Immunogenicity and Safety Study of GlaxoSmithKline (GSK)... | NCT01746108

ID	Type	Description	Link
2011-006013-34	EudraCT Number

Label	Type	Description	Intervention Names
At-risk-Unprimed Group	Experimental	Subjects who have not been previously vaccinated with any pneumococcal vaccine and are at an increased risk of pneumococcal infection.	Biological: Synflorix™
At-risk-Primed Group	Experimental	Subjects who have been previously vaccinated with at least one dose of a pneumococcal conjugate vaccine i.e. either Synflorix (10Pn-PD-DiT), Prevenar or Prevenar13. with plain polysaccharide pneumococcal vaccine more than 2 years and less than 5 years before enrollment. and are at an increased risk of pneumococcal infection.	Biological: Synflorix™
Healthy-Unprimed Group	Active Comparator	Subjects who have not been previously vaccinated with any pneumococcal vaccine and are healthy.	Biological: Synflorix™
Healthy-Primed Group	Active Comparator	Subjects who have been previously vaccinated with at least one dose of a pneumococcal vaccine and are healthy.	Biological: Synflorix™

Name	Type	Description	Arm Group Labels	Other Names
Synflorix™	Biological	1 or 2 doses depending on the priming status, intramuscularly in the non-dominant deltoid muscle or the thigh.	At-risk-Primed Group At-risk-Unprimed Group

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes in the At Risk Primed Group.	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.	One month after Dose 1 (At Month 1)
Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes in the At Risk Un-primed Group.	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.	One month after Dose 1 (At Month 1) and one month after Dose 2 (At Month 3)
Opsonophagocytic Titers Against Vaccine Pneumococcal Serotypes in the At Risk Primed Group.	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.	One month after Dose 1 (At Month 1)
Opsonophagocytic Titers Against Vaccine Pneumococcal Serotypes in the At Risk Un-primed Group.

Secondary Outcomes

Measure	Description	Time Frame
Number of Subjects With Any and Severe (Grade 3) Solicited Local Adverse Events (AEs) After Dose 1 for Subjects Aged Between 2 to 4 Years.	Solicited local AEs assessed were pain, redness and swelling. Any = incidence of any local symptom regardless of intensity grade. Grade 3 pain = cried when limb was moved/spontaneously painful. Grade 3 redness/swelling = redness/swelling above 30 millimetre. Primed subjects received one dose and Unprimed subjects received two doses.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Subjects who the investigator believes that parent(s)/Legally Acceptable Representative(s) [LAR(s)] can and will comply with the requirements of the protocol.
Written informed consent obtained from the parent(s)/LAR(s) of the subject and informed assent obtained from the subject, if appropriate, prior to enrollment.
Female subjects of non-child bearing potential may be enrolled in the study. (Non-child bearing potential is defined as pre-menarche, current tubal ligation, hysterectomy or ovariectomy).
Female subjects of child bearing potential may be enrolled in the study, if the subject:
- has practiced adequate contraception for 30 days prior to the first vaccination, and
- has a negative pregnancy test on the day of vaccination, and
- has agreed to continue adequate contraception during the entire treatment period and for 2 months after completion of the vaccination series.

Priming status:

Children who have not been previously vaccinated with any pneumococcal vaccine, i.e. either plain polysaccharide pneumococcal vaccine, Synflorix (10Pn-PD-DiT), Prevenar or Prevenar13 will be considered for inclusion in the unprimed groups.

Children who have been previously vaccinated with:

at least one dose of a pneumococcal conjugate vaccine, i.e. either Synflorix (10Pn-PD-DiT), Prevenar or Prevenar13
with plain polysaccharide pneumococcal vaccine more than 2 years and less than 5 years before enrollment.
will be considered for inclusion in the primed groups.

Additional inclusion criteria for the At-risk groups:

A male or female aged between, and including, 2 and 17 years at the time of first vaccination.
For the purpose of this study, at-risk subject is a subject with:
- Congenital or acquired asplenia such as anatomic, surgical or functional asplenia or
- Splenic dysfunction, chronic gastrointestinal disorders, liver disease, infiltrative disorders, vascular disorder etc or

Note: All individuals who are diagnosed by the investigator as with splenic dysfunction are eligible for enrollment in the At-risk group. When available, investigator will collect medical documentation for reduced splenic function diagnosed with an appropriate technique in the At-risk subject's medical records. No further assessment will be necessary. A maximum of 35 individuals with sickle-cell disease can be enrolled in the At-risk group. These subjects do not require assessment of the splenic function as sickle-cell disease is invariably associated with severe splenic dysfunction.

- Complement deficiencies. For all subjects defined as At-risk the Investigator will make all efforts to collect information from the subject/subject's parent(s)/LAR(s) during the interview and/or from previously available medical documentation on the date and conditions which have made a child at-risk of pneumococcal infection and/or the results of tests determining spleen dysfunction or complement deficiency. This should be documented in the medical records of the At-risk subject. No originals/copies of medical documentation are needed.

Additional inclusion criteria for the Healthy group:

A male or female matched (for age and country) to a subject aged 24-59 months from the At-risk group.
Healthy subjects as established by medical history and clinical examination before entering into the study.

Exclusion Criteria:

Child in care.
Use of any investigational or non-registered product other than the study vaccine(s) within 30 days preceding the first dose of study vaccine, or planned use during the study period.
Planned administration/administration of a vaccine not foreseen by the study protocol during the period starting 30 days before each dose of vaccine(s) and ending 30 days after*.

* In case an emergency mass vaccination for an unforeseen public health threat is organised by the public health authorities, outside the routine immunization program, vaccines can be administered at any time during the study period provided it is licensed and used according to its Summary of Product Characteristics or Prescribing Information and according to the local governmental recommendations and that a written approval of the Sponsor is provided. Vaccines that are recommended for subjects with an increased risk of bacterial infection, can be administered at any time to the subjects enrolled in the At-risk group.
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).
History of any neurological disorders or seizures.
Acute disease and/or fever at the time of enrollment.
History of chronic alcohol consumption and/or drug abuse.
Any confirmed or suspected Human Immunodeficiency virus (HIV) infection, based on medical history and physical examination.
History of any reaction or hypersensitivity likely to be exacerbated by any component of the vaccine.
Administration of immunoglobulins and/or any blood products within the 3 months preceding the first dose of study vaccine or planned administration during the study period.
Pregnant or lactating female.
Female planning to become pregnant or planning to discontinue contraceptive precautions.
Major congenital defects except medical conditions that define an At-risk subject.
Previous vaccination against pneumococcal infection with pneumococcal conjugate vaccine within the last 8 weeks.
Previous vaccination against pneumococcal infection with plain polysaccharide vaccine within the last 2 years.

Additional exclusion criteria for the Healthy group:

Chronic administration of immunosuppressants or other immune-modifying drugs within six months prior to the first vaccine dose. Inhaled and topical steroids are allowed.
Serious chronic illness.
Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination.
Family history of congenital or hereditary immunodeficiency.

Name	Affiliation	Role
GSK Clinical Trials	GlaxoSmithKline	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
GSK Investigational Site		Krakow		31-302	Poland
GSK Investigational Site

PubMed Identifier	Type	Citation	Retractions
28866290	Background	Szenborn L, Osipova IV, Czajka H, Kharit SM, Jackowska T, Francois N, Habib MA, Borys D. Immunogenicity, safety and reactogenicity of the pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) in 2-17-year-old children with asplenia or splenic dysfunction: A phase 3 study. Vaccine. 2017 Sep 25;35(40):5331-5338. doi: 10.1016/j.vaccine.2017.08.039. Epub 2017 Aug 31.

Label	URL
IPD for this study will be made available via the Clinical Study Data Request site.	View source

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	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.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Arm/Group Information

ID	Title	Description
BG000	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.
BG001	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.
BG002	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).
BG003	Total	Total of all reporting groups

Units	Counts
Participants	BG00018 BG00128 BG0026 BG00352

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes in the At Risk Primed Group.

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.

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.

Posted

Geometric Mean

95% Confidence Interval

μg/mL

One month after Dose 1 (At Month 1)

ID	Title	Description
OG000	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.

Units	Counts
Participants	OG00018

Title

Denominators

Categories

Anti-1 (N=18)

Title	Measurements
	OG0001.94(1.4 to 2.69)

Anti-4 (N=18)

Title	Measurements
	OG0006.16(3.89 to 9.76)

Anti-5 (N=18)

Primary

Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes in the At Risk Un-primed Group.

-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.

Posted

Geometric Mean

95% Confidence Interval

μg/mL

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

ID	Title	Description
OG000	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.

Primary

Opsonophagocytic Titers Against Vaccine Pneumococcal Serotypes in the At Risk Primed Group.

≥ 8. Antibody titers < 8 were given an arbitrary value of half the cut-off for the purpose of GMT calculation.

Posted

Geometric Mean

95% Confidence Interval

Titers

One month after Dose 1 (At Month 1)

ID	Title	Description
OG000	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.

Primary

Opsonophagocytic Titers Against Vaccine Pneumococcal Serotypes in the At Risk Un-primed Group.

≥ 8. Antibody titers < 8 were given an arbitrary value of half the cut-off for the purpose of GMT calculation.

Posted

Geometric Mean

95% Confidence Interval

Titers

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

ID	Title	Description
OG000	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.

Primary

Concentrations of Antibodies Against Protein D (PD) in the At Risk Primed Group.

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.

Posted

Geometric Mean

95% Confidence Interval

EL.U/mL

One month after Dose 1 (At Month 1)

ID	Title	Description
OG000	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.

Primary

Concentrations of Antibodies Against Protein D (PD) in the At Risk Unprimed Group.

Posted

Geometric Mean

95% Confidence Interval

EL.U/mL

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

ID	Title	Description
OG000	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.

Secondary

Number of Subjects With Any and Severe (Grade 3) Solicited Local Adverse Events (AEs) After Dose 1 for Subjects Aged Between 2 to 4 Years.

Solicited local AEs assessed were pain, redness and swelling. Any = incidence of any local symptom regardless of intensity grade. Grade 3 pain = cried when limb was moved/spontaneously painful. Grade 3 redness/swelling = redness/swelling above 30 millimetre. Primed subjects received one dose and Unprimed subjects received two doses.

The Total Vaccinated cohort included all vaccinated subjects.

Posted

Number

Subjects

During the 4-day (Days 0-3) after dose 1

ID	Title	Description
OG000	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).
OG001	Synflorix AR-PR-2-4Y Group	Subset of the AR-PR-2-17Y Group including subjects aged between 24 and 59 months.

Secondary

Number of Subjects With Any and Severe (Grade 3) Solicited Local Adverse Events (AEs) After Dose 2 for Subjects Aged Between 2 to 4 Years.

The Total Vaccinated cohort included all vaccinated subjects.

Posted

Number

Subjects

During the 4-day (Days 0-3) after dose 2

ID	Title	Description
OG000	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).
OG001	Synflorix AR-Un-2-4Y Group	Subset of the AR-UN-2-17Y Group including subjects aged between 24 and 59 months.

Secondary

Number of Subjects With Any and Severe (Grade 3) Solicited Local Adverse Events (AEs) After Dose 1 for Subjects Aged Between 5 to 17 Years.

Solicited local AEs assessed were pain, redness and swelling. Any = incidence of any local symptom regardless of intensity grade. Grade 3 pain =Significant pain at rest. Prevented normal every day activities. Grade 3 redness/swelling = redness/swelling above 50 millimetre. Primed subjects received one dose and Unprimed subjects received two doses.

The Total Vaccinated cohort included all vaccinated subjects.

Posted

Number

Subjects

During the 4-day (Days 0-3) after dose 1

ID	Title	Description
OG000	Synflorix AR-PR-5-17Y Group	Subset of the AR-PR-2-17Y Group including subjects aged between 5 and 17 years.
OG001	Synflorix AR- UN-5-17Y Group	Subset of the AR- UN-5-17Y Group including subjects aged between 5 and 17 years.

Units	Counts
Participants	OG000

Secondary

Number of Subjects With Any and Severe (Grade 3) Solicited Local Adverse Events (AEs) After Dose 2 for Subjects Aged Between 5 to 17 Years.

Solicited local AEs assessed were pain, redness and swelling. Any = incidence of any local symptom regardless of intensity grade. Grade 3 pain = Significant pain at rest. Prevented normal every day activities. Grade 3 redness/swelling = redness/swelling above 50 millimetre. Primed subjects received one dose and Unprimed subjects received two doses.

The Total Vaccinated cohort included all vaccinated subjects.

Posted

Number

Subjects

During the 4-day (Days 0-3) after dose 2

ID	Title	Description
OG000	Synflorix AR- UN-5-17Y Group	Subset of the AR- UN-5-17Y Group including subjects aged between 5 and 17 years.

Units	Counts
Participants	OG000

Secondary

Number of Subjects With Any, Severe (Grade 3) and Related Solicited General Adverse Events (AEs) After Dose 1 for Subjects Aged Between 2 to 4 Years.

General AEs = drowsiness, irritability, loss of appetite (loss of appet) and fever (axillary ≥ 37.5 degrees Celsius). Any= Incidence of any solicited general symptom regardless of intensity grade or relationship to vaccination. Grade 3: drowsiness = prevented normal activity; irritability = crying that could not be comforted/ prevented normal activity; loss of appetite = not eating at all; fever > 39.5°C. Related = symptom assessed by the investigator as related to the vaccination. Primed subjects received one dose and Unprimed subjects received two doses.

The Total Vaccinated cohort included all vaccinated subjects.

Posted

Number

Subjects

During the 4-day (Days 0-3) after dose 1

ID	Title	Description
OG000	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).

Secondary

Number of Subjects With Any, Severe (Grade 3) and Related Solicited General Adverse Events (AEs) After Dose 2 for Subjects Aged Between 2 to 4 Years.

The Total Vaccinated cohort included all vaccinated subjects.

Posted

Number

Subjects

During the 4-day (Days 0-3) after dose 2

ID	Title	Description
OG000	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).

Secondary

Number of Subjects With Any, Severe (Grade 3) and Related Solicited General Adverse Events (AEs) After Dose 1 for Subjects Aged Between 5 to 17 Years.

General AEs = headache, fatigue, gastrointestinal symptoms (gastro symp) (nausea, vomiting, diarrhoea and/or abdominal pain) and fever (axillary ≥ 37.5 degrees Celsius). Any= Incidence of any solicited general symptom regardless of intensity grade or relationship to vaccination. Grade 3: headache, fatigue and gastrointestinal symptoms = symptoms that prevented normal activity; Fever > 39.5°C. Related = symptom assessed by the investigator as related to the vaccination. Primed subjects received one dose and Unprimed subjects received two doses.

The Total Vaccinated cohort included all vaccinated subjects.

Posted

Number

Subjects

During the 4-day (Days 0-3) after dose 1

ID	Title	Description
OG000	Synflorix AR-PR-5-17Y Group	Subset of the AR-PR-2-17Y Group including subjects aged between 5 and 17 years.
OG001	Synflorix AR- UN-5-17Y Group	Subset of the AR- UN-5-17Y Group including subjects aged between 5 and 17 years.

Units	Counts
Participants

Secondary

Number of Subjects With Any, Severe (Grade 3) and Related Solicited General Adverse Events (AEs) After Dose 2 for Subjects Aged Between 5 to 17 Years.

The Total Vaccinated cohort included all vaccinated subjects.

Posted

Number

Subjects

During the 4-day (Days 0-3) after dose 2

ID	Title	Description
OG000	Synflorix AR- UN-5-17Y Group	Subset of the AR- UN-5-17Y Group including subjects aged between 5 and 17 years.

Units	Counts
Participants	OG000

Secondary

Number of Subjects With Unsolicited AEs.

An unsolicited adverse event is any adverse event (i.e. any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with use of a medicinal product, whether or not considered related to the medicinal product) 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.

The Total Vaccinated cohort included all vaccinated subjects.

Posted

Number

Subjects

Within the 31-day (Days 0-30) post- vaccination period

ID	Title	Description
OG000	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.

Secondary

Number of Subjects With Serious Adverse Events (SAEs).

SAEs assessed include medical occurrences that results in death, are life threatening, require hospitalization or prolongation of hospitalization, results in disability/incapacity or are a congenital anomaly/birth defect in the offspring of study subjects

The Total Vaccinated cohort included all vaccinated subjects.

Posted

Number

Subjects

From Dose 1 at Month 0 up to study end at Month 1 for primed subjects and at Month 3 for unprimed subjects.

ID	Title	Description
OG000	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.
OG001	Synflorix AR-Un-2-17Y Group

Secondary

Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes in the Healthy Un-primed Group.

Antibody concentrations < 0.05 μg/mL were given an arbitrary value of half the cut-off for the purpose of GMC calculation.

Posted

Geometric Mean

95% Confidence Interval

EL.U/mL

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

ID	Title	Description
OG000	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).

Secondary

Opsonophagocytic Titers Against Vaccine Pneumococcal Serotypes in the Healthy Un-primed Group.

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. When number of subjects analysed = 1, Lower limit and Upper Limit values were entered as equal to the Geometric mean value. "999999.9" was used as placeholder when Upper Limit value was greater than "1.0E8".

Posted

Geometric Mean

95% Confidence Interval

Titers

One month after Dose 1 (At Month 1) and/or one month after Dose 2 (At Month 3)

ID	Title	Description
OG000	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).

Secondary

Concentrations of Antibodies Against Protein D (PD) in the Healthy Unprimed Group.

Posted

Geometric Mean

95% Confidence Interval

EL.U/mL

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

ID	Title	Description
OG000	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).

Arm/Groups

ID	Title	Description	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	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.	0	18	17	18
EG001	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).	0	6	6	6
EG002	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.	1	28	27	28

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Respiratory disorder	Respiratory, thoracic and mediastinal disorders	MedDRA 18.1		EG0000 events0 affected18 at risk EG0010 events0 affected6 at risk EG0022 events2 affected28 at risk
Headache	Nervous system disorders	MedDRA 18.1		EG0005 events5 affected18 at risk EG0010 events0 affected6 at risk EG00211 events7 affected28 at risk
Somnolence	Nervous system disorders	MedDRA 18.1		EG0001 events1 affected18 at risk EG0012 events1 affected6 at risk EG0023 events3 affected28 at risk
Fatigue	General disorders	MedDRA 18.1		EG0005 events5 affected18 at risk EG0010 events0 affected6 at risk EG00212 events10 affected28 at risk
Injection site pruritus	General disorders	MedDRA 18.1		EG0000 events0 affected18 at risk EG0011 events1 affected6 at risk EG0020 events0 affected28 at risk
Pain	General disorders	MedDRA 18.1		EG00015 events15 affected18 at risk EG0018 events5 affected6 at risk EG00241 events24 affected28 at risk
Pyrexia	General disorders	MedDRA 18.1		EG0000 events0 affected18 at risk EG0011 events1 affected6 at risk EG0025 events4 affected28 at risk
Swelling	General disorders	MedDRA 18.1	Systematic Assessment	EG0005 events5 affected18 at risk EG0014 events3 affected6 at risk EG00213 events10 affected28 at risk
Irritability	Psychiatric disorders	MedDRA 18.1		EG0001 events1 affected18 at risk EG0014 events4 affected6 at risk EG0022 events1 affected28 at risk
Gastrointestinal disorder	Gastrointestinal disorders	MedDRA 18.1		EG0003 events3 affected18 at risk EG0010 events0 affected6 at risk EG0026 events5 affected28 at risk
Erythema	Skin and subcutaneous tissue disorders	MedDRA 18.1		EG0007 events7 affected18 at risk EG00110 events6 affected6 at risk EG00219 events12 affected28 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA 18.1		EG0001 events1 affected18 at risk EG0016 events4 affected6 at risk EG0023 events2 affected28 at risk
Vitamin D deficiency	Metabolism and nutrition disorders	MedDRA 18.1		EG0001 events1 affected18 at risk EG0010 events0 affected6 at risk EG0020 events0 affected28 at risk
Nasopharyngitis	Infections and infestations	MedDRA 18.1		EG0000 events0 affected18 at risk EG0011 events1 affected6 at risk EG0021 events1 affected28 at risk
Respiratory tract infection	Infections and infestations	MedDRA 18.1		EG0000 events0 affected18 at risk EG0011 events1 affected6 at risk EG0021 events1 affected28 at risk
Rhinitis	Infections and infestations	MedDRA 18.1		EG0000 events0 affected18 at risk EG0011 events1 affected6 at risk EG0024 events4 affected28 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA 18.1		EG0001 events1 affected18 at risk EG0011 events1 affected6 at risk EG0020 events0 affected28 at risk

ID	Term
D013290	Streptococcal Infections
D011008	Pneumococcal Infections

ID	Term
D016908	Gram-Positive Bacterial Infections
D001424	Bacterial Infections
D001423	Bacterial Infections and Mycoses
D007239	Infections