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

• Sponsor: GlaxoSmithKline (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00950833
• Collaborator: (none)
• Enrollment: 466
• Locations: 10
• Arms: 3
• Actual Duration (Months): 14.6
• Patients Per Site: 46.6
• Patients Per Site Per Month: 3.2

Study Details

Study Description

Brief Summary

The objective of this study is to evaluate the immune memory through the administration of an additional dose of GSK Biologicals' pneumococcal conjugate vaccine GSK1024850A, the antibody persistence and long-term effect on nasopharyngeal carriage of S. pneumoniae and H. influenzae in subjects primed and boosted with GSK Biologicals' pneumococcal conjugate vaccine GSK1024850A in previous primary and booster studies. For subjects that did not receive the investigational vaccine during the primary and booster study, the objective is to evaluate immunogenicity, safety and reactogenicity of a 2-dose catch-up vaccination with GSK Biologicals' pneumococcal conjugate vaccine GSK1024850A.

This protocol posting deals with objectives & outcome measures of the extension phase. The objectives & outcome measures of the primary phase are presented in a separate protocol posting (NCT00370318). The objectives & outcome measures of the booster phase are presented in a separate protocol posting (NCT00496015).

Condition or Disease	Intervention/Treatment	Phase
Infections, Streptococcal	Biological: Pneumococcal vaccine GSK1024850A	Phase 3

Detailed Description

This protocol posting has been updated according to Protocol Amendment 1, July 2009

Study Design

• Study Type: Interventional
• Actual Enrollment: 466 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: Vaccination Course in Children Primed and Boosted With Pneumococcal Vaccine GSK 1024850A and in Age-matched Unprimed Children
• Actual Study Start Date: Aug 10, 2009
• Actual Primary Completion Date: Sep 16, 2010
• Actual Study Completion Date: Oct 27, 2010

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: AP-AP Group subjects from the AP-AP group, previously vaccinated with pneumococcal conjugate vaccine GSK1024850A in study NCT00496015, receiving an additional dose of pneumococcal conjugate vaccine GSK1024850A for immune memory assessment	Biological: Pneumococcal vaccine GSK1024850A; 1 or 2 intramuscular injections
Active Comparator: NAP-pre Group subjects from the NAP-pre group, previously vaccinated with pneumococcal conjugate vaccine GSK1024850A in study NCT00496015 receiving an additional dose of pneumococcal conjugate vaccine GSK1024850A for immune memory assessment	Biological: Pneumococcal vaccine GSK1024850A; 1 or 2 intramuscular injections
Active Comparator: Unprimed Group Age-matched subjects from the unprimed group of the NCT00496015 study, not previously vaccinated with any pneumococcal vaccine, receiving two doses of pneumococcal conjugate vaccine GSK1024850A	Biological: Pneumococcal vaccine GSK1024850A; 1 or 2 intramuscular injections

Outcome Measures

Primary Outcome Measures

1. Antibody Concentrations Against Vaccine Pneumococcal Serotypes [At 7-10 days after the first vaccine dose]

   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.

Secondary Outcome Measures

1. Antibody Concentrations Against Vaccine Pneumococcal Serotypes [Prior to the first study vaccine dose (At Day 0)]

   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.

2. Opsonophagocytic Activity (OPA) Titers Against Vaccine Pneumococcal Serotypes [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).

3. Antibody Concentrations Against Vaccine Pneumococcal Cross-reactive Serotypes 6A and 19A [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.

4. Opsonophagocytic Activity (OPA) Titers Against Pneumococcal Cross-reactive Serotypes 6A and 19A [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).

5. Antibody Concentrations Against Protein D (Anti-PD) [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.

6. Memory B-cell Detection for Vaccine Polysaccharides (PS) [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.

7. Antibody Concentrations Against Vaccine Pneumococcal Serotypes [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.

8. Opsonophagocytic Activity (OPA) Titers Against Vaccine Pneumococcal Serotypes [At Month 12, one month after the second 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).

9. Antibody Concentrations Against Vaccine Pneumococcal Cross-reactive Serotypes 6A and 19A [At Month 12, one month after the second 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.

10. Opsonophagocytic Activity (OPA) Titers Against Pneumococcal Cross-reactive Serotypes 6A and 19A [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).

11. Antibody Concentrations Against Protein D (Anti-PD) [At Month 12, one month after the second 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.

12. Rabbit Complement-mediated Serum Bactericidal Activity Titers Against Neisseria Meningitidis Serogroups (rSBA-Men) [At 25-36 months post-vaccination in previous 107137 (NCT00496015) study]

    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.

13. Number of Subjects With Any and Grade 3 Solicited Local Symptoms [During the 4-day (Days 0-3) post-vaccination period]

    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.

14. Number of Subjects With Any and Grade 3 Solicited Local Symptoms [During the 4-day (Days 0-3) post-vaccination period following each dose and across doses]

    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 unprimed group.

15. Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms [During the 4-day (Days 0-3) post-vaccination period]

    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.

16. Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms [During the 4-day (Days 0-3) post-vaccination period following each dose and across doses]

    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 unprimed group.

17. Number of Subjects With Any Unsolicited Adverse Events (AEs) [Within 31 days (Days 0-30) after each vaccination]

    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.

18. Number of Subjects With Serious Adverse Events (SAEs) [During the entire study period (from Day 0 up to Month 10 or Month 12)]

    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.

19. Number of Nasopharyngeal Swabs With Streptococcus Pneumoniae (Vaccine Serotypes) [At 31-44 months of age and prior to the first vaccine dose, at 40-48 months of age]

    Positive cultures of S. pneumoniae Synflorix™ vaccine serotypes identified in the nasopharynx were recorded.

20. Number of Nasopharyngeal Swabs With S.Pneumoniae (Cross-reactive Serotypes) [At 31-44 months of age and prior to the first vaccine dose, at 40-48 months of age]

    Positive cultures of S. pneumoniae cross- reactive serotypes identified in the nasopharynx were recorded.

21. Number of Nasopharyngeal Swabs With S.Pneumoniae (Non-vaccine and Non-cross-reactive Serotypes) [At 31-44 months of age and prior to the first vaccine dose, at 40-48 months of age]

    Positive cultures of S. pneumoniae non- Synflorix™ vaccine, non-cross-reactive serotypes identified in the nasopharynx were recorded.

22. Number of Nasopharyngeal Swabs With Haemophilus Influenzae [At 31-44 months of age and prior to the first vaccine dose, at 40-48 months of age]

    Positive cultures of H. influenzae identified in the nasopharynx were recorded.

23. Number of Subjects With New Acquisition of S. Pneumoniae (Vaccine Serotypes) in Nasopharyngeal Swabs [At 31-44 months of age and prior to the first vaccine dose, at 40-48 months of age]

    The number of subjects with new acquisition of S. pneumoniae (Synflorix™ vaccine serotypes) detected in nasopharyngeal swabs was recorded.

24. Number of Subjects With New Acquisition of S. Pneumoniae (Cross-reactive Serotypes) in Nasopharyngeal Swabs [At 31-44 months of age and prior to the first vaccine dose, at 40-48 months of age]

    The number of subjects with new acquisition of S. pneumoniae (cross-reactive serotypes) detected in nasopharyngeal swabs was recorded.

25. Number of Subjects With New Acquisition of S. Pneumoniae (Non-vaccine and Non-cross-reactive Serotypes) in Nasopharyngeal Swabs [At 31-44 months of age and prior to the first vaccine dose, at 40-48 months of age]

    The number of subjects with new acquisition of S. pneumoniae (non-vaccine and non-cross-reactive serotypes) detected in nasopharyngeal swabs was recorded.

26. Number of Subjects With New Acquisition of H. Influenzae in Nasopharyngeal Swabs [At 31-44 months of age and prior to the first vaccine dose, at 40-48 months of age]

    The number of subjects with new acquisition of H. influenzae detected in nasopharyngeal swabs was recorded.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 31 Months to 44 Months
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Subjects who the investigator believes that their parents/ guardians can and will comply with the requirements of the protocol should be enrolled in the study.

• A male or female between, and including, 31 and 34 months of age at the time of the enrolment.

• Subjects who previously participated in study NCT00496015

• For the subjects in the primed AP-AP and NAP-pre groups: subjects who received a booster dose of the pneumococcal conjugate vaccine prior to the study amendment 3.

• For the subjects in the unprimed group: subjects who received a dose of the meningococcal vaccine GSK134612.

• Written informed consent obtained from the parent or guardian of the subject.

• Free of obvious health problems as established by medical history and clinical examination before entering into the study.

Exclusion Criteria:

• Use of any investigational or non-registered product (drug or vaccine) other than the study vaccine within 30 days preceding enrolment, or planned use during the entire study period.

• Chronic administration (defined as more than 14 days) of immunosuppressants or other immune-modifying drugs during the entire study period.

• Planned administration/ administration of a vaccine not foreseen by the study protocol during the period starting from 30 days before each dose of study vaccine and ending 30 days after.

• Concurrently participating in another clinical study, at any time during the study period, in which the subject has been or will be exposed to an investigational or a non-investigational product (pharmaceutical product or device).

• Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination (no laboratory testing required).

• History of allergic disease or reactions likely to be exacerbated by any component of the vaccine.

• History of seizures or progressive neurological disease.

• Acute disease at the time of enrolment, defined as the presence of a mild, moderate or severe illness with or without fever.

• Administration or planned use of immunoglobulins and/ or any blood products during the entire study period.

• A family history of congenital or hereditary immunodeficiency.

• Major congenital defects or serious chronic illness.

• Subjects of which both parents have a history of atopia (polinosis, asthma, atopic eczema).

• Administration of any pneumococcal vaccine since the end of study NCT00496015.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	GSK Investigational Site	Brno		Czechia	628 00
2	GSK Investigational Site	Hradec Kralove		Czechia	500 01
3	GSK Investigational Site	Jindrichuv Hradec		Czechia	377 01
4	GSK Investigational Site	Nachod		Czechia	547 01
5	GSK Investigational Site	Ostrava		Czechia	70800
6	GSK Investigational Site	Pardubice		Czechia	532 03
7	GSK Investigational Site	Praha 5		Czechia	150 00
8	GSK Investigational Site	Praha 6		Czechia	160 00
9	GSK Investigational Site	Praha 9		Czechia	190 00
10	GSK Investigational Site	Znojmo		Czechia	669 00

Sponsors and Collaborators

• GlaxoSmithKline

Investigators

• Study Director: GSK Clinical Trials, GlaxoSmithKline

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

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

Publications

• Prymula R et al. Immune memory 2-3 years after vaccination with pneumococcal non-typeable Heamophilus influenzae protein-D conjugate vaccine (PHiD-CV), with or without prophylactic paracetamol. Abstract presented at the 30th Annual Meeting of the European Society for Paediatric Infectious Diseases (ESPID), Thessaloniki, Greece, 8-12 May 2012.
• Prymula R et al. Long-term effect of 10-valent pneumococcal non-typeable Haemophilus Influenzae protein D conjugate vaccine (PHiD-CV) on nasopharyngeal bacterial carriage in Czech children. Abstract presented at the 8th International Symposium on Pneumococci and Pneumococcal Diseases (ISPPD), Iguaçu Falls, Brazil, 11-15 March, 2012.
• Prymula R, Habib A, François N, Borys D, Schuerman L. Immunological memory and nasopharyngeal carriage in 4-year-old children previously primed and boosted with 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) with or without concomitant prophylactic paracetamol. Vaccine. 2013 Apr 12;31(16):2080-8. doi: 10.1016/j.vaccine.2013.01.044. Epub 2013 Feb 5.
• Silfverdal SA et al. Immunogenicity and reactogenicity of 2-dose catch-up vaccination with 10-valent pneumococcal non-typeable Haemophilus Influenzae protein D conjugate vaccine (PHiD-CV) during the fourth year of life. Abstract presented at the 8th International Symposium on Pneumococci and Pneumococcal Diseases (ISPPD), Iguaçu Falls, Brazil, 11-15 March, 2012.

• Responsible Party: GlaxoSmithKline
• ClinicalTrials.gov Identifier: NCT00950833
• Other Study ID Numbers: 112801
• First Posted: Aug 3, 2009
• Last Update Posted: Sep 20, 2018
• Last Verified: Aug 1, 2018

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Keywords provided by GlaxoSmithKline: Catch-up vaccination; Pneumococcal vaccine; Immune memory; Nasopharyngeal carriage; Immunogenicity; Pneumococcal disease; Safety
• Additional relevant MeSH terms: Streptococcal Infections; Heptavalent Pneumococcal Conjugate Vaccine

Study Results

Participant Flow

Pre-assignment Detail	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).

Arm/Group Title	Synflorix I Group	Synflorix II Group	Synflorix III Group
Arm/Group Description	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.	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.	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.
Period Title: Overall Study
STARTED	112	108	223
COMPLETED	112	108	223
NOT COMPLETED	0	0	0

Baseline Characteristics

Arm/Group Title	Synflorix I Group	Synflorix II Group	Synflorix III Group	Total
Arm/Group Description	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.	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.	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 of all reporting groups
Overall Participants	112	108	223	443
Age (Months) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Months]	39.2 (1.53)	39.1 (1.54)	37.7 (3.36)	38.4 (2.71)
Sex: Female, Male (Count of Participants)
Female	60 53.6%	48 44.4%	99 44.4%	207 46.7%
Male	52 46.4%	60 55.6%	124 55.6%	236 53.3%
Race/Ethnicity, Customized (Count of Participants)
White - Caucasian / European heritage	111 99.1%	108 100%	214 96%	433 97.7%
White - Arabic / North African heritage	0 0%	0 0%	9 4%	9 2%
Unknown	1 0.9%	0 0%	0 0%	1 0.2%

Outcome Measures

1. Primary Outcome

Title	Antibody Concentrations Against Vaccine Pneumococcal Serotypes
Description	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.
Time Frame	At 7-10 days after the first vaccine dose

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Synflorix III Group	Pooled Synflorix I+II Group
Arm/Group Description	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.	For the purpose of the analysis, subjects from Synflorix I Group and Synflorix II Group have been pooled into a sub-group.
Measure Participants	204	215
Anti-1	1.24	7.63
Anti-4	4.52	12.95
Anti-5	0.72	9.76
Anti-6B	0.27	7.67
Anti-7F	1.37	6.51
Anti-9V	0.69	9.75
Anti-14	1.01	23.07
Anti-18C	3.25	32.54
Anti-19F	4.31	39.84
Anti-23F	0.25	9.24

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Synflorix III Group, Pooled Synflorix I+II Group
	Comments	To demonstrate the immunological memory induced for anti-pneumococcal serotype 1 following primary vaccination in study 107017 (NCT00370318) and booster vaccination in study 107137 (NCT00496015) with the Synflorix™ vaccine, through evaluation of early antibody responses after an additional dose of Synflorix™ vaccine at 40-48 months of age, compared to the Synflorix III Group.
	Type of Statistical Test	Non-Inferiority
	Comments	The immune memory would be demonstrated if the lower limit (LL) of the 95% confidence interval (CI) around the geometric mean concentration (GMC) ratios (Pooled Synflorix I+II Group over Synflorix III Group) was higher than 1 for pneumococcal serotype 1.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	GMC ratio for anti-1
	Estimated Value	6.17
	Confidence Interval	(2-Sided) 95%; 5.03 to 7.58
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Synflorix III Group, Pooled Synflorix I+II Group
	Comments	To demonstrate the immunological memory for anti-pneumococcal serotype 4 induced following primary vaccination in study 107017 (NCT00370318) and booster vaccination in study 107137 (NCT00496015) with the Synflorix™ vaccine, through evaluation of early antibody responses after an additional dose of Synflorix™ vaccine at 40-48 months of age, compared to the Synflorix III Group.
	Type of Statistical Test	Non-Inferiority
	Comments	The immune memory would be demonstrated if the lower limit (LL) of the 95% confidence interval (CI) around the geometric mean concentration (GMC) ratios (Pooled SynflorixI+II Group over Synflorix Group) was higher than 1 for pneumococcal serotype 4.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	GMC ratio for anti-4
	Estimated Value	2.86
	Confidence Interval	(2-Sided) 95%; 2.38 to 3.45
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Synflorix III Group, Pooled Synflorix I+II Group
	Comments	To demonstrate the immunological memory for anti-pneumococcal serotype 5 induced following primary vaccination in study 107017 (NCT00370318) and booster vaccination in study 107137 (NCT00496015) with the Synflorix™ vaccine, through evaluation of early antibody responses after an additional dose of Synflorix™ vaccine at 40-48 months of age, compared to the Synflorix III Group.
	Type of Statistical Test	Non-Inferiority
	Comments	The immune memory would be demonstrated if the lower limit (LL) of the 95% confidence interval (CI) around the geometric mean concentration (GMC) ratios (Pooled Synflorix I+II Group over Synflorix III Group) was higher than 1 for pneumococcal serotype 5.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	GMC ratio for anti-5
	Estimated Value	13.47
	Confidence Interval	(2-Sided) 95%; 10.96 to 16.55
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Synflorix III Group, Pooled Synflorix I+II Group
	Comments	To demonstrate the immunological memory for anti-pneumococcal serotype 6B induced following primary vaccination in study 107017 (NCT00370318) and booster vaccination in study 107137 (NCT00496015) with the Synflorix™ vaccine, through evaluation of early antibody responses after an additional dose of Synflorix™ vaccine at 40-48 months of age, compared to the Synflorix III Group.
	Type of Statistical Test	Non-Inferiority
	Comments	The immune memory would be demonstrated if the lower limit (LL) of the 95% confidence interval (CI) around the geometric mean concentration (GMC) ratios (Pooled Synflorix I+II Group over Synflorix III Group) was higher than 1 for pneumococcal serotype 6B.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	GMC ratio for anti-6B
	Estimated Value	28.81
	Confidence Interval	(2-Sided) 95%; 22.54 to 36.81
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Synflorix III Group, Pooled Synflorix I+II Group
	Comments	To demonstrate the immunological memory for anti-pneumococcal serotype 7F induced following primary vaccination in study 107017 (NCT00370318) and booster vaccination in study 107137 (NCT00496015) with the Synflorix™ vaccine, through evaluation of early antibody responses after an additional dose of Synflorix™ vaccine at 40-48 months of age, compared to the Synflorix III Group.
	Type of Statistical Test	Non-Inferiority
	Comments	The immune memory would be demonstrated if the lower limit (LL) of the 95% confidence interval (CI) around the geometric mean concentration (GMC) ratios (Pooled Synflorix I+II Group over Synflorix III Group) was higher than 1 for pneumococcal serotype 7F.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	GMC ratio for anti-7F
	Estimated Value	4.75
	Confidence Interval	(2-Sided) 95%; 3.9 to 5.78
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Synflorix III Group, Pooled Synflorix I+II Group
	Comments	To demonstrate the immunological memory for anti-pneumococcal serotype 9V induced following primary vaccination in study 107017 (NCT00370318) and booster vaccination in study 107137 (NCT00496015) with the Synflorix™ vaccine, through evaluation of early antibody responses after an additional dose of Synflorix™ vaccine at 40-48 months of age, compared to the Synflorix III Group.
	Type of Statistical Test	Non-Inferiority
	Comments	The immune memory would be demonstrated if the lower limit (LL) of the 95% confidence interval (CI) around the geometric mean concentration (GMC) ratios (Pooled Synflorix I+II Group over Synflorix III Group) was higher than 1 for pneumococcal serotype 9V.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	GMC ratio for anti-9V
	Estimated Value	14.1
	Confidence Interval	(2-Sided) 95%; 11.21 to 17.75
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Synflorix III Group, Pooled Synflorix I+II Group
	Comments	To demonstrate the immunological memory for anti-pneumococcal serotype 14 induced following primary vaccination in study 107017 (NCT00370318) and booster vaccination in study 107137 (NCT00496015) with the Synflorix™ vaccine, through evaluation of early antibody responses after an additional dose of Synflorix™ vaccine at 40-48 months of age, compared to the Synflorix III Group.
	Type of Statistical Test	Non-Inferiority
	Comments	The immune memory would be demonstrated if the lower limit (LL) of the 95% confidence interval (CI) around the geometric mean concentration (GMC) ratios (Pooled Synflorix I+II Group over Synflorix III Group) was higher than 1 for pneumococcal serotype 14.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	GMC ratio for anti-14
	Estimated Value	22.92
	Confidence Interval	(2-Sided) 95%; 17.51 to 30
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Synflorix III Group, Pooled Synflorix I+II Group
	Comments	To demonstrate the immunological memory for anti-pneumococcal serotype 18C induced following primary vaccination in study 107017 (NCT00370318) and booster vaccination in study 107137 (NCT00496015) with the Synflorix™ vaccine, through evaluation of early antibody responses after an additional dose of Synflorix™ vaccine at 40-48 months of age, compared to the Synflorix III Group.
	Type of Statistical Test	Non-Inferiority
	Comments	The immune memory would be demonstrated if the lower limit (LL) of the 95% confidence interval (CI) around the geometric mean concentration (GMC) ratios (Pooled Synflorix I+II Group over Synflorix III Group) was higher than 1 for pneumococcal serotype 18C.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	GMC ratio for anti-18C
	Estimated Value	10.01
	Confidence Interval	(2-Sided) 95%; 7.95 to 12.61
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Synflorix III Group, Pooled Synflorix I+II Group
	Comments	To demonstrate the immunological memory for anti-pneumococcal serotype 19F induced following primary vaccination in study 107017 (NCT00370318) and booster vaccination in study 107137 (NCT00496015) with the Synflorix™ vaccine, through evaluation of early antibody responses after an additional dose of Synflorix™ vaccine at 40-48 months of age, compared to the Synflorix III Group.
	Type of Statistical Test	Non-Inferiority
	Comments	The immune memory would be demonstrated if the lower limit (LL) of the 95% confidence interval (CI) around the geometric mean concentration (GMC) ratios (Pooled Synflorix I+II Group over Synflorix III Group) was higher than 1 for pneumococcal serotype 19F.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	GMC ratio for anti-19F
	Estimated Value	9.25
	Confidence Interval	(2-Sided) 95%; 7.29 to 11.74
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Synflorix III Group, Pooled Synflorix I+II Group
	Comments	To demonstrate the immunological memory for anti-pneumococcal serotype 23F induced following primary vaccination in study 107017 (NCT00370318) and booster vaccination in study 107137 (NCT00496015) with the Synflorix™ vaccine, through evaluation of early antibody responses after an additional dose of Synflorix™ vaccine at 40-48 months of age, compared to the Synflorix III Group.
	Type of Statistical Test	Non-Inferiority
	Comments	The immune memory would be demonstrated if the lower limit (LL) of the 95% confidence interval (CI) around the geometric mean concentration (GMC) ratios (Pooled Synflorix I+II Group over Synflorix III Group) was higher than 1 for pneumococcal serotype 23F.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	GMC ratio for anti-23F
	Estimated Value	36.52
	Confidence Interval	(2-Sided) 95%; 27.59 to 48.34
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Antibody Concentrations Against Vaccine Pneumococcal Serotypes
Description	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.
Time Frame	Prior to the first study vaccine dose (At Day 0)

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Synflorix III Group	Pooled Synflorix I+II Group
Arm/Group Description	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.	For the purpose of the analysis, subjects from Synflorix I Group and Synflorix II Group have been pooled into a sub-group.
Measure Participants	209	215
Anti-1	0.09	0.27
Anti-4	0.05	0.2
Anti-5	0.1	0.41
Anti-6B	0.1	0.8
Anti-7F	0.06	0.48
Anti-9V	0.07	0.5
Anti-14	0.28	1.21
Anti-18C	0.09	0.65
Anti-19F	0.44	2.35
Anti-23F	0.08	0.96

3. Secondary Outcome

Title	Opsonophagocytic Activity (OPA) Titers Against Vaccine Pneumococcal Serotypes
Description	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).
Time Frame	Prior to (Day 0) and 7-10 days after the first vaccine dose

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Synflorix III Group	Pooled Synflorix I+II Group
Arm/Group Description	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.	For the purpose of the analysis, subjects from Synflorix I Group and Synflorix II Group have been pooled into a sub-group.
Measure Participants	191	199
Opsono-1, D0	5.4	10.2
Opsono-1, D7-10	632	3106.5
Opsono-4, D0	9.1	18.1
Opsono-4, D7-10	13109.9	27273.3
Opsono-5, D0	4	8.9
Opsono-5, D7-10	145.8	1020
Opsono-6B, D0	46.7	163.5
Opsono-6B, D7-10	1472.2	5789.5
Opsono-7F, D0	973.4	1112.3
Opsono-7F, D7-10	13647.4	19988.9
Opsono-9V, D0	268.2	481.8
Opsono-9V, D7-10	14668.8	17952.5
Opsono-14, D0	145.3	267.6
Opsono-14, D7-10	4454.3	16256.8
Opsono-18C, D0	5.7	14.2
Opsono-18C, D7-10	9092.2	7413.8
Opsono-19F, D0	12.9	79.5
Opsono-19F, D7-10	902.5	6271.1
Opsono-23F, D0	220.6	462.7
Opsono-23F, D7-10	5776.5	15613.5

4. Secondary Outcome

Title	Antibody Concentrations Against Vaccine Pneumococcal Cross-reactive Serotypes 6A and 19A
Description	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.
Time Frame	Prior to (Day 0) and 7-10 days after the first vaccine dose

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Synflorix III Group	Pooled Synflorix I+II Group
Arm/Group Description	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.	For the purpose of the analysis, subjects from Synflorix I Group and Synflorix II Group have been pooled into a sub-group.
Measure Participants	207	215
Anti-6A, D0	0.11	0.39
Anti-6A, D7-10	0.2	2.4
Anti-19A, D0	0.22	0.52
Anti-19A, D7-10	0.65	6.75

5. Secondary Outcome

Title	Opsonophagocytic Activity (OPA) Titers Against Pneumococcal Cross-reactive Serotypes 6A and 19A
Description	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).
Time Frame	Prior to (Day 0) and 7-10 days after the first vaccine dose

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Synflorix III Group	Pooled Synflorix I+II Group
Arm/Group Description	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.	For the purpose of the analysis, subjects from Synflorix I Group and Synflorix II Group have been pooled into a sub-group.
Measure Participants	183	191
Opsono-6A, D0	49	95.2
Opsono-6A, D7-10	863.3	2408.4
Opsono-19A, D0	10.3	15.9
Opsono-19A, D7-10	880.5	2104.9

6. Secondary Outcome

Title	Antibody Concentrations Against Protein D (Anti-PD)
Description	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.
Time Frame	Prior to (Day 0) and 7-10 days after the first vaccine dose

Outcome Measure Data

Analysis Population Description

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 protein D were available after vaccination.

Arm/Group Title	Synflorix III Group	Pooled Synflorix I+II Group
Arm/Group Description	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.	For the purpose of the analysis, subjects from Synflorix I Group and Synflorix II Group have been pooled into a sub-group.
Measure Participants	204	215
Anti-PD, D0	105.6	464.2
Anti-PD, D7-10	374.3	2673.7

7. Secondary Outcome

Title	Memory B-cell Detection for Vaccine Polysaccharides (PS)
Description	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.
Time Frame	Prior to (Day 0) and 7-10 days after the first vaccine dose

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Synflorix I Group	Synflorix II Group	Synflorix III Group
Arm/Group Description	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.	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.	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.
Measure Participants	70	71	133
1 PS, D0	288.6 (352.5)	269.5 (432.2)	254.8 (368.4)
1 PS, D7-10	1488.8 (1584.2)	1017.4 (1309.9)	755.9 (1017.4)
5 PS, D0	139.4 (214.7)	141.9 (232.4)	81.5 (109.2)
5 PS, D7-10	233.5 (235.7)	406.6 (447.8)	152.6 (231)
6B PS, D0	372 (545.5)	327.2 (554.4)	639.9 (846.5)
6B PS, D7-10	629.1 (773.2)	1265.8 (1738.6)	526 (648.6)
18C PS, D0	537.7 (641.8)	530.9 (693.8)	135.2 (200.6)
18C PS, D7-10	3839 (5960.5)	8308.4 (7166.9)	2053.8 (2122.2)
19F PS, D0	169.7 (415.3)	149.1 (194.4)	164.5 (343.4)
19F PS, D7-10	1056.7 (1334)	1092.4 (1724.3)	708.2 (1609.4)
23F PS, D0	112.6 (176.1)	285 (484.3)	185.6 (270.1)
23F PS, D7-10	579.8 (632.5)	1123.7 (2095.4)	327.9 (470.5)
C-PS, D0	475.9 (682.3)	462.5 (704.5)	469.9 (639.2)
C-PS, D7-10	679.2 (885.8)	915.5 (1191.3)	762.6 (1039.4)

8. Secondary Outcome

Title	Antibody Concentrations Against Vaccine Pneumococcal Serotypes
Description	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.
Time Frame	At Month 12, one month after the second vaccine dose

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Synflorix III Group
Arm/Group Description	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.
Measure Participants	209
Anti-1	2.33
Anti-4	6.26
Anti-5	2.69
Anti-6B	0.84
Anti-7F	3.63
Anti-9V	1.73
Anti-14	5.21
Anti-18C	13.59
Anti-19F	11.83
Anti-23F	0.99

9. Secondary Outcome

Title	Opsonophagocytic Activity (OPA) Titers Against Vaccine Pneumococcal Serotypes
Description	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).
Time Frame	At Month 12, one month after the second vaccine dose

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Synflorix III Group
Arm/Group Description	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.
Measure Participants	201
Opsono-1	125.6
Opsono-4	2451.2
Opsono-5	57.2
Opsono-6B	1345
Opsono-7F	6527.2
Opsono-9V	6091.6
Opsono-14	4544.9
Opsono-18C	3827.5
Opsono-19F	1251
Opsono-23F	4629.1

10. Secondary Outcome

Title	Antibody Concentrations Against Vaccine Pneumococcal Cross-reactive Serotypes 6A and 19A
Description	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.
Time Frame	At Month 12, one month after the second vaccine dose

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Synflorix III Group
Arm/Group Description	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.
Measure Participants	209
Anti-6A	0.51
Anti-19A	1.99

11. Secondary Outcome

Title	Opsonophagocytic Activity (OPA) Titers Against Pneumococcal Cross-reactive Serotypes 6A and 19A
Description	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).
Time Frame	At Month 12, one month after the second vaccine dose

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Synflorix III Group
Arm/Group Description	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.
Measure Participants	196
Opsono-6A	918.6
Opsono-19A	597.6

12. Secondary Outcome

Title	Antibody Concentrations Against Protein D (Anti-PD)
Description	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.
Time Frame	At Month 12, one month after the second vaccine dose

Outcome Measure Data

Analysis Population Description

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 protein D were available after vaccination.

Arm/Group Title	Synflorix III Group
Arm/Group Description	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.
Measure Participants	209
Geometric Mean (95% Confidence Interval) [EL.U/mL]	785.9

13. Secondary Outcome

Title	Rabbit Complement-mediated Serum Bactericidal Activity Titers Against Neisseria Meningitidis Serogroups (rSBA-Men)
Description	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.
Time Frame	At 25-36 months post-vaccination in previous 107137 (NCT00496015) study

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Synflorix III Group
Arm/Group Description	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.
Measure Participants	83
rSBA-MenA	325.5
rSBA-MenC	63.6
rSBA-MenY	372.2
rSBA-MenW-135	247.6

14. Secondary Outcome

Title	Number of Subjects With Any and Grade 3 Solicited Local Symptoms
Description	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.
Time Frame	During the 4-day (Days 0-3) post-vaccination period

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Synflorix I Group	Synflorix II Group
Arm/Group Description	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.	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.
Measure Participants	112	108
Any Pain	75 67%	67 62%
Grade 3 Pain	7 6.3%	5 4.6%
Any Redness	58 51.8%	60 55.6%
Grade 3 Redness	13 11.6%	12 11.1%
Any Swelling	43 38.4%	41 38%
Grade 3 Swelling	11 9.8%	11 10.2%

15. Secondary Outcome

Title	Number of Subjects With Any and Grade 3 Solicited Local Symptoms
Description	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 unprimed group.
Time Frame	During the 4-day (Days 0-3) post-vaccination period following each dose and across doses

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Synflorix III Group
Arm/Group Description	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.
Measure Participants	223
Any pain, D1	150 133.9%
Grade 3 pain, D1	13 11.6%
Any redness, D1	102 91.1%
Grade 3 redness, D1	23 20.5%
Any swelling, D1	78 69.6%
Grade 3 swelling, D1	14 12.5%
Any pain, D2	121 108%
Grade 3 pain, D2	12 10.7%
Any redness, D2	93 83%
Grade 3 redness, D2	12 10.7%
Any swelling, D2	65 58%
Grade 3 swelling, D2	3 2.7%
Any pain, Across doses	167 149.1%
Grade 3 pain, Across doses	23 20.5%
Any redness, Across doses	127 113.4%
Grade 3 redness, Across doses	29 25.9%
Any swelling, Across doses	101 90.2%
Grade 3 swelling, Across doses	16 14.3%

16. Secondary Outcome

Title	Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms
Description	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.
Time Frame	During the 4-day (Days 0-3) post-vaccination period

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Synflorix I Group	Synflorix II Group
Arm/Group Description	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.	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.
Measure Participants	112	108
Any drowsiness	41 36.6%	34 31.5%
Grade 3 drowsiness	0 0%	0 0%
Related drowsiness	26 23.2%	26 24.1%
Any Irritability	33 29.5%	26 24.1%
Grade 3 Irritability	1 0.9%	0 0%
Related Irritability	21 18.8%	16 14.8%
Any loss of appetite	23 20.5%	15 13.9%
Grade 3 loss of appetite	1 0.9%	1 0.9%
Related loss of appetite	13 11.6%	10 9.3%
Any fever (Axillary)	12 10.7%	8 7.4%
Grade 3 fever (Axillary)	0 0%	1 0.9%
Related fever	10 8.9%	5 4.6%

17. Secondary Outcome

Title	Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms
Description	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 unprimed group.
Time Frame	During the 4-day (Days 0-3) post-vaccination period following each dose and across doses

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Synflorix III Group
Arm/Group Description	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.
Measure Participants	223
Any drowsiness, D1	79 70.5%
Grade 3 drowsiness, D1	1 0.9%
Related drowsiness, D1	56 50%
Any Irritability, D1	69 61.6%
Grade 3 Irritability, D1	2 1.8%
Related irritability, D1	49 43.8%
Any loss of appetite, D1	47 42%
Grade 3 loss of appetite, D1	5 4.5%
Related loss of appetite, D1	32 28.6%
Any fever (Axillary), D1	23 20.5%
Grade 3 fever (Axillary), D1	1 0.9%
Related fever, D1	15 13.4%
Any drowsiness, D2	60 53.6%
Grade 3 drowsiness, D2	1 0.9%
Related drowsiness, D2	43 38.4%
Any Irritability, D2	59 52.7%
Grade 3 Irritability, D2	1 0.9%
Related irritability, D2	44 39.3%
Any loss of appetite, D2	26 23.2%
Grade 3 loss of appetite, D2	1 0.9%
Related loss of appetite, D2	16 14.3%
Any fever (Axillary), D2	9 8%
Grade 3 fever (Axillary), D2	1 0.9%
Related fever, D2	5 4.5%
Any drowsiness, Across doses	102 91.1%
Grade 3 drowsiness, Across doses	2 1.8%
Related drowsiness, Across doses	73 65.2%
Any Irritability, Across doses	98 87.5%
Grade 3 Irritability, Across doses	3 2.7%
Related irritability, Across doses	74 66.1%
Any loss of appetite, Across doses	61 54.5%
Grade 3 loss of appetite, Across doses	6 5.4%
Related loss of appetite, Across doses	42 37.5%
Any fever (Axillary), Across doses	30 26.8%
Grade 3 fever (Axillary), Across doses	2 1.8%
Related fever, Across doses	19 17%

18. Secondary Outcome

Title	Number of Subjects With Any Unsolicited Adverse Events (AEs)
Description	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.
Time Frame	Within 31 days (Days 0-30) after each vaccination

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Synflorix I Group	Synflorix II Group	Synflorix III Group
Arm/Group Description	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.	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.	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.
Measure Participants	112	108	223
Count of Participants [Participants]	24 21.4%	29 26.9%	73 32.7%

19. Secondary Outcome

Title	Number of Subjects With Serious Adverse Events (SAEs)
Description	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.
Time Frame	During the entire study period (from Day 0 up to Month 10 or Month 12)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Synflorix I Group	Synflorix II Group	Synflorix III Group
Arm/Group Description	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.	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.	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.
Measure Participants	112	108	223
Count of Participants [Participants]	0 0%	0 0%	0 0%

20. Secondary Outcome

Title	Number of Nasopharyngeal Swabs With Streptococcus Pneumoniae (Vaccine Serotypes)
Description	Positive cultures of S. pneumoniae Synflorix™ vaccine serotypes identified in the nasopharynx were recorded.
Time Frame	At 31-44 months of age and prior to the first vaccine dose, at 40-48 months of age

Outcome Measure Data

Analysis Population Description

The analysis was performed on the ATP cohort for carriage, which included all evaluable subjects for whom carriage outcome measures were available after the swab time point.

Arm/Group Title	Synflorix III Group	Pooled Synflorix I+II Group
Arm/Group Description	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.	For the purpose of the analysis, subjects from Synflorix I Group and Synflorix II Group have been pooled into a sub-group.
Measure Participants	210	216
31-44 months	40	21
40-48 months	46	20

21. Secondary Outcome

Title	Number of Nasopharyngeal Swabs With S.Pneumoniae (Cross-reactive Serotypes)
Description	Positive cultures of S. pneumoniae cross- reactive serotypes identified in the nasopharynx were recorded.
Time Frame	At 31-44 months of age and prior to the first vaccine dose, at 40-48 months of age

Outcome Measure Data

Analysis Population Description

The analysis was performed on the ATP cohort for carriage, which included all evaluable subjects for whom carriage outcome measures were available after the swab time point.

Arm/Group Title	Synflorix III Group	Pooled Synflorix I+II Group
Arm/Group Description	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.	For the purpose of the analysis, subjects from Synflorix I Group and Synflorix II Group have been pooled into a sub-group.
Measure Participants	210	216
31-44 months	9	13
40-48 months	19	18

22. Secondary Outcome

Title	Number of Nasopharyngeal Swabs With S.Pneumoniae (Non-vaccine and Non-cross-reactive Serotypes)
Description	Positive cultures of S. pneumoniae non- Synflorix™ vaccine, non-cross-reactive serotypes identified in the nasopharynx were recorded.
Time Frame	At 31-44 months of age and prior to the first vaccine dose, at 40-48 months of age

Outcome Measure Data

Analysis Population Description

The analysis was performed on the ATP cohort for carriage, which included all evaluable subjects for whom carriage outcome measures were available after the swab time point.

Arm/Group Title	Synflorix III Group	Pooled Synflorix I+II Group
Arm/Group Description	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.	For the purpose of the analysis, subjects from Synflorix I Group and Synflorix II Group have been pooled into a sub-group.
Measure Participants	210	216
31-44 months	25	34
40-48 months	27	35

23. Secondary Outcome

Title	Number of Nasopharyngeal Swabs With Haemophilus Influenzae
Description	Positive cultures of H. influenzae identified in the nasopharynx were recorded.
Time Frame	At 31-44 months of age and prior to the first vaccine dose, at 40-48 months of age

Outcome Measure Data

Analysis Population Description

The analysis was performed on the ATP cohort for carriage, which included all evaluable subjects for whom carriage outcome measures were available after the swab time point.

Arm/Group Title	Synflorix III Group	Pooled Synflorix I+II Group
Arm/Group Description	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.	For the purpose of the analysis, subjects from Synflorix I Group and Synflorix II Group have been pooled into a sub-group.
Measure Participants	210	216
31-44 months	43	54
40-48 months	89	74

24. Secondary Outcome

Title	Number of Subjects With New Acquisition of S. Pneumoniae (Vaccine Serotypes) in Nasopharyngeal Swabs
Description	The number of subjects with new acquisition of S. pneumoniae (Synflorix™ vaccine serotypes) detected in nasopharyngeal swabs was recorded.
Time Frame	At 31-44 months of age and prior to the first vaccine dose, at 40-48 months of age

Outcome Measure Data

Analysis Population Description

The analysis was performed on the ATP cohort for carriage, which included all evaluable subjects for whom carriage outcome measures were available after the swab time point.

Arm/Group Title	Synflorix III Group	Pooled Synflorix I+II Group
Arm/Group Description	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.	For the purpose of the analysis, subjects from Synflorix I Group and Synflorix II Group have been pooled into a sub-group.
Measure Participants	210	216
31-44 months	39 34.8%	20 18.5%
40-48 months	41 36.6%	18 16.7%

25. Secondary Outcome

Title	Number of Subjects With New Acquisition of S. Pneumoniae (Cross-reactive Serotypes) in Nasopharyngeal Swabs
Description	The number of subjects with new acquisition of S. pneumoniae (cross-reactive serotypes) detected in nasopharyngeal swabs was recorded.
Time Frame	At 31-44 months of age and prior to the first vaccine dose, at 40-48 months of age

Outcome Measure Data

Analysis Population Description

The analysis was performed on the ATP cohort for carriage, which included all evaluable subjects for whom carriage outcome measures were available after the swab time point.

Arm/Group Title	Synflorix III Group	Pooled Synflorix I+II Group
Arm/Group Description	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.	For the purpose of the analysis, subjects from Synflorix I Group and Synflorix II Group have been pooled into a sub-group.
Measure Participants	210	216
31-44 months	9 8%	13 12%
40-48 months	18 16.1%	18 16.7%

26. Secondary Outcome

Title	Number of Subjects With New Acquisition of S. Pneumoniae (Non-vaccine and Non-cross-reactive Serotypes) in Nasopharyngeal Swabs
Description	The number of subjects with new acquisition of S. pneumoniae (non-vaccine and non-cross-reactive serotypes) detected in nasopharyngeal swabs was recorded.
Time Frame	At 31-44 months of age and prior to the first vaccine dose, at 40-48 months of age

Outcome Measure Data

Analysis Population Description

The analysis was performed on the ATP cohort for carriage, which included all evaluable subjects for whom carriage outcome measures were available after the swab time point.

Arm/Group Title	Synflorix III Group	Pooled Synflorix I+II Group
Arm/Group Description	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.	For the purpose of the analysis, subjects from Synflorix I Group and Synflorix II Group have been pooled into a sub-group.
Measure Participants	210	216
31-44 months	24 21.4%	32 29.6%
40-48 months	25 22.3%	33 30.6%

27. Secondary Outcome

Title	Number of Subjects With New Acquisition of H. Influenzae in Nasopharyngeal Swabs
Description	The number of subjects with new acquisition of H. influenzae detected in nasopharyngeal swabs was recorded.
Time Frame	At 31-44 months of age and prior to the first vaccine dose, at 40-48 months of age

Outcome Measure Data

Analysis Population Description

The analysis was performed on the ATP cohort for carriage, which included all evaluable subjects for whom carriage outcome measures were available after the swab time point.

Arm/Group Title	Synflorix III Group	Pooled Synflorix I+II Group
Arm/Group Description	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.	For the purpose of the analysis, subjects from Synflorix I Group and Synflorix II Group have been pooled into a sub-group.
Measure Participants	210	216
31-44 months	35 31.3%	49 45.4%
40-48 months	70 62.5%	50 46.3%

Adverse Events

Time Frame	Solicited symptoms: during the 4-day (Days 0-3) follow-up periods after vaccination. Unsolicited AEs: within the 31-day (Days 0-30) follow-up periods after vaccination. SAEs: during the entire study period (from Day 0 up to Month 10/12).
Arm/Group Title	Synflorix I Group		Synflorix II Group		Synflorix III Group
Arm/Group Description	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.		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.		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.
All Cause Mortality
	Synflorix I Group		Synflorix II Group		Synflorix III Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/112 (0%)		0/108 (0%)		0/223 (0%)
Serious Adverse Events
	Synflorix I Group		Synflorix II Group		Synflorix III Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/112 (0%)		0/108 (0%)		0/223 (0%)
Other (Not Including Serious) Adverse Events
	Synflorix I Group		Synflorix II Group		Synflorix III Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	96/112 (85.7%)		86/108 (79.6%)		190/223 (85.2%)
General disorders
Pain	75/112 (67%)		67/108 (62%)		167/223 (74.9%)
Redness	58/112 (51.8%)		60/108 (55.6%)		127/223 (57%)
Swelling	43/112 (38.4%)		41/108 (38%)		101/223 (45.3%)
Drowsiness	41/112 (36.6%)		34/108 (31.5%)		102/223 (45.7%)
Irritability	33/112 (29.5%)		26/108 (24.1%)		98/223 (43.9%)
Loss of appetite	23/112 (20.5%)		15/108 (13.9%)		61/223 (27.4%)
Fever/(Axillary)	12/112 (10.7%)		8/108 (7.4%)		30/223 (13.5%)

Limitations/Caveats

[Not Specified]

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Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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.