Immunogenicity and Safety Study of GlaxoSmithKline (GSK) Biologicals' 10-valent Pneumococcal Conjugate Vaccine

Anti-pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F antibody concentrations were assessed by 22F-inhibition Enzyme-Linked Immuno-Sorbent Assay (ELISA) method. The \>=0.20 microgram per milliliter (microg/mL) cut-off corresponded to the seroprotection cut-off as regards anti-pneumococcal serotypes antibody concentrations. Seropositivity status, defined as anti-pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F antibody concentrations ≥ 0.05 microg/mL.

Time frame: At one month after primary (Synflorix <6M & Synflorix 7-11M Groups) or after the full (Synflorix 12-23M & Synflorix >=24M Groups) vaccination course with Synflorix™, that is Month (M)3 for Synflorix <6M & 12-23M groups, M2 for Synflorix 7-11M Group, & M1

Population: The analysis was performed on the Primary According-To-Protocol cohort for immunogenicity,which included all evaluable subjects with immunogenicity data available.This included subjects with assay results available for antibodies against at least one study vaccine antigen component and at least one bloodsampling time point after primary vaccination

Antibodies assessed for this outcome measure were those against the vaccine pneumococcal serotypes 6A, 19A (ANTI-6A, -19A). Antibody concentrations were measured by 22F enzyme-linked immunosorbent assay (ELISA), expressed as geometric mean concentrations (GMCs), in micrograms per milliliter (µg/mL).Seropositivity = Anti-pneumococcal cross-reactive serotypes 6A and 19A antibody concentrations ≥ 0.05 μg/mL.

Time frame: Before and one month after the booster dose with Synflorix™ for the < 6 months and 7-11 months groups

Population: The analysis was performed on the Booster According-To-Protocol(ATP) cohort for immunogenicity,which included all evaluable subjects with immunogenicity data available(subjects from the Synflorix \<6M \& 7-11M groups for whom assay results were available for antibodies against at least one study vaccine antigen component after the booster vaccination

Antibodies assessed for this outcome measure were those against the vaccine pneumococcal serotypes 6A, 19A (ANTI-6A, -19A). Antibody concentrations were measured by 22F enzyme-linked immunosorbent assay (ELISA), expressed as geometric mean concentrations (GMCs), in micrograms per milliliter (µg/mL). Seropositivity = Anti-pneumococcal cross-reactive serotypes 6A and 19A antibody concentrations ≥ 0.05 µg/mL.

Time frame: At 1 month after the administration of the primary (< 6 months and 7-11 months groups) or the full (12-23 months and >= 24 months groups) vaccination course, with Synflorix™ vaccine.

Population: The analysis was performed on the Primary According-To-Protocol cohort for immunogenicity,which included all evaluable subjects with immunogenicity data available.This included subjects with assay results available for antibodies against at least one study vaccine antigen component and at least one bloodsampling time point after primary vaccination

Antibodies assessed for this outcome measure were those against the vaccine 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). Antibody concentrations were measured by 22F enzyme-linked immunosorbent assay (ELISA), expressed as geometric mean concentrations (GMCs), in micrograms per milliliter (µg/mL). Seropositivity = Anti-pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F antibody concentrations ≥0.05 µg/mL.

Time frame: At 1 month after the administration of the primary (< 6 months and 7-11 months groups) or the full (12-23 months and >= 24 months groups) vaccination course, with Synflorix™ vaccine.

Population: The analysis was performed on the Primary According-To-Protocol cohort for immunogenicity,which included all evaluable subjects with immunogenicity data available.This included subjects with assay results available for antibodies against at least one study vaccine antigen component and at least one bloodsampling time point after primary vaccination

Anti-protein D (Anti-PD) antibody concentrations by Enzyme-Linked Immunosorbent Assay (ELISA) were calculated, expressed as geometric mean concentrations (GMCs) in ELISA unit per milli-liter (EL.U/mL) and tabulated. Seropositivity = Anti-PD antibody concentrations \>= 100 EL.U/mL. Antibody concentrations \< 100 EL.U/mL were given an arbitrary value of half the cut-off for the purpose of GMC calculation.

Time frame: At 1 month after the administration of the primary (< 6 months and 7-11 months groups) or the full (12-23 months and >= 24 months groups) vaccination course, with Synflorix™ vaccine.

Population: The analysis was performed on the Primary According-To-Protocol cohort for immunogenicity,which included all evaluable subjects with immunogenicity data available.This included subjects with assay results available for antibodies against at least one study vaccine antigen component and at least one bloodsampling time point after primary vaccination

Anti-protein D (Anti-PD) antibody concentrations by Enzyme-Linked Immunosorbent Assay (ELISA) were calculated, expressed as geometric mean concentrations (GMCs) in ELISA unit per milli-liter (EL.U/mL) and tabulated. Seropositivity = Anti-PD antibody concentrations \>= 100 EL.U/mL. Antibody concentrations \< 100 EL.U/mL were given an arbitrary value of half the cut-off for the purpose of GMC calculation.

Time frame: Before and one month after the booster dose with Synflorix™ for the < 6 months and 7-11 months groups

Population: The analysis was performed on the Booster According-To-Protocol(ATP) cohort for immunogenicity,which included all evaluable subjects with immunogenicity data available(subjects from the Synflorix \<6M \& 7-11M groups for whom assay results were available for antibodies against at least one study vaccine antigen component after the booster vaccination

Concentrations of antibodies are presented as geometric mean concentrations expressed as International units per milliliter (IU/mL). Seroprotection status, defined as: Anti-D & anti-T antibody concentrations \>= 0.1 IU/mL.. Since only Synflorix \<6M Group had received DTPa-IPV/Hib, therefore only that group was assessed for this Outcome.

Time frame: Before (M9 = PRE-BST) and one month after the booster dose (M10 = POST-BST) with Infanrix™ IPV/Hib vaccine when co-administered with Synflorix™, for the < 6 months Group.

Population: The analysis was performed on the Booster ATP cohort for immunogenicity, which included all evaluable subjects (from Synflorix \<6M \& 7-11M groups) for whom assay results were available for at least one study vaccine antigen after the booster vaccination. Only Synflorix \<6M Group received DTPa-IPV/Hib, only that group was assessed for this Outcome.

Concentrations of antibodies are presented as geometric mean concentrations expressed as International units per milliliter (IU/mL). Seroprotection status, defined as: Anti-D & anti-T antibody concentrations \>=0.1 IU/mL. Since only Synflorix \<6M Group had received DTPa-IPV/Hib, therefore only that group was assessed for this Outcome.

Time frame: At 1 month after the administration of the primary vaccination course (Month [M]3 = POST-PRY) with Infanrix™ IPV/Hib vaccine when co-administered with Synflorix™, for the < 6 months Group.

Population: The analysis was performed on the Primary ATP cohort for immunogenicity, which included all evaluable subjects with immunogenicity data available for at least one study vaccine antigen component and at least one time point after primary vaccination. Only Synflorix \<6M Group received DTPa-IPV/Hib, thus only that group was assessed for this Outcome.

Concentrations of antibodies are presented as geometric mean concentrations expressed as enzyme-linked immunosorbent assay (ELISA) unit per milliliter (EL.U/mL). Seropositivity status, defined as: Anti-PT, anti-FHA & anti-PRN antibody concentrations \>=5 EL.U/mL. Since only Synflorix \<6M Group had received DTPa-IPV/Hib, therefore only that group was assessed for this Outcome.

Time frame: Before (M9 = PRE-BST) and one month after the booster dose (M10 = POST-BST) with Infanrix™ IPV/Hib vaccine when co-administered with Synflorix™, for the < 6 months Group.

Population: The analysis was performed on the Booster ATP cohort for immunogenicity, which included all evaluable subjects (from Synflorix \<6M \& 7-11M groups) for whom assay results were available for at least one study vaccine antigen after the booster vaccination. Only Synflorix \<6M Group received DTPa-IPV/Hib, only that group was assessed for this Outcome.

Concentrations of antibodies are presented as geometric mean concentrations expressed as enzyme-linked immunosorbent assay (ELISA) unit per milliliter (EL.U/mL). Seropositivity status, defined as: Anti-PT, anti-FHA & anti-PRN antibody concentrations \>= 5 EL.U/mL. Since only Synflorix \<6M Group had received DTPa-IPV/Hib, therefore only that group was assessed for this Outcome.

Time frame: At 1 month after the administration of the primary vaccination course(Month [M]3 = POST-PRY) with Infanrix™ IPV/Hib vaccine when co-administered with Synflorix™, for the < 6 months Group

Population: The analysis was performed on the Primary ATP cohort for immunogenicity, which included all evaluable subjects with immunogenicity data available for at least one study vaccine antigen component and at least one time point after primary vaccination. Only Synflorix \<6M Group received DTPa-IPV/Hib, thus only that group was assessed for this Outcome.

Anti-pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F antibody concentrations were assessed by 22F-inhibition Enzyme-Linked Immuno-Sorbent Assay (ELISA) method. The \>=0.20 microgram per millilitre (microg/mL) cut-off corresponded to the seroprotection cut-off as regards anti-pneumococcal serotypes antibody concentrations. Seropositivity = Anti-pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F antibody concentrations ≥0.05 µg/mL.

Time frame: Before and one month after the booster dose with Synflorix™ for the < 6 months and 7-11 months groups

Population: The analysis was performed on the Booster According-To-Protocol(ATP) cohort for immunogenicity,which included all evaluable subjects with immunogenicity data available(subjects from the Synflorix \<6M \& 7-11M groups for whom assay results were available for antibodies against at least one study vaccine antigen component after the booster vaccination

Anti-pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F antibody concentrations were assessed by 22F-inhibition Enzyme-Linked Immuno-Sorbent Assay (ELISA) method. The \>=0.20 microgram per millilitre (microg/mL) cut-off corresponded to the seroprotection cut-off as regards anti-pneumococcal serotypes antibody concentrations. Seropositivity status, defined as Anti-pneumococcal serotypes antibody concentrations \>=0.05 µg/mL.

Time frame: Before and one month after the booster dose with Synflorix™ for the < 6 months and 7-11 months groups

Population: The analysis was performed on the Booster According-To-Protocol(ATP) cohort for immunogenicity,which included all evaluable subjects with immunogenicity data available(subjects from the Synflorix \<6M \& 7-11M groups for whom assay results were available for antibodies against at least one study vaccine antigen component after the booster vaccination

Titers of antibodies are presented as geometric mean titers. Seroprotection status, defined as: Anti-polio type 1/2/3 titers \>= 8.

Time frame: At 1 month after the administration of the primary vaccination course (Month [M]3 = POST-PRY) with Infanrix™ IPV/Hib vaccine when co-administered with Synflorix™, for the < 6 months Group.

Population: The analysis was performed on the Primary ATP cohort for immunogenicity, which included all evaluable subjects with immunogenicity data available for at least one study vaccine antigen component and at least one time point after primary vaccination. Only Synflorix \<6M Group received DTPa-IPV/Hib, thus only that group was assessed for this Outcome.

Concentrations of antibodies are presented as geometric mean concentrations expressed as micrograms per milliliter (µg/mL). Seroprotection status, defined as: anti-PRP antibody concentrations \>= 0.15 µg/mL and \>= 1.0 µg/mL. Since only Synflorix \<6M Group had received DTPa-IPV/Hib, therefore only that group was assessed for this Outcome.

Time frame: Before (M9 = PRE-BST) and one month after the booster dose (M10 = POST-BST) with Infanrix™ IPV/Hib vaccine when co-administered with Synflorix™, for the < 6 months Group.

Population: The analysis was performed on the Booster ATP cohort for immunogenicity, which included all evaluable subjects (from Synflorix \<6M \& 7-11M groups) for whom assay results were available for at least one study vaccine antigen after the booster vaccination. Only Synflorix \<6M Group received DTPa-IPV/Hib, only that group was assessed for this Outcome.

Concentrations of antibodies are presented as geometric mean concentrations expressed as micrograms per milliliter (µg/mL). Seroprotection status, defined as: anti-PRP antibody concentrations \>=0.15 µg/mL and \>= 1.0 µg/mL. Since only Synflorix \<6M Group had received DTPa-IPV/Hib, therefore only that group was assessed for this Outcome.

Time frame: At 1 month after the administration of the primary vaccination course (Month [M]3 = POST-PRY) with Infanrix™ IPV/Hib vaccine when co-administered with Synflorix™, for the < 6 months Group

Population: The analysis was performed on the Primary ATP cohort for immunogenicity, which included all evaluable subjects with immunogenicity data available for at least one study vaccine antigen component and at least one time point after primary vaccination. Only Synflorix \<6M Group received DTPa-IPV/Hib, thus only that group was assessed for this Outcome.

Booster vaccine response to PT, FHA and PRN, defined as appearance of antibodies in subjects who were seronegative (S-) prior to the booster dose (i.e., with concentrations \< 5 EL.U/mL), and at least two-fold increase of pre-booster vaccination antibody concentrations in those who were seropositive (S+) prior to the booster dose (i.e., with concentrations \>= 5 EL.U/ mL). Since only Synflorix \<6M Group had received DTPa-IPV/Hib, therefore only that group was assessed for this Outcome.

Time frame: Before and one month after the booster dose with Synflorix™

Population: The analysis was performed on the Booster ATP cohort for immunogenicity, which included all evaluable subjects (from Synflorix \<6M \& 7-11M groups) for whom assay results were available for at least one study vaccine antigen after the booster vaccination. Only Synflorix \<6M Group received DTPa-IPV/Hib, only that group was assessed for this Outcome.

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 3 doses (D1, D2 and D3) of the Synflorix™ vaccine co-administered with Infranrix™ in the \<6 months priming group; across the 2 doses of the Synflorix™ vaccine in the 7-11 months priming group; across the 2 doses of the Synflorix™ vaccine in the 12-23 months priming group and in the 1 dose of Synflorix™ vaccine in the ≥24 months priming group.

Time frame: Within 4-day (Days 0-3) following the primary vaccination

Population: The analysis was performed on the Primary Total Vaccinated cohort, which included all vaccinated subjects (e.g. all subjects who received at least one primary 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 booster vaccination course

Population: The analysis was performed on the Booster Total Vaccinated, which cohort included all subjects from the Synflorix \<6M \& Synflorix 7-11M groups, who received 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 course up until start of Booster vaccination course

Population: The analysis was performed on the Primary Total Vaccinated cohort, which included all vaccinated subjects (e.g. all subjects who received at least one primary dose).

Assessed solicited general symptoms were Drowsiness, Irritability, 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. 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.

Time frame: Within 4 day (Days 0-3) following the booster vacination

Population: The analysis was performed on the Booster Total Vaccinated, which cohort included all subjects from the Synflorix \<6M \& Synflorix 7-11M groups months groups, who received the booster dose.

Assessed solicited general symptoms were Drowsiness, Irritability, 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. 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 3 doses (D1, D2 and D3) of the Synflorix™ vaccine co-administered with Infranrix™ in the \<6 months priming group; across the 2 doses of the Synflorix™ vaccine in the 7-11 months priming group; across the 2 doses of the Synflorix™ vaccine in the 12-23 months priming group and in the 1 dose of Synflorix™ vaccine in the ≥24 months priming group.

Time frame: Within 4-day (Days 0-3) following the primary vaccination

Population: The analysis was performed on the Primary Total Vaccinated cohort, which included all vaccinated subjects (e.g. all subjects who received at least one primary dose).

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).

Time frame: Within 4-day (Days 0-3) following the booster vaccination

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 31 day (Days 0-30) following the booster vaccination

Population: The analysis was performed on the Booster Total Vaccinated, which cohort included all subjects from the Synflorix \<6M \& Synflorix 7-11M groups months groups, who received 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 31-day (Days 0-30) post primary vaccination

Population: The analysis was performed on the Primary Total Vaccinated cohort, which included all vaccinated subjects (e.g. all subjects who received at least one primary dose).

OPA titers against pneumococcal serotypes 6A, 19A (Opsono-6A, 19A) were calculated, expressed as geometric mean titers (GMTs) and tabulated. Opsonophagocytic activity against cross-reactive pneumococcal serotypes 6A and 19A \>= 8. Antibody titers \< 8 were given an arbitrary value of half the cut-off for the purpose of GMT calculation.

Time frame: Before and one month after the booster dose with Synflorix™ for the < 6 months and 7-11 months groups

Population: The analysis was performed on the Booster According-To-Protocol(ATP) cohort for immunogenicity,which included all evaluable subjects with immunogenicity data available(subjects from the Synflorix \<6M \& 7-11M groups for whom assay results were available for antibodies against at least one study vaccine antigen component after the booster vaccination

OPA titers against pneumococcal serotypes 6A, 19A (Opsono-6A, 19A) were calculated, expressed as geometric mean titers (GMTs) and tabulated. Opsonophagocytic activity against cross-reactive pneumococcal serotypes 6A and 19A \>= 8. Antibody titers \< 8 were given an arbitrary value of half the cut-off for the purpose of GMT calculation.

Time frame: At 1 month after the administration of the primary (< 6 months and 7-11 months groups) or the full (12-23 months and >= 24 months groups) vaccination course, with Synflorix™ vaccine.

Population: The analysis was performed on the Primary According-To-Protocol cohort for immunogenicity,which included all evaluable subjects with immunogenicity data available.This included subjects with assay results available for antibodies against at least one study vaccine antigen component and at least one bloodsampling time point after primary vaccination

OPA titers against pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F (Opsono-1, -4, -5, -6B, -7F, -9V, -14, -18C, -19F and -23F) were calculated, expressed as geometric mean titers (GMTs) and tabulated. Seropositivity status, defined as Opsonophagocytic activity against pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F \>= 8. Antibody titers \< 8 were given an arbitrary value of half the cut-off for the purpose of GMT calculation.

Time frame: Before and one month after the booster dose with Synflorix™ for the < 6 months and 7-11 months groups

Population: The analysis was performed on the Booster According-To-Protocol(ATP) cohort for immunogenicity,which included all evaluable subjects with immunogenicity data available(subjects from the Synflorix \<6M \& 7-11M groups for whom assay results were available for antibodies against at least one study vaccine antigen component after the booster vaccination

OPA titers against pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F (Opsono-1, -4, -5, -6B, -7F, -9V, -14, -18C, -19F and -23F) were calculated, expressed as geometric mean titers (GMTs) and tabulated. Seropositivity = Opsonophagocytic activity against pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F \>= 8. Antibody titers \< 8 were given an arbitrary value of half the cut-off for the purpose of GMT calculation.

Time frame: At 1 month after the administration of the primary (< 6 months and 7-11 months groups) or the full (12-23 months and >= 24 months groups) vaccination course, with Synflorix™ vaccine.

Population: The analysis was performed on the Primary According-To-Protocol cohort for immunogenicity,which included all evaluable subjects with immunogenicity data available.This included subjects with assay results available for antibodies against at least one study vaccine antigen component and at least one bloodsampling time point after primary vaccination

Titers of antibodies are presented as geometric mean titers. Seroprotection status, defined as: Anti-polio type 1/2/3 titers \>= 8. Since only Synflorix \<6M Group had received DTPa-IPV/Hib, therefore only that group was assessed for this Outcome.

Time frame: Before (M9 = PRE-BST) and one month after the booster dose (M10 = POST-BST) with Infanrix™ IPV/Hib vaccine when co-administered with Synflorix™, for the < 6 months Group.

Population: The analysis was performed on the Booster ATP cohort for immunogenicity, which included all evaluable subjects (from Synflorix \<6M \& 7-11M groups) for whom assay results were available for at least one study vaccine antigen after the booster vaccination. Only Synflorix \<6M Group received DTPa-IPV/Hib, only that group was assessed for this Outcome.