Infections, Streptococcal, Streptococcus Pneumoniae
Conditions
Keywords
Pneumococcal disease, Pneumococcal vaccine, Safety, Primary vaccination, Immunogenicity
Brief summary
The purpose of this study is to assess the immunogenicity in terms of antibody response and the safety/reactogenicity in terms of solicited and unsolicited symptoms and serious adverse events following primary vaccination of Indian infants with pneumococcal conjugate vaccine GSK1024850A co-administered with a diphtheria, tetanus, whole cell pertussis (DTPw)-combined vaccine during the first 4 months of life. The study will be conducted in India.
Interventions
Intramuscular injection, 3 doses
BIOLOGICALTritanrix-HepB/Hib
Intramuscular injection, 3 doses
BIOLOGICALHiberix
Intramuscular injection, 3 doses
BIOLOGICALTritanrix-HepB
Intramuscular injection, 3 doses
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
6 Weeks to 10 Weeks
Healthy volunteers
Yes
Inclusion criteria
* Male or female subjects between, and including 6-10 weeks of age at the time of the first vaccination. * Subjects for whom the investigator believes that their parent(s)/guardian(s) can and will comply with the requirements of the protocol. * Written or oral, signed or thumb-printed informed consent obtained from the parent(s)/guardian(s) of the child/ward. Where parent(s)/guardian(s) are illiterate, the consent form will be countersigned by a witness. * Free of any known or suspected health problems (as established by medical history and clinical examination before entering into the study).
Exclusion criteria
* Use of any investigational or non-registered product (drug or vaccine) other than the study vaccines within 30 days preceding the first dose of the study vaccines, 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 (pharmaceutical product or device). * Chronic administration (defined as more than 14 days) of immunosuppressants or other immune-modifying drugs since birth. * A family history of congenital or hereditary immunodeficiency. * Any confirmed or suspected immunosuppressive or immunodeficient condition based on medical history and physical examination. * Administration of immunoglobulins and/or any blood products since birth or planned administration during the study period (with the exception of hepatitis B immunoglobulins at birth). * Previous vaccination against diphtheria, tetanus, pertussis, hepatitis B, Haemophilus influenzae type b and/or Streptococcus pneumoniae (with the exception of hepatitis B vaccination at birth or at least 30 days before the subject's first study visit). * History of, or intercurrent, diphtheria, tetanus, pertussis, hepatitis B, Streptococcus and Haemophilus influenzae type b disease. * History of allergic disease or reactions likely to be exacerbated by any component of the vaccines. * History of any neurological disorders or seizures. * Major congenital defects or serious chronic illness. * Acute disease at the time of enrolment. * Babies for which birth weight is \< 2 kilogram.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes | One month after primary immunization (month 3) | Concentrations were expressed as Geometric Mean Concentrations (GMCs) in microgram per milliliter (µg/mL). Pneumococcal serotypes included 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F. |
| Concentration of Antibody Against Protein D (PD) | One month after primary immunization (month 3) | Concentrations were expressed as GMCs GSK's 22F-inhibition in enzyme-linked-immunosorbent assay (ELISA) units per milliliter (EL.U/mL). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Concentrations of Antibodies Against Pneumococcal Cross-reactive Serotypes | One month after primary immunization (month 3) | Concentrations were expressed as GMCs in µg/mL. Pneumococcal cross-reactive serotypes included 6A and 19A. |
| Number of Subjects Seropositive for Pneumococcal Serotypes | One month after primary immunization (month 3) | Vaccine pneumococcal serotypes included 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F. Cross-reactive pneumococcal serotypes included 6A and 19A. Seropositivity was defined as a titer equal to or greater than 0.05 µg/mL |
| Number of Subjects Seropositive for Protein D (PD) | One month after primary immunization (month 3) | Seropositivity for PD was defined greater than or equal to 100 EL.U/mL. |
| Concentration of Antibody Against Polyribosyl-ribitol Phosphate (PRP) | One month after primary immunization (month 3) | Concentration is expressed as GMC in µg/mL. |
| Concentration of Antibodies Against Diphteria (Anti-DT) and Tetanus (Anti-TT) | One month after primary immunization (month 3) | Concentrations were expressed as GMCs in international units per milliliter (IU/mL). |
| Concentration of Antibody Against Bordetella Pertussis (B. Pertussis) | One month after primary immunization (month 3) | Concentration was expressed as GMC in EL.U/mL. |
| Number of Subjects With Opsonophagocytic Activity Against Pneumococcal Serotypes | One month after primary immunization (month 3) | Vaccine pneumococcal serotypes included 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F. Cross-reactive pneumococcal serotypes included 6A and 19A. Opsonophagocytic activity was defined as the dilution of serum (opsonic titer) able to sustain 50% killing of live pneumococci under the assay conditions. The cut-off of the assay was an opsonic titer equal to or greater than 8. |
| Number of Subjects Seropostive for B. Pertussis | One month after primary immunization (month 3) | Seropositivity was defined as and antibody concentration equal to or greater than 15 EL.U/mL. |
| Number of Seroprotected Subjects (Anti-DT, Anti-TT, Anti-PRP, Anti-HBs) | One month after primary immunization (month 3) | Seroprotection was defined as: Anti-DT antibody concentration equal to or greater than 0.1 IU/mL. Anti-TT antibody concentration equal to or greater than 0.1 IU/mL. Anti-PRP antibody concentration equal to or greater than 0.15 µg/mL Anti-HBs antibody concentration greater than or equal to 10 mIU/mL. |
| Number of Seroprotected Subjects (Anti-PRP Above the Cut-off of 1.0 µg/mL) | One month after primary immunization (month 3) | Anti-PRP antibody concentration equal to or greater than 1.0 µg/mL. |
| Number of Subjects With Solicited Local and General Symptoms | Within 4 days (day 0-3) after vaccination | Solicited local symptoms included pain, redness and swelling. Solicited general symptoms included drowsiness, fever (equal to or above 38 degrees Celsius and above 39 degrees Celsius), irritability and loss of appetite. |
| Number of Subjects With Unsolicited Adverse Events (AEs) | Within 31 days (day 0-30) after vaccination | An AE is 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. Unsolicited AE covers any AE 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 |
| Number of Subjects With Serious Adverse Events (SAEs) | Following first vaccination (Month 0) throughout the entire study period (month 3) | SAEs assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization, result in disability/incapacity or are a congenital anomaly/birth defect in the offspring of a study subject. |
| Concentration of Antibody Against Hepatitis B (Anti-HBs) by Enzyme-Linked ImmunoSorbent Assay (ELISA). | One month after primary immunization (month 3) | Concentration was expressed as GMC in milli international units per milliliter (mIU/mL). As a decrease in the specificity of the anti-HBs ELISA assay had been observed in some studies for low levels of antibody (10-100 mIU/mL), the table shows results following partial or complete retesting/reanalysis. |
| Number of Subjects With Antibody Concentrations Against Pneumococcal Serotypes Equal to or Above Cut-off Value | One month after primary immunization | Vaccine pneumococcal serotypes included 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F. Cross-reactive pneumococcal serotypes included 6A and 19A. The cut-off was defined as 0.20 microgram per milliliter (µg/mL). |
Countries
India
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Synflorix and Tritanrix-HepB/Hib Group Subjects received SynflorixTM (GSK1024850A) intramuscularly in the right thigh co-administered with TritanrixTM-HepB/Hib intramuscularly in the left thigh at 6-10-14 weeks of age (=study month 0, 1, 2) | 240 |
| Hiberix Group and Tritanrix-HepB Group Subjects received HiberixTM intramuscularly in the right thigh co-administered with TritanrixTM-HepB intramuscularly in the left thigh at 6-10-14 weeks of age (=study month 0, 1, 2) | 120 |
| Total | 360 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 |
| Overall Study | Lost to Follow-up | 7 | 3 |
Baseline characteristics
| Characteristic | Synflorix and Tritanrix-HepB/Hib Group | Hiberix Group and Tritanrix-HepB Group | Total |
|---|---|---|---|
| Age, Continuous | 6.7 Weeks STANDARD_DEVIATION 1.08 | 6.7 Weeks STANDARD_DEVIATION 1.05 | 6.7 Weeks STANDARD_DEVIATION 1.07 |
| Sex: Female, Male Female | 109 Participants | 66 Participants | 175 Participants |
| Sex: Female, Male Male | 131 Participants | 54 Participants | 185 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 231 / 240 | 114 / 120 |
| serious Total, serious adverse events | 5 / 240 | 1 / 120 |
Outcome results
Primary
Concentration of Antibody Against Protein D (PD)
Concentrations were expressed as GMCs GSK's 22F-inhibition in enzyme-linked-immunosorbent assay (ELISA) units per milliliter (EL.U/mL).
Time frame: One month after primary immunization (month 3)
Population: Analysis was performed on the According-to-Protocol cohort for immunogenicity, which included all evaluable subjects with available immunogenicity data.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Synflorix and Tritanrix-HepB/Hib Group | Concentration of Antibody Against Protein D (PD) | 2981.7 EL.U/mL |
| Hiberix Group and Tritanrix-HepB Group | Concentration of Antibody Against Protein D (PD) | 63.9 EL.U/mL |
Primary
Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes
Concentrations were expressed as Geometric Mean Concentrations (GMCs) in microgram per milliliter (µg/mL). Pneumococcal serotypes included 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F.
Time frame: One month after primary immunization (month 3)
Population: Analysis was performed on the According-to-Protocol cohort for immunogenicity, which included all evaluable subjects with available immunogenicity data.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Synflorix and Tritanrix-HepB/Hib Group | Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes | Anti-9V | 4.21 µg/mL |
| Synflorix and Tritanrix-HepB/Hib Group | Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes | Anti-5 | 4.17 µg/mL |
| Synflorix and Tritanrix-HepB/Hib Group | Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes | Anti-14 | 5.21 µg/mL |
| Synflorix and Tritanrix-HepB/Hib Group | Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes | Anti-4 | 3.80 µg/mL |
| Synflorix and Tritanrix-HepB/Hib Group | Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes | Anti-18C | 15.23 µg/mL |
| Synflorix and Tritanrix-HepB/Hib Group | Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes | Anti-6B | 0.71 µg/mL |
| Synflorix and Tritanrix-HepB/Hib Group | Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes | Anti-19F | 11.78 µg/mL |
| Synflorix and Tritanrix-HepB/Hib Group | Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes | Anti-7F | 3.87 µg/mL |
| Synflorix and Tritanrix-HepB/Hib Group | Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes | Anti-23F | 1.18 µg/mL |
| Synflorix and Tritanrix-HepB/Hib Group | Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes | Anti-1 | 3.27 µg/mL |
| Hiberix Group and Tritanrix-HepB Group | Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes | Anti-23F | 0.05 µg/mL |
| Hiberix Group and Tritanrix-HepB Group | Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes | Anti-1 | 0.03 µg/mL |
| Hiberix Group and Tritanrix-HepB Group | Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes | Anti-4 | 0.04 µg/mL |
| Hiberix Group and Tritanrix-HepB Group | Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes | Anti-5 | 0.05 µg/mL |
| Hiberix Group and Tritanrix-HepB Group | Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes | Anti-7F | 0.06 µg/mL |
| Hiberix Group and Tritanrix-HepB Group | Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes | Anti-9V | 0.06 µg/mL |
| Hiberix Group and Tritanrix-HepB Group | Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes | Anti-14 | 0.26 µg/mL |
| Hiberix Group and Tritanrix-HepB Group | Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes | Anti-18C | 0.07 µg/mL |
| Hiberix Group and Tritanrix-HepB Group | Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes | Anti-19F | 0.12 µg/mL |
| Hiberix Group and Tritanrix-HepB Group | Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes | Anti-6B | 0.05 µg/mL |
Secondary
Concentration of Antibodies Against Diphteria (Anti-DT) and Tetanus (Anti-TT)
Concentrations were expressed as GMCs in international units per milliliter (IU/mL).
Time frame: One month after primary immunization (month 3)
Population: Analysis was performed on the According-to-Protocol cohort for immunogenicity, which included all evaluable subjects with available immunogenicity data.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Synflorix and Tritanrix-HepB/Hib Group | Concentration of Antibodies Against Diphteria (Anti-DT) and Tetanus (Anti-TT) | Anti-DT | 2.580 IU/mL |
| Synflorix and Tritanrix-HepB/Hib Group | Concentration of Antibodies Against Diphteria (Anti-DT) and Tetanus (Anti-TT) | Anti-TT | 3.726 IU/mL |
| Hiberix Group and Tritanrix-HepB Group | Concentration of Antibodies Against Diphteria (Anti-DT) and Tetanus (Anti-TT) | Anti-DT | 2.065 IU/mL |
| Hiberix Group and Tritanrix-HepB Group | Concentration of Antibodies Against Diphteria (Anti-DT) and Tetanus (Anti-TT) | Anti-TT | 1.542 IU/mL |
Secondary
Concentration of Antibody Against Bordetella Pertussis (B. Pertussis)
Concentration was expressed as GMC in EL.U/mL.
Time frame: One month after primary immunization (month 3)
Population: Analysis was performed on the According-to-Protocol cohort for immunogenicity, which included all evaluable subjects with available immunogenicity data.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Synflorix and Tritanrix-HepB/Hib Group | Concentration of Antibody Against Bordetella Pertussis (B. Pertussis) | 90.3 EL.U/mL |
| Hiberix Group and Tritanrix-HepB Group | Concentration of Antibody Against Bordetella Pertussis (B. Pertussis) | 114.5 EL.U/mL |
Secondary
Concentration of Antibody Against Hepatitis B (Anti-HBs) by Enzyme-Linked ImmunoSorbent Assay (ELISA).
Concentration was expressed as GMC in milli international units per milliliter (mIU/mL). As a decrease in the specificity of the anti-HBs ELISA assay had been observed in some studies for low levels of antibody (10-100 mIU/mL), the table shows results following partial or complete retesting/reanalysis.
Time frame: One month after primary immunization (month 3)
Population: Analysis was performed on the According-to-Protocol cohort for immunogenicity, which included all evaluable subjects with available immunogenicity data.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Synflorix and Tritanrix-HepB/Hib Group | Concentration of Antibody Against Hepatitis B (Anti-HBs) by Enzyme-Linked ImmunoSorbent Assay (ELISA). | 1970.5 mIU/mL |
| Hiberix Group and Tritanrix-HepB Group | Concentration of Antibody Against Hepatitis B (Anti-HBs) by Enzyme-Linked ImmunoSorbent Assay (ELISA). | 1378.2 mIU/mL |
Secondary
Concentration of Antibody Against Polyribosyl-ribitol Phosphate (PRP)
Concentration is expressed as GMC in µg/mL.
Time frame: One month after primary immunization (month 3)
Population: Analysis was performed on the According-to-Protocol cohort for immunogenicity, which included all evaluable subjects with available immunogenicity data.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Synflorix and Tritanrix-HepB/Hib Group | Concentration of Antibody Against Polyribosyl-ribitol Phosphate (PRP) | 31.367 µg/mL |
| Hiberix Group and Tritanrix-HepB Group | Concentration of Antibody Against Polyribosyl-ribitol Phosphate (PRP) | 34.415 µg/mL |
Secondary
Concentrations of Antibodies Against Pneumococcal Cross-reactive Serotypes
Concentrations were expressed as GMCs in µg/mL. Pneumococcal cross-reactive serotypes included 6A and 19A.
Time frame: One month after primary immunization (month 3)
Population: Analysis was performed on the According-to-Protocol cohort for immunogenicity, which included all evaluable subjects with available immunogenicity data.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Synflorix and Tritanrix-HepB/Hib Group | Concentrations of Antibodies Against Pneumococcal Cross-reactive Serotypes | Anti-6A (N=229;115) | 0.15 µg/mL |
| Synflorix and Tritanrix-HepB/Hib Group | Concentrations of Antibodies Against Pneumococcal Cross-reactive Serotypes | Anti-19A | 0.33 µg/mL |
| Hiberix Group and Tritanrix-HepB Group | Concentrations of Antibodies Against Pneumococcal Cross-reactive Serotypes | Anti-6A (N=229;115) | 0.06 µg/mL |
| Hiberix Group and Tritanrix-HepB Group | Concentrations of Antibodies Against Pneumococcal Cross-reactive Serotypes | Anti-19A | 0.08 µg/mL |
Secondary
Number of Seroprotected Subjects (Anti-DT, Anti-TT, Anti-PRP, Anti-HBs)
Seroprotection was defined as: Anti-DT antibody concentration equal to or greater than 0.1 IU/mL. Anti-TT antibody concentration equal to or greater than 0.1 IU/mL. Anti-PRP antibody concentration equal to or greater than 0.15 µg/mL Anti-HBs antibody concentration greater than or equal to 10 mIU/mL.
Time frame: One month after primary immunization (month 3)
Population: Analysis was performed on the According-to-Protocol cohort for immunogenicity, which included all evaluable subjects with available immunogenicity data.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Synflorix and Tritanrix-HepB/Hib Group | Number of Seroprotected Subjects (Anti-DT, Anti-TT, Anti-PRP, Anti-HBs) | Anti-DT | 113 subjects |
| Synflorix and Tritanrix-HepB/Hib Group | Number of Seroprotected Subjects (Anti-DT, Anti-TT, Anti-PRP, Anti-HBs) | Anti-TT | 113 subjects |
| Synflorix and Tritanrix-HepB/Hib Group | Number of Seroprotected Subjects (Anti-DT, Anti-TT, Anti-PRP, Anti-HBs) | Anti-PRP 0.15 | 113 subjects |
| Synflorix and Tritanrix-HepB/Hib Group | Number of Seroprotected Subjects (Anti-DT, Anti-TT, Anti-PRP, Anti-HBs) | Anti-HBs (N=92,89) | 92 subjects |
| Hiberix Group and Tritanrix-HepB Group | Number of Seroprotected Subjects (Anti-DT, Anti-TT, Anti-PRP, Anti-HBs) | Anti-HBs (N=92,89) | 89 subjects |
| Hiberix Group and Tritanrix-HepB Group | Number of Seroprotected Subjects (Anti-DT, Anti-TT, Anti-PRP, Anti-HBs) | Anti-DT | 116 subjects |
| Hiberix Group and Tritanrix-HepB Group | Number of Seroprotected Subjects (Anti-DT, Anti-TT, Anti-PRP, Anti-HBs) | Anti-PRP 0.15 | 115 subjects |
| Hiberix Group and Tritanrix-HepB Group | Number of Seroprotected Subjects (Anti-DT, Anti-TT, Anti-PRP, Anti-HBs) | Anti-TT | 116 subjects |
Secondary
Number of Seroprotected Subjects (Anti-PRP Above the Cut-off of 1.0 µg/mL)
Anti-PRP antibody concentration equal to or greater than 1.0 µg/mL.
Time frame: One month after primary immunization (month 3)
Population: Analysis was performed on the According-to-Protocol cohort for immunogenicity, which included all evaluable subjects with available immunogenicity data.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Synflorix and Tritanrix-HepB/Hib Group | Number of Seroprotected Subjects (Anti-PRP Above the Cut-off of 1.0 µg/mL) | 113 subjects |
| Hiberix Group and Tritanrix-HepB Group | Number of Seroprotected Subjects (Anti-PRP Above the Cut-off of 1.0 µg/mL) | 114 subjects |
Secondary
Number of Subjects Seropositive for Pneumococcal Serotypes
Vaccine pneumococcal serotypes included 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F. Cross-reactive pneumococcal serotypes included 6A and 19A. Seropositivity was defined as a titer equal to or greater than 0.05 µg/mL
Time frame: One month after primary immunization (month 3)
Population: Analysis was performed on the According-to-Protocol cohort for immunogenicity, which included all evaluable subjects with available immunogenicity data.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Synflorix and Tritanrix-HepB/Hib Group | Number of Subjects Seropositive for Pneumococcal Serotypes | Anti-4 | 228 subjects |
| Synflorix and Tritanrix-HepB/Hib Group | Number of Subjects Seropositive for Pneumococcal Serotypes | Anti-14 | 229 subjects |
| Synflorix and Tritanrix-HepB/Hib Group | Number of Subjects Seropositive for Pneumococcal Serotypes | Anti-6B | 215 subjects |
| Synflorix and Tritanrix-HepB/Hib Group | Number of Subjects Seropositive for Pneumococcal Serotypes | Anti-18C | 227 subjects |
| Synflorix and Tritanrix-HepB/Hib Group | Number of Subjects Seropositive for Pneumococcal Serotypes | Anti-1 | 228 subjects |
| Synflorix and Tritanrix-HepB/Hib Group | Number of Subjects Seropositive for Pneumococcal Serotypes | Anti-19F | 229 subjects |
| Synflorix and Tritanrix-HepB/Hib Group | Number of Subjects Seropositive for Pneumococcal Serotypes | Anti-7F | 229 subjects |
| Synflorix and Tritanrix-HepB/Hib Group | Number of Subjects Seropositive for Pneumococcal Serotypes | Anti-23F | 220 subjects |
| Synflorix and Tritanrix-HepB/Hib Group | Number of Subjects Seropositive for Pneumococcal Serotypes | Anti-6A (N=229;115) | 188 subjects |
| Synflorix and Tritanrix-HepB/Hib Group | Number of Subjects Seropositive for Pneumococcal Serotypes | Anti-5 | 229 subjects |
| Synflorix and Tritanrix-HepB/Hib Group | Number of Subjects Seropositive for Pneumococcal Serotypes | Anti-19A | 207 subjects |
| Synflorix and Tritanrix-HepB/Hib Group | Number of Subjects Seropositive for Pneumococcal Serotypes | Anti-9V | 228 subjects |
| Hiberix Group and Tritanrix-HepB Group | Number of Subjects Seropositive for Pneumococcal Serotypes | Anti-19A | 71 subjects |
| Hiberix Group and Tritanrix-HepB Group | Number of Subjects Seropositive for Pneumococcal Serotypes | Anti-1 | 19 subjects |
| Hiberix Group and Tritanrix-HepB Group | Number of Subjects Seropositive for Pneumococcal Serotypes | Anti-4 | 24 subjects |
| Hiberix Group and Tritanrix-HepB Group | Number of Subjects Seropositive for Pneumococcal Serotypes | Anti-5 | 46 subjects |
| Hiberix Group and Tritanrix-HepB Group | Number of Subjects Seropositive for Pneumococcal Serotypes | Anti-6B | 40 subjects |
| Hiberix Group and Tritanrix-HepB Group | Number of Subjects Seropositive for Pneumococcal Serotypes | Anti-7F | 52 subjects |
| Hiberix Group and Tritanrix-HepB Group | Number of Subjects Seropositive for Pneumococcal Serotypes | Anti-9V | 49 subjects |
| Hiberix Group and Tritanrix-HepB Group | Number of Subjects Seropositive for Pneumococcal Serotypes | Anti-14 | 101 subjects |
| Hiberix Group and Tritanrix-HepB Group | Number of Subjects Seropositive for Pneumococcal Serotypes | Anti-18C | 56 subjects |
| Hiberix Group and Tritanrix-HepB Group | Number of Subjects Seropositive for Pneumococcal Serotypes | Anti-19F | 90 subjects |
| Hiberix Group and Tritanrix-HepB Group | Number of Subjects Seropositive for Pneumococcal Serotypes | Anti-6A (N=229;115) | 62 subjects |
| Hiberix Group and Tritanrix-HepB Group | Number of Subjects Seropositive for Pneumococcal Serotypes | Anti-23F | 37 subjects |
Secondary
Number of Subjects Seropositive for Protein D (PD)
Seropositivity for PD was defined greater than or equal to 100 EL.U/mL.
Time frame: One month after primary immunization (month 3)
Population: Analysis was performed on the According-to-Protocol cohort for immunogenicity, which included all evaluable subjects with available immunogenicity data.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Synflorix and Tritanrix-HepB/Hib Group | Number of Subjects Seropositive for Protein D (PD) | 226 subjects |
| Hiberix Group and Tritanrix-HepB Group | Number of Subjects Seropositive for Protein D (PD) | 16 subjects |
Secondary
Number of Subjects Seropostive for B. Pertussis
Seropositivity was defined as and antibody concentration equal to or greater than 15 EL.U/mL.
Time frame: One month after primary immunization (month 3)
Population: Analysis was performed on the According-to-Protocol cohort for immunogenicity, which included all evaluable subjects with available immunogenicity data.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Synflorix and Tritanrix-HepB/Hib Group | Number of Subjects Seropostive for B. Pertussis | 113 subjects |
| Hiberix Group and Tritanrix-HepB Group | Number of Subjects Seropostive for B. Pertussis | 116 subjects |
Secondary
Number of Subjects With Antibody Concentrations Against Pneumococcal Serotypes Equal to or Above Cut-off Value
Vaccine pneumococcal serotypes included 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F. Cross-reactive pneumococcal serotypes included 6A and 19A. The cut-off was defined as 0.20 microgram per milliliter (µg/mL).
Time frame: One month after primary immunization
Population: Analysis was performed on the According-to-Protocol cohort for immunogenicity, which included all evaluable subjects with available immunogenicity data.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Synflorix and Tritanrix-HepB/Hib Group | Number of Subjects With Antibody Concentrations Against Pneumococcal Serotypes Equal to or Above Cut-off Value | Anti-4 | 225 subjects |
| Synflorix and Tritanrix-HepB/Hib Group | Number of Subjects With Antibody Concentrations Against Pneumococcal Serotypes Equal to or Above Cut-off Value | Anti-14 | 229 subjects |
| Synflorix and Tritanrix-HepB/Hib Group | Number of Subjects With Antibody Concentrations Against Pneumococcal Serotypes Equal to or Above Cut-off Value | Anti-6B | 178 subjects |
| Synflorix and Tritanrix-HepB/Hib Group | Number of Subjects With Antibody Concentrations Against Pneumococcal Serotypes Equal to or Above Cut-off Value | Anti-18C | 227 subjects |
| Synflorix and Tritanrix-HepB/Hib Group | Number of Subjects With Antibody Concentrations Against Pneumococcal Serotypes Equal to or Above Cut-off Value | Anti-1 | 228 subjects |
| Synflorix and Tritanrix-HepB/Hib Group | Number of Subjects With Antibody Concentrations Against Pneumococcal Serotypes Equal to or Above Cut-off Value | Anti-19F | 227 subjects |
| Synflorix and Tritanrix-HepB/Hib Group | Number of Subjects With Antibody Concentrations Against Pneumococcal Serotypes Equal to or Above Cut-off Value | Anti-7F | 228 subjects |
| Synflorix and Tritanrix-HepB/Hib Group | Number of Subjects With Antibody Concentrations Against Pneumococcal Serotypes Equal to or Above Cut-off Value | Anti-23F | 205 subjects |
| Synflorix and Tritanrix-HepB/Hib Group | Number of Subjects With Antibody Concentrations Against Pneumococcal Serotypes Equal to or Above Cut-off Value | Anti-5 | 226 subjects |
| Synflorix and Tritanrix-HepB/Hib Group | Number of Subjects With Antibody Concentrations Against Pneumococcal Serotypes Equal to or Above Cut-off Value | Anti-6A (N=229;115) | 95 subjects |
| Synflorix and Tritanrix-HepB/Hib Group | Number of Subjects With Antibody Concentrations Against Pneumococcal Serotypes Equal to or Above Cut-off Value | Anti-9V | 227 subjects |
| Synflorix and Tritanrix-HepB/Hib Group | Number of Subjects With Antibody Concentrations Against Pneumococcal Serotypes Equal to or Above Cut-off Value | Anti-19A | 146 subjects |
| Hiberix Group and Tritanrix-HepB Group | Number of Subjects With Antibody Concentrations Against Pneumococcal Serotypes Equal to or Above Cut-off Value | Anti-9V | 21 subjects |
| Hiberix Group and Tritanrix-HepB Group | Number of Subjects With Antibody Concentrations Against Pneumococcal Serotypes Equal to or Above Cut-off Value | Anti-1 | 2 subjects |
| Hiberix Group and Tritanrix-HepB Group | Number of Subjects With Antibody Concentrations Against Pneumococcal Serotypes Equal to or Above Cut-off Value | Anti-4 | 10 subjects |
| Hiberix Group and Tritanrix-HepB Group | Number of Subjects With Antibody Concentrations Against Pneumococcal Serotypes Equal to or Above Cut-off Value | Anti-5 | 10 subjects |
| Hiberix Group and Tritanrix-HepB Group | Number of Subjects With Antibody Concentrations Against Pneumococcal Serotypes Equal to or Above Cut-off Value | Anti-6B | 9 subjects |
| Hiberix Group and Tritanrix-HepB Group | Number of Subjects With Antibody Concentrations Against Pneumococcal Serotypes Equal to or Above Cut-off Value | Anti-7F | 16 subjects |
| Hiberix Group and Tritanrix-HepB Group | Number of Subjects With Antibody Concentrations Against Pneumococcal Serotypes Equal to or Above Cut-off Value | Anti-19A | 21 subjects |
| Hiberix Group and Tritanrix-HepB Group | Number of Subjects With Antibody Concentrations Against Pneumococcal Serotypes Equal to or Above Cut-off Value | Anti-14 | 66 subjects |
| Hiberix Group and Tritanrix-HepB Group | Number of Subjects With Antibody Concentrations Against Pneumococcal Serotypes Equal to or Above Cut-off Value | Anti-18C | 20 subjects |
| Hiberix Group and Tritanrix-HepB Group | Number of Subjects With Antibody Concentrations Against Pneumococcal Serotypes Equal to or Above Cut-off Value | Anti-19F | 40 subjects |
| Hiberix Group and Tritanrix-HepB Group | Number of Subjects With Antibody Concentrations Against Pneumococcal Serotypes Equal to or Above Cut-off Value | Anti-23F | 12 subjects |
| Hiberix Group and Tritanrix-HepB Group | Number of Subjects With Antibody Concentrations Against Pneumococcal Serotypes Equal to or Above Cut-off Value | Anti-6A (N=229;115) | 12 subjects |
Secondary
Number of Subjects With Opsonophagocytic Activity Against Pneumococcal Serotypes
Vaccine pneumococcal serotypes included 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F. Cross-reactive pneumococcal serotypes included 6A and 19A. Opsonophagocytic activity was defined as the dilution of serum (opsonic titer) able to sustain 50% killing of live pneumococci under the assay conditions. The cut-off of the assay was an opsonic titer equal to or greater than 8.
Time frame: One month after primary immunization (month 3)
Population: Analysis was performed on the According-to-Protocol cohort for immunogenicity, which included all evaluable subjects with available immunogenicity data.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Synflorix and Tritanrix-HepB/Hib Group | Number of Subjects With Opsonophagocytic Activity Against Pneumococcal Serotypes | Opsono-1 (N=116; 57) | 105 subjects |
| Synflorix and Tritanrix-HepB/Hib Group | Number of Subjects With Opsonophagocytic Activity Against Pneumococcal Serotypes | Opsono-4 (N=116; 55) | 114 subjects |
| Synflorix and Tritanrix-HepB/Hib Group | Number of Subjects With Opsonophagocytic Activity Against Pneumococcal Serotypes | Opsono-5 (N= 116; 56) | 111 subjects |
| Synflorix and Tritanrix-HepB/Hib Group | Number of Subjects With Opsonophagocytic Activity Against Pneumococcal Serotypes | Opsono-6B (N=116; 54) | 98 subjects |
| Synflorix and Tritanrix-HepB/Hib Group | Number of Subjects With Opsonophagocytic Activity Against Pneumococcal Serotypes | Opsono-7F (N=116; 53) | 116 subjects |
| Synflorix and Tritanrix-HepB/Hib Group | Number of Subjects With Opsonophagocytic Activity Against Pneumococcal Serotypes | Opsono-9V (N=115; 56) | 113 subjects |
| Synflorix and Tritanrix-HepB/Hib Group | Number of Subjects With Opsonophagocytic Activity Against Pneumococcal Serotypes | Opsono-14 (N=115; 56) | 110 subjects |
| Synflorix and Tritanrix-HepB/Hib Group | Number of Subjects With Opsonophagocytic Activity Against Pneumococcal Serotypes | Opsono-18C (N=115; 55) | 113 subjects |
| Synflorix and Tritanrix-HepB/Hib Group | Number of Subjects With Opsonophagocytic Activity Against Pneumococcal Serotypes | Opsono-19F (N=116; 56) | 114 subjects |
| Synflorix and Tritanrix-HepB/Hib Group | Number of Subjects With Opsonophagocytic Activity Against Pneumococcal Serotypes | Opsono-23F (N=116; 54) | 113 subjects |
| Synflorix and Tritanrix-HepB/Hib Group | Number of Subjects With Opsonophagocytic Activity Against Pneumococcal Serotypes | Opsono-6A (N=110;57) | 54 subjects |
| Synflorix and Tritanrix-HepB/Hib Group | Number of Subjects With Opsonophagocytic Activity Against Pneumococcal Serotypes | Opsono-19A (N=109;57) | 35 subjects |
| Hiberix Group and Tritanrix-HepB Group | Number of Subjects With Opsonophagocytic Activity Against Pneumococcal Serotypes | Opsono-6A (N=110;57) | 7 subjects |
| Hiberix Group and Tritanrix-HepB Group | Number of Subjects With Opsonophagocytic Activity Against Pneumococcal Serotypes | Opsono-1 (N=116; 57) | 3 subjects |
| Hiberix Group and Tritanrix-HepB Group | Number of Subjects With Opsonophagocytic Activity Against Pneumococcal Serotypes | Opsono-14 (N=115; 56) | 14 subjects |
| Hiberix Group and Tritanrix-HepB Group | Number of Subjects With Opsonophagocytic Activity Against Pneumococcal Serotypes | Opsono-4 (N=116; 55) | 24 subjects |
| Hiberix Group and Tritanrix-HepB Group | Number of Subjects With Opsonophagocytic Activity Against Pneumococcal Serotypes | Opsono-23F (N=116; 54) | 9 subjects |
| Hiberix Group and Tritanrix-HepB Group | Number of Subjects With Opsonophagocytic Activity Against Pneumococcal Serotypes | Opsono-5 (N= 116; 56) | 2 subjects |
| Hiberix Group and Tritanrix-HepB Group | Number of Subjects With Opsonophagocytic Activity Against Pneumococcal Serotypes | Opsono-18C (N=115; 55) | 2 subjects |
| Hiberix Group and Tritanrix-HepB Group | Number of Subjects With Opsonophagocytic Activity Against Pneumococcal Serotypes | Opsono-6B (N=116; 54) | 5 subjects |
| Hiberix Group and Tritanrix-HepB Group | Number of Subjects With Opsonophagocytic Activity Against Pneumococcal Serotypes | Opsono-19A (N=109;57) | 0 subjects |
| Hiberix Group and Tritanrix-HepB Group | Number of Subjects With Opsonophagocytic Activity Against Pneumococcal Serotypes | Opsono-7F (N=116; 53) | 35 subjects |
| Hiberix Group and Tritanrix-HepB Group | Number of Subjects With Opsonophagocytic Activity Against Pneumococcal Serotypes | Opsono-19F (N=116; 56) | 7 subjects |
| Hiberix Group and Tritanrix-HepB Group | Number of Subjects With Opsonophagocytic Activity Against Pneumococcal Serotypes | Opsono-9V (N=115; 56) | 9 subjects |
Secondary
Number of Subjects With Serious Adverse Events (SAEs)
SAEs assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization, result in disability/incapacity or are a congenital anomaly/birth defect in the offspring of a study subject.
Time frame: Following first vaccination (Month 0) throughout the entire study period (month 3)
Population: Analysis was performed on the Total Vaccinated cohort, which included all vaccinated subjects.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Synflorix and Tritanrix-HepB/Hib Group | Number of Subjects With Serious Adverse Events (SAEs) | 5 subjects |
| Hiberix Group and Tritanrix-HepB Group | Number of Subjects With Serious Adverse Events (SAEs) | 1 subjects |
Secondary
Number of Subjects With Solicited Local and General Symptoms
Solicited local symptoms included pain, redness and swelling. Solicited general symptoms included drowsiness, fever (equal to or above 38 degrees Celsius and above 39 degrees Celsius), irritability and loss of appetite.
Time frame: Within 4 days (day 0-3) after vaccination
Population: Analysis was performed on the Total Vaccinated cohort, which included all vaccinated subjects. However, the total number of subjects analyzed in this Total Vaccinated cohort included all subjects having returned their symptom sheets.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Synflorix and Tritanrix-HepB/Hib Group | Number of Subjects With Solicited Local and General Symptoms | Pain | 209 subjects |
| Synflorix and Tritanrix-HepB/Hib Group | Number of Subjects With Solicited Local and General Symptoms | Redness | 128 subjects |
| Synflorix and Tritanrix-HepB/Hib Group | Number of Subjects With Solicited Local and General Symptoms | Swelling | 166 subjects |
| Synflorix and Tritanrix-HepB/Hib Group | Number of Subjects With Solicited Local and General Symptoms | Drowsiness | 73 subjects |
| Synflorix and Tritanrix-HepB/Hib Group | Number of Subjects With Solicited Local and General Symptoms | Fever ≥38.0˚C | 182 subjects |
| Synflorix and Tritanrix-HepB/Hib Group | Number of Subjects With Solicited Local and General Symptoms | Fever >39.0˚C | 24 subjects |
| Synflorix and Tritanrix-HepB/Hib Group | Number of Subjects With Solicited Local and General Symptoms | Irritability | 178 subjects |
| Synflorix and Tritanrix-HepB/Hib Group | Number of Subjects With Solicited Local and General Symptoms | Loss of appetite | 96 subjects |
| Hiberix Group and Tritanrix-HepB Group | Number of Subjects With Solicited Local and General Symptoms | Loss of appetite | 49 subjects |
| Hiberix Group and Tritanrix-HepB Group | Number of Subjects With Solicited Local and General Symptoms | Pain | 105 subjects |
| Hiberix Group and Tritanrix-HepB Group | Number of Subjects With Solicited Local and General Symptoms | Fever ≥38.0˚C | 85 subjects |
| Hiberix Group and Tritanrix-HepB Group | Number of Subjects With Solicited Local and General Symptoms | Redness | 76 subjects |
| Hiberix Group and Tritanrix-HepB Group | Number of Subjects With Solicited Local and General Symptoms | Irritability | 88 subjects |
| Hiberix Group and Tritanrix-HepB Group | Number of Subjects With Solicited Local and General Symptoms | Swelling | 83 subjects |
| Hiberix Group and Tritanrix-HepB Group | Number of Subjects With Solicited Local and General Symptoms | Fever >39.0˚C | 5 subjects |
| Hiberix Group and Tritanrix-HepB Group | Number of Subjects With Solicited Local and General Symptoms | Drowsiness | 34 subjects |
Secondary
Number of Subjects With Unsolicited Adverse Events (AEs)
An AE is 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. Unsolicited AE covers any AE 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
Time frame: Within 31 days (day 0-30) after vaccination
Population: Analysis was performed on the Total Vaccinated cohort, which included all vaccinated subjects.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Synflorix and Tritanrix-HepB/Hib Group | Number of Subjects With Unsolicited Adverse Events (AEs) | 38 subjects |
| Hiberix Group and Tritanrix-HepB Group | Number of Subjects With Unsolicited Adverse Events (AEs) | 17 subjects |