Trial Outcomes & Findings for Immunogenicity and Safety Study of GlaxoSmithKline (GSK) Biologicals' Pneumococcal Vaccine (Synflorix™) When Administered to Children Who Are at an Increased Risk of Pneumococcal Infection (NCT NCT01746108)

Results Overview

Antibodies assessed for this outcome measure were those against the vaccine pneumococcal serotypes 1, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F (ANTI-1, -4, -5, -6A, -6B, -7F, -9V, -14, -18C, -19A, -19F and -23F). Antibody concentrations were measured by 22F-inhibition enzyme-linked immunosorbent assay (ELISA), expressed as geometric mean concentrations (GMCs), in micrograms per millilitre (μg/mL). The seropositivity cut-off of the assay was an antibody concentration ≥ 0.05 μg/mL. Antibody concentrations \< 0.05 μg/mL were given an arbitrary value of half the cut-off for the purpose of GMC calculation.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

52 participants

Primary outcome timeframe

One month after Dose 1 (At Month 1)

Results posted on

2019-07-09

Participant Flow

No healthy primed subjects were enrolled in the study.

Participant milestones

Participant milestones
Measure	Synflorix AR-Pr-2-17Y Group Primed (Pr) subjects aged between 24 months and 17 years, who were at an increased risk (AR) of pneumococcal infection\, receiving 1 dose of SynflorixTM vaccine: Primed groups included subjects who have been previously vaccinated with at least one dose of a pneumococcal conjugate vaccine, i.e. either SynflorixTM, PrevenarTM or Prevenar13TM or with plain polysaccharide pneumococcal vaccine more than 2 years (24 months) and less than 5 years (60 months) before enrolment. \An at-risk subject was a subject with Congenital or acquired asplenia such as anatomic, surgical or functional asplenia, or Splenic dysfunction \[some degree of functional asplenia, such as sickle-cell disease and other hemoglobinopathies, Hodgkin disease, rheumatologic diseases, systemic lupus erythematous (SLE), chronic gastrointestinal disorders, liver disease, infiltrative disorders, vascular disorder etc.\] or Complement deficiencies, e.g.C1-C4, C5-C9, properdin factor H or factor D.	Synflorix AR-Un-2-17Y Group Unprimed (Un) subjects aged between 24 months and 17 years, who were at an increased risk (AR) of pneumococcal infection\, receiving 2 doses of SynflorixTM vaccine: Unprimed groups included subjects who have not been previously vaccinated with any pneumococcal vaccine, i.e. either plain polysaccharide pneumococcal vaccine, SynflorixTM, PrevenarTM or Prevenar13TM. \An at-risk subject was a subject with Congenital or acquired asplenia such as anatomic, surgical or functional asplenia, or Splenic dysfunction \[some degree of functional asplenia, such as sickle-cell disease and other hemoglobinopathies, Hodgkin disease, rheumatologic diseases, systemic lupus erythematous (SLE), chronic gastrointestinal disorders, liver disease, infiltrative disorders, vascular disorder etc.\] or Complement deficiencies, e.g.C1-C4, C5-C9, properdin factor H or factor D.	Synflorix HE-Un-2-4Y Group Healthy (HE) unprimed (Un) subjects, aged between 24 and 59 months of age (age-matched to the subjects aged 24-59 months in the At risk groups), receiving 2 doses of SynflorixTM vaccine. Unprimed groups included subjects who have not been previously vaccinated with any pneumococcal vaccine, i.e. either plain polysaccharide pneumococcal vaccine, SynflorixTM, PrevenarTM or Prevenar13TM. For each enrolled at-risk subject aged between 24-59 months, a healthy subject of the same age expressed in years from the same country should be enrolled regardless of the priming status (i.e.: a healthy subject could be enrolled only once if he/she could be matched with an unmatched at-risk subject of the same age and country).
Overall Study STARTED	18	28	6
Overall Study COMPLETED	18	24	6
Overall Study NOT COMPLETED	0	4	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Synflorix AR-Pr-2-17Y Group Primed (Pr) subjects aged between 24 months and 17 years, who were at an increased risk (AR) of pneumococcal infection\, receiving 1 dose of SynflorixTM vaccine: Primed groups included subjects who have been previously vaccinated with at least one dose of a pneumococcal conjugate vaccine, i.e. either SynflorixTM, PrevenarTM or Prevenar13TM or with plain polysaccharide pneumococcal vaccine more than 2 years (24 months) and less than 5 years (60 months) before enrolment. \An at-risk subject was a subject with Congenital or acquired asplenia such as anatomic, surgical or functional asplenia, or Splenic dysfunction \[some degree of functional asplenia, such as sickle-cell disease and other hemoglobinopathies, Hodgkin disease, rheumatologic diseases, systemic lupus erythematous (SLE), chronic gastrointestinal disorders, liver disease, infiltrative disorders, vascular disorder etc.\] or Complement deficiencies, e.g.C1-C4, C5-C9, properdin factor H or factor D.	Synflorix AR-Un-2-17Y Group Unprimed (Un) subjects aged between 24 months and 17 years, who were at an increased risk (AR) of pneumococcal infection\, receiving 2 doses of SynflorixTM vaccine: Unprimed groups included subjects who have not been previously vaccinated with any pneumococcal vaccine, i.e. either plain polysaccharide pneumococcal vaccine, SynflorixTM, PrevenarTM or Prevenar13TM. \An at-risk subject was a subject with Congenital or acquired asplenia such as anatomic, surgical or functional asplenia, or Splenic dysfunction \[some degree of functional asplenia, such as sickle-cell disease and other hemoglobinopathies, Hodgkin disease, rheumatologic diseases, systemic lupus erythematous (SLE), chronic gastrointestinal disorders, liver disease, infiltrative disorders, vascular disorder etc.\] or Complement deficiencies, e.g.C1-C4, C5-C9, properdin factor H or factor D.	Synflorix HE-Un-2-4Y Group Healthy (HE) unprimed (Un) subjects, aged between 24 and 59 months of age (age-matched to the subjects aged 24-59 months in the At risk groups), receiving 2 doses of SynflorixTM vaccine. Unprimed groups included subjects who have not been previously vaccinated with any pneumococcal vaccine, i.e. either plain polysaccharide pneumococcal vaccine, SynflorixTM, PrevenarTM or Prevenar13TM. For each enrolled at-risk subject aged between 24-59 months, a healthy subject of the same age expressed in years from the same country should be enrolled regardless of the priming status (i.e.: a healthy subject could be enrolled only once if he/she could be matched with an unmatched at-risk subject of the same age and country).
Overall Study Migrated /moved from study area	0	1	0
Overall Study Adverse event, non-fatal	0	1	0
Overall Study Withdrawal by Subject	0	1	0
Overall Study Lost to Follow-up	0	1	0

Baseline Characteristics

Immunogenicity and Safety Study of GlaxoSmithKline (GSK) Biologicals' Pneumococcal Vaccine (Synflorix™) When Administered to Children Who Are at an Increased Risk of Pneumococcal Infection

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Synflorix AR-Pr-2-17Y Group n=18 Participants Primed (Pr) subjects aged between 24 months and 17 years, who were at an increased risk (AR) of pneumococcal infection\, receiving 1 dose of SynflorixTM vaccine: Primed groups included subjects who have been previously vaccinated with at least one dose of a pneumococcal conjugate vaccine, i.e. either SynflorixTM, PrevenarTM or Prevenar13TM or with plain polysaccharide pneumococcal vaccine more than 2 years (24 months) and less than 5 years (60 months) before enrolment. \An at-risk subject was a subject with Congenital or acquired asplenia such as anatomic, surgical or functional asplenia, or Splenic dysfunction \[some degree of functional asplenia, such as sickle-cell disease and other hemoglobinopathies, Hodgkin disease, rheumatologic diseases, systemic lupus erythematous (SLE), chronic gastrointestinal disorders, liver disease, infiltrative disorders, vascular disorder etc.\] or Complement deficiencies, e.g.C1-C4, C5-C9, properdin factor H or factor D.	Synflorix AR-Un-2-17Y Group n=28 Participants Unprimed (Un) subjects aged between 24 months and 17 years, who were at an increased risk (AR) of pneumococcal infection\, receiving 2 doses of SynflorixTM vaccine: Unprimed groups included subjects who have not been previously vaccinated with any pneumococcal vaccine, i.e. either plain polysaccharide pneumococcal vaccine, SynflorixTM, PrevenarTM or Prevenar13TM. \An at-risk subject was a subject with Congenital or acquired asplenia such as anatomic, surgical or functional asplenia, or Splenic dysfunction \[some degree of functional asplenia, such as sickle-cell disease and other hemoglobinopathies, Hodgkin disease, rheumatologic diseases, systemic lupus erythematous (SLE), chronic gastrointestinal disorders, liver disease, infiltrative disorders, vascular disorder etc.\] or Complement deficiencies, e.g.C1-C4, C5-C9, properdin factor H or factor D.	Synflorix HE-Un-2-4Y Group n=6 Participants Healthy (HE) unprimed (Un) subjects, aged between 24 and 59 months of age (age-matched to the subjects aged 24-59 months in the At risk groups), receiving 2 doses of SynflorixTM vaccine. Unprimed groups included subjects who have not been previously vaccinated with any pneumococcal vaccine, i.e. either plain polysaccharide pneumococcal vaccine, SynflorixTM, PrevenarTM or Prevenar13TM. For each enrolled at-risk subject aged between 24-59 months, a healthy subject of the same age expressed in years from the same country should be enrolled regardless of the priming status (i.e.: a healthy subject could be enrolled only once if he/she could be matched with an unmatched at-risk subject of the same age and country).	Total n=52 Participants Total of all reporting groups
Age, Continuous	11.3 Years STANDARD_DEVIATION 3.8 • n=5 Participants	8.6 Years STANDARD_DEVIATION 4.2 • n=7 Participants	2.8 Years STANDARD_DEVIATION 0.8 • n=5 Participants	8.87 Years STANDARD_DEVIATION 4.55 • n=4 Participants
Sex: Female, Male Female	10 Participants n=5 Participants	14 Participants n=7 Participants	2 Participants n=5 Participants	26 Participants n=4 Participants
Sex: Female, Male Male	8 Participants n=5 Participants	14 Participants n=7 Participants	4 Participants n=5 Participants	26 Participants n=4 Participants

PRIMARY outcome

Timeframe: One month after Dose 1 (At Month 1)

Population: The analysis was performed on the ATP cohort for immunogenicity, which included all evaluable subjects for whom assay results were available for antibodies against at least one pneumococcal vaccine serotype or protein D for at least one blood sample taken after vaccination.

Antibodies assessed for this outcome measure were those against the vaccine pneumococcal serotypes 1, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F (ANTI-1, -4, -5, -6A, -6B, -7F, -9V, -14, -18C, -19A, -19F and -23F). Antibody concentrations were measured by 22F-inhibition enzyme-linked immunosorbent assay (ELISA), expressed as geometric mean concentrations (GMCs), in micrograms per millilitre (μg/mL). The seropositivity cut-off of the assay was an antibody concentration ≥ 0.05 μg/mL. Antibody concentrations \< 0.05 μg/mL were given an arbitrary value of half the cut-off for the purpose of GMC calculation.

Outcome measures

Outcome measures
Measure	Synflorix AR-Pr-2-17Y Group n=18 Participants Primed (Pr) subjects aged between 24 months and 17 years, who were at an increased risk (AR) of pneumococcal infection\, receiving 1 dose of SynflorixTM vaccine: Primed groups included subjects who have been previously vaccinated with at least one dose of a pneumococcal conjugate vaccine, i.e. either SynflorixTM, PrevenarTM or Prevenar13TM or with plain polysaccharide pneumococcal vaccine more than 2 years (24 months) and less than 5 years (60 months) before enrolment. \An at-risk subject was a subject with Congenital or acquired asplenia such as anatomic, surgical or functional asplenia, or Splenic dysfunction \[some degree of functional asplenia, such as sickle-cell disease and other hemoglobinopathies, Hodgkin disease, rheumatologic diseases, systemic lupus erythematous (SLE), chronic gastrointestinal disorders, liver disease, infiltrative disorders, vascular disorder etc.\] or Complement deficiencies, e.g.C1-C4, C5-C9, properdin factor H or factor D.	Synflorix AR-PR-2-4Y Group Subset of the AR-PR-2-17Y Group including subjects aged between 24 and 59 months.	Synflorix AR-Un-2-4Y Group Subset of the AR-UN-2-17Y Group including subjects aged between 24 and 59 months.
Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes in the At Risk Primed Group. Anti-1 (N=18)	1.94 μg/mL Interval 1.4 to 2.69	—	—
Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes in the At Risk Primed Group. Anti-4 (N=18)	6.16 μg/mL Interval 3.89 to 9.76	—	—
Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes in the At Risk Primed Group. Anti-5 (N=18)	2.44 μg/mL Interval 1.24 to 4.83	—	—
Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes in the At Risk Primed Group. Anti-6B (N=18)	3.66 μg/mL Interval 1.93 to 6.96	—	—
Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes in the At Risk Primed Group. Anti-7F (N=18)	3.34 μg/mL Interval 2.54 to 4.38	—	—
Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes in the At Risk Primed Group. Anti-9V (N=18)	2.87 μg/mL Interval 1.65 to 4.97	—	—
Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes in the At Risk Primed Group. Anti-14 (N=18)	21.08 μg/mL Interval 10.97 to 40.52	—	—
Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes in the At Risk Primed Group. Anti-18C (N=18)	10.84 μg/mL Interval 6.99 to 16.81	—	—
Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes in the At Risk Primed Group. Anti-19F (N=18)	18.22 μg/mL Interval 9.57 to 34.7	—	—
Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes in the At Risk Primed Group. Anti-23F (N=18)	2.24 μg/mL Interval 1.14 to 4.41	—	—
Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes in the At Risk Primed Group. Anti-6A (N=18)	3.76 μg/mL Interval 1.7 to 8.34	—	—
Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes in the At Risk Primed Group. Anti-19A (N=18)	4.44 μg/mL Interval 2.34 to 8.45	—	—

PRIMARY outcome

Timeframe: One month after Dose 1 (At Month 1) and one month after Dose 2 (At Month 3)

Population: The analysis was performed on the ATP cohort for immunogenicity, which included all evaluable subjects for whom assay results were available for antibodies against at least one pneumococcal vaccine serotype or protein D for at least one blood sample taken after vaccination.

Antibodies assessed for this outcome measure were those against the vaccine pneumococcal serotypes 1, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F (ANTI-1, -4, -5, -6A, -6B, -7F, -9V, -14, -18C, -19A, -19F and -23F). Antibody concentrations were measured by 22F-inhibition enzyme-linked immunosorbent assay (ELISA), expressed as geometric mean concentrations (GMCs), in micrograms per millilitre (μg/mL). The seropositivity cut-off of the assay was an antibody concentration ≥ 0.05 μg/mL. Antibody concentrations \< 0.05 μg/mL were given an arbitrary value of half the cut-off for the purpose of GMC calculation.

Outcome measures

Outcome measures
Measure	Synflorix AR-Pr-2-17Y Group n=23 Participants Primed (Pr) subjects aged between 24 months and 17 years, who were at an increased risk (AR) of pneumococcal infection\, receiving 1 dose of SynflorixTM vaccine: Primed groups included subjects who have been previously vaccinated with at least one dose of a pneumococcal conjugate vaccine, i.e. either SynflorixTM, PrevenarTM or Prevenar13TM or with plain polysaccharide pneumococcal vaccine more than 2 years (24 months) and less than 5 years (60 months) before enrolment. \An at-risk subject was a subject with Congenital or acquired asplenia such as anatomic, surgical or functional asplenia, or Splenic dysfunction \[some degree of functional asplenia, such as sickle-cell disease and other hemoglobinopathies, Hodgkin disease, rheumatologic diseases, systemic lupus erythematous (SLE), chronic gastrointestinal disorders, liver disease, infiltrative disorders, vascular disorder etc.\] or Complement deficiencies, e.g.C1-C4, C5-C9, properdin factor H or factor D.	Synflorix AR-PR-2-4Y Group Subset of the AR-PR-2-17Y Group including subjects aged between 24 and 59 months.	Synflorix AR-Un-2-4Y Group Subset of the AR-UN-2-17Y Group including subjects aged between 24 and 59 months.
Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes in the At Risk Un-primed Group. Anti-1 Month 1 (N=23)	1.52 μg/mL Interval 1.13 to 2.06	—	—
Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes in the At Risk Un-primed Group. Anti-1 Month 3 (N=21)	2.52 μg/mL Interval 1.87 to 3.4	—	—
Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes in the At Risk Un-primed Group. Anti-4 Month 1 (N=23)	9.26 μg/mL Interval 6.62 to 12.95	—	—
Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes in the At Risk Un-primed Group. Anti-4 Month 3 (N=21)	7.67 μg/mL Interval 5.59 to 10.53	—	—
Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes in the At Risk Un-primed Group. Anti-5 Month 1 (N=23)	2.74 μg/mL Interval 1.6 to 4.69	—	—
Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes in the At Risk Un-primed Group. Anti-5 Month 3 (N=21)	3.93 μg/mL Interval 2.46 to 6.27	—	—
Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes in the At Risk Un-primed Group. Anti-6B Month 1 (N=23)	1.21 μg/mL Interval 0.59 to 2.46	—	—
Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes in the At Risk Un-primed Group. Anti-6B Month 3 (N=21)	2.19 μg/mL Interval 1.26 to 3.8	—	—
Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes in the At Risk Un-primed Group. Anti-7F Month 1 (N=23)	3.25 μg/mL Interval 2.24 to 4.71	—	—
Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes in the At Risk Un-primed Group. Anti-7F Month 3 (N=21)	5.6 μg/mL Interval 3.95 to 7.93	—	—
Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes in the At Risk Un-primed Group. Anti-9V Month 1 (N=23)	1.89 μg/mL Interval 1.14 to 3.12	—	—
Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes in the At Risk Un-primed Group. Anti-9V Month 3 (N=21)	3.23 μg/mL Interval 2.07 to 5.03	—	—
Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes in the At Risk Un-primed Group. Anti-14 Month 1 (N=23)	7.78 μg/mL Interval 3.86 to 15.68	—	—
Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes in the At Risk Un-primed Group. Anti-14 Month 3 (N=21)	13.64 μg/mL Interval 8.42 to 22.12	—	—
Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes in the At Risk Un-primed Group. Anti-18C Month 1 (N=23)	13.04 μg/mL Interval 8.08 to 21.04	—	—
Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes in the At Risk Un-primed Group. Anti-18C Month 3 (N=21)	24.15 μg/mL Interval 15.4 to 37.86	—	—
Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes in the At Risk Un-primed Group. Anti-19F Month 1 (N=23)	12.41 μg/mL Interval 6.05 to 25.44	—	—
Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes in the At Risk Un-primed Group. Anti-19F Month 3 (N=21)	20.53 μg/mL Interval 11.42 to 36.9	—	—
Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes in the At Risk Un-primed Group. Anti-23F Month 1 (N=23)	1.09 μg/mL Interval 0.5 to 2.4	—	—
Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes in the At Risk Un-primed Group. Anti-23F Month 3 (N=21)	2.26 μg/mL Interval 1.27 to 4.04	—	—
Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes in the At Risk Un-primed Group. Anti-6A Month 1 (N=23)	1.02 μg/mL Interval 0.53 to 1.97	—	—
Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes in the At Risk Un-primed Group. Anti-6A Month 3 (N=21)	1.5 μg/mL Interval 0.87 to 2.58	—	—
Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes in the At Risk Un-primed Group. Anti-19A Month 1 (N=23)	2.18 μg/mL Interval 0.96 to 4.95	—	—
Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes in the At Risk Un-primed Group. Anti-19A Month 3 (N=21)	4.05 μg/mL Interval 1.96 to 8.38	—	—

PRIMARY outcome

Timeframe: One month after Dose 1 (At Month 1)

Population: The analysis was performed on the ATP cohort for immunogenicity, which included all evaluable subjects for whom assay results were available for antibodies against at least one pneumococcal vaccine serotype or protein D for at least one blood sample taken after vaccination.

Pneumococcal vaccine serotypes assessed were 1, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F and were calculated, expressed as geometric mean titers (GMTs). The seropositivity cut-off for the assay was ≥ 8. Antibody titers \< 8 were given an arbitrary value of half the cut-off for the purpose of GMT calculation.

Outcome measures

Outcome measures
Measure	Synflorix AR-Pr-2-17Y Group n=15 Participants Primed (Pr) subjects aged between 24 months and 17 years, who were at an increased risk (AR) of pneumococcal infection\, receiving 1 dose of SynflorixTM vaccine: Primed groups included subjects who have been previously vaccinated with at least one dose of a pneumococcal conjugate vaccine, i.e. either SynflorixTM, PrevenarTM or Prevenar13TM or with plain polysaccharide pneumococcal vaccine more than 2 years (24 months) and less than 5 years (60 months) before enrolment. \An at-risk subject was a subject with Congenital or acquired asplenia such as anatomic, surgical or functional asplenia, or Splenic dysfunction \[some degree of functional asplenia, such as sickle-cell disease and other hemoglobinopathies, Hodgkin disease, rheumatologic diseases, systemic lupus erythematous (SLE), chronic gastrointestinal disorders, liver disease, infiltrative disorders, vascular disorder etc.\] or Complement deficiencies, e.g.C1-C4, C5-C9, properdin factor H or factor D.	Synflorix AR-PR-2-4Y Group Subset of the AR-PR-2-17Y Group including subjects aged between 24 and 59 months.	Synflorix AR-Un-2-4Y Group Subset of the AR-UN-2-17Y Group including subjects aged between 24 and 59 months.
Opsonophagocytic Titers Against Vaccine Pneumococcal Serotypes in the At Risk Primed Group. Opsono-1 (N=14)	12.4 Titers Interval 5.3 to 29.3	—	—
Opsonophagocytic Titers Against Vaccine Pneumococcal Serotypes in the At Risk Primed Group. Opsono-4 (N=15)	1291.6 Titers Interval 722.5 to 2308.9	—	—
Opsonophagocytic Titers Against Vaccine Pneumococcal Serotypes in the At Risk Primed Group. Opsono-5 (N=15)	75.9 Titers Interval 26.9 to 214.2	—	—
Opsonophagocytic Titers Against Vaccine Pneumococcal Serotypes in the At Risk Primed Group. Opsono-6B (N=15)	698.1 Titers Interval 348.8 to 1397.2	—	—
Opsonophagocytic Titers Against Vaccine Pneumococcal Serotypes in the At Risk Primed Group. Opsono-7F (N=15)	2787.4 Titers Interval 1959.9 to 3964.4	—	—
Opsonophagocytic Titers Against Vaccine Pneumococcal Serotypes in the At Risk Primed Group. Opsono-9V (N=15)	1955.3 Titers Interval 1209.8 to 3160.3	—	—
Opsonophagocytic Titers Against Vaccine Pneumococcal Serotypes in the At Risk Primed Group. Opsono-14 (N=15)	2495.7 Titers Interval 1220.6 to 5103.1	—	—
Opsonophagocytic Titers Against Vaccine Pneumococcal Serotypes in the At Risk Primed Group. Opsono-18C (N=15)	4421.4 Titers Interval 2982.8 to 6553.9	—	—
Opsonophagocytic Titers Against Vaccine Pneumococcal Serotypes in the At Risk Primed Group. Opsono-19F (N=15)	3272.4 Titers Interval 1849.4 to 5790.5	—	—
Opsonophagocytic Titers Against Vaccine Pneumococcal Serotypes in the At Risk Primed Group. Opsono-23F (N=15)	613.8 Titers Interval 244.9 to 1538.5	—	—
Opsonophagocytic Titers Against Vaccine Pneumococcal Serotypes in the At Risk Primed Group. Opsono-6A (N=15)	2590.9 Titers Interval 1394.2 to 4814.7	—	—
Opsonophagocytic Titers Against Vaccine Pneumococcal Serotypes in the At Risk Primed Group. Opsono-19A (N=15)	961.2 Titers Interval 376.4 to 2454.8	—	—

PRIMARY outcome

Timeframe: One month after Dose 1 (At Month 1) and one month after Dose 2 (At Month 3)

Population: The analysis was performed on the ATP cohort for immunogenicity, which included all evaluable subjects for whom assay results were available for antibodies against at least one pneumococcal vaccine serotype or protein D for at least one blood sample taken after vaccination.

Pneumococcal vaccine serotypes assessed were 1, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F and were calculated, expressed as geometric mean titers (GMTs). The seropositivity cut-off for the assay was ≥ 8. Antibody titers \< 8 were given an arbitrary value of half the cut-off for the purpose of GMT calculation.

Outcome measures

Outcome measures
Measure	Synflorix AR-Pr-2-17Y Group n=17 Participants Primed (Pr) subjects aged between 24 months and 17 years, who were at an increased risk (AR) of pneumococcal infection\, receiving 1 dose of SynflorixTM vaccine: Primed groups included subjects who have been previously vaccinated with at least one dose of a pneumococcal conjugate vaccine, i.e. either SynflorixTM, PrevenarTM or Prevenar13TM or with plain polysaccharide pneumococcal vaccine more than 2 years (24 months) and less than 5 years (60 months) before enrolment. \An at-risk subject was a subject with Congenital or acquired asplenia such as anatomic, surgical or functional asplenia, or Splenic dysfunction \[some degree of functional asplenia, such as sickle-cell disease and other hemoglobinopathies, Hodgkin disease, rheumatologic diseases, systemic lupus erythematous (SLE), chronic gastrointestinal disorders, liver disease, infiltrative disorders, vascular disorder etc.\] or Complement deficiencies, e.g.C1-C4, C5-C9, properdin factor H or factor D.	Synflorix AR-PR-2-4Y Group Subset of the AR-PR-2-17Y Group including subjects aged between 24 and 59 months.	Synflorix AR-Un-2-4Y Group Subset of the AR-UN-2-17Y Group including subjects aged between 24 and 59 months.
Opsonophagocytic Titers Against Vaccine Pneumococcal Serotypes in the At Risk Un-primed Group. Opsono-1 Month 1 (N=14)	8.6 Titers Interval 4.0 to 18.6	—	—
Opsonophagocytic Titers Against Vaccine Pneumococcal Serotypes in the At Risk Un-primed Group. Opsono-1 Month 3 (N=15)	29.1 Titers Interval 12.1 to 70.1	—	—
Opsonophagocytic Titers Against Vaccine Pneumococcal Serotypes in the At Risk Un-primed Group. Opsono-4 Month 1 (N=17)	1497.1 Titers Interval 696.6 to 3217.4	—	—
Opsonophagocytic Titers Against Vaccine Pneumococcal Serotypes in the At Risk Un-primed Group. Opsono-4 Month 3 (N=16)	2657 Titers Interval 1763.5 to 4003.3	—	—
Opsonophagocytic Titers Against Vaccine Pneumococcal Serotypes in the At Risk Un-primed Group. Opsono-5 Month 1 (N=16)	112.5 Titers Interval 49.1 to 258.0	—	—
Opsonophagocytic Titers Against Vaccine Pneumococcal Serotypes in the At Risk Un-primed Group. Opsono-5 Month 3 (N=16)	212.9 Titers Interval 116.0 to 390.7	—	—
Opsonophagocytic Titers Against Vaccine Pneumococcal Serotypes in the At Risk Un-primed Group. Opsono-6B Month 1 (N=16)	1188.8 Titers Interval 548.7 to 2575.7	—	—
Opsonophagocytic Titers Against Vaccine Pneumococcal Serotypes in the At Risk Un-primed Group. Opsono-6B Month 3 (N=16)	2384.3 Titers Interval 1483.2 to 3832.8	—	—
Opsonophagocytic Titers Against Vaccine Pneumococcal Serotypes in the At Risk Un-primed Group. Opsono-7F Month 1 (N=17)	4433.6 Titers Interval 3110.8 to 6319.0	—	—
Opsonophagocytic Titers Against Vaccine Pneumococcal Serotypes in the At Risk Un-primed Group. Opsono-7F Month 3 (N=16)	6724.3 Titers Interval 4240.9 to 10661.8	—	—
Opsonophagocytic Titers Against Vaccine Pneumococcal Serotypes in the At Risk Un-primed Group. Opsono-9V Month 1 (N=17)	1076.5 Titers Interval 330.8 to 3502.8	—	—
Opsonophagocytic Titers Against Vaccine Pneumococcal Serotypes in the At Risk Un-primed Group. Opsono-9V Month 3 (N=16)	1319.5 Titers Interval 677.2 to 2571.1	—	—
Opsonophagocytic Titers Against Vaccine Pneumococcal Serotypes in the At Risk Un-primed Group. Opsono-14 Month 1 (N=17)	2724.6 Titers Interval 1473.1 to 5039.1	—	—
Opsonophagocytic Titers Against Vaccine Pneumococcal Serotypes in the At Risk Un-primed Group. Opsono-14 Month 3 (N=16)	6590.5 Titers Interval 3329.7 to 13044.6	—	—
Opsonophagocytic Titers Against Vaccine Pneumococcal Serotypes in the At Risk Un-primed Group. Opsono-18C Month 1 (N=17)	8665.8 Titers Interval 5076.4 to 14793.2	—	—
Opsonophagocytic Titers Against Vaccine Pneumococcal Serotypes in the At Risk Un-primed Group. Opsono-18C Month 3 (N=16)	9939.8 Titers Interval 7045.0 to 14024.1	—	—
Opsonophagocytic Titers Against Vaccine Pneumococcal Serotypes in the At Risk Un-primed Group. Opsono-19F Month 1 (N=16)	4569.1 Titers Interval 2695.3 to 7745.5	—	—
Opsonophagocytic Titers Against Vaccine Pneumococcal Serotypes in the At Risk Un-primed Group. Opsono-19F Month 3 (N=16)	3441.8 Titers Interval 1709.8 to 6928.0	—	—
Opsonophagocytic Titers Against Vaccine Pneumococcal Serotypes in the At Risk Un-primed Group. Opsono-23F Month 1 (N=16)	1326.4 Titers Interval 796.1 to 2210.0	—	—
Opsonophagocytic Titers Against Vaccine Pneumococcal Serotypes in the At Risk Un-primed Group. Opsono-23F Month 3 (N=16)	1949.3 Titers Interval 1145.5 to 3317.2	—	—
Opsonophagocytic Titers Against Vaccine Pneumococcal Serotypes in the At Risk Un-primed Group. Opsono-6A Month 1 (N=16)	1982.6 Titers Interval 648.9 to 6057.2	—	—
Opsonophagocytic Titers Against Vaccine Pneumococcal Serotypes in the At Risk Un-primed Group. Opsono-6A Month 3 (N=14)	1908.3 Titers Interval 975.1 to 3734.8	—	—
Opsonophagocytic Titers Against Vaccine Pneumococcal Serotypes in the At Risk Un-primed Group. Opsono-19A Month 1 (N=16)	1037.4 Titers Interval 373.5 to 2881.5	—	—
Opsonophagocytic Titers Against Vaccine Pneumococcal Serotypes in the At Risk Un-primed Group. Opsono-19A Month 3 (N=16)	2769.3 Titers Interval 1490.6 to 5145.0	—	—

PRIMARY outcome

Timeframe: One month after Dose 1 (At Month 1)

Population: The analysis was performed on the ATP cohort for immunogenicity, which included all evaluable subjects for whom assay results were available for antibodies against at least one pneumococcal vaccine serotype or protein D for at least one blood sample taken after 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 millilitre (EL.U/mL) and tabulated. The seropositivity cut-off for the assay was ≥ 153 EL.U/mL. Antibody concentrations \< 153 EL.U/mL were given an arbitrary value of half the cut-off for the purpose of GMC calculation.

Outcome measures

Outcome measures
Measure	Synflorix AR-Pr-2-17Y Group n=18 Participants Primed (Pr) subjects aged between 24 months and 17 years, who were at an increased risk (AR) of pneumococcal infection\, receiving 1 dose of SynflorixTM vaccine: Primed groups included subjects who have been previously vaccinated with at least one dose of a pneumococcal conjugate vaccine, i.e. either SynflorixTM, PrevenarTM or Prevenar13TM or with plain polysaccharide pneumococcal vaccine more than 2 years (24 months) and less than 5 years (60 months) before enrolment. \An at-risk subject was a subject with Congenital or acquired asplenia such as anatomic, surgical or functional asplenia, or Splenic dysfunction \[some degree of functional asplenia, such as sickle-cell disease and other hemoglobinopathies, Hodgkin disease, rheumatologic diseases, systemic lupus erythematous (SLE), chronic gastrointestinal disorders, liver disease, infiltrative disorders, vascular disorder etc.\] or Complement deficiencies, e.g.C1-C4, C5-C9, properdin factor H or factor D.	Synflorix AR-PR-2-4Y Group Subset of the AR-PR-2-17Y Group including subjects aged between 24 and 59 months.	Synflorix AR-Un-2-4Y Group Subset of the AR-UN-2-17Y Group including subjects aged between 24 and 59 months.
Concentrations of Antibodies Against Protein D (PD) in the At Risk Primed Group.	173.1 EL.U/mL Interval 109.2 to 274.3	—	—

PRIMARY outcome

Timeframe: One month after Dose 1 (At Month 1) and one month after Dose 2 (At Month 3)

Population: The analysis was performed on the ATP cohort for immunogenicity, which included all evaluable subjects for whom assay results were available for antibodies against at least one pneumococcal vaccine serotype or protein D for at least one blood sample taken after 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 millilitre (EL.U/mL) and tabulated. The seropositivity cut-off for the assay was ≥ 153 EL.U/mL. Antibody concentrations \< 153 EL.U/mL were given an arbitrary value of half the cut-off for the purpose of GMC calculation.