Infections, Streptococcal
Conditions
Keywords
safety, Streptococcus pneumoniae, immunogenicity, Pneumococcal conjugate vaccine, Haemophilus influenzae
Brief summary
This primary purpose of this study is the evaluation of the immunological persistence following completion of the 3-dose primary vaccination course with either a clinical or a commercial lot of pneumococcal conjugate vaccine GSK1024850A in study NCT00808444. In addition, the study will also assess the safety, reactogenicity and immunogenicity of a fourth dose of pneumococcal conjugate vaccine GSK1024850A (commercial lot) when co-administered with Infanrix-IPV/Hib at 18-21 months of age in children primed in study NCT00808444. The primary vaccination study was conducted in Malaysia and Singapore. The booster vaccination study will not be performed in Malaysia since the pneumococcal conjugate vaccine GSK1024850A has been registered in September 2009. However, subjects in Malaysia will be offered a booster dose of the commercial pneumococcal conjugate vaccine licensed in Malaysia and Infanrix-IPV/Hib vaccine during the second year of life according to the nationally recommended regimen. Administration of the booster dose will be outside the set-up of a clinical trial. Hence no data will be collected, no blood samples will be taken in Malaysia.
Interventions
BIOLOGICALPneumococcal vaccine GSK1024850A
Intramuscular injection, one dose
BIOLOGICALInfanrix-IPV/Hib
Intramuscular injection, one dose
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Months to 21 Months
Healthy volunteers
Yes
Inclusion criteria
* Subjects who the investigator believes that their parent(s)/Legally Acceptable Representative(s) (LAR) can and will comply with the requirements of the protocol * Male or female between, and including, 18 and 21 months of age at the time of booster vaccination. * Subjects who received three doses of pneumococcal conjugate vaccine in study NCT00808444 * Written informed consent obtained from the parents/LAR(s) of the subject. * Healthy subjects as established by medical history and clinical examination before entering into the study.
Exclusion criteria
* Use of any investigational or non-registered product other than the study vaccine(s) within 30 days preceding vaccination, or planned use during the study period. * 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. * Chronic administration of immunosuppressants or other immune-modifying drugs within six months prior to vaccination. * A family history of congenital or hereditary immunodeficiency. * Administration of immunoglobulins and/ or any blood products within the 3 months preceding vaccination or planned use during the study period. * Administration of any pneumococcal and/or vaccine containing diphtheria, tetanus, pertussis, poliomyelitis or Haemophilus influenzae type b antigens since the end of study NCT00808444. * Planned administration/administration of a vaccine not foreseen by the study protocol during the study period starting from 30 days before vaccination and ending 30 days after vaccination. * Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination (no laboratory testing required). * History of any reaction or allergic disease likely to be exacerbated by any component of the study vaccines. * Known hypersensitivity to any component of the study vaccines including anaphylactic reactions following the administration of the study vaccines. * Major congenital defects or serious chronic illness. * History of any neurologic disorders or seizures. (Subjects who have had a single uncomplicated febrile convulsion in the past can be included) * Fever at the time of vaccination. * Fever is defined as rectal temperature \>= 38.0°C or tympanic/axillary/ oral temperature \>= 37.5°C. * Acute disease at the time of enrolment. * Subjects with a minor illness without fever may be enrolled at the discretion of the investigator. * Child in care.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes. | Before booster vaccination at Month 0 | Vaccine pneumococcal serotypes assessed were serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F. Concentrations were expressed as geometric mean concentrations (GMCs) in microgram per millilitre (µg/mL). Pneumococcal serotype specific total imunoglobuline G (IgG) antibodies were measured by 22F-inhibition Enzyme-linked immunosorbent assay (ELISA). The cut-off of the assay was 0.05 µg/mL. |
| Concentrations of Antibodies Against Protein D (PD). | Before booster vaccination at Month 0 | Anti-PD antibodies were determined using an ELISA assay. Concentration of specific PD antibodies was determined, using a standard reference serum. The cut-off of the assay is 100 ELISA units per millilitre (EU/mL). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects Reporting Any and Grade 3 Solicited Local Adverse Events (AEs). | Within 4 days (Days 0-3) after booster vaccination. | Solicited AEs = AEs to be recorded as endpoints in the clinical study. The presence/occurrence/intensity of these events is actively solicited from the subject or an observer during a specified post-vaccination follow-up period. Solicited local symptoms assessed were pain, redness and swelling. Any = occurrence 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 (mm). |
| Number of Subjects Reporting Any, Grade 3 and Related Solicited General Adverse Events (AEs). | Within 4 days (Days 0-3) after booster vaccination. | Solicited general symptoms assessed were drowsiness, irritability, loss of appetite and fever (= axillary temperature equal to or above 37.5 degrees Celsius (°C)). Any= occurrence of any general symptom regardless of intensity grade or relationship to vaccination Grade 3 drowsiness = drowsiness which prevented normal activity. Grade 3 irritability = crying that could not be comforted/ prevented normal activity. Grade 3 loss of appetite = not eating at all. Grade 3 fever = temperature \>39.5°C. Related = solicited symptom assessed by the investigator as causally related to study vaccination. |
| Number of Subjects Reporting Unsolicited Adverse Events (AEs). | Within 31 days (Days 0-30) after booster vaccination | Unsolicited AEs = Any AE (i.e. any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product) reported in addition to those solicited during the clinical study. Also any solicited symptom with onset outside the specified period of follow-up for solicited symptoms was reported as an unsolicited adverse event. |
| Number of Subjects Reporting Serious Adverse Events (SAEs). | During the entire study period, from the booster vaccination, at Month 0, up to the study end, at Month 1 | 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 a study subjects. |
| Opsonophagocytic Activity Against Vaccine Pneumococcal Serotypes. | Before and one month after booster vaccination (at Month 0 and Month 1) | Opsonophagocytic activity (OPA) testing was not performed. |
| Concentrations of Antibodies Against Diphtheria and Tetanus. | Before booster vaccination at Month 0 | Concentrations were expressed as geometric mean concentrations (GMCs) in International units per millilitre (IU/mL). The cut-off of the assay was 0.1 IU/mL. |
| Concentrations of Antibodies Against Cross-reactive Pneumococcal Serotypes. | Before booster vaccination at Month 0 | Cross-reactive pneumococcal serotypes assessed were serotypes 6A and 19A. Concentrations were expressed as geometric mean concentrations (GMCs) in microgram per millilitre (µg/mL). The antibody concentrations against the cross-reactive pneumococcal serotypes 6A and 19A were determined by 22F-inhibition Enzyme-linked immunosorbent assay (ELISA). The cut-off of the assay was 0.05 µg/mL. |
| Concentrations of Antibodies Against Polyribosyl-ribitol Phosphate (PRP). | Before booster vaccination at Month 0 | Concentrations were expressed as geometric mean concentrations (GMCs) in microgram per millilitre (µg/mL). The cut-off of the assay was 0.15 µg/mL. |
| Titers of Antibodies Against Poliovirus Types 1, 2 and 3. | Before booster vaccination at Month 0 | Titers were expresses as geometric mean titers (GMTs). The cut-off of the assay was 8. |
| Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes. | Before and one month after booster vaccination (at Month 0 and Month 1) | Vaccine pneumococcal serotypes assessed were serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F. Concentrations were expressed as geometric mean concentrations (GMCs) in microgram per millilitre (µg/mL). Pneumococcal serotype specific total imunoglobuline G (IgG) antibodies were measured by 22F-inhibition Enzyme-linked immunosorbent assay (ELISA). The cut-off of the assay was 0.05 µg/mL. |
| Concentrations of Antibodies Against Protein D (PD). | Before and one month after booster vaccination (at Month 0 and Month 1) | Anti-PD antibodies were determined using an ELISA assay. Concentration of specific PD antibodies was determined, using a standard reference serum. The cut-off of the assay is 100 ELISA units per millilitre (EU/mL). |
| Opsonophagocytic Activity Against Cross-reactive Pneumococcal Serotypes 6A and 19A. | Before and one month after booster vaccination (at Month 0 and Month 1) | Opsonophagocytic activity (OPA) testing was not performed. |
| Concentrations of Antibodies Against Pertussis Toxoid (PT), Filamentous Haemagglutinin (FHA) and Pertactin (PRN). | Before booster vaccination at Month 0 | Concentrations were expressed as geometric mean concentrations (GMCs) in ELISA units per millilitre (EU/mL). The cut-off of the assay was 5 EU/mL. |
Countries
Singapore
Participant flow
Recruitment details
This booster study was conducted in Singapore only wheras the primary vaccination phase (NCT00808444) was conducted in Singapore and Malaysia.
Participants by arm
| Arm | Count |
|---|---|
| Synflorix™ Clinical-Commercial + Infanrix™-IPV/Hib Group children primed with 3 doses of clinical lot of Synflorix™ + Rotarix™ co-administered with Infanrix™-hexa in the primary phase of the study (NCT00808444) and boosted with commercial lot of Synflorix™ co-administered with Infanrix™-IPV/Hib. The Synflorix™ vaccine (clinical and commercial lots) was administered intramuscularly in the right deltoid or anterolateral thigh and the Infanrix™-IPV/Hib vaccine was administered intramuscularly in the left deltoid or anterolateral thigh. | 118 |
| Synflorix™ Commercial-Commercial + Infanrix™-IPV/Hib Group children primed with 3 doses of commercial lot of Synflorix™ co-administered with Rotarix™ and Infanrix™-hexa in the primary phase of the study (NCT00808444) and boosted with commercial lot of Synflorix™ co-administered with Infanrix™-IPV/Hib. The Synflorix™ vaccine (clinical and commercial lots) was administered intramuscularly in the right deltoid or anterolateral thigh and the Infanrix™-IPV/Hib vaccine was administered intramuscularly in the left deltoid or anterolateral thigh. | 120 |
| Total | 238 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 1 | 2 |
| Overall Study | Other | 0 | 1 |
| Overall Study | Withdrawal by Subject | 2 | 1 |
Baseline characteristics
| Characteristic | Synflorix™ Clinical-Commercial + Infanrix™-IPV/Hib Group | Synflorix™ Commercial-Commercial + Infanrix™-IPV/Hib Group | Total |
|---|---|---|---|
| Age, Continuous | 18.8 Months STANDARD_DEVIATION 0.84 | 18.9 Months STANDARD_DEVIATION 0.87 | 18.9 Months STANDARD_DEVIATION 0.86 |
| Sex: Female, Male Female | 62 Participants | 49 Participants | 111 Participants |
| Sex: Female, Male Male | 56 Participants | 71 Participants | 127 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 98 / 118 | 108 / 120 |
| serious Total, serious adverse events | 0 / 118 | 4 / 120 |
Outcome results
Primary
Concentrations of Antibodies Against Protein D (PD).
Anti-PD antibodies were determined using an ELISA assay. Concentration of specific PD antibodies was determined, using a standard reference serum. The cut-off of the assay is 100 ELISA units per millilitre (EU/mL).
Time frame: Before booster vaccination at Month 0
Population: The analysis was performed on the According-To-Protocol cohort for analysis of antibody persistence which included subjects primed in the primary study (NCT00808444) and for whom assay results were available for antibodies against at least 1 vaccine antigen component for the blood sampling taken before the administration of the booster dose.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Synflorix™ Clinical-Commercial + Infanrix™-IPV/Hib Group | Concentrations of Antibodies Against Protein D (PD). | 801.6 EU/mL |
| Synflorix™ Commercial-Commercial + Infanrix™-IPV/Hib Group | Concentrations of Antibodies Against Protein D (PD). | 619.7 EU/mL |
Primary
Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes.
Vaccine pneumococcal serotypes assessed were serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F. Concentrations were expressed as geometric mean concentrations (GMCs) in microgram per millilitre (µg/mL). Pneumococcal serotype specific total imunoglobuline G (IgG) antibodies were measured by 22F-inhibition Enzyme-linked immunosorbent assay (ELISA). The cut-off of the assay was 0.05 µg/mL.
Time frame: Before booster vaccination at Month 0
Population: The analysis was performed on the According-To-Protocol cohort for analysis of antibody persistence which included subjects primed in the primary study (NCT00808444) and for whom assay results were available for antibodies against at least 1 vaccine antigen component for the blood sampling taken before the administration of the booster dose.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Synflorix™ Clinical-Commercial + Infanrix™-IPV/Hib Group | Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes. | Anti-1 [Pre-booster] | 0.48 µg/mL |
| Synflorix™ Clinical-Commercial + Infanrix™-IPV/Hib Group | Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes. | Anti-4 [Pre-booster] | 0.56 µg/mL |
| Synflorix™ Clinical-Commercial + Infanrix™-IPV/Hib Group | Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes. | Anti-5 [Pre-booster] | 0.76 µg/mL |
| Synflorix™ Clinical-Commercial + Infanrix™-IPV/Hib Group | Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes. | Anti-6B [Pre-booster] | 0.34 µg/mL |
| Synflorix™ Clinical-Commercial + Infanrix™-IPV/Hib Group | Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes. | Anti-7F [Pre-booster] | 0.88 µg/mL |
| Synflorix™ Clinical-Commercial + Infanrix™-IPV/Hib Group | Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes. | Anti-9V [Pre-booster] | 0.90 µg/mL |
| Synflorix™ Clinical-Commercial + Infanrix™-IPV/Hib Group | Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes. | Anti-14 [Pre-booster] | 1.06 µg/mL |
| Synflorix™ Clinical-Commercial + Infanrix™-IPV/Hib Group | Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes. | Anti-18C [Pre-booster] | 0.83 µg/mL |
| Synflorix™ Clinical-Commercial + Infanrix™-IPV/Hib Group | Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes. | Anti-19F [Pre-booster] | 1.10 µg/mL |
| Synflorix™ Clinical-Commercial + Infanrix™-IPV/Hib Group | Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes. | Anti-23F [Pre-booster] | 0.66 µg/mL |
| Synflorix™ Commercial-Commercial + Infanrix™-IPV/Hib Group | Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes. | Anti-18C [Pre-booster] | 0.78 µg/mL |
| Synflorix™ Commercial-Commercial + Infanrix™-IPV/Hib Group | Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes. | Anti-1 [Pre-booster] | 0.35 µg/mL |
| Synflorix™ Commercial-Commercial + Infanrix™-IPV/Hib Group | Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes. | Anti-9V [Pre-booster] | 0.73 µg/mL |
| Synflorix™ Commercial-Commercial + Infanrix™-IPV/Hib Group | Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes. | Anti-4 [Pre-booster] | 0.48 µg/mL |
| Synflorix™ Commercial-Commercial + Infanrix™-IPV/Hib Group | Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes. | Anti-23F [Pre-booster] | 0.47 µg/mL |
| Synflorix™ Commercial-Commercial + Infanrix™-IPV/Hib Group | Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes. | Anti-5 [Pre-booster] | 0.54 µg/mL |
| Synflorix™ Commercial-Commercial + Infanrix™-IPV/Hib Group | Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes. | Anti-14 [Pre-booster] | 0.91 µg/mL |
| Synflorix™ Commercial-Commercial + Infanrix™-IPV/Hib Group | Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes. | Anti-6B [Pre-booster] | 0.32 µg/mL |
| Synflorix™ Commercial-Commercial + Infanrix™-IPV/Hib Group | Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes. | Anti-19F [Pre-booster] | 0.96 µg/mL |
| Synflorix™ Commercial-Commercial + Infanrix™-IPV/Hib Group | Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes. | Anti-7F [Pre-booster] | 0.91 µg/mL |
Secondary
Concentrations of Antibodies Against Cross-reactive Pneumococcal Serotypes.
Cross-reactive pneumococcal serotypes assessed were serotypes 6A and 19A. Concentrations were expressed as geometric mean concentrations (GMCs) in microgram per millilitre (µg/mL). The antibody concentrations against the cross-reactive pneumococcal serotypes 6A and 19A were determined by 22F-inhibition Enzyme-linked immunosorbent assay (ELISA). The cut-off of the assay was 0.05 µg/mL.
Time frame: Before booster vaccination at Month 0
Population: The analysis was performed on the According-To-Protocol cohort for analysis of antibody persistence which included subjects primed in the primary study (NCT00808444) and for whom assay results were available for antibodies against at least 1 vaccine antigen component for the blood sampling taken before the administration of the booster dose.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Synflorix™ Clinical-Commercial + Infanrix™-IPV/Hib Group | Concentrations of Antibodies Against Cross-reactive Pneumococcal Serotypes. | Anti-6A [pre-booster] | 0.23 µg/mL |
| Synflorix™ Clinical-Commercial + Infanrix™-IPV/Hib Group | Concentrations of Antibodies Against Cross-reactive Pneumococcal Serotypes. | Anti-19A [pre-booster] | 0.18 µg/mL |
| Synflorix™ Commercial-Commercial + Infanrix™-IPV/Hib Group | Concentrations of Antibodies Against Cross-reactive Pneumococcal Serotypes. | Anti-6A [pre-booster] | 0.21 µg/mL |
| Synflorix™ Commercial-Commercial + Infanrix™-IPV/Hib Group | Concentrations of Antibodies Against Cross-reactive Pneumococcal Serotypes. | Anti-19A [pre-booster] | 0.19 µg/mL |
Secondary
Concentrations of Antibodies Against Cross-reactive Pneumococcal Serotypes.
Cross-reactive pneumococcal serotypes assessed were serotypes 6A and 19A. Concentrations were expressed as geometric mean concentrations (GMCs) in microgram per millilitre (µg/mL). The antibody concentrations against the cross-reactive pneumococcal serotypes 6A and 19A were determined by 22F-inhibition Enzyme-linked immunosorbent assay (ELISA). The cut-off of the assay was 0.05 µg/mL.
Time frame: Before and one month after booster vaccination (at Month 0 and Month 1)
Population: The ATP cohort for immunogenicity included evaluable subjects for whom assay results were available for antibodies against at least 1 study vaccine antigen component after booster vaccination.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Synflorix™ Clinical-Commercial + Infanrix™-IPV/Hib Group | Concentrations of Antibodies Against Cross-reactive Pneumococcal Serotypes. | Anti-6A [pre-booster] | 0.23 µg/mL |
| Synflorix™ Clinical-Commercial + Infanrix™-IPV/Hib Group | Concentrations of Antibodies Against Cross-reactive Pneumococcal Serotypes. | Anti-6A [post-booster] | 2.13 µg/mL |
| Synflorix™ Clinical-Commercial + Infanrix™-IPV/Hib Group | Concentrations of Antibodies Against Cross-reactive Pneumococcal Serotypes. | Anti-19A [pre-booster] | 0.18 µg/mL |
| Synflorix™ Clinical-Commercial + Infanrix™-IPV/Hib Group | Concentrations of Antibodies Against Cross-reactive Pneumococcal Serotypes. | Anti-19A [post-booster] | 2.13 µg/mL |
| Synflorix™ Commercial-Commercial + Infanrix™-IPV/Hib Group | Concentrations of Antibodies Against Cross-reactive Pneumococcal Serotypes. | Anti-19A [post-booster] | 2.96 µg/mL |
| Synflorix™ Commercial-Commercial + Infanrix™-IPV/Hib Group | Concentrations of Antibodies Against Cross-reactive Pneumococcal Serotypes. | Anti-6A [pre-booster] | 0.21 µg/mL |
| Synflorix™ Commercial-Commercial + Infanrix™-IPV/Hib Group | Concentrations of Antibodies Against Cross-reactive Pneumococcal Serotypes. | Anti-19A [pre-booster] | 0.20 µg/mL |
| Synflorix™ Commercial-Commercial + Infanrix™-IPV/Hib Group | Concentrations of Antibodies Against Cross-reactive Pneumococcal Serotypes. | Anti-6A [post-booster] | 1.99 µg/mL |
Secondary
Concentrations of Antibodies Against Diphtheria and Tetanus.
Concentrations were expressed as geometric mean concentrations (GMCs) in International units per millilitre (IU/mL). The cut-off of the assay was 0.1 IU/mL.
Time frame: Before and one month after booster vaccination (at Month 0 and Month 1)
Population: The ATP cohort for immunogenicity included evaluable subjects for whom assay results were available for antibodies against at least 1 study vaccine antigen component after booster vaccination.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Synflorix™ Clinical-Commercial + Infanrix™-IPV/Hib Group | Concentrations of Antibodies Against Diphtheria and Tetanus. | Anti-diphtheria [pre-booster] | 0.31 IU/mL |
| Synflorix™ Clinical-Commercial + Infanrix™-IPV/Hib Group | Concentrations of Antibodies Against Diphtheria and Tetanus. | Anti-diphtheria [post-booster] | 8.17 IU/mL |
| Synflorix™ Clinical-Commercial + Infanrix™-IPV/Hib Group | Concentrations of Antibodies Against Diphtheria and Tetanus. | Anti-tetanus [pre-booster] | 0.52 IU/mL |
| Synflorix™ Clinical-Commercial + Infanrix™-IPV/Hib Group | Concentrations of Antibodies Against Diphtheria and Tetanus. | Anti-tetanus [post-booster] | 14.35 IU/mL |
| Synflorix™ Commercial-Commercial + Infanrix™-IPV/Hib Group | Concentrations of Antibodies Against Diphtheria and Tetanus. | Anti-tetanus [post-booster] | 14.73 IU/mL |
| Synflorix™ Commercial-Commercial + Infanrix™-IPV/Hib Group | Concentrations of Antibodies Against Diphtheria and Tetanus. | Anti-diphtheria [pre-booster] | 0.29 IU/mL |
| Synflorix™ Commercial-Commercial + Infanrix™-IPV/Hib Group | Concentrations of Antibodies Against Diphtheria and Tetanus. | Anti-tetanus [pre-booster] | 0.46 IU/mL |
| Synflorix™ Commercial-Commercial + Infanrix™-IPV/Hib Group | Concentrations of Antibodies Against Diphtheria and Tetanus. | Anti-diphtheria [post-booster] | 10.89 IU/mL |
Secondary
Concentrations of Antibodies Against Diphtheria and Tetanus.
Concentrations were expressed as geometric mean concentrations (GMCs) in International units per millilitre (IU/mL). The cut-off of the assay was 0.1 IU/mL.
Time frame: Before booster vaccination at Month 0
Population: The analysis was performed on the According-To-Protocol cohort for analysis of antibody persistence which included subjects primed in the primary study (NCT00808444) and for whom assay results were available for antibodies against at least 1 vaccine antigen component for the blood sampling taken before the administration of the booster dose.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Synflorix™ Clinical-Commercial + Infanrix™-IPV/Hib Group | Concentrations of Antibodies Against Diphtheria and Tetanus. | Anti-diphtheria [pre-booster] | 0.32 IU/mL |
| Synflorix™ Clinical-Commercial + Infanrix™-IPV/Hib Group | Concentrations of Antibodies Against Diphtheria and Tetanus. | Anti-tetanus [pre-booster] | 0.51 IU/mL |
| Synflorix™ Commercial-Commercial + Infanrix™-IPV/Hib Group | Concentrations of Antibodies Against Diphtheria and Tetanus. | Anti-diphtheria [pre-booster] | 0.30 IU/mL |
| Synflorix™ Commercial-Commercial + Infanrix™-IPV/Hib Group | Concentrations of Antibodies Against Diphtheria and Tetanus. | Anti-tetanus [pre-booster] | 0.47 IU/mL |
Secondary
Concentrations of Antibodies Against Pertussis Toxoid (PT), Filamentous Haemagglutinin (FHA) and Pertactin (PRN).
Concentrations were expressed as geometric mean concentrations (GMCs) in ELISA units per millilitre (EU/mL). The cut-off of the assay was 5 EU/mL.
Time frame: Before booster vaccination at Month 0
Population: The analysis was performed on the According-To-Protocol cohort for analysis of antibody persistence which included subjects primed in the primary study (NCT00808444) and for whom assay results were available for antibodies against at least 1 vaccine antigen component for the blood sampling taken before the administration of the booster dose.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Synflorix™ Clinical-Commercial + Infanrix™-IPV/Hib Group | Concentrations of Antibodies Against Pertussis Toxoid (PT), Filamentous Haemagglutinin (FHA) and Pertactin (PRN). | Anti-PT [pre-booster] | 5.7 EU/mL |
| Synflorix™ Clinical-Commercial + Infanrix™-IPV/Hib Group | Concentrations of Antibodies Against Pertussis Toxoid (PT), Filamentous Haemagglutinin (FHA) and Pertactin (PRN). | Anti-FHA [pre-booster] | 19.5 EU/mL |
| Synflorix™ Clinical-Commercial + Infanrix™-IPV/Hib Group | Concentrations of Antibodies Against Pertussis Toxoid (PT), Filamentous Haemagglutinin (FHA) and Pertactin (PRN). | Anti-PRN [pre-booster] | 14.8 EU/mL |
| Synflorix™ Commercial-Commercial + Infanrix™-IPV/Hib Group | Concentrations of Antibodies Against Pertussis Toxoid (PT), Filamentous Haemagglutinin (FHA) and Pertactin (PRN). | Anti-PT [pre-booster] | 6.5 EU/mL |
| Synflorix™ Commercial-Commercial + Infanrix™-IPV/Hib Group | Concentrations of Antibodies Against Pertussis Toxoid (PT), Filamentous Haemagglutinin (FHA) and Pertactin (PRN). | Anti-FHA [pre-booster] | 29.2 EU/mL |
| Synflorix™ Commercial-Commercial + Infanrix™-IPV/Hib Group | Concentrations of Antibodies Against Pertussis Toxoid (PT), Filamentous Haemagglutinin (FHA) and Pertactin (PRN). | Anti-PRN [pre-booster] | 15.1 EU/mL |
Secondary
Concentrations of Antibodies Against Pertussis Toxoid (PT), Filamentous Haemagglutinin (FHA) and Pertactin (PRN).
Concentrations were expressed as geometric mean concentrations (GMCs) in ELISA units per millilitre (EU/mL). The cut-off of the assay was 5 EU/mL.
Time frame: Before and one month after booster vaccination (at Month 0 and Month 1)
Population: The ATP cohort for immunogenicity included evaluable subjects for whom assay results were available for antibodies against at least 1 study vaccine antigen component after booster vaccination.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Synflorix™ Clinical-Commercial + Infanrix™-IPV/Hib Group | Concentrations of Antibodies Against Pertussis Toxoid (PT), Filamentous Haemagglutinin (FHA) and Pertactin (PRN). | Anti-PT [pre-booster] | 5.8 EU/mL |
| Synflorix™ Clinical-Commercial + Infanrix™-IPV/Hib Group | Concentrations of Antibodies Against Pertussis Toxoid (PT), Filamentous Haemagglutinin (FHA) and Pertactin (PRN). | Anti-PT [post-booster] | 80.8 EU/mL |
| Synflorix™ Clinical-Commercial + Infanrix™-IPV/Hib Group | Concentrations of Antibodies Against Pertussis Toxoid (PT), Filamentous Haemagglutinin (FHA) and Pertactin (PRN). | Anti-FHA [pre-booster] | 19.3 EU/mL |
| Synflorix™ Clinical-Commercial + Infanrix™-IPV/Hib Group | Concentrations of Antibodies Against Pertussis Toxoid (PT), Filamentous Haemagglutinin (FHA) and Pertactin (PRN). | Anti-FHA [post-booster] | 358.3 EU/mL |
| Synflorix™ Clinical-Commercial + Infanrix™-IPV/Hib Group | Concentrations of Antibodies Against Pertussis Toxoid (PT), Filamentous Haemagglutinin (FHA) and Pertactin (PRN). | Anti-PRN [pre-booster] | 15.0 EU/mL |
| Synflorix™ Clinical-Commercial + Infanrix™-IPV/Hib Group | Concentrations of Antibodies Against Pertussis Toxoid (PT), Filamentous Haemagglutinin (FHA) and Pertactin (PRN). | Anti-PRN [post-booster] | 314.3 EU/mL |
| Synflorix™ Commercial-Commercial + Infanrix™-IPV/Hib Group | Concentrations of Antibodies Against Pertussis Toxoid (PT), Filamentous Haemagglutinin (FHA) and Pertactin (PRN). | Anti-PRN [pre-booster] | 15.4 EU/mL |
| Synflorix™ Commercial-Commercial + Infanrix™-IPV/Hib Group | Concentrations of Antibodies Against Pertussis Toxoid (PT), Filamentous Haemagglutinin (FHA) and Pertactin (PRN). | Anti-PT [pre-booster] | 6.8 EU/mL |
| Synflorix™ Commercial-Commercial + Infanrix™-IPV/Hib Group | Concentrations of Antibodies Against Pertussis Toxoid (PT), Filamentous Haemagglutinin (FHA) and Pertactin (PRN). | Anti-FHA [post-booster] | 484.3 EU/mL |
| Synflorix™ Commercial-Commercial + Infanrix™-IPV/Hib Group | Concentrations of Antibodies Against Pertussis Toxoid (PT), Filamentous Haemagglutinin (FHA) and Pertactin (PRN). | Anti-PT [post-booster] | 86.0 EU/mL |
| Synflorix™ Commercial-Commercial + Infanrix™-IPV/Hib Group | Concentrations of Antibodies Against Pertussis Toxoid (PT), Filamentous Haemagglutinin (FHA) and Pertactin (PRN). | Anti-PRN [post-booster] | 509.5 EU/mL |
| Synflorix™ Commercial-Commercial + Infanrix™-IPV/Hib Group | Concentrations of Antibodies Against Pertussis Toxoid (PT), Filamentous Haemagglutinin (FHA) and Pertactin (PRN). | Anti-FHA [pre-booster] | 29.6 EU/mL |
Secondary
Concentrations of Antibodies Against Polyribosyl-ribitol Phosphate (PRP).
Concentrations were expressed as geometric mean concentrations (GMCs) in microgram per millilitre (µg/mL). The cut-off of the assay was 0.15 µg/mL.
Time frame: Before booster vaccination at Month 0
Population: The analysis was performed on the According-To-Protocol cohort for analysis of antibody persistence which included subjects primed in the primary study (NCT00808444) and for whom assay results were available for antibodies against at least 1 vaccine antigen component for the blood sampling taken before the administration of the booster dose.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Synflorix™ Clinical-Commercial + Infanrix™-IPV/Hib Group | Concentrations of Antibodies Against Polyribosyl-ribitol Phosphate (PRP). | 0.68 µg/mL |
| Synflorix™ Commercial-Commercial + Infanrix™-IPV/Hib Group | Concentrations of Antibodies Against Polyribosyl-ribitol Phosphate (PRP). | 0.85 µg/mL |
Secondary
Concentrations of Antibodies Against Polyribosyl-ribitol Phosphate (PRP).
Concentrations were expressed as geometric mean concentrations (GMCs) in microgram per millilitre (µg/mL). The cut-off of the assay was 0.15 µg/mL.
Time frame: Before and one month after booster vaccination (at Month 0 and Month 1)
Population: The ATP cohort for immunogenicity included evaluable subjects for whom assay results were available for antibodies against at least 1 study vaccine antigen component after booster vaccination.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Synflorix™ Clinical-Commercial + Infanrix™-IPV/Hib Group | Concentrations of Antibodies Against Polyribosyl-ribitol Phosphate (PRP). | Anti-PRP [pre-booster] | 0.66 µg/mL |
| Synflorix™ Clinical-Commercial + Infanrix™-IPV/Hib Group | Concentrations of Antibodies Against Polyribosyl-ribitol Phosphate (PRP). | Anti-PRP [post-booster] | 58.26 µg/mL |
| Synflorix™ Commercial-Commercial + Infanrix™-IPV/Hib Group | Concentrations of Antibodies Against Polyribosyl-ribitol Phosphate (PRP). | Anti-PRP [pre-booster] | 0.84 µg/mL |
| Synflorix™ Commercial-Commercial + Infanrix™-IPV/Hib Group | Concentrations of Antibodies Against Polyribosyl-ribitol Phosphate (PRP). | Anti-PRP [post-booster] | 49.36 µg/mL |
Secondary
Concentrations of Antibodies Against Protein D (PD).
Anti-PD antibodies were determined using an ELISA assay. Concentration of specific PD antibodies was determined, using a standard reference serum. The cut-off of the assay is 100 ELISA units per millilitre (EU/mL).
Time frame: Before and one month after booster vaccination (at Month 0 and Month 1)
Population: The ATP cohort for immunogenicity included evaluable subjects for whom assay results were available for antibodies against at least 1 study vaccine antigen component after booster vaccination.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Synflorix™ Clinical-Commercial + Infanrix™-IPV/Hib Group | Concentrations of Antibodies Against Protein D (PD). | Anti-PD [pre-booster] | 794.9 EU/mL |
| Synflorix™ Clinical-Commercial + Infanrix™-IPV/Hib Group | Concentrations of Antibodies Against Protein D (PD). | Anti-PD [post-booster] | 3631.3 EU/mL |
| Synflorix™ Commercial-Commercial + Infanrix™-IPV/Hib Group | Concentrations of Antibodies Against Protein D (PD). | Anti-PD [pre-booster] | 618.4 EU/mL |
| Synflorix™ Commercial-Commercial + Infanrix™-IPV/Hib Group | Concentrations of Antibodies Against Protein D (PD). | Anti-PD [post-booster] | 3115.9 EU/mL |
Secondary
Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes.
Vaccine pneumococcal serotypes assessed were serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F. Concentrations were expressed as geometric mean concentrations (GMCs) in microgram per millilitre (µg/mL). Pneumococcal serotype specific total imunoglobuline G (IgG) antibodies were measured by 22F-inhibition Enzyme-linked immunosorbent assay (ELISA). The cut-off of the assay was 0.05 µg/mL.
Time frame: Before and one month after booster vaccination (at Month 0 and Month 1)
Population: The ATP cohort for immunogenicity included evaluable subjects for whom assay results were available for antibodies against at least 1 study vaccine antigen component after booster vaccination.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Synflorix™ Clinical-Commercial + Infanrix™-IPV/Hib Group | Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes. | Anti-1 [pre-booster] | 0.48 µg/mL |
| Synflorix™ Clinical-Commercial + Infanrix™-IPV/Hib Group | Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes. | Anti-1 [post-booster] | 7.14 µg/mL |
| Synflorix™ Clinical-Commercial + Infanrix™-IPV/Hib Group | Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes. | Anti-4 [pre-booster] | 0.56 µg/mL |
| Synflorix™ Clinical-Commercial + Infanrix™-IPV/Hib Group | Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes. | Anti-4 [post-booster] | 7.53 µg/mL |
| Synflorix™ Clinical-Commercial + Infanrix™-IPV/Hib Group | Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes. | Anti-5 [pre-booster] | 0.77 µg/mL |
| Synflorix™ Clinical-Commercial + Infanrix™-IPV/Hib Group | Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes. | Anti-5 [post-booster] | 7.91 µg/mL |
| Synflorix™ Clinical-Commercial + Infanrix™-IPV/Hib Group | Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes. | Anti-6B [pre-booster] | 0.34 µg/mL |
| Synflorix™ Clinical-Commercial + Infanrix™-IPV/Hib Group | Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes. | Anti-6B [post-booster] | 3.30 µg/mL |
| Synflorix™ Clinical-Commercial + Infanrix™-IPV/Hib Group | Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes. | Anti-7F [pre-booster] | 0.88 µg/mL |
| Synflorix™ Clinical-Commercial + Infanrix™-IPV/Hib Group | Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes. | Anti-7F [post-booster] | 9.02 µg/mL |
| Synflorix™ Clinical-Commercial + Infanrix™-IPV/Hib Group | Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes. | Anti-9V [pre-booster] | 0.90 µg/mL |
| Synflorix™ Clinical-Commercial + Infanrix™-IPV/Hib Group | Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes. | Anti-9V [post-booster] | 9.36 µg/mL |
| Synflorix™ Clinical-Commercial + Infanrix™-IPV/Hib Group | Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes. | Anti-14 [pre-booster] | 1.05 µg/mL |
| Synflorix™ Clinical-Commercial + Infanrix™-IPV/Hib Group | Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes. | Anti-14 [post-booster] | 13.03 µg/mL |
| Synflorix™ Clinical-Commercial + Infanrix™-IPV/Hib Group | Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes. | Anti-18C [pre-booster] | 0.83 µg/mL |
| Synflorix™ Clinical-Commercial + Infanrix™-IPV/Hib Group | Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes. | Anti-18C [post-booster] | 19.80 µg/mL |
| Synflorix™ Clinical-Commercial + Infanrix™-IPV/Hib Group | Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes. | Anti-19F [pre-booster] | 1.11 µg/mL |
| Synflorix™ Clinical-Commercial + Infanrix™-IPV/Hib Group | Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes. | Anti-19F [post-booster] | 19.68 µg/mL |
| Synflorix™ Clinical-Commercial + Infanrix™-IPV/Hib Group | Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes. | Anti-23F [pre-booster] | 0.65 µg/mL |
| Synflorix™ Clinical-Commercial + Infanrix™-IPV/Hib Group | Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes. | Anti-23F [post-booster] | 7.19 µg/mL |
| Synflorix™ Commercial-Commercial + Infanrix™-IPV/Hib Group | Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes. | Anti-19F [post-booster] | 20.55 µg/mL |
| Synflorix™ Commercial-Commercial + Infanrix™-IPV/Hib Group | Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes. | Anti-1 [pre-booster] | 0.35 µg/mL |
| Synflorix™ Commercial-Commercial + Infanrix™-IPV/Hib Group | Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes. | Anti-9V [pre-booster] | 0.72 µg/mL |
| Synflorix™ Commercial-Commercial + Infanrix™-IPV/Hib Group | Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes. | Anti-1 [post-booster] | 6.29 µg/mL |
| Synflorix™ Commercial-Commercial + Infanrix™-IPV/Hib Group | Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes. | Anti-18C [post-booster] | 24.19 µg/mL |
| Synflorix™ Commercial-Commercial + Infanrix™-IPV/Hib Group | Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes. | Anti-4 [pre-booster] | 0.48 µg/mL |
| Synflorix™ Commercial-Commercial + Infanrix™-IPV/Hib Group | Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes. | Anti-9V [post-booster] | 10.42 µg/mL |
| Synflorix™ Commercial-Commercial + Infanrix™-IPV/Hib Group | Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes. | Anti-4 [post-booster] | 7.43 µg/mL |
| Synflorix™ Commercial-Commercial + Infanrix™-IPV/Hib Group | Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes. | Anti-23F [post-booster] | 6.83 µg/mL |
| Synflorix™ Commercial-Commercial + Infanrix™-IPV/Hib Group | Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes. | Anti-5 [pre-booster] | 0.54 µg/mL |
| Synflorix™ Commercial-Commercial + Infanrix™-IPV/Hib Group | Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes. | Anti-14 [pre-booster] | 0.93 µg/mL |
| Synflorix™ Commercial-Commercial + Infanrix™-IPV/Hib Group | Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes. | Anti-5 [post-booster] | 7.16 µg/mL |
| Synflorix™ Commercial-Commercial + Infanrix™-IPV/Hib Group | Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes. | Anti-19F [pre-booster] | 0.97 µg/mL |
| Synflorix™ Commercial-Commercial + Infanrix™-IPV/Hib Group | Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes. | Anti-6B [pre-booster] | 0.32 µg/mL |
| Synflorix™ Commercial-Commercial + Infanrix™-IPV/Hib Group | Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes. | Anti-14 [post-booster] | 13.28 µg/mL |
| Synflorix™ Commercial-Commercial + Infanrix™-IPV/Hib Group | Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes. | Anti-6B [post-booster] | 3.12 µg/mL |
| Synflorix™ Commercial-Commercial + Infanrix™-IPV/Hib Group | Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes. | Anti-23F [pre-booster] | 0.47 µg/mL |
| Synflorix™ Commercial-Commercial + Infanrix™-IPV/Hib Group | Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes. | Anti-7F [pre-booster] | 0.93 µg/mL |
| Synflorix™ Commercial-Commercial + Infanrix™-IPV/Hib Group | Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes. | Anti-18C [pre-booster] | 0.78 µg/mL |
| Synflorix™ Commercial-Commercial + Infanrix™-IPV/Hib Group | Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes. | Anti-7F [post-booster] | 9.25 µg/mL |
Secondary
Number of Subjects Reporting Any and Grade 3 Solicited Local Adverse Events (AEs).
Solicited AEs = AEs to be recorded as endpoints in the clinical study. The presence/occurrence/intensity of these events is actively solicited from the subject or an observer during a specified post-vaccination follow-up period. Solicited local symptoms assessed were pain, redness and swelling. Any = occurrence 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 (mm).
Time frame: Within 4 days (Days 0-3) after booster vaccination.
Population: The analysis of safety was performed on the Total vaccinated cohort which included all subjects with booster dose administration documented. The analysis of the solicited symptoms based on the Total Vaccinated cohort included subjects with documented safety data.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Synflorix™ Clinical-Commercial + Infanrix™-IPV/Hib Group | Number of Subjects Reporting Any and Grade 3 Solicited Local Adverse Events (AEs). | Any pain | 61 Participants |
| Synflorix™ Clinical-Commercial + Infanrix™-IPV/Hib Group | Number of Subjects Reporting Any and Grade 3 Solicited Local Adverse Events (AEs). | Grade 3 pain | 8 Participants |
| Synflorix™ Clinical-Commercial + Infanrix™-IPV/Hib Group | Number of Subjects Reporting Any and Grade 3 Solicited Local Adverse Events (AEs). | Any redness | 66 Participants |
| Synflorix™ Clinical-Commercial + Infanrix™-IPV/Hib Group | Number of Subjects Reporting Any and Grade 3 Solicited Local Adverse Events (AEs). | Grade 3 redness | 0 Participants |
| Synflorix™ Clinical-Commercial + Infanrix™-IPV/Hib Group | Number of Subjects Reporting Any and Grade 3 Solicited Local Adverse Events (AEs). | Any swelling | 45 Participants |
| Synflorix™ Clinical-Commercial + Infanrix™-IPV/Hib Group | Number of Subjects Reporting Any and Grade 3 Solicited Local Adverse Events (AEs). | Grade 3 swelling | 1 Participants |
| Synflorix™ Commercial-Commercial + Infanrix™-IPV/Hib Group | Number of Subjects Reporting Any and Grade 3 Solicited Local Adverse Events (AEs). | Any swelling | 49 Participants |
| Synflorix™ Commercial-Commercial + Infanrix™-IPV/Hib Group | Number of Subjects Reporting Any and Grade 3 Solicited Local Adverse Events (AEs). | Any pain | 70 Participants |
| Synflorix™ Commercial-Commercial + Infanrix™-IPV/Hib Group | Number of Subjects Reporting Any and Grade 3 Solicited Local Adverse Events (AEs). | Grade 3 redness | 0 Participants |
| Synflorix™ Commercial-Commercial + Infanrix™-IPV/Hib Group | Number of Subjects Reporting Any and Grade 3 Solicited Local Adverse Events (AEs). | Grade 3 pain | 13 Participants |
| Synflorix™ Commercial-Commercial + Infanrix™-IPV/Hib Group | Number of Subjects Reporting Any and Grade 3 Solicited Local Adverse Events (AEs). | Grade 3 swelling | 0 Participants |
| Synflorix™ Commercial-Commercial + Infanrix™-IPV/Hib Group | Number of Subjects Reporting Any and Grade 3 Solicited Local Adverse Events (AEs). | Any redness | 61 Participants |
Secondary
Number of Subjects Reporting Any, Grade 3 and Related Solicited General Adverse Events (AEs).
Solicited general symptoms assessed were drowsiness, irritability, loss of appetite and fever (= axillary temperature equal to or above 37.5 degrees Celsius (°C)). Any= occurrence of any general symptom regardless of intensity grade or relationship to vaccination Grade 3 drowsiness = drowsiness which prevented normal activity. Grade 3 irritability = crying that could not be comforted/ prevented normal activity. Grade 3 loss of appetite = not eating at all. Grade 3 fever = temperature \>39.5°C. Related = solicited symptom assessed by the investigator as causally related to study vaccination.
Time frame: Within 4 days (Days 0-3) after booster vaccination.
Population: The analysis of safety was performed on the Total vaccinated cohort which included all subjects with booster dose administration documented. The analysis of the solicited symptoms based on the Total Vaccinated cohort included subjects with documented safety data.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Synflorix™ Clinical-Commercial + Infanrix™-IPV/Hib Group | Number of Subjects Reporting Any, Grade 3 and Related Solicited General Adverse Events (AEs). | Any drowsiness | 38 Participants |
| Synflorix™ Clinical-Commercial + Infanrix™-IPV/Hib Group | Number of Subjects Reporting Any, Grade 3 and Related Solicited General Adverse Events (AEs). | Grade 3 drowsiness | 2 Participants |
| Synflorix™ Clinical-Commercial + Infanrix™-IPV/Hib Group | Number of Subjects Reporting Any, Grade 3 and Related Solicited General Adverse Events (AEs). | Related drowsiness | 38 Participants |
| Synflorix™ Clinical-Commercial + Infanrix™-IPV/Hib Group | Number of Subjects Reporting Any, Grade 3 and Related Solicited General Adverse Events (AEs). | Fever >= 37.5°C | 56 Participants |
| Synflorix™ Clinical-Commercial + Infanrix™-IPV/Hib Group | Number of Subjects Reporting Any, Grade 3 and Related Solicited General Adverse Events (AEs). | Fever > 39.5°C | 1 Participants |
| Synflorix™ Clinical-Commercial + Infanrix™-IPV/Hib Group | Number of Subjects Reporting Any, Grade 3 and Related Solicited General Adverse Events (AEs). | Related fever | 55 Participants |
| Synflorix™ Clinical-Commercial + Infanrix™-IPV/Hib Group | Number of Subjects Reporting Any, Grade 3 and Related Solicited General Adverse Events (AEs). | Any irritability | 51 Participants |
| Synflorix™ Clinical-Commercial + Infanrix™-IPV/Hib Group | Number of Subjects Reporting Any, Grade 3 and Related Solicited General Adverse Events (AEs). | Grade 3 irritability | 3 Participants |
| Synflorix™ Clinical-Commercial + Infanrix™-IPV/Hib Group | Number of Subjects Reporting Any, Grade 3 and Related Solicited General Adverse Events (AEs). | Related irritability | 50 Participants |
| Synflorix™ Clinical-Commercial + Infanrix™-IPV/Hib Group | Number of Subjects Reporting Any, Grade 3 and Related Solicited General Adverse Events (AEs). | Any loss of appetite | 42 Participants |
| Synflorix™ Clinical-Commercial + Infanrix™-IPV/Hib Group | Number of Subjects Reporting Any, Grade 3 and Related Solicited General Adverse Events (AEs). | Grade 3 loss of appetite | 1 Participants |
| Synflorix™ Clinical-Commercial + Infanrix™-IPV/Hib Group | Number of Subjects Reporting Any, Grade 3 and Related Solicited General Adverse Events (AEs). | Related loss of appetite | 41 Participants |
| Synflorix™ Commercial-Commercial + Infanrix™-IPV/Hib Group | Number of Subjects Reporting Any, Grade 3 and Related Solicited General Adverse Events (AEs). | Grade 3 loss of appetite | 1 Participants |
| Synflorix™ Commercial-Commercial + Infanrix™-IPV/Hib Group | Number of Subjects Reporting Any, Grade 3 and Related Solicited General Adverse Events (AEs). | Any drowsiness | 49 Participants |
| Synflorix™ Commercial-Commercial + Infanrix™-IPV/Hib Group | Number of Subjects Reporting Any, Grade 3 and Related Solicited General Adverse Events (AEs). | Any irritability | 67 Participants |
| Synflorix™ Commercial-Commercial + Infanrix™-IPV/Hib Group | Number of Subjects Reporting Any, Grade 3 and Related Solicited General Adverse Events (AEs). | Grade 3 drowsiness | 2 Participants |
| Synflorix™ Commercial-Commercial + Infanrix™-IPV/Hib Group | Number of Subjects Reporting Any, Grade 3 and Related Solicited General Adverse Events (AEs). | Any loss of appetite | 49 Participants |
| Synflorix™ Commercial-Commercial + Infanrix™-IPV/Hib Group | Number of Subjects Reporting Any, Grade 3 and Related Solicited General Adverse Events (AEs). | Related drowsiness | 48 Participants |
| Synflorix™ Commercial-Commercial + Infanrix™-IPV/Hib Group | Number of Subjects Reporting Any, Grade 3 and Related Solicited General Adverse Events (AEs). | Grade 3 irritability | 5 Participants |
| Synflorix™ Commercial-Commercial + Infanrix™-IPV/Hib Group | Number of Subjects Reporting Any, Grade 3 and Related Solicited General Adverse Events (AEs). | Fever >= 37.5°C | 75 Participants |
| Synflorix™ Commercial-Commercial + Infanrix™-IPV/Hib Group | Number of Subjects Reporting Any, Grade 3 and Related Solicited General Adverse Events (AEs). | Related loss of appetite | 47 Participants |
| Synflorix™ Commercial-Commercial + Infanrix™-IPV/Hib Group | Number of Subjects Reporting Any, Grade 3 and Related Solicited General Adverse Events (AEs). | Fever > 39.5°C | 1 Participants |
| Synflorix™ Commercial-Commercial + Infanrix™-IPV/Hib Group | Number of Subjects Reporting Any, Grade 3 and Related Solicited General Adverse Events (AEs). | Related irritability | 67 Participants |
| Synflorix™ Commercial-Commercial + Infanrix™-IPV/Hib Group | Number of Subjects Reporting Any, Grade 3 and Related Solicited General Adverse Events (AEs). | Related fever | 72 Participants |
Secondary
Number of Subjects Reporting 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 a study subjects.
Time frame: During the entire study period, from the booster vaccination, at Month 0, up to the study end, at Month 1
Population: The analysis of safety was performed on the Total vaccinated cohort which included all subjects with booster dose administration documented.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Synflorix™ Clinical-Commercial + Infanrix™-IPV/Hib Group | Number of Subjects Reporting Serious Adverse Events (SAEs). | 0 Participants |
| Synflorix™ Commercial-Commercial + Infanrix™-IPV/Hib Group | Number of Subjects Reporting Serious Adverse Events (SAEs). | 4 Participants |
Secondary
Number of Subjects Reporting Unsolicited Adverse Events (AEs).
Unsolicited AEs = Any AE (i.e. any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product) reported in addition to those solicited during the clinical study. Also any solicited symptom with onset outside the specified period of follow-up for solicited symptoms was reported as an unsolicited adverse event.
Time frame: Within 31 days (Days 0-30) after booster vaccination
Population: The analysis of safety was performed on the Total vaccinated cohort which included all subjects with booster dose administration documented.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Synflorix™ Clinical-Commercial + Infanrix™-IPV/Hib Group | Number of Subjects Reporting Unsolicited Adverse Events (AEs). | 18 Participants |
| Synflorix™ Commercial-Commercial + Infanrix™-IPV/Hib Group | Number of Subjects Reporting Unsolicited Adverse Events (AEs). | 25 Participants |
Secondary
Opsonophagocytic Activity Against Cross-reactive Pneumococcal Serotypes 6A and 19A.
Opsonophagocytic activity (OPA) testing was not performed.
Time frame: Before and one month after booster vaccination (at Month 0 and Month 1)
Secondary
Opsonophagocytic Activity Against Vaccine Pneumococcal Serotypes.
Opsonophagocytic activity (OPA) testing was not performed.
Time frame: Before and one month after booster vaccination (at Month 0 and Month 1)
Secondary
Titers of Antibodies Against Poliovirus Types 1, 2 and 3.
Titers were expresses as geometric mean titers (GMTs). The cut-off of the assay was 8.
Time frame: Before and one month after booster vaccination (at Month 0 and Month 1)
Population: The ATP cohort for immunogenicity included evaluable subjects for whom assay results were available for antibodies against at least 1 study vaccine antigen component after booster vaccination.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Synflorix™ Clinical-Commercial + Infanrix™-IPV/Hib Group | Titers of Antibodies Against Poliovirus Types 1, 2 and 3. | Anti-polio 1 [post-booster] | 982.2 Titers |
| Synflorix™ Clinical-Commercial + Infanrix™-IPV/Hib Group | Titers of Antibodies Against Poliovirus Types 1, 2 and 3. | Anti-polio 2 [post-booster] | 1144.1 Titers |
| Synflorix™ Clinical-Commercial + Infanrix™-IPV/Hib Group | Titers of Antibodies Against Poliovirus Types 1, 2 and 3. | Anti-polio 1 [pre-booster] | 44.2 Titers |
| Synflorix™ Clinical-Commercial + Infanrix™-IPV/Hib Group | Titers of Antibodies Against Poliovirus Types 1, 2 and 3. | Anti-polio 3 [pre-booster] | 41.0 Titers |
| Synflorix™ Clinical-Commercial + Infanrix™-IPV/Hib Group | Titers of Antibodies Against Poliovirus Types 1, 2 and 3. | Anti-polio 3 [post-booster] | 1350.8 Titers |
| Synflorix™ Clinical-Commercial + Infanrix™-IPV/Hib Group | Titers of Antibodies Against Poliovirus Types 1, 2 and 3. | Anti-polio 2 [pre-booster] | 38.0 Titers |
| Synflorix™ Commercial-Commercial + Infanrix™-IPV/Hib Group | Titers of Antibodies Against Poliovirus Types 1, 2 and 3. | Anti-polio 3 [post-booster] | 1527.4 Titers |
| Synflorix™ Commercial-Commercial + Infanrix™-IPV/Hib Group | Titers of Antibodies Against Poliovirus Types 1, 2 and 3. | Anti-polio 1 [pre-booster] | 32.8 Titers |
| Synflorix™ Commercial-Commercial + Infanrix™-IPV/Hib Group | Titers of Antibodies Against Poliovirus Types 1, 2 and 3. | Anti-polio 1 [post-booster] | 985.2 Titers |
| Synflorix™ Commercial-Commercial + Infanrix™-IPV/Hib Group | Titers of Antibodies Against Poliovirus Types 1, 2 and 3. | Anti-polio 2 [pre-booster] | 34.9 Titers |
| Synflorix™ Commercial-Commercial + Infanrix™-IPV/Hib Group | Titers of Antibodies Against Poliovirus Types 1, 2 and 3. | Anti-polio 2 [post-booster] | 823.4 Titers |
| Synflorix™ Commercial-Commercial + Infanrix™-IPV/Hib Group | Titers of Antibodies Against Poliovirus Types 1, 2 and 3. | Anti-polio 3 [pre-booster] | 43.3 Titers |
Secondary
Titers of Antibodies Against Poliovirus Types 1, 2 and 3.
Titers were expresses as geometric mean titers (GMTs). The cut-off of the assay was 8.
Time frame: Before booster vaccination at Month 0
Population: The analysis was performed on the According-To-Protocol cohort for analysis of antibody persistence which included subjects primed in the primary study (NCT00808444) and for whom assay results were available for antibodies against at least 1 vaccine antigen component for the blood sampling taken before the administration of the booster dose.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Synflorix™ Clinical-Commercial + Infanrix™-IPV/Hib Group | Titers of Antibodies Against Poliovirus Types 1, 2 and 3. | Anti-polio 1 [pre-booster] | 40.7 Titers |
| Synflorix™ Clinical-Commercial + Infanrix™-IPV/Hib Group | Titers of Antibodies Against Poliovirus Types 1, 2 and 3. | Anti-polio 2 [pre-booster] | 38.7 Titers |
| Synflorix™ Clinical-Commercial + Infanrix™-IPV/Hib Group | Titers of Antibodies Against Poliovirus Types 1, 2 and 3. | Anti-polio 3 [pre-booster] | 40.7 Titers |
| Synflorix™ Commercial-Commercial + Infanrix™-IPV/Hib Group | Titers of Antibodies Against Poliovirus Types 1, 2 and 3. | Anti-polio 1 [pre-booster] | 32.8 Titers |
| Synflorix™ Commercial-Commercial + Infanrix™-IPV/Hib Group | Titers of Antibodies Against Poliovirus Types 1, 2 and 3. | Anti-polio 2 [pre-booster] | 34.9 Titers |
| Synflorix™ Commercial-Commercial + Infanrix™-IPV/Hib Group | Titers of Antibodies Against Poliovirus Types 1, 2 and 3. | Anti-polio 3 [pre-booster] | 43.3 Titers |