Trial Outcomes & Findings for Long-term Follow-up Study of Children Previously Primed With GSK Pneumococcal Vaccine (GSK1024850A) and of Unprimed Children (NCT NCT00950833)

Last Updated: 2018-09-20

Results Overview

Antibody concentrations against pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F (Anti-1, -4, -5, -6B, -7F, -9V, -14, -18C, -19F and -23F) have been assessed by 22F-inhibition enzyme linked immunosorbent assay (ELISA), presented as geometric mean concentrations (GMCs) and expressed in micrograms per milliliter (μg/mL). The seropositivity cut-off value of the assay was an antibody concentration greater than or equal to (≥) 0.05 μg/mL.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

466 participants

Primary outcome timeframe

At 7-10 days after the first vaccine dose

Results posted on

2018-09-20

Participant Flow

Out of the 466 subjects enrolled in the study, 5 subjects were not included in the Total effective cohort as they did not meet eligibility criteria. Out of the 461 subjects enrolled in the Total effective cohort, 18 subjects were not included in the Total vaccinated cohort as these subjects withdrew before the first vaccination visit (Visit 2).

Participant milestones

Participant milestones
Measure	Synflorix I Group Healthy male or female subjects between and including 31 and 44 months of age at the time of enrolment, who were previously given 3 primary vaccination doses of Synflorix™ vaccine co-administered with Infanrix™ Hexa vaccine in study 107017 (NCT00370318) and one booster dose of Synflorix™ vaccine co-administered with Infanrix™ Hexa vaccine in study 107137 (NCT00496015), additionally received in the current study one dose of Synflorix™ vaccine at Month 9 (40-48 months of age), administered intramuscularly in the deltoid muscle. At the time of both primary and booster vaccinations, subjects received prophylactic antipyretic (AP) treatment with paracetamol.	Synflorix II Group Healthy male or female subjects between and including 31 and 44 months of age at the time of enrolment, who were previously given 3 primary vaccination doses of Synflorix™ vaccine co-administered with Infanrix™ Hexa vaccine in study 107017 (NCT00370318) and one booster dose of Synflorix™ vaccine co-administered with Infanrix™ Hexa vaccine in study 107137 (NCT00496015), additionally received in the current study one dose of Synflorix™ vaccine at Month 9 (40-48 months of age), administered intramuscularly in the deltoid muscle. At the time of both primary and booster vaccinations, subjects did not receive any prophylactic antipyretic (AP) treatment.	Synflorix III Group Healthy male or female subjects between and including 31 and 44 months of age at the time of enrolment, who were not previously primed with Synflorix™ vaccine co-administered with Infanrix™ Hexa vaccine in study 107137 (NCT00496015), but vaccinated with Nimenrix™ vaccine co-administered with Infanrix™ Hexa vaccine in study 107137 (NCT00496015), additionally received in the current study 2 doses of Synflorix™ vaccine at Month 9 (40-48 months of age) and at Month 11 (42-50 months of age), administered intramuscularly in the deltoid muscle.
Overall Study STARTED	112	108	223
Overall Study COMPLETED	112	108	223
Overall Study NOT COMPLETED	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Long-term Follow-up Study of Children Previously Primed With GSK Pneumococcal Vaccine (GSK1024850A) and of Unprimed Children

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Synflorix I Group n=112 Participants Healthy male or female subjects between and including 31 and 44 months of age at the time of enrolment, who were previously given 3 primary vaccination doses of Synflorix™ vaccine co-administered with Infanrix™ Hexa vaccine in study 107017 (NCT00370318) and one booster dose of Synflorix™ vaccine co-administered with Infanrix™ Hexa vaccine in study 107137 (NCT00496015), additionally received in the current study one dose of Synflorix™ vaccine at Month 9 (40-48 months of age), administered intramuscularly in the deltoid muscle. At the time of both primary and booster vaccinations, subjects received prophylactic antipyretic (AP) treatment with paracetamol.	Synflorix II Group n=108 Participants Healthy male or female subjects between and including 31 and 44 months of age at the time of enrolment, who were previously given 3 primary vaccination doses of Synflorix™ vaccine co-administered with Infanrix™ Hexa vaccine in study 107017 (NCT00370318) and one booster dose of Synflorix™ vaccine co-administered with Infanrix™ Hexa vaccine in study 107137 (NCT00496015), additionally received in the current study one dose of Synflorix™ vaccine at Month 9 (40-48 months of age), administered intramuscularly in the deltoid muscle. At the time of both primary and booster vaccinations, subjects did not receive any prophylactic antipyretic (AP) treatment.	Synflorix III Group n=223 Participants Healthy male or female subjects between and including 31 and 44 months of age at the time of enrolment, who were not previously primed with Synflorix™ vaccine co-administered with Infanrix™ Hexa vaccine in study 107137 (NCT00496015), but vaccinated with Nimenrix™ vaccine co-administered with Infanrix™ Hexa vaccine in study 107137 (NCT00496015), additionally received in the current study 2 doses of Synflorix™ vaccine at Month 9 (40-48 months of age) and at Month 11 (42-50 months of age), administered intramuscularly in the deltoid muscle.	Total n=443 Participants Total of all reporting groups
Age, Continuous	39.2 Months STANDARD_DEVIATION 1.53 • n=5 Participants	39.1 Months STANDARD_DEVIATION 1.54 • n=7 Participants	37.7 Months STANDARD_DEVIATION 3.36 • n=5 Participants	38.4 Months STANDARD_DEVIATION 2.71 • n=4 Participants
Sex: Female, Male Female	60 Participants n=5 Participants	48 Participants n=7 Participants	99 Participants n=5 Participants	207 Participants n=4 Participants
Sex: Female, Male Male	52 Participants n=5 Participants	60 Participants n=7 Participants	124 Participants n=5 Participants	236 Participants n=4 Participants
Race/Ethnicity, Customized White - Caucasian / European heritage	111 Participants n=5 Participants	108 Participants n=7 Participants	214 Participants n=5 Participants	433 Participants n=4 Participants
Race/Ethnicity, Customized White - Arabic / North African heritage	0 Participants n=5 Participants	0 Participants n=7 Participants	9 Participants n=5 Participants	9 Participants n=4 Participants
Race/Ethnicity, Customized Unknown	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants

PRIMARY outcome

Timeframe: At 7-10 days after the first vaccine dose

Population: The analysis was performed on the According-to-Protocol (ATP) cohort for immunogenicity, which included all evaluable subjects for whom data concerning immunogenicity outcome measures and assay results for antibodies against at least one pneumococcal vaccine serotype were available after vaccination.

Outcome measures

Outcome measures
Measure	Synflorix III Group n=204 Participants Healthy male or female subjects between and including 31 and 44 months of age at the time of enrolment, who were not previously primed with Synflorix™ vaccine co-administered with Infanrix™ Hexa vaccine in study 107137 (NCT00496015), but vaccinated with Nimenrix™ vaccine co-administered with Infanrix™ Hexa vaccine in study 107137 (NCT00496015), additionally received in the current study 2 doses of Synflorix™ vaccine at Month 9 (40-48 months of age) and at Month 11 (42-50 months of age), administered intramuscularly in the deltoid muscle.	Pooled Synflorix I+II Group n=215 Participants For the purpose of the analysis, subjects from Synflorix I Group and Synflorix II Group have been pooled into a sub-group.	Synflorix III Group Healthy male or female subjects between and including 31 and 44 months of age at the time of enrolment, who were not previously primed with Synflorix™ vaccine co-administered with Infanrix™ Hexa vaccine in study 107137 (NCT00496015), but vaccinated with Nimenrix™ vaccine co-administered with Infanrix™ Hexa vaccine in study 107137 (NCT00496015), additionally received in the current study 2 doses of Synflorix™ vaccine at Month 9 (40-48 months of age) and at Month 11 (42-50 months of age), administered intramuscularly in the deltoid muscle.
Antibody Concentrations Against Vaccine Pneumococcal Serotypes Anti-1	1.24 μg/mL Interval 1.07 to 1.42	7.63 μg/mL Interval 6.57 to 8.86	—
Antibody Concentrations Against Vaccine Pneumococcal Serotypes Anti-4	4.52 μg/mL Interval 3.96 to 5.17	12.95 μg/mL Interval 11.37 to 14.75	—
Antibody Concentrations Against Vaccine Pneumococcal Serotypes Anti-5	0.72 μg/mL Interval 0.63 to 0.84	9.76 μg/mL Interval 8.44 to 11.29	—
Antibody Concentrations Against Vaccine Pneumococcal Serotypes Anti-6B	0.27 μg/mL Interval 0.22 to 0.33	7.67 μg/mL Interval 6.7 to 8.78	—
Antibody Concentrations Against Vaccine Pneumococcal Serotypes Anti-7F	1.37 μg/mL Interval 1.19 to 1.58	6.51 μg/mL Interval 5.69 to 7.46	—
Antibody Concentrations Against Vaccine Pneumococcal Serotypes Anti-9V	0.69 μg/mL Interval 0.58 to 0.83	9.75 μg/mL Interval 8.46 to 11.24	—
Antibody Concentrations Against Vaccine Pneumococcal Serotypes Anti-14	1.01 μg/mL Interval 0.8 to 1.27	23.07 μg/mL Interval 20.03 to 26.57	—
Antibody Concentrations Against Vaccine Pneumococcal Serotypes Anti-18C	3.25 μg/mL Interval 2.71 to 3.9	32.54 μg/mL Interval 28.15 to 37.61	—
Antibody Concentrations Against Vaccine Pneumococcal Serotypes Anti-19F	4.31 μg/mL Interval 3.59 to 5.17	39.84 μg/mL Interval 34.12 to 46.51	—
Antibody Concentrations Against Vaccine Pneumococcal Serotypes Anti-23F	0.25 μg/mL Interval 0.2 to 0.32	9.24 μg/mL Interval 7.86 to 10.86	—

SECONDARY outcome

Timeframe: Prior to the first study vaccine dose (At Day 0)

Population: The analysis was performed on the ATP cohort for immunogenicity, which included all evaluable subjects for whom data concerning immunogenicity outcome measures and assay results for antibodies against at least one pneumococcal vaccine serotype were available after vaccination.

Antibody concentrations against pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F (Anti-1, -4, -5, -6B, -7F, -9V, -14, -18C, -19F and -23F) have been assessed by 22F-inhibition ELISA, presented as GMCs and expressed in μg/mL. The seropositivity cut-off value of the assay was an antibody concentration ≥ 0.05 μg/mL.

Outcome measures

Outcome measures
Measure	Synflorix III Group n=209 Participants Healthy male or female subjects between and including 31 and 44 months of age at the time of enrolment, who were not previously primed with Synflorix™ vaccine co-administered with Infanrix™ Hexa vaccine in study 107137 (NCT00496015), but vaccinated with Nimenrix™ vaccine co-administered with Infanrix™ Hexa vaccine in study 107137 (NCT00496015), additionally received in the current study 2 doses of Synflorix™ vaccine at Month 9 (40-48 months of age) and at Month 11 (42-50 months of age), administered intramuscularly in the deltoid muscle.	Pooled Synflorix I+II Group n=215 Participants For the purpose of the analysis, subjects from Synflorix I Group and Synflorix II Group have been pooled into a sub-group.	Synflorix III Group Healthy male or female subjects between and including 31 and 44 months of age at the time of enrolment, who were not previously primed with Synflorix™ vaccine co-administered with Infanrix™ Hexa vaccine in study 107137 (NCT00496015), but vaccinated with Nimenrix™ vaccine co-administered with Infanrix™ Hexa vaccine in study 107137 (NCT00496015), additionally received in the current study 2 doses of Synflorix™ vaccine at Month 9 (40-48 months of age) and at Month 11 (42-50 months of age), administered intramuscularly in the deltoid muscle.
Antibody Concentrations Against Vaccine Pneumococcal Serotypes Anti-19F	0.44 μg/mL Interval 0.32 to 0.59	2.35 μg/mL Interval 1.75 to 3.15	—
Antibody Concentrations Against Vaccine Pneumococcal Serotypes Anti-1	0.09 μg/mL Interval 0.08 to 0.11	0.27 μg/mL Interval 0.23 to 0.33	—
Antibody Concentrations Against Vaccine Pneumococcal Serotypes Anti-4	0.05 μg/mL Interval 0.04 to 0.06	0.2 μg/mL Interval 0.17 to 0.23	—
Antibody Concentrations Against Vaccine Pneumococcal Serotypes Anti-5	0.1 μg/mL Interval 0.09 to 0.11	0.41 μg/mL Interval 0.36 to 0.47	—
Antibody Concentrations Against Vaccine Pneumococcal Serotypes Anti-6B	0.1 μg/mL Interval 0.08 to 0.12	0.8 μg/mL Interval 0.61 to 1.05	—
Antibody Concentrations Against Vaccine Pneumococcal Serotypes Anti-7F	0.06 μg/mL Interval 0.05 to 0.07	0.48 μg/mL Interval 0.41 to 0.56	—
Antibody Concentrations Against Vaccine Pneumococcal Serotypes Anti-9V	0.07 μg/mL Interval 0.06 to 0.09	0.5 μg/mL Interval 0.41 to 0.61	—
Antibody Concentrations Against Vaccine Pneumococcal Serotypes Anti-14	0.28 μg/mL Interval 0.22 to 0.36	1.21 μg/mL Interval 0.97 to 1.5	—
Antibody Concentrations Against Vaccine Pneumococcal Serotypes Anti-18C	0.09 μg/mL Interval 0.07 to 0.11	0.65 μg/mL Interval 0.54 to 0.79	—
Antibody Concentrations Against Vaccine Pneumococcal Serotypes Anti-23F	0.08 μg/mL Interval 0.07 to 0.1	0.96 μg/mL Interval 0.72 to 1.29	—

SECONDARY outcome

Timeframe: Prior to (Day 0) and 7-10 days after the first vaccine dose

Seropositivity status was defined as the opsonophagocytic activity (OPA) against pneumococcal serotypes ≥ the value of 8, presented as geometric mean titers (GMTs). The vaccine pneumococcal serotypes assessed were 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F (Opsono-1, -4, -5, -6B, -7F, -9V, -14, -18C, -19F and -23F).

Outcome measures

Outcome measures
Measure	Synflorix III Group n=191 Participants Healthy male or female subjects between and including 31 and 44 months of age at the time of enrolment, who were not previously primed with Synflorix™ vaccine co-administered with Infanrix™ Hexa vaccine in study 107137 (NCT00496015), but vaccinated with Nimenrix™ vaccine co-administered with Infanrix™ Hexa vaccine in study 107137 (NCT00496015), additionally received in the current study 2 doses of Synflorix™ vaccine at Month 9 (40-48 months of age) and at Month 11 (42-50 months of age), administered intramuscularly in the deltoid muscle.	Pooled Synflorix I+II Group n=199 Participants For the purpose of the analysis, subjects from Synflorix I Group and Synflorix II Group have been pooled into a sub-group.	Synflorix III Group Healthy male or female subjects between and including 31 and 44 months of age at the time of enrolment, who were not previously primed with Synflorix™ vaccine co-administered with Infanrix™ Hexa vaccine in study 107137 (NCT00496015), but vaccinated with Nimenrix™ vaccine co-administered with Infanrix™ Hexa vaccine in study 107137 (NCT00496015), additionally received in the current study 2 doses of Synflorix™ vaccine at Month 9 (40-48 months of age) and at Month 11 (42-50 months of age), administered intramuscularly in the deltoid muscle.
Opsonophagocytic Activity (OPA) Titers Against Vaccine Pneumococcal Serotypes Opsono-14, D7-10	4454.3 Titers Interval 3921.1 to 5059.9	16256.8 Titers Interval 13573.0 to 19471.4	—
Opsonophagocytic Activity (OPA) Titers Against Vaccine Pneumococcal Serotypes Opsono-1, D0	5.4 Titers Interval 4.7 to 6.2	10.2 Titers Interval 8.0 to 12.9	—
Opsonophagocytic Activity (OPA) Titers Against Vaccine Pneumococcal Serotypes Opsono-1, D7-10	632 Titers Interval 524.4 to 761.7	3106.5 Titers Interval 2670.0 to 3614.5	—
Opsonophagocytic Activity (OPA) Titers Against Vaccine Pneumococcal Serotypes Opsono-4, D0	9.1 Titers Interval 6.8 to 12.1	18.1 Titers Interval 13.1 to 24.9	—
Opsonophagocytic Activity (OPA) Titers Against Vaccine Pneumococcal Serotypes Opsono-4, D7-10	13109.9 Titers Interval 11080.6 to 15510.7	27273.3 Titers Interval 22682.9 to 32792.6	—
Opsonophagocytic Activity (OPA) Titers Against Vaccine Pneumococcal Serotypes Opsono-5, D0	4 Titers Interval 4.0 to 4.1	8.9 Titers Interval 7.6 to 10.5	—
Opsonophagocytic Activity (OPA) Titers Against Vaccine Pneumococcal Serotypes Opsono-5, D7-10	145.8 Titers Interval 111.7 to 190.3	1020 Titers Interval 874.0 to 1190.2	—
Opsonophagocytic Activity (OPA) Titers Against Vaccine Pneumococcal Serotypes Opsono-6B, D0	46.7 Titers Interval 29.8 to 73.3	163.5 Titers Interval 108.5 to 246.4	—
Opsonophagocytic Activity (OPA) Titers Against Vaccine Pneumococcal Serotypes Opsono-6B, D7-10	1472.2 Titers Interval 1053.2 to 2057.8	5789.5 Titers Interval 4637.3 to 7227.9	—
Opsonophagocytic Activity (OPA) Titers Against Vaccine Pneumococcal Serotypes Opsono-7F, D0	973.4 Titers Interval 798.5 to 1186.6	1112.3 Titers Interval 951.4 to 1300.4	—
Opsonophagocytic Activity (OPA) Titers Against Vaccine Pneumococcal Serotypes Opsono-7F, D7-10	13647.4 Titers Interval 11801.9 to 15781.3	19988.9 Titers Interval 16834.5 to 23734.2	—
Opsonophagocytic Activity (OPA) Titers Against Vaccine Pneumococcal Serotypes Opsono-9V, D0	268.2 Titers Interval 192.2 to 374.3	481.8 Titers Interval 394.6 to 588.1	—
Opsonophagocytic Activity (OPA) Titers Against Vaccine Pneumococcal Serotypes Opsono-9V, D7-10	14668.8 Titers Interval 12476.1 to 17247.0	17952.5 Titers Interval 14699.2 to 21925.7	—
Opsonophagocytic Activity (OPA) Titers Against Vaccine Pneumococcal Serotypes Opsono-14, D0	145.3 Titers Interval 97.5 to 216.6	267.6 Titers Interval 196.9 to 363.8	—
Opsonophagocytic Activity (OPA) Titers Against Vaccine Pneumococcal Serotypes Opsono-18C, D0	5.7 Titers Interval 4.7 to 7.0	14.2 Titers Interval 10.6 to 19.2	—
Opsonophagocytic Activity (OPA) Titers Against Vaccine Pneumococcal Serotypes Opsono-18C, D7-10	9092.2 Titers Interval 7381.2 to 11199.9	7413.8 Titers Interval 6072.3 to 9051.6	—
Opsonophagocytic Activity (OPA) Titers Against Vaccine Pneumococcal Serotypes Opsono-19F, D0	12.9 Titers Interval 9.6 to 17.2	79.5 Titers Interval 55.4 to 113.9	—
Opsonophagocytic Activity (OPA) Titers Against Vaccine Pneumococcal Serotypes Opsono-19F, D7-10	902.5 Titers Interval 659.2 to 1235.6	6271.1 Titers Interval 4814.8 to 8168.0	—
Opsonophagocytic Activity (OPA) Titers Against Vaccine Pneumococcal Serotypes Opsono-23F, D0	220.6 Titers Interval 132.0 to 368.7	462.7 Titers Interval 292.9 to 730.9	—
Opsonophagocytic Activity (OPA) Titers Against Vaccine Pneumococcal Serotypes Opsono-23F, D7-10	5776.5 Titers Interval 4686.8 to 7119.5	15613.5 Titers Interval 12386.9 to 19680.6	—

SECONDARY outcome

Timeframe: Prior to (Day 0) and 7-10 days after the first vaccine dose

The vaccine pneumococcal cross-reactive serotypes 6A and 19A have been assessed by 22F-inhibition ELISA, presented as geometric mean concentrations (GMCs) and expressed in μg/mL. The seropositivity cut-off of the assay was an antibody concentration ≥ 0.05 μg/mL.

Outcome measures

Outcome measures
Measure	Synflorix III Group n=207 Participants Healthy male or female subjects between and including 31 and 44 months of age at the time of enrolment, who were not previously primed with Synflorix™ vaccine co-administered with Infanrix™ Hexa vaccine in study 107137 (NCT00496015), but vaccinated with Nimenrix™ vaccine co-administered with Infanrix™ Hexa vaccine in study 107137 (NCT00496015), additionally received in the current study 2 doses of Synflorix™ vaccine at Month 9 (40-48 months of age) and at Month 11 (42-50 months of age), administered intramuscularly in the deltoid muscle.	Pooled Synflorix I+II Group n=215 Participants For the purpose of the analysis, subjects from Synflorix I Group and Synflorix II Group have been pooled into a sub-group.	Synflorix III Group Healthy male or female subjects between and including 31 and 44 months of age at the time of enrolment, who were not previously primed with Synflorix™ vaccine co-administered with Infanrix™ Hexa vaccine in study 107137 (NCT00496015), but vaccinated with Nimenrix™ vaccine co-administered with Infanrix™ Hexa vaccine in study 107137 (NCT00496015), additionally received in the current study 2 doses of Synflorix™ vaccine at Month 9 (40-48 months of age) and at Month 11 (42-50 months of age), administered intramuscularly in the deltoid muscle.
Antibody Concentrations Against Vaccine Pneumococcal Cross-reactive Serotypes 6A and 19A Anti-6A, D0	0.11 μg/mL Interval 0.09 to 0.13	0.39 μg/mL Interval 0.3 to 0.5	—
Antibody Concentrations Against Vaccine Pneumococcal Cross-reactive Serotypes 6A and 19A Anti-6A, D7-10	0.2 μg/mL Interval 0.17 to 0.25	2.4 μg/mL Interval 2.01 to 2.85	—
Antibody Concentrations Against Vaccine Pneumococcal Cross-reactive Serotypes 6A and 19A Anti-19A, D0	0.22 μg/mL Interval 0.18 to 0.28	0.52 μg/mL Interval 0.41 to 0.67	—
Antibody Concentrations Against Vaccine Pneumococcal Cross-reactive Serotypes 6A and 19A Anti-19A, D7-10	0.65 μg/mL Interval 0.52 to 0.82	6.75 μg/mL Interval 5.41 to 8.41	—

SECONDARY outcome

Timeframe: Prior to (Day 0) and 7-10 days after the first vaccine dose

Seropositivity status was defined as the opsonophagocytic activity against pneumococcal cross-reactive serotypes 6A and 19A (Opsono-16A and opsono-19A) ≥ the value of 8, presented as geometric mean titers (GMTs).

Outcome measures

Outcome measures
Measure	Synflorix III Group n=183 Participants Healthy male or female subjects between and including 31 and 44 months of age at the time of enrolment, who were not previously primed with Synflorix™ vaccine co-administered with Infanrix™ Hexa vaccine in study 107137 (NCT00496015), but vaccinated with Nimenrix™ vaccine co-administered with Infanrix™ Hexa vaccine in study 107137 (NCT00496015), additionally received in the current study 2 doses of Synflorix™ vaccine at Month 9 (40-48 months of age) and at Month 11 (42-50 months of age), administered intramuscularly in the deltoid muscle.	Pooled Synflorix I+II Group n=191 Participants For the purpose of the analysis, subjects from Synflorix I Group and Synflorix II Group have been pooled into a sub-group.	Synflorix III Group Healthy male or female subjects between and including 31 and 44 months of age at the time of enrolment, who were not previously primed with Synflorix™ vaccine co-administered with Infanrix™ Hexa vaccine in study 107137 (NCT00496015), but vaccinated with Nimenrix™ vaccine co-administered with Infanrix™ Hexa vaccine in study 107137 (NCT00496015), additionally received in the current study 2 doses of Synflorix™ vaccine at Month 9 (40-48 months of age) and at Month 11 (42-50 months of age), administered intramuscularly in the deltoid muscle.
Opsonophagocytic Activity (OPA) Titers Against Pneumococcal Cross-reactive Serotypes 6A and 19A Opsono-6A, D0	49 Titers Interval 32.4 to 74.0	95.2 Titers Interval 65.3 to 138.7	—
Opsonophagocytic Activity (OPA) Titers Against Pneumococcal Cross-reactive Serotypes 6A and 19A Opsono-6A, D7-10	863.3 Titers Interval 619.3 to 1203.4	2408.4 Titers Interval 1815.7 to 3194.5	—
Opsonophagocytic Activity (OPA) Titers Against Pneumococcal Cross-reactive Serotypes 6A and 19A Opsono-19A, D0	10.3 Titers Interval 7.9 to 13.4	15.9 Titers Interval 11.7 to 21.6	—
Opsonophagocytic Activity (OPA) Titers Against Pneumococcal Cross-reactive Serotypes 6A and 19A Opsono-19A, D7-10	880.5 Titers Interval 622.7 to 1245.0	2104.9 Titers Interval 1560.9 to 2838.7	—

SECONDARY outcome

Timeframe: Prior to (Day 0) and 7-10 days after the first vaccine dose

Anti-protein D (anti-PD) concentrations were presented as geometric mean concentrations (GMCs), expressed in ELISA units per milliliter (EL.U/mL). The seropositivity cut-off value of the assay was an antibody concentration ≥ 100 EL.U/mL.

Outcome measures

Outcome measures
Measure	Synflorix III Group n=204 Participants Healthy male or female subjects between and including 31 and 44 months of age at the time of enrolment, who were not previously primed with Synflorix™ vaccine co-administered with Infanrix™ Hexa vaccine in study 107137 (NCT00496015), but vaccinated with Nimenrix™ vaccine co-administered with Infanrix™ Hexa vaccine in study 107137 (NCT00496015), additionally received in the current study 2 doses of Synflorix™ vaccine at Month 9 (40-48 months of age) and at Month 11 (42-50 months of age), administered intramuscularly in the deltoid muscle.	Pooled Synflorix I+II Group n=215 Participants For the purpose of the analysis, subjects from Synflorix I Group and Synflorix II Group have been pooled into a sub-group.	Synflorix III Group Healthy male or female subjects between and including 31 and 44 months of age at the time of enrolment, who were not previously primed with Synflorix™ vaccine co-administered with Infanrix™ Hexa vaccine in study 107137 (NCT00496015), but vaccinated with Nimenrix™ vaccine co-administered with Infanrix™ Hexa vaccine in study 107137 (NCT00496015), additionally received in the current study 2 doses of Synflorix™ vaccine at Month 9 (40-48 months of age) and at Month 11 (42-50 months of age), administered intramuscularly in the deltoid muscle.
Antibody Concentrations Against Protein D (Anti-PD) Anti-PD, D0	105.6 EL.U/mL Interval 93.8 to 119.0	464.2 EL.U/mL Interval 401.6 to 536.5	—
Antibody Concentrations Against Protein D (Anti-PD) Anti-PD, D7-10	374.3 EL.U/mL Interval 315.1 to 444.6	2673.7 EL.U/mL Interval 2359.1 to 3030.2	—

SECONDARY outcome

Timeframe: Prior to (Day 0) and 7-10 days after the first vaccine dose

B-cell detection for the pneumococcal serotype specific polysaccharides (1, 5, 6B, 18C, 19F, 23F and C) was tabulated for a subset of subjects from each group. The results are expressed as the frequencies of antigen-specific memory B-cells within the total memory B-cell population.

Outcome measures

Outcome measures
Measure	Synflorix III Group n=70 Participants Healthy male or female subjects between and including 31 and 44 months of age at the time of enrolment, who were not previously primed with Synflorix™ vaccine co-administered with Infanrix™ Hexa vaccine in study 107137 (NCT00496015), but vaccinated with Nimenrix™ vaccine co-administered with Infanrix™ Hexa vaccine in study 107137 (NCT00496015), additionally received in the current study 2 doses of Synflorix™ vaccine at Month 9 (40-48 months of age) and at Month 11 (42-50 months of age), administered intramuscularly in the deltoid muscle.	Pooled Synflorix I+II Group n=71 Participants For the purpose of the analysis, subjects from Synflorix I Group and Synflorix II Group have been pooled into a sub-group.	Synflorix III Group n=133 Participants Healthy male or female subjects between and including 31 and 44 months of age at the time of enrolment, who were not previously primed with Synflorix™ vaccine co-administered with Infanrix™ Hexa vaccine in study 107137 (NCT00496015), but vaccinated with Nimenrix™ vaccine co-administered with Infanrix™ Hexa vaccine in study 107137 (NCT00496015), additionally received in the current study 2 doses of Synflorix™ vaccine at Month 9 (40-48 months of age) and at Month 11 (42-50 months of age), administered intramuscularly in the deltoid muscle.
Memory B-cell Detection for Vaccine Polysaccharides (PS) 1 PS, D0	288.6 Memory B-cells Standard Deviation 352.5	269.5 Memory B-cells Standard Deviation 432.2	254.8 Memory B-cells Standard Deviation 368.4
Memory B-cell Detection for Vaccine Polysaccharides (PS) 1 PS, D7-10	1488.8 Memory B-cells Standard Deviation 1584.2	1017.4 Memory B-cells Standard Deviation 1309.9	755.9 Memory B-cells Standard Deviation 1017.4
Memory B-cell Detection for Vaccine Polysaccharides (PS) 5 PS, D0	139.4 Memory B-cells Standard Deviation 214.7	141.9 Memory B-cells Standard Deviation 232.4	81.5 Memory B-cells Standard Deviation 109.2
Memory B-cell Detection for Vaccine Polysaccharides (PS) 5 PS, D7-10	233.5 Memory B-cells Standard Deviation 235.7	406.6 Memory B-cells Standard Deviation 447.8	152.6 Memory B-cells Standard Deviation 231
Memory B-cell Detection for Vaccine Polysaccharides (PS) 6B PS, D0	372 Memory B-cells Standard Deviation 545.5	327.2 Memory B-cells Standard Deviation 554.4	639.9 Memory B-cells Standard Deviation 846.5
Memory B-cell Detection for Vaccine Polysaccharides (PS) 6B PS, D7-10	629.1 Memory B-cells Standard Deviation 773.2	1265.8 Memory B-cells Standard Deviation 1738.6	526 Memory B-cells Standard Deviation 648.6
Memory B-cell Detection for Vaccine Polysaccharides (PS) 18C PS, D0	537.7 Memory B-cells Standard Deviation 641.8	530.9 Memory B-cells Standard Deviation 693.8	135.2 Memory B-cells Standard Deviation 200.6
Memory B-cell Detection for Vaccine Polysaccharides (PS) 18C PS, D7-10	3839 Memory B-cells Standard Deviation 5960.5	8308.4 Memory B-cells Standard Deviation 7166.9	2053.8 Memory B-cells Standard Deviation 2122.2
Memory B-cell Detection for Vaccine Polysaccharides (PS) 19F PS, D0	169.7 Memory B-cells Standard Deviation 415.3	149.1 Memory B-cells Standard Deviation 194.4	164.5 Memory B-cells Standard Deviation 343.4
Memory B-cell Detection for Vaccine Polysaccharides (PS) 19F PS, D7-10	1056.7 Memory B-cells Standard Deviation 1334	1092.4 Memory B-cells Standard Deviation 1724.3	708.2 Memory B-cells Standard Deviation 1609.4
Memory B-cell Detection for Vaccine Polysaccharides (PS) 23F PS, D0	112.6 Memory B-cells Standard Deviation 176.1	285 Memory B-cells Standard Deviation 484.3	185.6 Memory B-cells Standard Deviation 270.1
Memory B-cell Detection for Vaccine Polysaccharides (PS) 23F PS, D7-10	579.8 Memory B-cells Standard Deviation 632.5	1123.7 Memory B-cells Standard Deviation 2095.4	327.9 Memory B-cells Standard Deviation 470.5
Memory B-cell Detection for Vaccine Polysaccharides (PS) C-PS, D0	475.9 Memory B-cells Standard Deviation 682.3	462.5 Memory B-cells Standard Deviation 704.5	469.9 Memory B-cells Standard Deviation 639.2
Memory B-cell Detection for Vaccine Polysaccharides (PS) C-PS, D7-10	679.2 Memory B-cells Standard Deviation 885.8	915.5 Memory B-cells Standard Deviation 1191.3	762.6 Memory B-cells Standard Deviation 1039.4

SECONDARY outcome

Timeframe: At Month 12, one month after the second vaccine dose

The vaccine pneumococcal serotypes assessed were 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F (anti-1, -4, -5, -6B, -7F, -9V, -14, -18C, -19F and -23F). Antibody concentrations were measured by 22F-inhibition ELISA, presented as geometric mean concentrations (GMCs), expressed in μg/mL. The seropositivity cut-off of the assay was an antibody concentration ≥ 0.05 μg/mL.

Outcome measures

Outcome measures
Measure	Synflorix III Group n=209 Participants Healthy male or female subjects between and including 31 and 44 months of age at the time of enrolment, who were not previously primed with Synflorix™ vaccine co-administered with Infanrix™ Hexa vaccine in study 107137 (NCT00496015), but vaccinated with Nimenrix™ vaccine co-administered with Infanrix™ Hexa vaccine in study 107137 (NCT00496015), additionally received in the current study 2 doses of Synflorix™ vaccine at Month 9 (40-48 months of age) and at Month 11 (42-50 months of age), administered intramuscularly in the deltoid muscle.	Pooled Synflorix I+II Group For the purpose of the analysis, subjects from Synflorix I Group and Synflorix II Group have been pooled into a sub-group.	Synflorix III Group Healthy male or female subjects between and including 31 and 44 months of age at the time of enrolment, who were not previously primed with Synflorix™ vaccine co-administered with Infanrix™ Hexa vaccine in study 107137 (NCT00496015), but vaccinated with Nimenrix™ vaccine co-administered with Infanrix™ Hexa vaccine in study 107137 (NCT00496015), additionally received in the current study 2 doses of Synflorix™ vaccine at Month 9 (40-48 months of age) and at Month 11 (42-50 months of age), administered intramuscularly in the deltoid muscle.
Antibody Concentrations Against Vaccine Pneumococcal Serotypes Anti-1	2.33 μg/mL Interval 2.13 to 2.54	—	—
Antibody Concentrations Against Vaccine Pneumococcal Serotypes Anti-4	6.26 μg/mL Interval 5.73 to 6.84	—	—
Antibody Concentrations Against Vaccine Pneumococcal Serotypes Anti-5	2.69 μg/mL Interval 2.44 to 2.96	—	—
Antibody Concentrations Against Vaccine Pneumococcal Serotypes Anti-6B	0.84 μg/mL Interval 0.73 to 0.97	—	—
Antibody Concentrations Against Vaccine Pneumococcal Serotypes Anti-7F	3.63 μg/mL Interval 3.33 to 3.95	—	—
Antibody Concentrations Against Vaccine Pneumococcal Serotypes Anti-9V	1.73 μg/mL Interval 1.56 to 1.93	—	—
Antibody Concentrations Against Vaccine Pneumococcal Serotypes Anti-14	5.21 μg/mL Interval 4.6 to 5.89	—	—
Antibody Concentrations Against Vaccine Pneumococcal Serotypes Anti-18C	13.59 μg/mL Interval 11.91 to 15.51	—	—
Antibody Concentrations Against Vaccine Pneumococcal Serotypes Anti-19F	11.83 μg/mL Interval 10.35 to 13.52	—	—
Antibody Concentrations Against Vaccine Pneumococcal Serotypes Anti-23F	0.99 μg/mL Interval 0.86 to 1.15	—	—

SECONDARY outcome

Timeframe: At Month 12, one month after the second vaccine dose

Outcome measures

Outcome measures
Measure	Synflorix III Group n=201 Participants Healthy male or female subjects between and including 31 and 44 months of age at the time of enrolment, who were not previously primed with Synflorix™ vaccine co-administered with Infanrix™ Hexa vaccine in study 107137 (NCT00496015), but vaccinated with Nimenrix™ vaccine co-administered with Infanrix™ Hexa vaccine in study 107137 (NCT00496015), additionally received in the current study 2 doses of Synflorix™ vaccine at Month 9 (40-48 months of age) and at Month 11 (42-50 months of age), administered intramuscularly in the deltoid muscle.	Pooled Synflorix I+II Group For the purpose of the analysis, subjects from Synflorix I Group and Synflorix II Group have been pooled into a sub-group.	Synflorix III Group Healthy male or female subjects between and including 31 and 44 months of age at the time of enrolment, who were not previously primed with Synflorix™ vaccine co-administered with Infanrix™ Hexa vaccine in study 107137 (NCT00496015), but vaccinated with Nimenrix™ vaccine co-administered with Infanrix™ Hexa vaccine in study 107137 (NCT00496015), additionally received in the current study 2 doses of Synflorix™ vaccine at Month 9 (40-48 months of age) and at Month 11 (42-50 months of age), administered intramuscularly in the deltoid muscle.
Opsonophagocytic Activity (OPA) Titers Against Vaccine Pneumococcal Serotypes Opsono-14	4544.9 Titers Interval 4030.2 to 5125.4	—	—
Opsonophagocytic Activity (OPA) Titers Against Vaccine Pneumococcal Serotypes Opsono-18C	3827.5 Titers Interval 3367.5 to 4350.4	—	—
Opsonophagocytic Activity (OPA) Titers Against Vaccine Pneumococcal Serotypes Opsono-19F	1251 Titers Interval 1045.6 to 1496.8	—	—
Opsonophagocytic Activity (OPA) Titers Against Vaccine Pneumococcal Serotypes Opsono-23F	4629.1 Titers Interval 3890.6 to 5507.8	—	—
Opsonophagocytic Activity (OPA) Titers Against Vaccine Pneumococcal Serotypes Opsono-1	125.6 Titers Interval 105.0 to 150.1	—	—
Opsonophagocytic Activity (OPA) Titers Against Vaccine Pneumococcal Serotypes Opsono-4	2451.2 Titers Interval 2203.6 to 2726.8	—	—
Opsonophagocytic Activity (OPA) Titers Against Vaccine Pneumococcal Serotypes Opsono-5	57.2 Titers Interval 47.3 to 69.1	—	—
Opsonophagocytic Activity (OPA) Titers Against Vaccine Pneumococcal Serotypes Opsono-6B	1345 Titers Interval 1066.8 to 1695.7	—	—
Opsonophagocytic Activity (OPA) Titers Against Vaccine Pneumococcal Serotypes Opsono-7F	6527.2 Titers Interval 5836.5 to 7299.6	—	—
Opsonophagocytic Activity (OPA) Titers Against Vaccine Pneumococcal Serotypes Opsono-9V	6091.6 Titers Interval 5328.7 to 6963.8	—	—

SECONDARY outcome

Timeframe: At Month 12, one month after the second vaccine dose

Outcome measures

Outcome measures
Measure	Synflorix III Group n=209 Participants Healthy male or female subjects between and including 31 and 44 months of age at the time of enrolment, who were not previously primed with Synflorix™ vaccine co-administered with Infanrix™ Hexa vaccine in study 107137 (NCT00496015), but vaccinated with Nimenrix™ vaccine co-administered with Infanrix™ Hexa vaccine in study 107137 (NCT00496015), additionally received in the current study 2 doses of Synflorix™ vaccine at Month 9 (40-48 months of age) and at Month 11 (42-50 months of age), administered intramuscularly in the deltoid muscle.	Pooled Synflorix I+II Group For the purpose of the analysis, subjects from Synflorix I Group and Synflorix II Group have been pooled into a sub-group.	Synflorix III Group Healthy male or female subjects between and including 31 and 44 months of age at the time of enrolment, who were not previously primed with Synflorix™ vaccine co-administered with Infanrix™ Hexa vaccine in study 107137 (NCT00496015), but vaccinated with Nimenrix™ vaccine co-administered with Infanrix™ Hexa vaccine in study 107137 (NCT00496015), additionally received in the current study 2 doses of Synflorix™ vaccine at Month 9 (40-48 months of age) and at Month 11 (42-50 months of age), administered intramuscularly in the deltoid muscle.
Antibody Concentrations Against Vaccine Pneumococcal Cross-reactive Serotypes 6A and 19A Anti-6A	0.51 μg/mL Interval 0.43 to 0.6	—	—
Antibody Concentrations Against Vaccine Pneumococcal Cross-reactive Serotypes 6A and 19A Anti-19A	1.99 μg/mL Interval 1.68 to 2.36	—	—

SECONDARY outcome

Timeframe: At Month 12, one month after the second vaccine dose

Seropositivity status was defined as the opsonophagocytic activity against pneumococcal cross-reactive serotypes 6A and 19A (opsono-16A and opsono-19A) ≥ the value of 8, presented as geometric mean titers (GMTs).

Outcome measures

Outcome measures
Measure	Synflorix III Group n=196 Participants Healthy male or female subjects between and including 31 and 44 months of age at the time of enrolment, who were not previously primed with Synflorix™ vaccine co-administered with Infanrix™ Hexa vaccine in study 107137 (NCT00496015), but vaccinated with Nimenrix™ vaccine co-administered with Infanrix™ Hexa vaccine in study 107137 (NCT00496015), additionally received in the current study 2 doses of Synflorix™ vaccine at Month 9 (40-48 months of age) and at Month 11 (42-50 months of age), administered intramuscularly in the deltoid muscle.	Pooled Synflorix I+II Group For the purpose of the analysis, subjects from Synflorix I Group and Synflorix II Group have been pooled into a sub-group.	Synflorix III Group Healthy male or female subjects between and including 31 and 44 months of age at the time of enrolment, who were not previously primed with Synflorix™ vaccine co-administered with Infanrix™ Hexa vaccine in study 107137 (NCT00496015), but vaccinated with Nimenrix™ vaccine co-administered with Infanrix™ Hexa vaccine in study 107137 (NCT00496015), additionally received in the current study 2 doses of Synflorix™ vaccine at Month 9 (40-48 months of age) and at Month 11 (42-50 months of age), administered intramuscularly in the deltoid muscle.
Opsonophagocytic Activity (OPA) Titers Against Pneumococcal Cross-reactive Serotypes 6A and 19A Opsono-6A	918.6 Titers Interval 742.7 to 1136.1	—	—
Opsonophagocytic Activity (OPA) Titers Against Pneumococcal Cross-reactive Serotypes 6A and 19A Opsono-19A	597.6 Titers Interval 467.2 to 764.4	—	—

SECONDARY outcome

Timeframe: At Month 12, one month after the second vaccine dose

Outcome measures

Outcome measures
Measure	Synflorix III Group n=209 Participants Healthy male or female subjects between and including 31 and 44 months of age at the time of enrolment, who were not previously primed with Synflorix™ vaccine co-administered with Infanrix™ Hexa vaccine in study 107137 (NCT00496015), but vaccinated with Nimenrix™ vaccine co-administered with Infanrix™ Hexa vaccine in study 107137 (NCT00496015), additionally received in the current study 2 doses of Synflorix™ vaccine at Month 9 (40-48 months of age) and at Month 11 (42-50 months of age), administered intramuscularly in the deltoid muscle.	Pooled Synflorix I+II Group For the purpose of the analysis, subjects from Synflorix I Group and Synflorix II Group have been pooled into a sub-group.	Synflorix III Group Healthy male or female subjects between and including 31 and 44 months of age at the time of enrolment, who were not previously primed with Synflorix™ vaccine co-administered with Infanrix™ Hexa vaccine in study 107137 (NCT00496015), but vaccinated with Nimenrix™ vaccine co-administered with Infanrix™ Hexa vaccine in study 107137 (NCT00496015), additionally received in the current study 2 doses of Synflorix™ vaccine at Month 9 (40-48 months of age) and at Month 11 (42-50 months of age), administered intramuscularly in the deltoid muscle.
Antibody Concentrations Against Protein D (Anti-PD)	785.9 EL.U/mL Interval 695.7 to 887.7	—	—

SECONDARY outcome

Timeframe: At 25-36 months post-vaccination in previous 107137 (NCT00496015) study

Population: The analysis was performed on the ATP cohort for antibody persistence, which included all subjects with the vaccine administration documented, for whom assay results were available for antibodies against each considered antigen for the blood sample taken before the administration of Synflorix™ vaccine.

The Neisseria meningitidis serogroups assessed using rabbit complement were: A, C, W-135 and Y (rSBA-MenA, rSBA-MenC, rSBA-MenW-135 and rSBA-MenY), presented as geometric mean titers (GMTs). The seropositivity cut-off of the assay was an antibody titer ≥ 8.

Outcome measures

Outcome measures
Measure	Synflorix III Group n=83 Participants Healthy male or female subjects between and including 31 and 44 months of age at the time of enrolment, who were not previously primed with Synflorix™ vaccine co-administered with Infanrix™ Hexa vaccine in study 107137 (NCT00496015), but vaccinated with Nimenrix™ vaccine co-administered with Infanrix™ Hexa vaccine in study 107137 (NCT00496015), additionally received in the current study 2 doses of Synflorix™ vaccine at Month 9 (40-48 months of age) and at Month 11 (42-50 months of age), administered intramuscularly in the deltoid muscle.	Pooled Synflorix I+II Group For the purpose of the analysis, subjects from Synflorix I Group and Synflorix II Group have been pooled into a sub-group.	Synflorix III Group Healthy male or female subjects between and including 31 and 44 months of age at the time of enrolment, who were not previously primed with Synflorix™ vaccine co-administered with Infanrix™ Hexa vaccine in study 107137 (NCT00496015), but vaccinated with Nimenrix™ vaccine co-administered with Infanrix™ Hexa vaccine in study 107137 (NCT00496015), additionally received in the current study 2 doses of Synflorix™ vaccine at Month 9 (40-48 months of age) and at Month 11 (42-50 months of age), administered intramuscularly in the deltoid muscle.
Rabbit Complement-mediated Serum Bactericidal Activity Titers Against Neisseria Meningitidis Serogroups (rSBA-Men) rSBA-MenA	325.5 Titers Interval 243.9 to 434.5	—	—
Rabbit Complement-mediated Serum Bactericidal Activity Titers Against Neisseria Meningitidis Serogroups (rSBA-Men) rSBA-MenC	63.6 Titers Interval 41.2 to 98.0	—	—
Rabbit Complement-mediated Serum Bactericidal Activity Titers Against Neisseria Meningitidis Serogroups (rSBA-Men) rSBA-MenY	372.2 Titers Interval 270.0 to 513.0	—	—
Rabbit Complement-mediated Serum Bactericidal Activity Titers Against Neisseria Meningitidis Serogroups (rSBA-Men) rSBA-MenW-135	247.6 Titers Interval 190.7 to 321.5	—	—

SECONDARY outcome

Timeframe: During the 4-day (Days 0-3) post-vaccination period

Population: The analysis was performed on the Total Vaccinated Cohort, which included all vaccinated subjects.

Assessed solicited local symptoms were pain, redness and swelling. Any = occurrence of any local symptom regardless of intensity grade. Grade 3 pain = cried when limb was moved/spontaneously painful. Grade 3 redness/swelling = redness/swelling spreading beyond 30 millimeters (mm) of injection site. This outcome measure refers only to the primed groups.

Outcome measures

Outcome measures
Measure	Synflorix III Group n=112 Participants Healthy male or female subjects between and including 31 and 44 months of age at the time of enrolment, who were not previously primed with Synflorix™ vaccine co-administered with Infanrix™ Hexa vaccine in study 107137 (NCT00496015), but vaccinated with Nimenrix™ vaccine co-administered with Infanrix™ Hexa vaccine in study 107137 (NCT00496015), additionally received in the current study 2 doses of Synflorix™ vaccine at Month 9 (40-48 months of age) and at Month 11 (42-50 months of age), administered intramuscularly in the deltoid muscle.	Pooled Synflorix I+II Group n=108 Participants For the purpose of the analysis, subjects from Synflorix I Group and Synflorix II Group have been pooled into a sub-group.	Synflorix III Group Healthy male or female subjects between and including 31 and 44 months of age at the time of enrolment, who were not previously primed with Synflorix™ vaccine co-administered with Infanrix™ Hexa vaccine in study 107137 (NCT00496015), but vaccinated with Nimenrix™ vaccine co-administered with Infanrix™ Hexa vaccine in study 107137 (NCT00496015), additionally received in the current study 2 doses of Synflorix™ vaccine at Month 9 (40-48 months of age) and at Month 11 (42-50 months of age), administered intramuscularly in the deltoid muscle.
Number of Subjects With Any and Grade 3 Solicited Local Symptoms Any Pain	75 Participants	67 Participants	—
Number of Subjects With Any and Grade 3 Solicited Local Symptoms Grade 3 Pain	7 Participants	5 Participants	—
Number of Subjects With Any and Grade 3 Solicited Local Symptoms Any Redness	58 Participants	60 Participants	—
Number of Subjects With Any and Grade 3 Solicited Local Symptoms Grade 3 Redness	13 Participants	12 Participants	—
Number of Subjects With Any and Grade 3 Solicited Local Symptoms Any Swelling	43 Participants	41 Participants	—
Number of Subjects With Any and Grade 3 Solicited Local Symptoms Grade 3 Swelling	11 Participants	11 Participants	—

SECONDARY outcome

Timeframe: During the 4-day (Days 0-3) post-vaccination period following each dose and across doses

Population: The analysis was performed on the Total Vaccinated Cohort, which included all vaccinated subjects.

Outcome measures

Outcome measures
Measure	Synflorix III Group n=223 Participants Healthy male or female subjects between and including 31 and 44 months of age at the time of enrolment, who were not previously primed with Synflorix™ vaccine co-administered with Infanrix™ Hexa vaccine in study 107137 (NCT00496015), but vaccinated with Nimenrix™ vaccine co-administered with Infanrix™ Hexa vaccine in study 107137 (NCT00496015), additionally received in the current study 2 doses of Synflorix™ vaccine at Month 9 (40-48 months of age) and at Month 11 (42-50 months of age), administered intramuscularly in the deltoid muscle.	Pooled Synflorix I+II Group For the purpose of the analysis, subjects from Synflorix I Group and Synflorix II Group have been pooled into a sub-group.	Synflorix III Group Healthy male or female subjects between and including 31 and 44 months of age at the time of enrolment, who were not previously primed with Synflorix™ vaccine co-administered with Infanrix™ Hexa vaccine in study 107137 (NCT00496015), but vaccinated with Nimenrix™ vaccine co-administered with Infanrix™ Hexa vaccine in study 107137 (NCT00496015), additionally received in the current study 2 doses of Synflorix™ vaccine at Month 9 (40-48 months of age) and at Month 11 (42-50 months of age), administered intramuscularly in the deltoid muscle.
Number of Subjects With Any and Grade 3 Solicited Local Symptoms Any pain, D1	150 Participants	—	—
Number of Subjects With Any and Grade 3 Solicited Local Symptoms Grade 3 pain, D1	13 Participants	—	—
Number of Subjects With Any and Grade 3 Solicited Local Symptoms Any redness, D1	102 Participants	—	—
Number of Subjects With Any and Grade 3 Solicited Local Symptoms Grade 3 redness, D1	23 Participants	—	—
Number of Subjects With Any and Grade 3 Solicited Local Symptoms Any swelling, D1	78 Participants	—	—
Number of Subjects With Any and Grade 3 Solicited Local Symptoms Grade 3 swelling, D1	14 Participants	—	—
Number of Subjects With Any and Grade 3 Solicited Local Symptoms Any pain, D2	121 Participants	—	—
Number of Subjects With Any and Grade 3 Solicited Local Symptoms Grade 3 pain, D2	12 Participants	—	—
Number of Subjects With Any and Grade 3 Solicited Local Symptoms Any redness, D2	93 Participants	—	—
Number of Subjects With Any and Grade 3 Solicited Local Symptoms Grade 3 redness, D2	12 Participants	—	—
Number of Subjects With Any and Grade 3 Solicited Local Symptoms Any swelling, D2	65 Participants	—	—
Number of Subjects With Any and Grade 3 Solicited Local Symptoms Grade 3 swelling, D2	3 Participants	—	—
Number of Subjects With Any and Grade 3 Solicited Local Symptoms Any pain, Across doses	167 Participants	—	—
Number of Subjects With Any and Grade 3 Solicited Local Symptoms Grade 3 pain, Across doses	23 Participants	—	—
Number of Subjects With Any and Grade 3 Solicited Local Symptoms Any redness, Across doses	127 Participants	—	—
Number of Subjects With Any and Grade 3 Solicited Local Symptoms Grade 3 redness, Across doses	29 Participants	—	—
Number of Subjects With Any and Grade 3 Solicited Local Symptoms Any swelling, Across doses	101 Participants	—	—
Number of Subjects With Any and Grade 3 Solicited Local Symptoms Grade 3 swelling, Across doses	16 Participants	—	—

SECONDARY outcome

Timeframe: During the 4-day (Days 0-3) post-vaccination period

Population: The analysis was performed on the Total Vaccinated Cohort, which included all vaccinated subjects.

Assessed solicited general symptoms were drowsiness, irritability, loss of appetite and fever \[defined as axillary temperature equal to or above 37.5 degrees Celsius (°C)\]. Any = occurrence of any general symptom regardless of intensity grade or relationship to vaccination. Grade 3 drowsiness = drowsiness that prevented normal activity. Grade 3 irritability = crying that could not be comforted/ prevented normal activity. Grade 3 loss of appetite = not eating at all. Grade 3 fever = fever \> 39.5 °C. Related = symptom assessed by the investigator as causally related to study vaccination. This outcome measure refers only to the primed groups.

Outcome measures

Outcome measures
Measure	Synflorix III Group n=112 Participants Healthy male or female subjects between and including 31 and 44 months of age at the time of enrolment, who were not previously primed with Synflorix™ vaccine co-administered with Infanrix™ Hexa vaccine in study 107137 (NCT00496015), but vaccinated with Nimenrix™ vaccine co-administered with Infanrix™ Hexa vaccine in study 107137 (NCT00496015), additionally received in the current study 2 doses of Synflorix™ vaccine at Month 9 (40-48 months of age) and at Month 11 (42-50 months of age), administered intramuscularly in the deltoid muscle.	Pooled Synflorix I+II Group n=108 Participants For the purpose of the analysis, subjects from Synflorix I Group and Synflorix II Group have been pooled into a sub-group.	Synflorix III Group Healthy male or female subjects between and including 31 and 44 months of age at the time of enrolment, who were not previously primed with Synflorix™ vaccine co-administered with Infanrix™ Hexa vaccine in study 107137 (NCT00496015), but vaccinated with Nimenrix™ vaccine co-administered with Infanrix™ Hexa vaccine in study 107137 (NCT00496015), additionally received in the current study 2 doses of Synflorix™ vaccine at Month 9 (40-48 months of age) and at Month 11 (42-50 months of age), administered intramuscularly in the deltoid muscle.
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms Any drowsiness	41 Participants	34 Participants	—
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms Grade 3 drowsiness	0 Participants	0 Participants	—
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms Related drowsiness	26 Participants	26 Participants	—
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms Any Irritability	33 Participants	26 Participants	—
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms Grade 3 Irritability	1 Participants	0 Participants	—
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms Related Irritability	21 Participants	16 Participants	—
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms Any loss of appetite	23 Participants	15 Participants	—
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms Grade 3 loss of appetite	1 Participants	1 Participants	—
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms Related loss of appetite	13 Participants	10 Participants	—
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms Any fever (Axillary)	12 Participants	8 Participants	—
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms Grade 3 fever (Axillary)	0 Participants	1 Participants	—
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms Related fever	10 Participants	5 Participants	—

SECONDARY outcome

Timeframe: During the 4-day (Days 0-3) post-vaccination period following each dose and across doses

Population: The analysis was performed on the Total Vaccinated Cohort, which included all vaccinated subjects.

Outcome measures

Outcome measures
Measure	Synflorix III Group n=223 Participants Healthy male or female subjects between and including 31 and 44 months of age at the time of enrolment, who were not previously primed with Synflorix™ vaccine co-administered with Infanrix™ Hexa vaccine in study 107137 (NCT00496015), but vaccinated with Nimenrix™ vaccine co-administered with Infanrix™ Hexa vaccine in study 107137 (NCT00496015), additionally received in the current study 2 doses of Synflorix™ vaccine at Month 9 (40-48 months of age) and at Month 11 (42-50 months of age), administered intramuscularly in the deltoid muscle.	Pooled Synflorix I+II Group For the purpose of the analysis, subjects from Synflorix I Group and Synflorix II Group have been pooled into a sub-group.	Synflorix III Group Healthy male or female subjects between and including 31 and 44 months of age at the time of enrolment, who were not previously primed with Synflorix™ vaccine co-administered with Infanrix™ Hexa vaccine in study 107137 (NCT00496015), but vaccinated with Nimenrix™ vaccine co-administered with Infanrix™ Hexa vaccine in study 107137 (NCT00496015), additionally received in the current study 2 doses of Synflorix™ vaccine at Month 9 (40-48 months of age) and at Month 11 (42-50 months of age), administered intramuscularly in the deltoid muscle.
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms Any drowsiness, D1	79 Participants	—	—
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms Grade 3 drowsiness, D1	1 Participants	—	—
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms Related drowsiness, D1	56 Participants	—	—
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms Any Irritability, D1	69 Participants	—	—
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms Grade 3 Irritability, D1	2 Participants	—	—
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms Related irritability, D1	49 Participants	—	—
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms Any loss of appetite, D1	47 Participants	—	—
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms Grade 3 loss of appetite, D1	5 Participants	—	—
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms Related loss of appetite, D1	32 Participants	—	—
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms Any fever (Axillary), D1	23 Participants	—	—
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms Grade 3 fever (Axillary), D1	1 Participants	—	—
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms Related fever, D1	15 Participants	—	—
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms Any drowsiness, D2	60 Participants	—	—
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms Grade 3 drowsiness, D2	1 Participants	—	—
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms Related drowsiness, D2	43 Participants	—	—
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms Any Irritability, D2	59 Participants	—	—
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms Grade 3 Irritability, D2	1 Participants	—	—
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms Related irritability, D2	44 Participants	—	—
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms Any loss of appetite, D2	26 Participants	—	—
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms Grade 3 loss of appetite, D2	1 Participants	—	—
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms Related loss of appetite, D2	16 Participants	—	—
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms Any fever (Axillary), D2	9 Participants	—	—
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms Grade 3 fever (Axillary), D2	1 Participants	—	—
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms Related fever, D2	5 Participants	—	—
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms Any drowsiness, Across doses	102 Participants	—	—
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms Grade 3 drowsiness, Across doses	2 Participants	—	—
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms Related drowsiness, Across doses	73 Participants	—	—
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms Any Irritability, Across doses	98 Participants	—	—
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms Grade 3 Irritability, Across doses	3 Participants	—	—
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms Related irritability, Across doses	74 Participants	—	—
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms Any loss of appetite, Across doses	61 Participants	—	—
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms Grade 3 loss of appetite, Across doses	6 Participants	—	—
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms Related loss of appetite, Across doses	42 Participants	—	—
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms Any fever (Axillary), Across doses	30 Participants	—	—
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms Grade 3 fever (Axillary), Across doses	2 Participants	—	—
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms Related fever, Across doses	19 Participants	—	—

SECONDARY outcome

Timeframe: Within 31 days (Days 0-30) after each vaccination

Population: The analysis was performed on the Total Vaccinated Cohort, which included all vaccinated subjects.

An unsolicited AE covers any untoward medical occurrence in a clinical investigation subject temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product and reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for solicited symptoms. Any was defined as the occurrence of any unsolicited AE regardless of intensity grade or relation to vaccination.

Outcome measures

Outcome measures
Measure	Synflorix III Group n=112 Participants Healthy male or female subjects between and including 31 and 44 months of age at the time of enrolment, who were not previously primed with Synflorix™ vaccine co-administered with Infanrix™ Hexa vaccine in study 107137 (NCT00496015), but vaccinated with Nimenrix™ vaccine co-administered with Infanrix™ Hexa vaccine in study 107137 (NCT00496015), additionally received in the current study 2 doses of Synflorix™ vaccine at Month 9 (40-48 months of age) and at Month 11 (42-50 months of age), administered intramuscularly in the deltoid muscle.	Pooled Synflorix I+II Group n=108 Participants For the purpose of the analysis, subjects from Synflorix I Group and Synflorix II Group have been pooled into a sub-group.	Synflorix III Group n=223 Participants Healthy male or female subjects between and including 31 and 44 months of age at the time of enrolment, who were not previously primed with Synflorix™ vaccine co-administered with Infanrix™ Hexa vaccine in study 107137 (NCT00496015), but vaccinated with Nimenrix™ vaccine co-administered with Infanrix™ Hexa vaccine in study 107137 (NCT00496015), additionally received in the current study 2 doses of Synflorix™ vaccine at Month 9 (40-48 months of age) and at Month 11 (42-50 months of age), administered intramuscularly in the deltoid muscle.
Number of Subjects With Any Unsolicited Adverse Events (AEs)	24 Participants	29 Participants	73 Participants

SECONDARY outcome

Timeframe: During the entire study period (from Day 0 up to Month 10 or Month 12)

Population: The analysis was performed on the Total Vaccinated Cohort, which included all vaccinated subjects.

Serious adverse events (SAEs) assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity.