Safety & Immunogenicity Study of 10-Valent Pneumococcal Conjugate Vaccine When Administered as a 2-Dose Schedule

A seroprotected subject was defined as a subject who had anti-pneumococcal serotypes antibody concentrations greater than or equal to (≥) the threshold value of 0.20 micrograms per milliliter (μg/mL). 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 enzyme-linked immunosorbent assay (ELISA), expressed as geometric mean concentrations (GMCs). The results presented for the Group 1 correspond to the primary outcome.

Time frame: One month post-dose 2 (Month 3) administration of Synflorix™ vaccine

Population: The analysis was performed on the According-to-Protocol (ATP) cohort for immunogenicity, which included all evaluable subjects for whom immunogenicity concerning data were available.

Concentrations of antibodies are presented as geometric mean concentrations, expressed as international units per milliliter (IU/mL). Seroprotection status was defined as anti-diphteria and anti-tetanus toxoid antibody concentrations greater than or equal to (≥) the value of 0.1 IU/mL. This outcome concerns results for the Primary and Booster Phases of the study.

Time frame: One month post-dose 2 (Month 3) administration, one month before (Month 9) and one month after (Month 10) the booster dose of Synflorix™ vaccine

Population: The analysis was performed on the ATP cohort for immunogenicity, which included all evaluable subjects for whom immunogenicity concerning data were available.

Concentrations of antibodies are presented as geometric mean concentrations, expressed as milli international units per milliliter (mIU/mL). Seroprotection status was defined as anti-hepatitis B surface antigen (anti-HBs) antibody concentrations greater than or equal to (≥) the cut-off value of 10 mIU/mL. This outcome concerns results for the Primary and Booster Phases of the study and included only the subset of subjects who received Infanrix Hexa™ as the co-administered vaccine.

Time frame: One month post-dose 2 (Month 3) administration, one month before (Month 9) and one month after (Month 10) the booster dose of Synflorix™ vaccine

Population: The analysis was performed on the ATP cohort for immunogenicity, which included all evaluable subjects for whom immunogenicity concerning data were available.

Concentrations of antibodies are presented as geometric mean concentrations, expressed as enzyme-linked immunosorbent assay (ELISA) units per milliliter (EL.U/mL). Seropositivity status was defined as anti-pertussis toxoid (Anti-PT), anti-filamentous haemagglutinin (Anti-FHA) and anti-pertactin (Anti-PRN) antibody concentrations greater than or equal to (≥) the cut-off value of 5 EL.U/mL. This outcome concerns results for the Primary and Booster Phases of the study.

Time frame: One month post-dose 2 (Month 3) administration, one month before (Month 9) and after (Month 10) the booster dose of Synflorix™ vaccine

Population: The analysis was performed on the ATP cohort for immunogenicity, which included all evaluable subjects for whom immunogenicity concerning data were available.

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 enzyme-linked immunosorbent assay (ELISA), expressed as geometric mean concentrations (GMCs), in micrograms per milliliter (μg/mL). The seropositivity cut-off of the assay was an antibody concentration ≥ 0.05 μg/mL. This outcome concerns results for the Primary and Booster Phases of the study.

Time frame: One month post-dose 2 or post-dose 3 (Month 3) administration, one month before (Month 9) and one month after (Month 10) the booster dose of Synflorix™ vaccine

Population: The analysis was performed on the ATP cohort for immunogenicity, which included all evaluable subjects for whom immunogenicity concerning data were available.

Concentrations of antibodies are presented as geometric mean concentrations, expressed as micrograms per milliliter (μg/mL). Seroprotection status was defined as anti-polyribosyl ribitol phosphate (Anti-PRP) antibody concentrations greater than or equal to (≥) the cut-off values of 0.15 μg/mL and ≥ 1.0 μg/mL. This outcome concerns results for the Primary and Booster Phases of the study.

Time frame: One month post-dose 2 (Month 3) administration, one month before (Month 9) and one month after (Month 10) booster dose of Synflorix™ vaccine

Population: The analysis was performed on the ATP cohort for immunogenicity, which included all evaluable subjects for whom immunogenicity concerning data were available.

Anti-protein D concentrations are expressed as geometric mean concentrations (GMCs), in enzyme-linked immunosorbent assay (ELISA) units per milliliter (EL.U/mL).Seropositivity status was defined as Anti-PD antibody concentrations greater than or equal to (≥) the value of 100 EL.U/mL. This outcome concerns results for the Primary and Booster Phases of the study.

Time frame: One month post-dose 2 or post-dose 3 (Month 3) administration, one month before (Month 9) and one month after (Month 10) the booster dose of Synflorix™ vaccine

Population: The analysis was performed on the ATP cohort for immunogenicity, which included all evaluable subjects for whom immunogenicity concerning data were available.

Titers of antibodies are presented as geometric mean titers. Seroprotection status was defined as anti-polio types 1, 2 and 3 (Anti-polio 1, 2 and 3) antibody titers greater than or equal to (≥) the value of 8. This outcome concerns results for the Primary and Booster Phases of the study and included only the subset of subjects who received Infanrix Hexa™ as the co-administered vaccine.

Time frame: One month post-dose 2 (Month 3) administration, one month before (Month 9) and one month after (Month 10) the booster dose of Synflorix™ vaccine

Population: The analysis was performed on the ATP cohort for immunogenicity, which included all evaluable subjects for whom immunogenicity concerning data were available.

A seroprotected subject was defined as a subject who had anti-pneumococcal serotypes antibody concentrations greater than or equal to (≥) the threshold value of 0.20 micrograms per milliliter (μg/mL). 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 enzyme-linked immunosorbent assay (ELISA), expressed as geometric mean concentrations (GMCs).

Time frame: One month before (Month 9) and one month after (Month 10) the booster dose of Synflorix™ vaccine

Population: The analysis was performed on the ATP cohort for immunogenicity, which included all evaluable subjects for whom immunogenicity concerning data were available.

Assessed local symptoms were pain, redness and swelling. Any = Occurrence of the specified solicited local symptom, regardless of intensity. Grade 3 Pain = Crying when limb was moved/spontaneously painful. Grade 3 Redness/Swelling = Redness/swelling at injection site larger than (\>) 30 millimeters (mm). Across doses= across the 2 doses of the Synflorix™ vaccine in the Synflorix I group and across the 3 doses of the Synflorix™ vaccine in the Synflorix II group.

Time frame: During the 4-day (Days 0-3) period following the primary vaccination (across doses) and during the 4-day (Days 0-3) period following the booster vaccination (post Booster) with the Synflorix™ vaccine

Population: The analysis was performed on the Total Vaccinated Cohort, which included all vaccinated subjects (i.e. who had received at least one dose of study vaccine during the primary vaccination course or the booster dose).

Booster vaccine response to pertussis toxoid (PT), filamentous haemagglutinin (FHA) and pertactin (PRN), defined as the appearance of antibodies in subjects who were seronegative (Pre-booster status S-) (i.e., with antibody concentrations \< 5 EL.U/mL) just before booster dose, and at least two-fold increase of pre-vaccination antibody concentrations in those who were seropositive (Pre-booster status S+) (i.e., with antibody concentrations ≥ 5 EL.U/mL) just before booster dose.

Time frame: One month after (Month 9) the administration of the booster dose of Synflorix™ vaccine

Population: The analysis was performed on the ATP cohort for immunogenicity, which included all evaluable subjects for whom immunogenicity concerning data were available.

A SAE was defined as any medical occurrence that resulted in death, was life-threatening, required hospitalization or prolongation of hospitalization, resulted in disability/incapacity in a subject. AE(s) considered as SAE(s) also included invasive or malignant cancers, intensive treatment in an emergency room or at home for allergic bronchospasm, blood dyscrasias or convulsions that did not result in hospitalisation, as per the medical or scientific judgement of the physician. Any = Occurrence of a SAE, regardless of relationship to vaccination.

Time frame: During the booster vaccination period

Population: The analysis was performed on the Total Vaccinated Cohort, which included all vaccinated subjects (i.e. who had received at least one dose of study vaccine during the primary vaccination course or the booster dose).

A SAE was defined as any medical occurrence that resulted in death, was life-threatening, required hospitalization or prolongation of hospitalization, resulted in disability/incapacity in a subject. AE(s) considered as SAE(s) also included invasive or malignant cancers, intensive treatment in an emergency room or at home for allergic bronchospasm, blood dyscrasias or convulsions that did not result in hospitalisation, as per the medical or scientific judgement of the physician. Any = Occurrence of a SAE, regardless of relationship to vaccination.

Time frame: During the primary vaccination period

Population: The analysis was performed on the Total Vaccinated Cohort, which included all vaccinated subjects (i.e. who had received at least one dose of study vaccine during the primary vaccination course or the booster dose).

Assessed solicited general symptoms were drowsiness, irritability/fussiness (Irr./Fuss.), loss of appetite (Loss Appet.) and fever (rectal temperature higher than \[≥\] 38.0 degrees Celsius \[°C\]). Any = Occurrence of the specified solicited general symptom, regardless of intensity or relationship to vaccination. Related = Occurrence of the specified symptom assessed by the investigators as causally related to vaccination. Grade 3 Drowsiness = Drowsiness that prevented normal activity. Grade 3 Irr./Fuss. = Crying that could not be comforted/prevented normal activity. Grade 3 Loss of appetite = Subject did not eat at all. Grade 3 Fever = Rectal temperature higher than (\>) 40.0°C. Across doses= across the 2 doses of the Synflorix™ vaccine in the Synflorix I group and across the 3 doses of the Synflorix™ vaccine in the Synflorix II group.

Time frame: During the 4-day (Days 0-3) period following the primary vaccination (across doses) and during the 4-day (Days 0-3) period following the booster vaccination (post Booster) with the Synflorix™ vaccine

Population: The analysis was performed on the Total Vaccinated Cohort, which included all vaccinated subjects (i.e. who had received at least one dose of study vaccine during the primary vaccination course or the booster dose).

An unsolicited AE was defined as 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. An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. For the marketed products administered in the study, this also included failure to produce expected benefits (i.e. lack of efficacy), abuse or misuse of the product. Any = Occurrence of an unsolicited AE, regardless of intensity or relationship to vaccination.

Time frame: Within the 31-day (Days 0-30) post-primary vaccination period, across doses

Population: The analysis was performed on the Total Vaccinated Cohort, which included all vaccinated subjects (i.e. who had received at least one dose of study vaccine during the primary vaccination course or the booster dose).

An unsolicited AE was defined as 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. An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. For the marketed products administered in the study, this also included failure to produce expected benefits (i.e. lack of efficacy), abuse or misuse of the product. Any = Occurrence of an unsolicited AE, regardless of intensity or relationship to vaccination.

Time frame: Within the 31-day (Days 0-30) post booster vaccination period

Population: The analysis was performed on the Total Vaccinated Cohort, which included all vaccinated subjects (i.e. who had received at least one dose of study vaccine during the primary vaccination course or the booster dose).

Seropositivity status was defined as the opsonophacocytic activity against pneumococcal serotypes greater than or egual to (≥) the value of 8. 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).This outcome concerns results for the Primary and Booster Phases of the study.

Time frame: One month post-dose 2 or post-dose 3 (Month 3) administration, one month before (Month 9) and one month after (Month 10) the booster dose of Synflorix™ vaccine

Population: The analysis was performed on the ATP cohort for immunogenicity, which included all evaluable subjects for whom immunogenicity concerning data were available.