 and 6 months of age 2 primary doses of Meningitec intramuscularly into the lower left thigh at 2 and 4 months of age and 3 primary doses of Infanrix hexa intramuscularly into the upper left thigh at 2, 4 and 6 months of age. (In Poland subjects were offered a third dose of Meningitec at 7 months of age to comply with national recommendations). During the booster study (NCT00463437) subjects received the same vaccines as during the primary study at 11-18 months of age, with the exception of Spain, where Infanrix IPV/Hib was given instead of Infanrix hexa.	Synflorix-NeisVac-C Group n=137 Participants Subjects who received concomitantly in the primary study (NCT00334334): 3 primary doses of Synflorix intramuscularly into the right thigh at 2, 4 and 6 months of age, 2 primary doses of Neis-Vac-C intramuscularly into the lower left thigh at 2 and 4 months of age and 3 primary doses of Infanrix hexa intramuscularly into the upper left thigh at 2, 4 and 6 months of age. (In Poland subjects were offered a third dose of Neis-Vac-C at 7 months of age to comply with national recommendations). During the booster study (NCT00463437) subjects received the same vaccines as during the primary study at 11-18 months of age, with the exception of Spain, where Infanrix IPV/Hib was given instead of Infanrix hexa.	Synflorix-Menitorix Group n=130 Participants Subjects who received concomitantly in the primary study (NCT00334334): 3 primary doses of Synflorix intramuscularly into the right thigh at 2, 4 and 6 months of age, 3 primary doses of Menitorix intramuscularly into the lower left thigh at 2, 4 and 6 months of age and 3 primary doses of Infanrix penta intramuscularly into the upper left thigh at 2, 4 and 6 months of age. During the booster study (NCT00463437) subjects received the same vaccines as during the primary study at 11-18 months of age, with the exception of Spain, where Infanrix IPV was given instead of Infanrix penta.	Prevenar-Menitorix Group n=134 Participants Subjects who received concomitantly in the primary study (NCT00334334): 3 primary doses of Prevenar intramuscularly into the right thigh at 2, 4 and 6 months of age, 3 primary doses of Menitorix intramuscularly into the lower left thigh at 2, 4 and 6 months of age and 3 primary doses of Infanrix penta intramuscularly into the upper left thigh at 2, 4 and 6 months of age. During the booster study (NCT00463437) subjects received the same vaccines as during the primary study at 11-18 months of age, with the exception of Spain, where Infanrix IPV was given instead of Infanrix penta.
Number of Subjects With rSBA-MenC Titer Equal to or Above Cut-off Value	11 Subjects	19 Subjects	15 Subjects	14 Subjects

SECONDARY outcome

Timeframe: At 6 years of age

Population: Analysis was performed on the According-to-Protocol cohort for antibody persistence at 6 years of age, which included all evaluable subjects who had received the full vaccination course in the primary study (NCT00334334) and in the booster study (NCT00463437) and had available results at 6 years of age

Titers are given as Geometric Mean Titers (GMTs).

Outcome measures

Measure	Synflorix-Meningitec Group n=128 Participants Subjects who received concomitantly in the primary study (NCT00334334): 3 primary doses of Synflorix intramuscularly into the right thigh at 2, 4 and 6 months of age 2 primary doses of Meningitec intramuscularly into the lower left thigh at 2 and 4 months of age and 3 primary doses of Infanrix hexa intramuscularly into the upper left thigh at 2, 4 and 6 months of age. (In Poland subjects were offered a third dose of Meningitec at 7 months of age to comply with national recommendations). During the booster study (NCT00463437) subjects received the same vaccines as during the primary study at 11-18 months of age, with the exception of Spain, where Infanrix IPV/Hib was given instead of Infanrix hexa.	Synflorix-NeisVac-C Group n=137 Participants Subjects who received concomitantly in the primary study (NCT00334334): 3 primary doses of Synflorix intramuscularly into the right thigh at 2, 4 and 6 months of age, 2 primary doses of Neis-Vac-C intramuscularly into the lower left thigh at 2 and 4 months of age and 3 primary doses of Infanrix hexa intramuscularly into the upper left thigh at 2, 4 and 6 months of age. (In Poland subjects were offered a third dose of Neis-Vac-C at 7 months of age to comply with national recommendations). During the booster study (NCT00463437) subjects received the same vaccines as during the primary study at 11-18 months of age, with the exception of Spain, where Infanrix IPV/Hib was given instead of Infanrix hexa.	Synflorix-Menitorix Group n=130 Participants Subjects who received concomitantly in the primary study (NCT00334334): 3 primary doses of Synflorix intramuscularly into the right thigh at 2, 4 and 6 months of age, 3 primary doses of Menitorix intramuscularly into the lower left thigh at 2, 4 and 6 months of age and 3 primary doses of Infanrix penta intramuscularly into the upper left thigh at 2, 4 and 6 months of age. During the booster study (NCT00463437) subjects received the same vaccines as during the primary study at 11-18 months of age, with the exception of Spain, where Infanrix IPV was given instead of Infanrix penta.	Prevenar-Menitorix Group n=134 Participants Subjects who received concomitantly in the primary study (NCT00334334): 3 primary doses of Prevenar intramuscularly into the right thigh at 2, 4 and 6 months of age, 3 primary doses of Menitorix intramuscularly into the lower left thigh at 2, 4 and 6 months of age and 3 primary doses of Infanrix penta intramuscularly into the upper left thigh at 2, 4 and 6 months of age. During the booster study (NCT00463437) subjects received the same vaccines as during the primary study at 11-18 months of age, with the exception of Spain, where Infanrix IPV was given instead of Infanrix penta.
rSBA-MenC Titers	7.2 Titer Interval 5.8 to 8.9	11.9 Titer Interval 8.9 to 16.0	10.1 Titer Interval 7.9 to 12.9	8.5 Titer Interval 6.6 to 11.1

SECONDARY outcome

Timeframe: At 6 years of age

Population: Analysis was performed on the According-to-Protocol cohort for antibody persistence at 6 years of age, which included all evaluable subjects who had received the full vaccination course in the primary study (NCT00334334) and in the booster study (NCT00463437) and had available results at 6 years of age.

The cut-off values were defined as a concentration ≥ 0.15 microgram per milliliter (μg/mL) and ≥ 1.0 μg/mL.

Outcome measures

Measure	Synflorix-Meningitec Group n=127 Participants Subjects who received concomitantly in the primary study (NCT00334334): 3 primary doses of Synflorix intramuscularly into the right thigh at 2, 4 and 6 months of age 2 primary doses of Meningitec intramuscularly into the lower left thigh at 2 and 4 months of age and 3 primary doses of Infanrix hexa intramuscularly into the upper left thigh at 2, 4 and 6 months of age. (In Poland subjects were offered a third dose of Meningitec at 7 months of age to comply with national recommendations). During the booster study (NCT00463437) subjects received the same vaccines as during the primary study at 11-18 months of age, with the exception of Spain, where Infanrix IPV/Hib was given instead of Infanrix hexa.	Synflorix-NeisVac-C Group n=134 Participants Subjects who received concomitantly in the primary study (NCT00334334): 3 primary doses of Synflorix intramuscularly into the right thigh at 2, 4 and 6 months of age, 2 primary doses of Neis-Vac-C intramuscularly into the lower left thigh at 2 and 4 months of age and 3 primary doses of Infanrix hexa intramuscularly into the upper left thigh at 2, 4 and 6 months of age. (In Poland subjects were offered a third dose of Neis-Vac-C at 7 months of age to comply with national recommendations). During the booster study (NCT00463437) subjects received the same vaccines as during the primary study at 11-18 months of age, with the exception of Spain, where Infanrix IPV/Hib was given instead of Infanrix hexa.	Synflorix-Menitorix Group n=130 Participants Subjects who received concomitantly in the primary study (NCT00334334): 3 primary doses of Synflorix intramuscularly into the right thigh at 2, 4 and 6 months of age, 3 primary doses of Menitorix intramuscularly into the lower left thigh at 2, 4 and 6 months of age and 3 primary doses of Infanrix penta intramuscularly into the upper left thigh at 2, 4 and 6 months of age. During the booster study (NCT00463437) subjects received the same vaccines as during the primary study at 11-18 months of age, with the exception of Spain, where Infanrix IPV was given instead of Infanrix penta.	Prevenar-Menitorix Group n=132 Participants Subjects who received concomitantly in the primary study (NCT00334334): 3 primary doses of Prevenar intramuscularly into the right thigh at 2, 4 and 6 months of age, 3 primary doses of Menitorix intramuscularly into the lower left thigh at 2, 4 and 6 months of age and 3 primary doses of Infanrix penta intramuscularly into the upper left thigh at 2, 4 and 6 months of age. During the booster study (NCT00463437) subjects received the same vaccines as during the primary study at 11-18 months of age, with the exception of Spain, where Infanrix IPV was given instead of Infanrix penta.
Number of Subjects With Anti-polyribosyl-ribitol Phosphate (Anti-PRP) Antibody Concentrations Equal to or Above Cut-off Values ≥ 0.15 µg/mL	126 Subjects	132 Subjects	130 Subjects	132 Subjects
Number of Subjects With Anti-polyribosyl-ribitol Phosphate (Anti-PRP) Antibody Concentrations Equal to or Above Cut-off Values ≥ 1.0 µg/mL	85 Subjects	77 Subjects	110 Subjects	100 Subjects

SECONDARY outcome

Timeframe: At 6 years of age

Population: Analysis was performed on the According-to-Protocol cohort for antibody persistence at 6 years of age, which included all evaluable subjects who had received the full vaccination course in the primary study (NCT00334334) and in the booster study (NCT00463437) and had available results at 6 years of age.

Concentrations were defined as Geometric Mean Concentrations (GMCs) in μg/mL

Outcome measures

Measure	Synflorix-Meningitec Group n=127 Participants Subjects who received concomitantly in the primary study (NCT00334334): 3 primary doses of Synflorix intramuscularly into the right thigh at 2, 4 and 6 months of age 2 primary doses of Meningitec intramuscularly into the lower left thigh at 2 and 4 months of age and 3 primary doses of Infanrix hexa intramuscularly into the upper left thigh at 2, 4 and 6 months of age. (In Poland subjects were offered a third dose of Meningitec at 7 months of age to comply with national recommendations). During the booster study (NCT00463437) subjects received the same vaccines as during the primary study at 11-18 months of age, with the exception of Spain, where Infanrix IPV/Hib was given instead of Infanrix hexa.	Synflorix-NeisVac-C Group n=134 Participants Subjects who received concomitantly in the primary study (NCT00334334): 3 primary doses of Synflorix intramuscularly into the right thigh at 2, 4 and 6 months of age, 2 primary doses of Neis-Vac-C intramuscularly into the lower left thigh at 2 and 4 months of age and 3 primary doses of Infanrix hexa intramuscularly into the upper left thigh at 2, 4 and 6 months of age. (In Poland subjects were offered a third dose of Neis-Vac-C at 7 months of age to comply with national recommendations). During the booster study (NCT00463437) subjects received the same vaccines as during the primary study at 11-18 months of age, with the exception of Spain, where Infanrix IPV/Hib was given instead of Infanrix hexa.	Synflorix-Menitorix Group n=130 Participants Subjects who received concomitantly in the primary study (NCT00334334): 3 primary doses of Synflorix intramuscularly into the right thigh at 2, 4 and 6 months of age, 3 primary doses of Menitorix intramuscularly into the lower left thigh at 2, 4 and 6 months of age and 3 primary doses of Infanrix penta intramuscularly into the upper left thigh at 2, 4 and 6 months of age. During the booster study (NCT00463437) subjects received the same vaccines as during the primary study at 11-18 months of age, with the exception of Spain, where Infanrix IPV was given instead of Infanrix penta.	Prevenar-Menitorix Group n=132 Participants Subjects who received concomitantly in the primary study (NCT00334334): 3 primary doses of Prevenar intramuscularly into the right thigh at 2, 4 and 6 months of age, 3 primary doses of Menitorix intramuscularly into the lower left thigh at 2, 4 and 6 months of age and 3 primary doses of Infanrix penta intramuscularly into the upper left thigh at 2, 4 and 6 months of age. During the booster study (NCT00463437) subjects received the same vaccines as during the primary study at 11-18 months of age, with the exception of Spain, where Infanrix IPV was given instead of Infanrix penta.
Anti-PRP Concentrations	1.655 μg/mL Interval 1.339 to 2.045	1.647 μg/mL Interval 1.298 to 2.09	2.947 μg/mL Interval 2.396 to 3.624	2.558 μg/mL Interval 2.065 to 3.168

SECONDARY outcome

Timeframe: At 6 years of age

Population: Analysis was performed on the According-to-Protocol cohort for antibody persistence at 6 years of age, which included all evaluable subjects who had received the full vaccination course in the primary study (NCT00334334) and in the booster study (NCT00463437) and had available results at 6 years of age.

Antibody concentrations were expressed as GMCs in μg/mL. Vaccine pneumococcal serotypes assessed included 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F.

Outcome measures

Measure	Synflorix-Meningitec Group n=128 Participants Subjects who received concomitantly in the primary study (NCT00334334): 3 primary doses of Synflorix intramuscularly into the right thigh at 2, 4 and 6 months of age 2 primary doses of Meningitec intramuscularly into the lower left thigh at 2 and 4 months of age and 3 primary doses of Infanrix hexa intramuscularly into the upper left thigh at 2, 4 and 6 months of age. (In Poland subjects were offered a third dose of Meningitec at 7 months of age to comply with national recommendations). During the booster study (NCT00463437) subjects received the same vaccines as during the primary study at 11-18 months of age, with the exception of Spain, where Infanrix IPV/Hib was given instead of Infanrix hexa.	Synflorix-NeisVac-C Group n=137 Participants Subjects who received concomitantly in the primary study (NCT00334334): 3 primary doses of Synflorix intramuscularly into the right thigh at 2, 4 and 6 months of age, 2 primary doses of Neis-Vac-C intramuscularly into the lower left thigh at 2 and 4 months of age and 3 primary doses of Infanrix hexa intramuscularly into the upper left thigh at 2, 4 and 6 months of age. (In Poland subjects were offered a third dose of Neis-Vac-C at 7 months of age to comply with national recommendations). During the booster study (NCT00463437) subjects received the same vaccines as during the primary study at 11-18 months of age, with the exception of Spain, where Infanrix IPV/Hib was given instead of Infanrix hexa.	Synflorix-Menitorix Group n=131 Participants Subjects who received concomitantly in the primary study (NCT00334334): 3 primary doses of Synflorix intramuscularly into the right thigh at 2, 4 and 6 months of age, 3 primary doses of Menitorix intramuscularly into the lower left thigh at 2, 4 and 6 months of age and 3 primary doses of Infanrix penta intramuscularly into the upper left thigh at 2, 4 and 6 months of age. During the booster study (NCT00463437) subjects received the same vaccines as during the primary study at 11-18 months of age, with the exception of Spain, where Infanrix IPV was given instead of Infanrix penta.	Prevenar-Menitorix Group n=134 Participants Subjects who received concomitantly in the primary study (NCT00334334): 3 primary doses of Prevenar intramuscularly into the right thigh at 2, 4 and 6 months of age, 3 primary doses of Menitorix intramuscularly into the lower left thigh at 2, 4 and 6 months of age and 3 primary doses of Infanrix penta intramuscularly into the upper left thigh at 2, 4 and 6 months of age. During the booster study (NCT00463437) subjects received the same vaccines as during the primary study at 11-18 months of age, with the exception of Spain, where Infanrix IPV was given instead of Infanrix penta.
Antibody Concentrations Against Vaccine Pneumococcal Serotypes Anti-1 (N=128;136;130;134)	0.19 μg/mL Interval 0.16 to 0.23	0.22 μg/mL Interval 0.17 to 0.27	0.20 μg/mL Interval 0.15 to 0.26	0.11 μg/mL Interval 0.09 to 0.13
Antibody Concentrations Against Vaccine Pneumococcal Serotypes Anti-4 (N=128;135;130;134)	0.14 μg/mL Interval 0.11 to 0.17	0.14 μg/mL Interval 0.11 to 0.17	0.12 μg/mL Interval 0.1 to 0.15	0.24 μg/mL Interval 0.19 to 0.29
Antibody Concentrations Against Vaccine Pneumococcal Serotypes Anti-5 (N=128;135;130;131)	0.37 μg/mL Interval 0.3 to 0.45	0.31 μg/mL Interval 0.26 to 0.37	0.30 μg/mL Interval 0.25 to 0.37	0.13 μg/mL Interval 0.11 to 0.15
Antibody Concentrations Against Vaccine Pneumococcal Serotypes Anti-6B (N=128;135;131;131)	1.71 μg/mL Interval 1.32 to 2.23	1.13 μg/mL Interval 0.87 to 1.48	1.28 μg/mL Interval 1.0 to 1.64	1.73 μg/mL Interval 1.38 to 2.16
Antibody Concentrations Against Vaccine Pneumococcal Serotypes Anti-7F (N=127;137;130;132)	0.61 μg/mL Interval 0.49 to 0.78	0.59 μg/mL Interval 0.46 to 0.74	0.64 μg/mL Interval 0.5 to 0.82	0.24 μg/mL Interval 0.18 to 0.32
Antibody Concentrations Against Vaccine Pneumococcal Serotypes Anti-9V (N=128;137;131;132)	0.76 μg/mL Interval 0.56 to 1.01	0.67 μg/mL Interval 0.51 to 0.88	0.57 μg/mL Interval 0.42 to 0.79	0.65 μg/mL Interval 0.51 to 0.83
Antibody Concentrations Against Vaccine Pneumococcal Serotypes Anti-14 (N=128;137;130;133)	2.84 μg/mL Interval 2.17 to 3.73	2.22 μg/mL Interval 1.72 to 2.86	2.81 μg/mL Interval 2.07 to 3.81	2.59 μg/mL Interval 2.08 to 3.23
Antibody Concentrations Against Vaccine Pneumococcal Serotypes Anti-18C (N=128;137;130;132)	0.52 μg/mL Interval 0.41 to 0.66	0.75 μg/mL Interval 0.6 to 0.94	0.56 μg/mL Interval 0.43 to 0.74	0.49 μg/mL Interval 0.39 to 0.62
Antibody Concentrations Against Vaccine Pneumococcal Serotypes Anti-19F (N=128;137;130;133)	3.91 μg/mL Interval 3.01 to 5.1	3.94 μg/mL Interval 2.99 to 5.2	4.24 μg/mL Interval 3.3 to 5.45	3.11 μg/mL Interval 2.48 to 3.91
Antibody Concentrations Against Vaccine Pneumococcal Serotypes Anti-23F (N=128;136;130;133)	1.71 μg/mL Interval 1.26 to 2.3	1.70 μg/mL Interval 1.27 to 2.26	1.41 μg/mL Interval 1.06 to 1.87	2.99 μg/mL Interval 2.32 to 3.86

SECONDARY outcome

Timeframe: At 6 years of age

Population: Analysis was performed on the According-to-Protocol cohort for antibody persistence at 6 years of age, which included all evaluable subjects who had received the full vaccination course in the primary study (NCT00334334) and in the booster study (NCT00463437) and had available results at 6 years of age.

Concentrations were expressed as GMCs in enzyme-linked immunosorbent-assay (ELISA) units per milliliter (EL.U/mL).

Outcome measures

Measure	Synflorix-Meningitec Group n=128 Participants Subjects who received concomitantly in the primary study (NCT00334334): 3 primary doses of Synflorix intramuscularly into the right thigh at 2, 4 and 6 months of age 2 primary doses of Meningitec intramuscularly into the lower left thigh at 2 and 4 months of age and 3 primary doses of Infanrix hexa intramuscularly into the upper left thigh at 2, 4 and 6 months of age. (In Poland subjects were offered a third dose of Meningitec at 7 months of age to comply with national recommendations). During the booster study (NCT00463437) subjects received the same vaccines as during the primary study at 11-18 months of age, with the exception of Spain, where Infanrix IPV/Hib was given instead of Infanrix hexa.	Synflorix-NeisVac-C Group n=137 Participants Subjects who received concomitantly in the primary study (NCT00334334): 3 primary doses of Synflorix intramuscularly into the right thigh at 2, 4 and 6 months of age, 2 primary doses of Neis-Vac-C intramuscularly into the lower left thigh at 2 and 4 months of age and 3 primary doses of Infanrix hexa intramuscularly into the upper left thigh at 2, 4 and 6 months of age. (In Poland subjects were offered a third dose of Neis-Vac-C at 7 months of age to comply with national recommendations). During the booster study (NCT00463437) subjects received the same vaccines as during the primary study at 11-18 months of age, with the exception of Spain, where Infanrix IPV/Hib was given instead of Infanrix hexa.	Synflorix-Menitorix Group n=131 Participants Subjects who received concomitantly in the primary study (NCT00334334): 3 primary doses of Synflorix intramuscularly into the right thigh at 2, 4 and 6 months of age, 3 primary doses of Menitorix intramuscularly into the lower left thigh at 2, 4 and 6 months of age and 3 primary doses of Infanrix penta intramuscularly into the upper left thigh at 2, 4 and 6 months of age. During the booster study (NCT00463437) subjects received the same vaccines as during the primary study at 11-18 months of age, with the exception of Spain, where Infanrix IPV was given instead of Infanrix penta.	Prevenar-Menitorix Group n=133 Participants Subjects who received concomitantly in the primary study (NCT00334334): 3 primary doses of Prevenar intramuscularly into the right thigh at 2, 4 and 6 months of age, 3 primary doses of Menitorix intramuscularly into the lower left thigh at 2, 4 and 6 months of age and 3 primary doses of Infanrix penta intramuscularly into the upper left thigh at 2, 4 and 6 months of age. During the booster study (NCT00463437) subjects received the same vaccines as during the primary study at 11-18 months of age, with the exception of Spain, where Infanrix IPV was given instead of Infanrix penta.
Concentration of Antibodies Against Protein D	284.7 EL.U/mL Interval 239.5 to 338.4	278.0 EL.U/mL Interval 236.3 to 327.1	266.1 EL.U/mL Interval 222.2 to 318.8	105.2 EL.U/mL Interval 92.4 to 119.8

SECONDARY outcome

Timeframe: At 3 and 4 years of age

Population: Analysis was performed on the According-to-Protocol cohort for antibody persistence at 6 years of age, which included all evaluable subjects who had received the full vaccination course in the primary study (NCT00334334) and in the booster study (NCT00463437) and had available results at 6 years of age

Cut-off values assessed were defined as equal to or above 10 milli-international units per milliliter (mIU/mL) or equal to or above 100 mIU/mL.

Outcome measures

Measure	Synflorix-Meningitec Group n=94 Participants Subjects who received concomitantly in the primary study (NCT00334334): 3 primary doses of Synflorix intramuscularly into the right thigh at 2, 4 and 6 months of age 2 primary doses of Meningitec intramuscularly into the lower left thigh at 2 and 4 months of age and 3 primary doses of Infanrix hexa intramuscularly into the upper left thigh at 2, 4 and 6 months of age. (In Poland subjects were offered a third dose of Meningitec at 7 months of age to comply with national recommendations). During the booster study (NCT00463437) subjects received the same vaccines as during the primary study at 11-18 months of age, with the exception of Spain, where Infanrix IPV/Hib was given instead of Infanrix hexa.	Synflorix-NeisVac-C Group n=98 Participants Subjects who received concomitantly in the primary study (NCT00334334): 3 primary doses of Synflorix intramuscularly into the right thigh at 2, 4 and 6 months of age, 2 primary doses of Neis-Vac-C intramuscularly into the lower left thigh at 2 and 4 months of age and 3 primary doses of Infanrix hexa intramuscularly into the upper left thigh at 2, 4 and 6 months of age. (In Poland subjects were offered a third dose of Neis-Vac-C at 7 months of age to comply with national recommendations). During the booster study (NCT00463437) subjects received the same vaccines as during the primary study at 11-18 months of age, with the exception of Spain, where Infanrix IPV/Hib was given instead of Infanrix hexa.	Synflorix-Menitorix Group n=94 Participants Subjects who received concomitantly in the primary study (NCT00334334): 3 primary doses of Synflorix intramuscularly into the right thigh at 2, 4 and 6 months of age, 3 primary doses of Menitorix intramuscularly into the lower left thigh at 2, 4 and 6 months of age and 3 primary doses of Infanrix penta intramuscularly into the upper left thigh at 2, 4 and 6 months of age. During the booster study (NCT00463437) subjects received the same vaccines as during the primary study at 11-18 months of age, with the exception of Spain, where Infanrix IPV was given instead of Infanrix penta.	Prevenar-Menitorix Group n=91 Participants Subjects who received concomitantly in the primary study (NCT00334334): 3 primary doses of Prevenar intramuscularly into the right thigh at 2, 4 and 6 months of age, 3 primary doses of Menitorix intramuscularly into the lower left thigh at 2, 4 and 6 months of age and 3 primary doses of Infanrix penta intramuscularly into the upper left thigh at 2, 4 and 6 months of age. During the booster study (NCT00463437) subjects received the same vaccines as during the primary study at 11-18 months of age, with the exception of Spain, where Infanrix IPV was given instead of Infanrix penta.
Number of Subjects With Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentrations Equal to or Above Cut-off Values as Measured by ELISA. ≥ 10 mIU/mL; 4 years (N= 87, 94, 91, 91)	78 Subjects	86 Subjects	79 Subjects	83 Subjects
Number of Subjects With Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentrations Equal to or Above Cut-off Values as Measured by ELISA. ≥ 10 mIU/mL; 3 years (N= 94, 98, 94, 90)	92 Subjects	92 Subjects	91 Subjects	87 Subjects
Number of Subjects With Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentrations Equal to or Above Cut-off Values as Measured by ELISA. ≥ 100mIU/mL; 3 years (N= 94, 98, 94, 90)	71 Subjects	79 Subjects	67 Subjects	67 Subjects
Number of Subjects With Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentrations Equal to or Above Cut-off Values as Measured by ELISA. ≥ 100mIU/mL; 4 years (N= 87, 94, 91, 91)	61 Subjects	69 Subjects	57 Subjects	67 Subjects

SECONDARY outcome

Timeframe: At 3 and 4 years of age

Population: Analysis was performed on the According-to-Protocol cohort for antibody persistence at 6 years of age, which included all evaluable subjects who had received the full vaccination course in the primary study (NCT00334334) and in the booster study (NCT00463437) and had available results at 6 years of age.

Concentrations were expressed as GMCs in mIU/mL.

Outcome measures

Measure	Synflorix-Meningitec Group n=94 Participants Subjects who received concomitantly in the primary study (NCT00334334): 3 primary doses of Synflorix intramuscularly into the right thigh at 2, 4 and 6 months of age 2 primary doses of Meningitec intramuscularly into the lower left thigh at 2 and 4 months of age and 3 primary doses of Infanrix hexa intramuscularly into the upper left thigh at 2, 4 and 6 months of age. (In Poland subjects were offered a third dose of Meningitec at 7 months of age to comply with national recommendations). During the booster study (NCT00463437) subjects received the same vaccines as during the primary study at 11-18 months of age, with the exception of Spain, where Infanrix IPV/Hib was given instead of Infanrix hexa.	Synflorix-NeisVac-C Group n=98 Participants Subjects who received concomitantly in the primary study (NCT00334334): 3 primary doses of Synflorix intramuscularly into the right thigh at 2, 4 and 6 months of age, 2 primary doses of Neis-Vac-C intramuscularly into the lower left thigh at 2 and 4 months of age and 3 primary doses of Infanrix hexa intramuscularly into the upper left thigh at 2, 4 and 6 months of age. (In Poland subjects were offered a third dose of Neis-Vac-C at 7 months of age to comply with national recommendations). During the booster study (NCT00463437) subjects received the same vaccines as during the primary study at 11-18 months of age, with the exception of Spain, where Infanrix IPV/Hib was given instead of Infanrix hexa.	Synflorix-Menitorix Group n=94 Participants Subjects who received concomitantly in the primary study (NCT00334334): 3 primary doses of Synflorix intramuscularly into the right thigh at 2, 4 and 6 months of age, 3 primary doses of Menitorix intramuscularly into the lower left thigh at 2, 4 and 6 months of age and 3 primary doses of Infanrix penta intramuscularly into the upper left thigh at 2, 4 and 6 months of age. During the booster study (NCT00463437) subjects received the same vaccines as during the primary study at 11-18 months of age, with the exception of Spain, where Infanrix IPV was given instead of Infanrix penta.	Prevenar-Menitorix Group n=91 Participants Subjects who received concomitantly in the primary study (NCT00334334): 3 primary doses of Prevenar intramuscularly into the right thigh at 2, 4 and 6 months of age, 3 primary doses of Menitorix intramuscularly into the lower left thigh at 2, 4 and 6 months of age and 3 primary doses of Infanrix penta intramuscularly into the upper left thigh at 2, 4 and 6 months of age. During the booster study (NCT00463437) subjects received the same vaccines as during the primary study at 11-18 months of age, with the exception of Spain, where Infanrix IPV was given instead of Infanrix penta.
Anti-HBs Antibody Concentrations as Measured by ELISA anti-HBs; 3 years (N= 94, 98, 94, 90)	433.8 mIU/mL Interval 296.2 to 635.2	332.3 mIU/mL Interval 230.5 to 479.1	302.7 mIU/mL Interval 201.7 to 454.3	396.5 mIU/mL Interval 263.4 to 596.9
Anti-HBs Antibody Concentrations as Measured by ELISA anti-HBs; 4 years (N= 87, 94, 91, 91)	270.5 mIU/mL Interval 177.0 to 413.5	263.1 mIU/mL Interval 180.9 to 382.9	172.7 mIU/mL Interval 110.4 to 270.1	280.2 mIU/mL Interval 183.6 to 427.7

SECONDARY outcome

Timeframe: At 3, 4 and 6 years of age

Population: Analysis was performed on the According-to-Protocol cohort for antibody persistence at 6 years of age, which included all evaluable subjects who had received the full vaccination course in the primary study (NCT00334334) and in the booster study (NCT00463437) and had available results at 6 years of age.

Cut-off values assessed were defined as equal to or above (≥) 6.2 milli-international units per milliliter (mIU/mL), 10 mIU/mL and 100 mIU/mL.

Note: A decrease in the specificity of the anti-HB ELISA assay had been observed in some studies for low levels of antibody (10-100 mIU/mL) when tested by Enzyme-Linked Immunosorbent Assay (ELISA). The tables show both the results obtained by ELISA as well as updated results following complete retesting and reanalysis by a Chemiluminescence immunoassay (CLIA). Anti-HBs seroprotection was redefined as CLIA concentration above 10 mIU/mL.

Outcome measures

Measure	Synflorix-Meningitec Group n=122 Participants Subjects who received concomitantly in the primary study (NCT00334334): 3 primary doses of Synflorix intramuscularly into the right thigh at 2, 4 and 6 months of age 2 primary doses of Meningitec intramuscularly into the lower left thigh at 2 and 4 months of age and 3 primary doses of Infanrix hexa intramuscularly into the upper left thigh at 2, 4 and 6 months of age. (In Poland subjects were offered a third dose of Meningitec at 7 months of age to comply with national recommendations). During the booster study (NCT00463437) subjects received the same vaccines as during the primary study at 11-18 months of age, with the exception of Spain, where Infanrix IPV/Hib was given instead of Infanrix hexa.	Synflorix-NeisVac-C Group n=130 Participants Subjects who received concomitantly in the primary study (NCT00334334): 3 primary doses of Synflorix intramuscularly into the right thigh at 2, 4 and 6 months of age, 2 primary doses of Neis-Vac-C intramuscularly into the lower left thigh at 2 and 4 months of age and 3 primary doses of Infanrix hexa intramuscularly into the upper left thigh at 2, 4 and 6 months of age. (In Poland subjects were offered a third dose of Neis-Vac-C at 7 months of age to comply with national recommendations). During the booster study (NCT00463437) subjects received the same vaccines as during the primary study at 11-18 months of age, with the exception of Spain, where Infanrix IPV/Hib was given instead of Infanrix hexa.	Synflorix-Menitorix Group n=125 Participants Subjects who received concomitantly in the primary study (NCT00334334): 3 primary doses of Synflorix intramuscularly into the right thigh at 2, 4 and 6 months of age, 3 primary doses of Menitorix intramuscularly into the lower left thigh at 2, 4 and 6 months of age and 3 primary doses of Infanrix penta intramuscularly into the upper left thigh at 2, 4 and 6 months of age. During the booster study (NCT00463437) subjects received the same vaccines as during the primary study at 11-18 months of age, with the exception of Spain, where Infanrix IPV was given instead of Infanrix penta.	Prevenar-Menitorix Group n=128 Participants Subjects who received concomitantly in the primary study (NCT00334334): 3 primary doses of Prevenar intramuscularly into the right thigh at 2, 4 and 6 months of age, 3 primary doses of Menitorix intramuscularly into the lower left thigh at 2, 4 and 6 months of age and 3 primary doses of Infanrix penta intramuscularly into the upper left thigh at 2, 4 and 6 months of age. During the booster study (NCT00463437) subjects received the same vaccines as during the primary study at 11-18 months of age, with the exception of Spain, where Infanrix IPV was given instead of Infanrix penta.
Number of Subjects With Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentrations Equal to or Above Cut-off Values ≥ 6.2 mIU/mL; 3 years (N=118,130, 122, 119)	110 Subjects	121 Subjects	110 Subjects	113 Subjects
Number of Subjects With Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentrations Equal to or Above Cut-off Values ≥ 6.2 mIU/mL; 4 years (N= 120, 127, 118, 119)	110 Subjects	113 Subjects	104 Subjects	109 Subjects
Number of Subjects With Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentrations Equal to or Above Cut-off Values ≥ 6.2 mIU/mL; 6 years (N=122, 129, 125, 128)	102 Subjects	108 Subjects	98 Subjects	112 Subjects
Number of Subjects With Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentrations Equal to or Above Cut-off Values ≥ 10 mIU/mL; 3 years (N=118,130, 122, 119)	109 Subjects	118 Subjects	108 Subjects	111 Subjects
Number of Subjects With Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentrations Equal to or Above Cut-off Values ≥ 10 mIU/mL; 4 years (N= 120, 127, 118, 119)	104 Subjects	112 Subjects	100 Subjects	107 Subjects
Number of Subjects With Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentrations Equal to or Above Cut-off Values ≥ 10 mIU/mL; 6 years (N=122, 129, 125, 128)	100 Subjects	103 Subjects	91 Subjects	108 Subjects
Number of Subjects With Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentrations Equal to or Above Cut-off Values ≥ 100 mIU/mL; 3 years (N=118,130, 122, 119)	80 Subjects	84 Subjects	75 Subjects	74 Subjects
Number of Subjects With Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentrations Equal to or Above Cut-off Values ≥ 100 mIU/mL; 4 years (N= 120, 127, 118, 119)	70 Subjects	76 Subjects	60 Subjects	73 Subjects
Number of Subjects With Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentrations Equal to or Above Cut-off Values ≥ 100 mIU/mL; 6 years (N=122, 129, 125, 128)	57 Subjects	62 Subjects	45 Subjects	66 Subjects

SECONDARY outcome

Timeframe: At 3, 4 and 6 years of age

Population: Analysis was performed on the According-to-Protocol cohort for antibody persistence at 6 years of age, which included all evaluable subjects who had received the full vaccination course in the primary study (NCT00334334) and in the booster study (NCT00463437) and had available results at 6 years of age.

Concentrations were expressed as GMCs in mIU/mL. Note: A decrease in the specificity of the anti-HB ELISA assay had been observed in some studies for low levels of antibody (10-100 mIU/mL) when tested by ELISA. The tables show both the results obtained by ELISA as well as updated results following complete retesting and reanalysis by a Chemiluminescence immunoassay (CLIA).

Outcome measures

Measure	Synflorix-Meningitec Group n=122 Participants Subjects who received concomitantly in the primary study (NCT00334334): 3 primary doses of Synflorix intramuscularly into the right thigh at 2, 4 and 6 months of age 2 primary doses of Meningitec intramuscularly into the lower left thigh at 2 and 4 months of age and 3 primary doses of Infanrix hexa intramuscularly into the upper left thigh at 2, 4 and 6 months of age. (In Poland subjects were offered a third dose of Meningitec at 7 months of age to comply with national recommendations). During the booster study (NCT00463437) subjects received the same vaccines as during the primary study at 11-18 months of age, with the exception of Spain, where Infanrix IPV/Hib was given instead of Infanrix hexa.	Synflorix-NeisVac-C Group n=129 Participants Subjects who received concomitantly in the primary study (NCT00334334): 3 primary doses of Synflorix intramuscularly into the right thigh at 2, 4 and 6 months of age, 2 primary doses of Neis-Vac-C intramuscularly into the lower left thigh at 2 and 4 months of age and 3 primary doses of Infanrix hexa intramuscularly into the upper left thigh at 2, 4 and 6 months of age. (In Poland subjects were offered a third dose of Neis-Vac-C at 7 months of age to comply with national recommendations). During the booster study (NCT00463437) subjects received the same vaccines as during the primary study at 11-18 months of age, with the exception of Spain, where Infanrix IPV/Hib was given instead of Infanrix hexa.	Synflorix-Menitorix Group n=125 Participants Subjects who received concomitantly in the primary study (NCT00334334): 3 primary doses of Synflorix intramuscularly into the right thigh at 2, 4 and 6 months of age, 3 primary doses of Menitorix intramuscularly into the lower left thigh at 2, 4 and 6 months of age and 3 primary doses of Infanrix penta intramuscularly into the upper left thigh at 2, 4 and 6 months of age. During the booster study (NCT00463437) subjects received the same vaccines as during the primary study at 11-18 months of age, with the exception of Spain, where Infanrix IPV was given instead of Infanrix penta.	Prevenar-Menitorix Group n=128 Participants Subjects who received concomitantly in the primary study (NCT00334334): 3 primary doses of Prevenar intramuscularly into the right thigh at 2, 4 and 6 months of age, 3 primary doses of Menitorix intramuscularly into the lower left thigh at 2, 4 and 6 months of age and 3 primary doses of Infanrix penta intramuscularly into the upper left thigh at 2, 4 and 6 months of age. During the booster study (NCT00463437) subjects received the same vaccines as during the primary study at 11-18 months of age, with the exception of Spain, where Infanrix IPV was given instead of Infanrix penta.
Anti-HBs Antibody Concentrations anti-HBs; 3 years (N= 118, 130, 122, 119)	211.1 mIU/mL Interval 147.1 to 303.1	189.2 mIU/mL Interval 134.2 to 266.7	154.5 mIU/mL Interval 106.8 to 223.5	218.9 mIU/mL Interval 152.4 to 314.4
Anti-HBs Antibody Concentrations anti-HBs; 4 years (N=120, 127, 118, 119)	130.8 mIU/mL Interval 91.9 to 186.2	128.4 mIU/mL Interval 91.3 to 180.6	92.3 mIU/mL Interval 63.8 to 133.6	142.5 mIU/mL Interval 100.3 to 202.6
Anti-HBs Antibody Concentrations anti-HBs; 6 years (N=122, 129, 125, 128)	66.7 mIU/mL Interval 47.2 to 94.1	64.7 mIU/mL Interval 46.4 to 90.2	45.7 mIU/mL Interval 32.2 to 64.8	85.4 mIU/mL Interval 60.4 to 120.6

SECONDARY outcome

Timeframe: From last study contact of the study (NCT00463437) at 17-24 months of age until 6 years of age

Population: Analysis was performed on the Total Enrolled cohort at 6 years of age, which included all subjects vaccinated in the booster study (NCT00463437) and who were part of the blood sample subset.

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. Related = SAE assessed by the investigator as being related to the study procedures.

Outcome measures

Measure	Synflorix-Meningitec Group n=131 Participants Subjects who received concomitantly in the primary study (NCT00334334): 3 primary doses of Synflorix intramuscularly into the right thigh at 2, 4 and 6 months of age 2 primary doses of Meningitec intramuscularly into the lower left thigh at 2 and 4 months of age and 3 primary doses of Infanrix hexa intramuscularly into the upper left thigh at 2, 4 and 6 months of age. (In Poland subjects were offered a third dose of Meningitec at 7 months of age to comply with national recommendations). During the booster study (NCT00463437) subjects received the same vaccines as during the primary study at 11-18 months of age, with the exception of Spain, where Infanrix IPV/Hib was given instead of Infanrix hexa.	Synflorix-NeisVac-C Group n=138 Participants Subjects who received concomitantly in the primary study (NCT00334334): 3 primary doses of Synflorix intramuscularly into the right thigh at 2, 4 and 6 months of age, 2 primary doses of Neis-Vac-C intramuscularly into the lower left thigh at 2 and 4 months of age and 3 primary doses of Infanrix hexa intramuscularly into the upper left thigh at 2, 4 and 6 months of age. (In Poland subjects were offered a third dose of Neis-Vac-C at 7 months of age to comply with national recommendations). During the booster study (NCT00463437) subjects received the same vaccines as during the primary study at 11-18 months of age, with the exception of Spain, where Infanrix IPV/Hib was given instead of Infanrix hexa.	Synflorix-Menitorix Group n=135 Participants Subjects who received concomitantly in the primary study (NCT00334334): 3 primary doses of Synflorix intramuscularly into the right thigh at 2, 4 and 6 months of age, 3 primary doses of Menitorix intramuscularly into the lower left thigh at 2, 4 and 6 months of age and 3 primary doses of Infanrix penta intramuscularly into the upper left thigh at 2, 4 and 6 months of age. During the booster study (NCT00463437) subjects received the same vaccines as during the primary study at 11-18 months of age, with the exception of Spain, where Infanrix IPV was given instead of Infanrix penta.	Prevenar-Menitorix Group n=135 Participants Subjects who received concomitantly in the primary study (NCT00334334): 3 primary doses of Prevenar intramuscularly into the right thigh at 2, 4 and 6 months of age, 3 primary doses of Menitorix intramuscularly into the lower left thigh at 2, 4 and 6 months of age and 3 primary doses of Infanrix penta intramuscularly into the upper left thigh at 2, 4 and 6 months of age. During the booster study (NCT00463437) subjects received the same vaccines as during the primary study at 11-18 months of age, with the exception of Spain, where Infanrix IPV was given instead of Infanrix penta.
Number of Subjects With Serious Adverse Events (SAEs) SAE(s)	0 Subjects	0 Subjects	0 Subjects	0 Subjects
Number of Subjects With Serious Adverse Events (SAEs) Related SAE(s)	0 Subjects	0 Subjects	0 Subjects	0 Subjects

Adverse Events

Synflorix-Meningitec Group

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Synflorix-NeisVac-C Group

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Synflorix-Menitorix Group

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Prevenar-Menitorix Group

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

GSK Response Center

GlaxoSmithKline

Phone: 866-435-7343

Results disclosure agreements

• Principal investigator is a sponsor employee GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
• Publication restrictions are in place

Restriction type: OTHER