The purpose of this phase IIIb study is to determine whether children who have not received a 3-dose primary vaccination with the pneumococcal conjugate vaccine before their 6 months of age, can receive the vaccine as part of a catch-up immunization schedule. The immunogenicity, safety and reactogenicity of GSK Biologicals' pneumococcal conjugate vaccine will be evaluated for four different age groups with different schedules: \< 6 months of age group: 3-dose primary vaccination + a booster dose. 7 to 11 months of age group: 2-dose primary vaccination + a booster dose. 12 to 23 months of age group: 2-dose vaccination; no booster dose. 24 months to 5 years of age group: 1-dose vaccination; no booster dose. Children below 6 months of age will receive concomitantly a DTPa-IPV/Hib vaccine.
The Protocol Posting has been updated in order to comply with the FDA Amendment Act, Sep 2007
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
PREVENTION
Masking
NONE
Enrollment
600
1, 2, 3 or 4 Intramuscular injections, depending on age group
4 intramuscular injections
GSK Investigational Site
Espoo, Finland
GSK Investigational Site
Helsinki, Finland
GSK Investigational Site
Helsinki, Finland
GSK Investigational Site
Jarvenpaa, Finland
GSK Investigational Site
Kotka, Finland
GSK Investigational Site
Lahti, Finland
GSK Investigational Site
Seinäjoki, Finland
GSK Investigational Site
Tampere, Finland
GSK Investigational Site
Vantaa, Finland
GSK Investigational Site
Vantaa, Finland
Number of Subjects With Anti-pneumococcal Serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F Antibody Concentrations >= 0.20 Microgram Per Milliliter (µg/mL). (Primary/Full 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 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
Antibody Concentrations Against Pneumococcal Serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F. (Primary/Full 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.
Antibody Concentrations Against Pneumococcal Cross-reactive Serotypes 6A and 19A. (Primary/Full 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.
Opsonophagocytic Activity Against Pneumococcal Serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F. (Primary/Full 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.
Opsonophagocytic Activity Against Pneumococcal Cross-reactive Serotypes 6A and 19A. (Primary/Full 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.
Antibody Concentrations Against Protein D (Anti-PD). (Primary/Full 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.
Anti-pneumococcal Serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F Antibody Concentrations >= 0.20 µg/mL. (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 = 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
Anti-pneumococcal Serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F Antibody Concentrations. (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
Antibody Concentrations Against Pneumococcal Cross-reactive Serotypes 6A and 19A.(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: Before and one month after the booster dose with Synflorix™ for the < 6 months and 7-11 months groups
Opsonophagocytic Activity Against Pneumococcal Serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F. (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 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
Opsonophagocytic Activity Against Pneumococcal Cross-reactive Serotypes 6A and 19A. (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: Before and one month after the booster dose with Synflorix™ for the < 6 months and 7-11 months groups
Antibody Concentrations Against Protein D. (Booster 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
Anti-diphtheria (Anti-D) and Anti-tetanus Toxoids (Anti-T) Antibody Concentrations. (Primary 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: 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.
Anti-polyribosyl Ribitol Phosphate (PRP) Antibody Concentrations. (Primary Vaccination)
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
Anti-pertussis Toxoid (PT), Anti-filamentous Haemagglutinin (FHA) and Anti-pertactin (PRN) Antibody Concentrations. (Primary Vaccination)
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
Anti-polio Type 1, 2 and 3 Titers. (Primary 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.
Booster Vaccine Response to PT, FHA and PRN
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™
Number of Subjects Solicited Local Symptoms (Any and Grade 3). (Primary Vaccination)
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
Number of Subjects With Solicited Local Symptoms (Any and Grade 3). (Booster Vaccination)
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
Number of Subjects With Solicited General Symptoms (Any and Grade 3). (Booster Vaccination)
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
Number of Subjects With Unsolicited Adverse Events (AEs). (Primary 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) post primary vaccination
Number of Subjects With Unsolicited Adverse Events (AEs). (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
Number of Subjects With Serious Adverse Events (SAEs) (Primary Vaccination)
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
Number of Subjects With Serious Adverse Events (SAEs). (Booster Vaccination)
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
Number of Subjects With Solicited General Symptoms (Primary Vaccination)
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
Anti-diphtheria (Anti-D) and Anti-tetanus Toxoids (Anti-T) Antibody Concentrations.(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.
Anti-polyribosyl Ribitol Phosphate (PRP) Antibody Concentrations. (Booster Vaccination)
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.
Anti-pertussis Toxoid (PT), Anti-filamentous Haemagglutinin (FHA) and Anti-pertactin (PRN) Antibody Concentrations. (Booster Vaccination)
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.
Titers of Antibodies Against Polio Type 1, 2 and 3 (Anti-polio 1, 2 and 3). (Booster 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.
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