Infections, Streptococcal
Conditions
Keywords
pneumococcal conjugate vaccine, Streptococcus pneumoniae
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 African Sub-Saharan infants with pneumococcal conjugate vaccine GSK 1024850A co-administered with a diphtheria, tetanus, whole cell pertussis (DTPw)-combined vaccine and oral polio vaccine in children during the first 4 months of life.
Detailed description
Vaccination course at 6, 10, 14 weeks of age.
Interventions
BIOLOGICALGSK Biologicals' Synflorix™
3 IM doses.
BIOLOGICALGSK Biologicals' Polio Sabin™
3 oral doses
BIOLOGICALGSK Biologicals' Zilbrix™ Hib
3 IM doses.
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
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 should be enrolled in the study. * 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), that would contraindicate the initiation of routine immunizations outside a clinical trial context.
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 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 (Hepatitis B immunoglobulins at birth are allowed). * Previous vaccination against, diphtheria, tetanus, pertussis, Haemophilus influenzae type b and/or Streptococcus pneumoniae. * 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. Study entry should be delayed until the illness has improved. * Babies for which birth weight is \< 2 kilogram (if known) at Visit 1
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes | At Month 3, one month after the administration of the third dose of Synflorix vaccine | Pneumococcal serotypes assessed were vaccine pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F. Seropositivity cut-off for the assay was an anti-pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F antibody (Anti-1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F) concentrations greater than or equal to (≥) 0.05 microgram per milliliter (μg/mL). |
| Antibody Concentrations Against Protein D (Anti-PD Antibodies) | At Month 3, one month after the administration of the third dose of Synflorix vaccine | Anti-PD antibody concentrations were expressed in enzyme-linked immunsorbent assay (ELISA) units per milliliter (EL.U/mL). Seropositivity cut-off for the assay was an anti-PD antibody concentrations ≥ 100 EL.U/mL. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Titers for Opsonophagocytic Activity (OPA) Against Vaccine Pneumococcal Serotypes | At Month 3, one month after the administration of the third dose of Synflorix vaccine | Pneumococcal serotypes assessed were vaccine pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F. Seropositivity status was defined as an opsonophagocytic activity against vaccine pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F (OPA-1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F) ≥ 8. |
| Titers for Opsonophagocytic Activity (OPA) Against Cross-reactive Pneumococcal Serotypes | At Month 3, one month after the administration of the third dose of Synflorix vaccine | Pneumococcal serotypes assessed were cross-reactive pneumococcal serotypes 6A and 19A. Seropositivity status was defined as an opsonophagocytic activity against cross-reactive pneumococcal serotypes 6A and 19A (OPA-6A and 19A) ≥ 8. |
| Number of Subjects Seropositive for Antibodies Against Vaccine Pneumococcal Serotypes | At Month 3, one month after the administration of the third dose of Synflorix vaccine | Pneumococcal serotypes assessed were vaccine pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F. Seropositivity cut-off for the assay was an anti-pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F antibody (Anti-1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F) concentrations ≥ 0.05 microgram per milliliter (μg/mL). |
| Number of Subjects Seroprotected Against Vaccine Pneumococcal Serotypes | At Month 3, one month after the administration of the third dose of Synflorix vaccine | Pneumococcal serotypes assessed were vaccine pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F. Seroprotection cut-off for the assay was an anti-pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F antibody (Anti-1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F) concentrations ≥ 0.2 microgram per milliliter (μg/mL). |
| Number of Subjects Seropositive for Antibodies Against Cross-reactive Pneumococcal Serotypes 6A and 19A (Anti-6A and -19A) | At Month 3, one month after the administration of the third dose of Synflorix vaccine | Serotypes assessed were cross-reactive pneumococcal serotypes 6A and 19A. Seropositivity status was defined as anti-pneumococcal cross-reactive serotypes 6A/19A antibody concentrations (Anti-6A/19A) ≥ 0.05 microgram per milliliter (μg/mL). |
| Number of Subjects Seroprotected Against Cross-reactive Pneumococcal Serotypes 6A and 19A (Anti-6A and -19A) | At Month 3, one month after the administration of the third dose of Synflorix vaccine | Serotypes assessed were cross-reactive pneumococcal serotypes 6A and 19 A. Seroprotection cut-off for the assay was an anti-6A/19A antibody concentrations ≥ 0.2 microgram per milliliter (μg/mL). |
| Number of Subjects Seropositive for Antibodies Against Protein D (Anti-PD Antibodies) | At Month 3, one month after the administration of the third dose of Synflorix vaccine | Seropositivity cut-off for the assay was an anti-PD antibody concentrations ≥ 100 EL.U/mL. |
| Number of Subjects Seropositive for Opsonophagocytic Activity Against Vaccine Pneumococcal Serotypes | At Month 3, one month after the administration of the third dose of Synflorix vaccine | Pneumococcal serotypes assessed were vaccine pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F. Seropositivity status was defined as an opsonophagocytic activity against vaccine pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F (OPA-1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F) ≥ 8. |
| Number of Subjects Seropositive for Opsonophagocytic Activity Against Cross-reactive Pneumococcal Serotypes | At Month 3, one month after the administration of the third dose of Synflorix vaccine | Pneumococcal serotypes assessed were cross-reactive pneumococcal serotypes 6A and 19A. Seropositivity status was defined as an opsonophagocytic activity against cross-reactive pneumococcal serotypes 6A and 19A (OPA-6A and 19A) ≥ 8. |
| Anti-Bordetella Pertussis (Anti-BPT) Antibody Concentrations | At Month 3, one month after the administration of the third dose of Synflorix vaccine | Anti-BPT antibody concentrations were expressed in enzyme-linked immunosorbent assay (ELISA) unit per millilitre (EL.U/mL). Seropositivity cut-off for the assay was defined as an anti-BPT antibody concentrations ≥ 15 EL.U/mL |
| Number of Subjects Seropositive for Antibodies Against Bordetella Pertussis (Anti-BPT) | At Month 3, one month after the administration of the third dose of DTPw-HBV/Hib vaccine | Seropositivity cut-off for the assay was defined as an anti-BPT antibody concentration ≥ 15 enzyme-linked immunosorbent assay (ELISA) unit per milliliter (EL.U/mL). |
| Number of Subjects With Fever (Temperature Measured Rectally) > the Cut-off | Within the 4-day (Days 0 to 3) follow-up periods after each vaccination, across doses and across vaccines | The cut-off for the assay was \> 39.0°C. |
| Number of Subjects Seroprotected Against Diphtheria (D) and Tetanus Toxoids (TT) Antigens | At Month 3, one month after the administration of the third dose of Tritanrix -HepB/ Hiberix vaccine | A subject seroprotected against D/TT antigens was defined as a subject with an Anti-D/-TT antibody concentration ≥ 0.1 IU/mL. |
| Anti-polyribosyl-ribitol-phosphate (Anti-PRP) Antibody Concentrations | At Month 3, one month after the administration of the third dose of Tritanrix -HepB/ Hiberix vaccine | Anti-PRP antibody concentrations were measured and tabulated in microgram per milliliter (μg/mL). Cut-off for the assay was ≥ 0.15 μg/mL. |
| Number of Subjects Seroprotected Against Polyribosyl-ribitol Phosphate (PRP) | At Month 3, one month after the administration of the third dose of Tritanrix -HepB/ Hiberix vaccine | Anti-PRP antibody concentrations were expressed in microgram per milliliter (μg/mL). The seroprotection cut-off applied for the assay was ≥ 0.15 μg/mL. |
| Number of Subjects Seroprotected Against Polyribosyl-ribitol Phosphate (PRP) Antigens | At Month 3, one month after the administration of the third dose of Tritanrix -HepB/ Hiberix vaccine | Anti-PRP antibody concentrations were expressed in microgram per milliliter (μg/mL). The seroprotection cut-off applied for the assay was ≥ 1 μg/mL. |
| Anti-hepatitis B Surface Antigen (HBs) Antibody Concentrations | At Month 3, one month after the administration of the third dose of Tritanrix -HepB /Hiberix vaccine | The seroprotection cut-off for the endpoint was an anti-HBs antibody concentration ≥ 10 milli-international units per milliliter (mIU/mL). |
| Number of Subjects Seroprotected Against Anti-Hepatitis B Surface Antigens (HBs). | At Month 3, one month after the administration of the third dose of Tritanrix HepB/ Hiberix vaccine | The seroprotection cut-off values considered for this endpoint were an anti-HBs antibody concentration ≥ 10 and 100 milli-international units per milliliter (mIU/mL). |
| Number of Subjects With Any and Any Grade 3 Solicited Local Symptoms | Within the 4-day (Days 0 to 3) follow-up periods after each vaccination, across doses and across vaccines | Solicited local symptoms assessed included pain, redness and swelling. Grade 3 pain was defined as crying when limb was moved/ spontaneously painful. Grade 3 swelling/ redness was defined as swelling/ redness greater than (\>) 30 millimeters (mm). Any was defined as incidence of the specified symptom regardless of intensity. |
| Number of Subjects With Any and Any Grade 3 and Related Solicited General Symptoms | Within the 4-day (Days 0 to 3) follow-up periods after each vaccination, across doses and across vaccines | Solicited general symptoms assessed include drowsiness, fever (defined as rectal temperature ≥ 38.0°C), irritability, and loss of appetite. Any was defined as incidence of the specified symptom regardless of intensity or relationship to study vaccination. Grade 3 drowsiness was defined as drowsiness which prevented normal everyday activities. Grade 3 fever was defined as fever (rectal temperature) greater than (\>) 40.0 degree Celsius (°C). Grade 3 irritability was defined as crying that could not be comforted/ preventing normal activity. Grade 3 loss of appetite was defined as the subject not eating at all. |
| Number of Subjects With Unsolicited Adverse Events (AEs) | Within the 31-day (Days 0-30) follow-up periods post vaccination, across doses and across vaccines | 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. Any was defined an incidence of an unsolicited AE regardless of intensity or relationship to study vaccination. |
| Number of Subjects With Serious Adverse Events (SAEs) | Throughout the entire study period, from Month 0 to Month 3 | Serious adverse events (SAEs) assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization or result in disability/ incapacity. |
| Anti-diphtheria (Anti-D) and Anti-tetanus Toxoids (Anti-TT) Antibody Concentrations | At Month 3, one month after the administration of the third dose of Tritanrix -HepB/ Hiberix vaccine | The seroprotection cut-off for the assay was an anti-diphtheria toxoid or anti-tetanus toxoid antibody concentrations ≥ 0.1 international unit per milliliter (IU/mL). |
| Concentrations of Antibodies Against Cross-reactive Pneumococcal Serotypes 6A and 19A (Anti-6A and -19A) | At Month 3, one month after the administration of the third dose of Synflorix vaccine | Seropositivity status was defined as anti-pneumococcal cross-reactive serotypes 6A/19A antibody concentrations (Anti-6A/19A) ≥ 0.05 microgram per milliliter (μg/mL). |
Countries
Mali, Nigeria
Participant flow
Recruitment details
At screening, the following steps occurred: check for inclusion/exclusion criteria, contraindications/ precautions, medical and vaccination history of the subjects and signing or thumb-printing informed consent forms.
Pre-assignment details
Among 365 enrolled participants, 8 were not administered any study vaccine and hence were not considered as starting the study.
Participants by arm
| Arm | Count |
|---|---|
| Synflorix™ + Zilbrix™ Hib + Polio Sabin™ Subjects in this group received 3 doses of Synflorix™ vaccine, according to a 3-dose schedule at 6-10-14 weeks of age co-administered with 3 doses of Expanded Program on Immunization (EPI) vaccines Zilbrix™ Hib and Polio Sabin™ according to the same schedule. The Synflorix™ and Zilbrix™ Hib vaccines were administered by intramuscular injection, in the right and left thigh respectively. The Polio Sabin™ vaccine was administered orally. | 239 |
| Zilbrix™ Hib + Polio Sabin™ Subjects in this group received 3 doses of Expanded Program on Immunization (EPI) vaccines Zilbrix™ Hib and Polio Sabin™ according to a 3-dose schedule at 6-10-14 weeks of age. The Zilbrix™ Hib vaccine was administered by intramuscular injection, in the left thigh. The Polio Sabin™ vaccine was administered orally. | 118 |
| Total | 357 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 |
| Overall Study | Lost to Follow-up | 3 | 1 |
| Overall Study | Non-compliance with study procedures | 0 | 1 |
| Overall Study | Withdrawal by Subject | 4 | 0 |
Baseline characteristics
| Characteristic | Synflorix™ + Zilbrix™ Hib + Polio Sabin™ | Zilbrix™ Hib + Polio Sabin™ | Total |
|---|---|---|---|
| Age, Continuous | 7.1 Weeks STANDARD_DEVIATION 1.15 | 7 Weeks STANDARD_DEVIATION 1.18 | 7.07 Weeks STANDARD_DEVIATION 1.16 |
| Race/Ethnicity, Customized African heritage/African American | 239 Participants | 118 Participants | 357 Participants |
| Sex: Female, Male Female | 119 Participants | 62 Participants | 181 Participants |
| Sex: Female, Male Male | 120 Participants | 56 Participants | 176 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 239 | 0 / 118 |
| other Total, other adverse events | 238 / 239 | 117 / 118 |
| serious Total, serious adverse events | 5 / 239 | 0 / 118 |
Outcome results
Primary
Antibody Concentrations Against Protein D (Anti-PD Antibodies)
Anti-PD antibody concentrations were expressed in enzyme-linked immunsorbent assay (ELISA) units per milliliter (EL.U/mL). Seropositivity cut-off for the assay was an anti-PD antibody concentrations ≥ 100 EL.U/mL.
Time frame: At Month 3, one month after the administration of the third dose of Synflorix vaccine
Population: The According-To-Protocol (ATP) cohort for immunogenicity included all evaluable subjects with available immunogenicity data. The ATP cohort for immunogenicity included subjects for whom assay results were available for antibodies against at least one study vaccine antigen component after vaccination.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Synflorix™ + Zilbrix™ Hib + Polio Sabin™ | Antibody Concentrations Against Protein D (Anti-PD Antibodies) | 3791.8 EL.U/mL |
| Zilbrix™ Hib + Polio Sabin™ | Antibody Concentrations Against Protein D (Anti-PD Antibodies) | 85.4 EL.U/mL |
Primary
Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes
Pneumococcal serotypes assessed were vaccine pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F. Seropositivity cut-off for the assay was an anti-pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F antibody (Anti-1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F) concentrations greater than or equal to (≥) 0.05 microgram per milliliter (μg/mL).
Time frame: At Month 3, one month after the administration of the third dose of Synflorix vaccine
Population: The According-To-Protocol (ATP) cohort for immunogenicity included all evaluable subjects with available immunogenicity data. The ATP cohort for immunogenicity included subjects for whom assay results were available for antibodies against at least one study vaccine antigen component after vaccination.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Synflorix™ + Zilbrix™ Hib + Polio Sabin™ | Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes | Anti-1 | 2.69 μg/mL |
| Synflorix™ + Zilbrix™ Hib + Polio Sabin™ | Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes | Anti-4 | 3.44 μg/mL |
| Synflorix™ + Zilbrix™ Hib + Polio Sabin™ | Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes | Anti-5 | 4.17 μg/mL |
| Synflorix™ + Zilbrix™ Hib + Polio Sabin™ | Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes | Anti-6B | 0.95 μg/mL |
| Synflorix™ + Zilbrix™ Hib + Polio Sabin™ | Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes | Anti-7F | 3.33 μg/mL |
| Synflorix™ + Zilbrix™ Hib + Polio Sabin™ | Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes | Anti-9V | 2.39 μg/mL |
| Synflorix™ + Zilbrix™ Hib + Polio Sabin™ | Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes | Anti-14 | 3.8 μg/mL |
| Synflorix™ + Zilbrix™ Hib + Polio Sabin™ | Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes | Anti-18C | 10.01 μg/mL |
| Synflorix™ + Zilbrix™ Hib + Polio Sabin™ | Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes | Anti-19F | 7.65 μg/mL |
| Synflorix™ + Zilbrix™ Hib + Polio Sabin™ | Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes | Anti-23F | 1.1 μg/mL |
| Zilbrix™ Hib + Polio Sabin™ | Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes | Anti-18C | 0.03 μg/mL |
| Zilbrix™ Hib + Polio Sabin™ | Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes | Anti-1 | 0.03 μg/mL |
| Zilbrix™ Hib + Polio Sabin™ | Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes | Anti-9V | 0.04 μg/mL |
| Zilbrix™ Hib + Polio Sabin™ | Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes | Anti-4 | 0.03 μg/mL |
| Zilbrix™ Hib + Polio Sabin™ | Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes | Anti-23F | 0.03 μg/mL |
| Zilbrix™ Hib + Polio Sabin™ | Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes | Anti-5 | 0.03 μg/mL |
| Zilbrix™ Hib + Polio Sabin™ | Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes | Anti-14 | 0.14 μg/mL |
| Zilbrix™ Hib + Polio Sabin™ | Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes | Anti-6B | 0.03 μg/mL |
| Zilbrix™ Hib + Polio Sabin™ | Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes | Anti-19F | 0.08 μg/mL |
| Zilbrix™ Hib + Polio Sabin™ | Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes | Anti-7F | 0.03 μg/mL |
Secondary
Anti-Bordetella Pertussis (Anti-BPT) Antibody Concentrations
Anti-BPT antibody concentrations were expressed in enzyme-linked immunosorbent assay (ELISA) unit per millilitre (EL.U/mL). Seropositivity cut-off for the assay was defined as an anti-BPT antibody concentrations ≥ 15 EL.U/mL
Time frame: At Month 3, one month after the administration of the third dose of Synflorix vaccine
Population: The According-To-Protocol (ATP) cohort for immunogenicity included all evaluable subjects with available immunogenicity data. The ATP cohort for immunogenicity included subjects for whom assay results were available for antibodies against at least one study vaccine antigen component after vaccination.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Synflorix™ + Zilbrix™ Hib + Polio Sabin™ | Anti-Bordetella Pertussis (Anti-BPT) Antibody Concentrations | 111.9 EL.U/mL |
| Zilbrix™ Hib + Polio Sabin™ | Anti-Bordetella Pertussis (Anti-BPT) Antibody Concentrations | 124.9 EL.U/mL |
Secondary
Anti-diphtheria (Anti-D) and Anti-tetanus Toxoids (Anti-TT) Antibody Concentrations
The seroprotection cut-off for the assay was an anti-diphtheria toxoid or anti-tetanus toxoid antibody concentrations ≥ 0.1 international unit per milliliter (IU/mL).
Time frame: At Month 3, one month after the administration of the third dose of Tritanrix -HepB/ Hiberix vaccine
Population: The According-To-Protocol (ATP) cohort for immunogenicity included all evaluable subjects with available immunogenicity data. The ATP cohort for immunogenicity included subjects for whom assay results were available for antibodies against at least one study vaccine antigen component after vaccination.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Synflorix™ + Zilbrix™ Hib + Polio Sabin™ | Anti-diphtheria (Anti-D) and Anti-tetanus Toxoids (Anti-TT) Antibody Concentrations | Anti-D | 4.103 IU/mL |
| Synflorix™ + Zilbrix™ Hib + Polio Sabin™ | Anti-diphtheria (Anti-D) and Anti-tetanus Toxoids (Anti-TT) Antibody Concentrations | Anti-T | 6.484 IU/mL |
| Zilbrix™ Hib + Polio Sabin™ | Anti-diphtheria (Anti-D) and Anti-tetanus Toxoids (Anti-TT) Antibody Concentrations | Anti-D | 3.13 IU/mL |
| Zilbrix™ Hib + Polio Sabin™ | Anti-diphtheria (Anti-D) and Anti-tetanus Toxoids (Anti-TT) Antibody Concentrations | Anti-T | 4.588 IU/mL |
Secondary
Anti-hepatitis B Surface Antigen (HBs) Antibody Concentrations
The seroprotection cut-off for the endpoint was an anti-HBs antibody concentration ≥ 10 milli-international units per milliliter (mIU/mL).
Time frame: At Month 3, one month after the administration of the third dose of Tritanrix -HepB /Hiberix vaccine
Population: The According-To-Protocol (ATP) cohort for immunogenicity included all evaluable subjects with available immunogenicity data. The ATP cohort for immunogenicity included subjects for whom assay results were available for antibodies against at least one study vaccine antigen component after vaccination.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Synflorix™ + Zilbrix™ Hib + Polio Sabin™ | Anti-hepatitis B Surface Antigen (HBs) Antibody Concentrations | 1835.1 mIU/mL |
| Zilbrix™ Hib + Polio Sabin™ | Anti-hepatitis B Surface Antigen (HBs) Antibody Concentrations | 1485.5 mIU/mL |
Secondary
Anti-polyribosyl-ribitol-phosphate (Anti-PRP) Antibody Concentrations
Anti-PRP antibody concentrations were measured and tabulated in microgram per milliliter (μg/mL). Cut-off for the assay was ≥ 0.15 μg/mL.
Time frame: At Month 3, one month after the administration of the third dose of Tritanrix -HepB/ Hiberix vaccine
Population: The According-To-Protocol (ATP) cohort for immunogenicity included all evaluable subjects with available immunogenicity data. The ATP cohort for immunogenicity included subjects for whom assay results were available for antibodies against at least one study vaccine antigen component after vaccination.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Synflorix™ + Zilbrix™ Hib + Polio Sabin™ | Anti-polyribosyl-ribitol-phosphate (Anti-PRP) Antibody Concentrations | 18.461 μg/mL |
| Zilbrix™ Hib + Polio Sabin™ | Anti-polyribosyl-ribitol-phosphate (Anti-PRP) Antibody Concentrations | 10.137 μg/mL |
Secondary
Concentrations of Antibodies Against Cross-reactive Pneumococcal Serotypes 6A and 19A (Anti-6A and -19A)
Seropositivity status was defined as anti-pneumococcal cross-reactive serotypes 6A/19A antibody concentrations (Anti-6A/19A) ≥ 0.05 microgram per milliliter (μg/mL).
Time frame: At Month 3, one month after the administration of the third dose of Synflorix vaccine
Population: The According-To-Protocol (ATP) cohort for immunogenicity included all evaluable subjects with available immunogenicity data. The ATP cohort for immunogenicity included subjects for whom assay results were available for antibodies against at least one study vaccine antigen component after vaccination.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Synflorix™ + Zilbrix™ Hib + Polio Sabin™ | Concentrations of Antibodies Against Cross-reactive Pneumococcal Serotypes 6A and 19A (Anti-6A and -19A) | Anti-6A | 0.09 μg/mL |
| Synflorix™ + Zilbrix™ Hib + Polio Sabin™ | Concentrations of Antibodies Against Cross-reactive Pneumococcal Serotypes 6A and 19A (Anti-6A and -19A) | Anti-19A | 0.15 μg/mL |
| Zilbrix™ Hib + Polio Sabin™ | Concentrations of Antibodies Against Cross-reactive Pneumococcal Serotypes 6A and 19A (Anti-6A and -19A) | Anti-6A | 0.04 μg/mL |
| Zilbrix™ Hib + Polio Sabin™ | Concentrations of Antibodies Against Cross-reactive Pneumococcal Serotypes 6A and 19A (Anti-6A and -19A) | Anti-19A | 0.06 μg/mL |
Secondary
Number of Subjects Seropositive for Antibodies Against Bordetella Pertussis (Anti-BPT)
Seropositivity cut-off for the assay was defined as an anti-BPT antibody concentration ≥ 15 enzyme-linked immunosorbent assay (ELISA) unit per milliliter (EL.U/mL).
Time frame: At Month 3, one month after the administration of the third dose of DTPw-HBV/Hib vaccine
Population: The According-To-Protocol (ATP) cohort for immunogenicity included all evaluable subjects with available immunogenicity data. The ATP cohort for immunogenicity included subjects for whom assay results were available for antibodies against at least one study vaccine antigen component after vaccination.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Synflorix™ + Zilbrix™ Hib + Polio Sabin™ | Number of Subjects Seropositive for Antibodies Against Bordetella Pertussis (Anti-BPT) | 110 Participants |
| Zilbrix™ Hib + Polio Sabin™ | Number of Subjects Seropositive for Antibodies Against Bordetella Pertussis (Anti-BPT) | 111 Participants |
Secondary
Number of Subjects Seropositive for Antibodies Against Cross-reactive Pneumococcal Serotypes 6A and 19A (Anti-6A and -19A)
Serotypes assessed were cross-reactive pneumococcal serotypes 6A and 19A. Seropositivity status was defined as anti-pneumococcal cross-reactive serotypes 6A/19A antibody concentrations (Anti-6A/19A) ≥ 0.05 microgram per milliliter (μg/mL).
Time frame: At Month 3, one month after the administration of the third dose of Synflorix vaccine
Population: The According-To-Protocol (ATP) cohort for immunogenicity included all evaluable subjects with available immunogenicity data. The ATP cohort for immunogenicity included subjects for whom assay results were available for antibodies against at least one study vaccine antigen component after vaccination.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Synflorix™ + Zilbrix™ Hib + Polio Sabin™ | Number of Subjects Seropositive for Antibodies Against Cross-reactive Pneumococcal Serotypes 6A and 19A (Anti-6A and -19A) | Anti-6A | 152 Participants |
| Synflorix™ + Zilbrix™ Hib + Polio Sabin™ | Number of Subjects Seropositive for Antibodies Against Cross-reactive Pneumococcal Serotypes 6A and 19A (Anti-6A and -19A) | Anti-19A | 176 Participants |
| Zilbrix™ Hib + Polio Sabin™ | Number of Subjects Seropositive for Antibodies Against Cross-reactive Pneumococcal Serotypes 6A and 19A (Anti-6A and -19A) | Anti-6A | 36 Participants |
| Zilbrix™ Hib + Polio Sabin™ | Number of Subjects Seropositive for Antibodies Against Cross-reactive Pneumococcal Serotypes 6A and 19A (Anti-6A and -19A) | Anti-19A | 49 Participants |
Secondary
Number of Subjects Seropositive for Antibodies Against Protein D (Anti-PD Antibodies)
Seropositivity cut-off for the assay was an anti-PD antibody concentrations ≥ 100 EL.U/mL.
Time frame: At Month 3, one month after the administration of the third dose of Synflorix vaccine
Population: The According-To-Protocol (ATP) cohort for immunogenicity included all evaluable subjects with available immunogenicity data. The ATP cohort for immunogenicity included subjects for whom assay results were available for antibodies against at least one study vaccine antigen component after vaccination.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Synflorix™ + Zilbrix™ Hib + Polio Sabin™ | Number of Subjects Seropositive for Antibodies Against Protein D (Anti-PD Antibodies) | 217 Participants |
| Zilbrix™ Hib + Polio Sabin™ | Number of Subjects Seropositive for Antibodies Against Protein D (Anti-PD Antibodies) | 34 Participants |
Secondary
Number of Subjects Seropositive for Antibodies Against Vaccine Pneumococcal Serotypes
Pneumococcal serotypes assessed were vaccine pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F. Seropositivity cut-off for the assay was an anti-pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F antibody (Anti-1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F) concentrations ≥ 0.05 microgram per milliliter (μg/mL).
Time frame: At Month 3, one month after the administration of the third dose of Synflorix vaccine
Population: The According-To-Protocol (ATP) cohort for immunogenicity included all evaluable subjects with available immunogenicity data. The ATP cohort for immunogenicity included subjects for whom assay results were available for antibodies against at least one study vaccine antigen component after vaccination.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Synflorix™ + Zilbrix™ Hib + Polio Sabin™ | Number of Subjects Seropositive for Antibodies Against Vaccine Pneumococcal Serotypes | Anti-1 | 217 Participants |
| Synflorix™ + Zilbrix™ Hib + Polio Sabin™ | Number of Subjects Seropositive for Antibodies Against Vaccine Pneumococcal Serotypes | Anti-4 | 217 Participants |
| Synflorix™ + Zilbrix™ Hib + Polio Sabin™ | Number of Subjects Seropositive for Antibodies Against Vaccine Pneumococcal Serotypes | Anti-5 | 217 Participants |
| Synflorix™ + Zilbrix™ Hib + Polio Sabin™ | Number of Subjects Seropositive for Antibodies Against Vaccine Pneumococcal Serotypes | Anti-6B | 196 Participants |
| Synflorix™ + Zilbrix™ Hib + Polio Sabin™ | Number of Subjects Seropositive for Antibodies Against Vaccine Pneumococcal Serotypes | Anti-7F | 217 Participants |
| Synflorix™ + Zilbrix™ Hib + Polio Sabin™ | Number of Subjects Seropositive for Antibodies Against Vaccine Pneumococcal Serotypes | Anti-9V | 213 Participants |
| Synflorix™ + Zilbrix™ Hib + Polio Sabin™ | Number of Subjects Seropositive for Antibodies Against Vaccine Pneumococcal Serotypes | Anti-14 | 217 Participants |
| Synflorix™ + Zilbrix™ Hib + Polio Sabin™ | Number of Subjects Seropositive for Antibodies Against Vaccine Pneumococcal Serotypes | Anti-18C | 216 Participants |
| Synflorix™ + Zilbrix™ Hib + Polio Sabin™ | Number of Subjects Seropositive for Antibodies Against Vaccine Pneumococcal Serotypes | Anti-19F | 217 Participants |
| Synflorix™ + Zilbrix™ Hib + Polio Sabin™ | Number of Subjects Seropositive for Antibodies Against Vaccine Pneumococcal Serotypes | Anti-23F | 207 Participants |
| Zilbrix™ Hib + Polio Sabin™ | Number of Subjects Seropositive for Antibodies Against Vaccine Pneumococcal Serotypes | Anti-18C | 23 Participants |
| Zilbrix™ Hib + Polio Sabin™ | Number of Subjects Seropositive for Antibodies Against Vaccine Pneumococcal Serotypes | Anti-1 | 14 Participants |
| Zilbrix™ Hib + Polio Sabin™ | Number of Subjects Seropositive for Antibodies Against Vaccine Pneumococcal Serotypes | Anti-9V | 31 Participants |
| Zilbrix™ Hib + Polio Sabin™ | Number of Subjects Seropositive for Antibodies Against Vaccine Pneumococcal Serotypes | Anti-4 | 12 Participants |
| Zilbrix™ Hib + Polio Sabin™ | Number of Subjects Seropositive for Antibodies Against Vaccine Pneumococcal Serotypes | Anti-23F | 23 Participants |
| Zilbrix™ Hib + Polio Sabin™ | Number of Subjects Seropositive for Antibodies Against Vaccine Pneumococcal Serotypes | Anti-5 | 18 Participants |
| Zilbrix™ Hib + Polio Sabin™ | Number of Subjects Seropositive for Antibodies Against Vaccine Pneumococcal Serotypes | Anti-14 | 91 Participants |
| Zilbrix™ Hib + Polio Sabin™ | Number of Subjects Seropositive for Antibodies Against Vaccine Pneumococcal Serotypes | Anti-6B | 15 Participants |
| Zilbrix™ Hib + Polio Sabin™ | Number of Subjects Seropositive for Antibodies Against Vaccine Pneumococcal Serotypes | Anti-19F | 73 Participants |
| Zilbrix™ Hib + Polio Sabin™ | Number of Subjects Seropositive for Antibodies Against Vaccine Pneumococcal Serotypes | Anti-7F | 19 Participants |
Secondary
Number of Subjects Seropositive for Opsonophagocytic Activity Against Cross-reactive Pneumococcal Serotypes
Pneumococcal serotypes assessed were cross-reactive pneumococcal serotypes 6A and 19A. Seropositivity status was defined as an opsonophagocytic activity against cross-reactive pneumococcal serotypes 6A and 19A (OPA-6A and 19A) ≥ 8.
Time frame: At Month 3, one month after the administration of the third dose of Synflorix vaccine
Population: The According-To-Protocol (ATP) cohort for immunogenicity included all evaluable subjects with available immunogenicity data. The ATP cohort for immunogenicity included subjects for whom assay results were available for antibodies against at least one study vaccine antigen component after vaccination.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Synflorix™ + Zilbrix™ Hib + Polio Sabin™ | Number of Subjects Seropositive for Opsonophagocytic Activity Against Cross-reactive Pneumococcal Serotypes | OPA-6A | 31 Participants |
| Synflorix™ + Zilbrix™ Hib + Polio Sabin™ | Number of Subjects Seropositive for Opsonophagocytic Activity Against Cross-reactive Pneumococcal Serotypes | OPA-19A | 39 Participants |
| Zilbrix™ Hib + Polio Sabin™ | Number of Subjects Seropositive for Opsonophagocytic Activity Against Cross-reactive Pneumococcal Serotypes | OPA-6A | 6 Participants |
| Zilbrix™ Hib + Polio Sabin™ | Number of Subjects Seropositive for Opsonophagocytic Activity Against Cross-reactive Pneumococcal Serotypes | OPA-19A | 3 Participants |
Secondary
Number of Subjects Seropositive for Opsonophagocytic Activity Against Vaccine Pneumococcal Serotypes
Pneumococcal serotypes assessed were vaccine pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F. Seropositivity status was defined as an opsonophagocytic activity against vaccine pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F (OPA-1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F) ≥ 8.
Time frame: At Month 3, one month after the administration of the third dose of Synflorix vaccine
Population: The According-To-Protocol (ATP) cohort for immunogenicity included all evaluable subjects with available immunogenicity data. The ATP cohort for immunogenicity included subjects for whom assay results were available for antibodies against at least one study vaccine antigen component after vaccination.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Synflorix™ + Zilbrix™ Hib + Polio Sabin™ | Number of Subjects Seropositive for Opsonophagocytic Activity Against Vaccine Pneumococcal Serotypes | OPA-1 | 92 Participants |
| Synflorix™ + Zilbrix™ Hib + Polio Sabin™ | Number of Subjects Seropositive for Opsonophagocytic Activity Against Vaccine Pneumococcal Serotypes | OPA-4 | 105 Participants |
| Synflorix™ + Zilbrix™ Hib + Polio Sabin™ | Number of Subjects Seropositive for Opsonophagocytic Activity Against Vaccine Pneumococcal Serotypes | OPA-5 | 100 Participants |
| Synflorix™ + Zilbrix™ Hib + Polio Sabin™ | Number of Subjects Seropositive for Opsonophagocytic Activity Against Vaccine Pneumococcal Serotypes | OPA-6B | 88 Participants |
| Synflorix™ + Zilbrix™ Hib + Polio Sabin™ | Number of Subjects Seropositive for Opsonophagocytic Activity Against Vaccine Pneumococcal Serotypes | OPA-7F | 105 Participants |
| Synflorix™ + Zilbrix™ Hib + Polio Sabin™ | Number of Subjects Seropositive for Opsonophagocytic Activity Against Vaccine Pneumococcal Serotypes | OPA-9V | 103 Participants |
| Synflorix™ + Zilbrix™ Hib + Polio Sabin™ | Number of Subjects Seropositive for Opsonophagocytic Activity Against Vaccine Pneumococcal Serotypes | OPA-14 | 100 Participants |
| Synflorix™ + Zilbrix™ Hib + Polio Sabin™ | Number of Subjects Seropositive for Opsonophagocytic Activity Against Vaccine Pneumococcal Serotypes | OPA-18C | 103 Participants |
| Synflorix™ + Zilbrix™ Hib + Polio Sabin™ | Number of Subjects Seropositive for Opsonophagocytic Activity Against Vaccine Pneumococcal Serotypes | OPA-19F | 101 Participants |
| Synflorix™ + Zilbrix™ Hib + Polio Sabin™ | Number of Subjects Seropositive for Opsonophagocytic Activity Against Vaccine Pneumococcal Serotypes | OPA-23F | 97 Participants |
| Zilbrix™ Hib + Polio Sabin™ | Number of Subjects Seropositive for Opsonophagocytic Activity Against Vaccine Pneumococcal Serotypes | OPA-18C | 2 Participants |
| Zilbrix™ Hib + Polio Sabin™ | Number of Subjects Seropositive for Opsonophagocytic Activity Against Vaccine Pneumococcal Serotypes | OPA-1 | 3 Participants |
| Zilbrix™ Hib + Polio Sabin™ | Number of Subjects Seropositive for Opsonophagocytic Activity Against Vaccine Pneumococcal Serotypes | OPA-9V | 13 Participants |
| Zilbrix™ Hib + Polio Sabin™ | Number of Subjects Seropositive for Opsonophagocytic Activity Against Vaccine Pneumococcal Serotypes | OPA-4 | 3 Participants |
| Zilbrix™ Hib + Polio Sabin™ | Number of Subjects Seropositive for Opsonophagocytic Activity Against Vaccine Pneumococcal Serotypes | OPA-23F | 5 Participants |
| Zilbrix™ Hib + Polio Sabin™ | Number of Subjects Seropositive for Opsonophagocytic Activity Against Vaccine Pneumococcal Serotypes | OPA-5 | 2 Participants |
| Zilbrix™ Hib + Polio Sabin™ | Number of Subjects Seropositive for Opsonophagocytic Activity Against Vaccine Pneumococcal Serotypes | OPA-14 | 13 Participants |
| Zilbrix™ Hib + Polio Sabin™ | Number of Subjects Seropositive for Opsonophagocytic Activity Against Vaccine Pneumococcal Serotypes | OPA-6B | 5 Participants |
| Zilbrix™ Hib + Polio Sabin™ | Number of Subjects Seropositive for Opsonophagocytic Activity Against Vaccine Pneumococcal Serotypes | OPA-19F | 2 Participants |
| Zilbrix™ Hib + Polio Sabin™ | Number of Subjects Seropositive for Opsonophagocytic Activity Against Vaccine Pneumococcal Serotypes | OPA-7F | 21 Participants |
Secondary
Number of Subjects Seroprotected Against Anti-Hepatitis B Surface Antigens (HBs).
The seroprotection cut-off values considered for this endpoint were an anti-HBs antibody concentration ≥ 10 and 100 milli-international units per milliliter (mIU/mL).
Time frame: At Month 3, one month after the administration of the third dose of Tritanrix HepB/ Hiberix vaccine
Population: The According-To-Protocol (ATP) cohort for immunogenicity included all evaluable subjects with available immunogenicity data. The ATP cohort for immunogenicity included subjects for whom assay results were available for antibodies against at least one study vaccine antigen component after vaccination.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Synflorix™ + Zilbrix™ Hib + Polio Sabin™ | Number of Subjects Seroprotected Against Anti-Hepatitis B Surface Antigens (HBs). | Anti-HBs ≥ 100 mIU/mL | 89 Participants |
| Synflorix™ + Zilbrix™ Hib + Polio Sabin™ | Number of Subjects Seroprotected Against Anti-Hepatitis B Surface Antigens (HBs). | Anti-HBs ≥ 10 mIU/mL | 89 Participants |
| Zilbrix™ Hib + Polio Sabin™ | Number of Subjects Seroprotected Against Anti-Hepatitis B Surface Antigens (HBs). | Anti-HBs ≥ 10 mIU/mL | 96 Participants |
| Zilbrix™ Hib + Polio Sabin™ | Number of Subjects Seroprotected Against Anti-Hepatitis B Surface Antigens (HBs). | Anti-HBs ≥ 100 mIU/mL | 94 Participants |
Secondary
Number of Subjects Seroprotected Against Cross-reactive Pneumococcal Serotypes 6A and 19A (Anti-6A and -19A)
Serotypes assessed were cross-reactive pneumococcal serotypes 6A and 19 A. Seroprotection cut-off for the assay was an anti-6A/19A antibody concentrations ≥ 0.2 microgram per milliliter (μg/mL).
Time frame: At Month 3, one month after the administration of the third dose of Synflorix vaccine
Population: The According-To-Protocol (ATP) cohort for immunogenicity included all evaluable subjects with available immunogenicity data. The ATP cohort for immunogenicity included subjects for whom assay results were available for antibodies against at least one study vaccine antigen component after vaccination.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Synflorix™ + Zilbrix™ Hib + Polio Sabin™ | Number of Subjects Seroprotected Against Cross-reactive Pneumococcal Serotypes 6A and 19A (Anti-6A and -19A) | Anti-6A | 56 Participants |
| Synflorix™ + Zilbrix™ Hib + Polio Sabin™ | Number of Subjects Seroprotected Against Cross-reactive Pneumococcal Serotypes 6A and 19A (Anti-6A and -19A) | Anti-19A | 95 Participants |
| Zilbrix™ Hib + Polio Sabin™ | Number of Subjects Seroprotected Against Cross-reactive Pneumococcal Serotypes 6A and 19A (Anti-6A and -19A) | Anti-6A | 8 Participants |
| Zilbrix™ Hib + Polio Sabin™ | Number of Subjects Seroprotected Against Cross-reactive Pneumococcal Serotypes 6A and 19A (Anti-6A and -19A) | Anti-19A | 15 Participants |
Secondary
Number of Subjects Seroprotected Against Diphtheria (D) and Tetanus Toxoids (TT) Antigens
A subject seroprotected against D/TT antigens was defined as a subject with an Anti-D/-TT antibody concentration ≥ 0.1 IU/mL.
Time frame: At Month 3, one month after the administration of the third dose of Tritanrix -HepB/ Hiberix vaccine
Population: The According-To-Protocol (ATP) cohort for immunogenicity included all evaluable subjects with available immunogenicity data. The ATP cohort for immunogenicity included subjects for whom assay results were available for antibodies against at least one study vaccine antigen component after vaccination.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Synflorix™ + Zilbrix™ Hib + Polio Sabin™ | Number of Subjects Seroprotected Against Diphtheria (D) and Tetanus Toxoids (TT) Antigens | Anti-D | 110 Participants |
| Synflorix™ + Zilbrix™ Hib + Polio Sabin™ | Number of Subjects Seroprotected Against Diphtheria (D) and Tetanus Toxoids (TT) Antigens | Anti-T | 110 Participants |
| Zilbrix™ Hib + Polio Sabin™ | Number of Subjects Seroprotected Against Diphtheria (D) and Tetanus Toxoids (TT) Antigens | Anti-D | 112 Participants |
| Zilbrix™ Hib + Polio Sabin™ | Number of Subjects Seroprotected Against Diphtheria (D) and Tetanus Toxoids (TT) Antigens | Anti-T | 112 Participants |
Secondary
Number of Subjects Seroprotected Against Polyribosyl-ribitol Phosphate (PRP)
Anti-PRP antibody concentrations were expressed in microgram per milliliter (μg/mL). The seroprotection cut-off applied for the assay was ≥ 0.15 μg/mL.
Time frame: At Month 3, one month after the administration of the third dose of Tritanrix -HepB/ Hiberix vaccine
Population: The According-To-Protocol (ATP) cohort for immunogenicity included all evaluable subjects with available immunogenicity data. The ATP cohort for immunogenicity included subjects for whom assay results were available for antibodies against at least one study vaccine antigen component after vaccination.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Synflorix™ + Zilbrix™ Hib + Polio Sabin™ | Number of Subjects Seroprotected Against Polyribosyl-ribitol Phosphate (PRP) | 110 Participants |
| Zilbrix™ Hib + Polio Sabin™ | Number of Subjects Seroprotected Against Polyribosyl-ribitol Phosphate (PRP) | 111 Participants |
Secondary
Number of Subjects Seroprotected Against Polyribosyl-ribitol Phosphate (PRP) Antigens
Anti-PRP antibody concentrations were expressed in microgram per milliliter (μg/mL). The seroprotection cut-off applied for the assay was ≥ 1 μg/mL.
Time frame: At Month 3, one month after the administration of the third dose of Tritanrix -HepB/ Hiberix vaccine
Population: The According-To-Protocol (ATP) cohort for immunogenicity included all evaluable subjects with available immunogenicity data. The ATP cohort for immunogenicity included subjects for whom assay results were available for antibodies against at least one study vaccine antigen component after vaccination.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Synflorix™ + Zilbrix™ Hib + Polio Sabin™ | Number of Subjects Seroprotected Against Polyribosyl-ribitol Phosphate (PRP) Antigens | 107 Participants |
| Zilbrix™ Hib + Polio Sabin™ | Number of Subjects Seroprotected Against Polyribosyl-ribitol Phosphate (PRP) Antigens | 102 Participants |
Secondary
Number of Subjects Seroprotected Against Vaccine Pneumococcal Serotypes
Pneumococcal serotypes assessed were vaccine pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F. Seroprotection cut-off for the assay was an anti-pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F antibody (Anti-1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F) concentrations ≥ 0.2 microgram per milliliter (μg/mL).
Time frame: At Month 3, one month after the administration of the third dose of Synflorix vaccine
Population: The According-To-Protocol (ATP) cohort for immunogenicity included all evaluable subjects with available immunogenicity data. The ATP cohort for immunogenicity included subjects for whom assay results were available for antibodies against at least one study vaccine antigen component after vaccination.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Synflorix™ + Zilbrix™ Hib + Polio Sabin™ | Number of Subjects Seroprotected Against Vaccine Pneumococcal Serotypes | Anti-1 | 217 Participants |
| Synflorix™ + Zilbrix™ Hib + Polio Sabin™ | Number of Subjects Seroprotected Against Vaccine Pneumococcal Serotypes | Anti-4 | 217 Participants |
| Synflorix™ + Zilbrix™ Hib + Polio Sabin™ | Number of Subjects Seroprotected Against Vaccine Pneumococcal Serotypes | Anti-5 | 217 Participants |
| Synflorix™ + Zilbrix™ Hib + Polio Sabin™ | Number of Subjects Seroprotected Against Vaccine Pneumococcal Serotypes | Anti-6B | 178 Participants |
| Synflorix™ + Zilbrix™ Hib + Polio Sabin™ | Number of Subjects Seroprotected Against Vaccine Pneumococcal Serotypes | Anti-7F | 216 Participants |
| Synflorix™ + Zilbrix™ Hib + Polio Sabin™ | Number of Subjects Seroprotected Against Vaccine Pneumococcal Serotypes | Anti-9V | 211 Participants |
| Synflorix™ + Zilbrix™ Hib + Polio Sabin™ | Number of Subjects Seroprotected Against Vaccine Pneumococcal Serotypes | Anti-14 | 215 Participants |
| Synflorix™ + Zilbrix™ Hib + Polio Sabin™ | Number of Subjects Seroprotected Against Vaccine Pneumococcal Serotypes | Anti-18C | 216 Participants |
| Synflorix™ + Zilbrix™ Hib + Polio Sabin™ | Number of Subjects Seroprotected Against Vaccine Pneumococcal Serotypes | Anti-19F | 214 Participants |
| Synflorix™ + Zilbrix™ Hib + Polio Sabin™ | Number of Subjects Seroprotected Against Vaccine Pneumococcal Serotypes | Anti-23F | 190 Participants |
| Zilbrix™ Hib + Polio Sabin™ | Number of Subjects Seroprotected Against Vaccine Pneumococcal Serotypes | Anti-18C | 4 Participants |
| Zilbrix™ Hib + Polio Sabin™ | Number of Subjects Seroprotected Against Vaccine Pneumococcal Serotypes | Anti-1 | 2 Participants |
| Zilbrix™ Hib + Polio Sabin™ | Number of Subjects Seroprotected Against Vaccine Pneumococcal Serotypes | Anti-9V | 11 Participants |
| Zilbrix™ Hib + Polio Sabin™ | Number of Subjects Seroprotected Against Vaccine Pneumococcal Serotypes | Anti-4 | 3 Participants |
| Zilbrix™ Hib + Polio Sabin™ | Number of Subjects Seroprotected Against Vaccine Pneumococcal Serotypes | Anti-23F | 3 Participants |
| Zilbrix™ Hib + Polio Sabin™ | Number of Subjects Seroprotected Against Vaccine Pneumococcal Serotypes | Anti-5 | 4 Participants |
| Zilbrix™ Hib + Polio Sabin™ | Number of Subjects Seroprotected Against Vaccine Pneumococcal Serotypes | Anti-14 | 40 Participants |
| Zilbrix™ Hib + Polio Sabin™ | Number of Subjects Seroprotected Against Vaccine Pneumococcal Serotypes | Anti-6B | 2 Participants |
| Zilbrix™ Hib + Polio Sabin™ | Number of Subjects Seroprotected Against Vaccine Pneumococcal Serotypes | Anti-19F | 25 Participants |
| Zilbrix™ Hib + Polio Sabin™ | Number of Subjects Seroprotected Against Vaccine Pneumococcal Serotypes | Anti-7F | 2 Participants |
Secondary
Number of Subjects With Any and Any Grade 3 and Related Solicited General Symptoms
Solicited general symptoms assessed include drowsiness, fever (defined as rectal temperature ≥ 38.0°C), irritability, and loss of appetite. Any was defined as incidence of the specified symptom regardless of intensity or relationship to study vaccination. Grade 3 drowsiness was defined as drowsiness which prevented normal everyday activities. Grade 3 fever was defined as fever (rectal temperature) greater than (\>) 40.0 degree Celsius (°C). Grade 3 irritability was defined as crying that could not be comforted/ preventing normal activity. Grade 3 loss of appetite was defined as the subject not eating at all.
Time frame: Within the 4-day (Days 0 to 3) follow-up periods after each vaccination, across doses and across vaccines
Population: The Total Vaccinated Cohort included all evaluable subjects.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Synflorix™ + Zilbrix™ Hib + Polio Sabin™ | Number of Subjects With Any and Any Grade 3 and Related Solicited General Symptoms | Any Drowsiness | 24 Participants |
| Synflorix™ + Zilbrix™ Hib + Polio Sabin™ | Number of Subjects With Any and Any Grade 3 and Related Solicited General Symptoms | Grade 3 Drowsiness | 0 Participants |
| Synflorix™ + Zilbrix™ Hib + Polio Sabin™ | Number of Subjects With Any and Any Grade 3 and Related Solicited General Symptoms | Any Fever (Rectally) | 207 Participants |
| Synflorix™ + Zilbrix™ Hib + Polio Sabin™ | Number of Subjects With Any and Any Grade 3 and Related Solicited General Symptoms | Grade 3 Fever (Rectally) | 1 Participants |
| Synflorix™ + Zilbrix™ Hib + Polio Sabin™ | Number of Subjects With Any and Any Grade 3 and Related Solicited General Symptoms | Any Irritability | 192 Participants |
| Synflorix™ + Zilbrix™ Hib + Polio Sabin™ | Number of Subjects With Any and Any Grade 3 and Related Solicited General Symptoms | Grade 3 Irritability | 6 Participants |
| Synflorix™ + Zilbrix™ Hib + Polio Sabin™ | Number of Subjects With Any and Any Grade 3 and Related Solicited General Symptoms | Any Loss of appetite | 37 Participants |
| Synflorix™ + Zilbrix™ Hib + Polio Sabin™ | Number of Subjects With Any and Any Grade 3 and Related Solicited General Symptoms | Grade 3 Loss of appetite | 1 Participants |
| Zilbrix™ Hib + Polio Sabin™ | Number of Subjects With Any and Any Grade 3 and Related Solicited General Symptoms | Grade 3 Loss of appetite | 0 Participants |
| Zilbrix™ Hib + Polio Sabin™ | Number of Subjects With Any and Any Grade 3 and Related Solicited General Symptoms | Any Drowsiness | 12 Participants |
| Zilbrix™ Hib + Polio Sabin™ | Number of Subjects With Any and Any Grade 3 and Related Solicited General Symptoms | Any Irritability | 88 Participants |
| Zilbrix™ Hib + Polio Sabin™ | Number of Subjects With Any and Any Grade 3 and Related Solicited General Symptoms | Grade 3 Drowsiness | 0 Participants |
| Zilbrix™ Hib + Polio Sabin™ | Number of Subjects With Any and Any Grade 3 and Related Solicited General Symptoms | Any Loss of appetite | 15 Participants |
| Zilbrix™ Hib + Polio Sabin™ | Number of Subjects With Any and Any Grade 3 and Related Solicited General Symptoms | Any Fever (Rectally) | 105 Participants |
| Zilbrix™ Hib + Polio Sabin™ | Number of Subjects With Any and Any Grade 3 and Related Solicited General Symptoms | Grade 3 Irritability | 2 Participants |
| Zilbrix™ Hib + Polio Sabin™ | Number of Subjects With Any and Any Grade 3 and Related Solicited General Symptoms | Grade 3 Fever (Rectally) | 0 Participants |
Secondary
Number of Subjects With Any and Any Grade 3 Solicited Local Symptoms
Solicited local symptoms assessed included pain, redness and swelling. Grade 3 pain was defined as crying when limb was moved/ spontaneously painful. Grade 3 swelling/ redness was defined as swelling/ redness greater than (\>) 30 millimeters (mm). Any was defined as incidence of the specified symptom regardless of intensity.
Time frame: Within the 4-day (Days 0 to 3) follow-up periods after each vaccination, across doses and across vaccines
Population: The Total Vaccinated Cohort included all evaluable subjects.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Synflorix™ + Zilbrix™ Hib + Polio Sabin™ | Number of Subjects With Any and Any Grade 3 Solicited Local Symptoms | Any Pain | 234 Participants |
| Synflorix™ + Zilbrix™ Hib + Polio Sabin™ | Number of Subjects With Any and Any Grade 3 Solicited Local Symptoms | Grade 3 Pain | 8 Participants |
| Synflorix™ + Zilbrix™ Hib + Polio Sabin™ | Number of Subjects With Any and Any Grade 3 Solicited Local Symptoms | Any Redness | 57 Participants |
| Synflorix™ + Zilbrix™ Hib + Polio Sabin™ | Number of Subjects With Any and Any Grade 3 Solicited Local Symptoms | Grade 3 Redness | 0 Participants |
| Synflorix™ + Zilbrix™ Hib + Polio Sabin™ | Number of Subjects With Any and Any Grade 3 Solicited Local Symptoms | Any Swelling | 173 Participants |
| Synflorix™ + Zilbrix™ Hib + Polio Sabin™ | Number of Subjects With Any and Any Grade 3 Solicited Local Symptoms | Grade 3 Swelling | 22 Participants |
| Zilbrix™ Hib + Polio Sabin™ | Number of Subjects With Any and Any Grade 3 Solicited Local Symptoms | Any Swelling | 83 Participants |
| Zilbrix™ Hib + Polio Sabin™ | Number of Subjects With Any and Any Grade 3 Solicited Local Symptoms | Any Pain | 112 Participants |
| Zilbrix™ Hib + Polio Sabin™ | Number of Subjects With Any and Any Grade 3 Solicited Local Symptoms | Grade 3 Redness | 0 Participants |
| Zilbrix™ Hib + Polio Sabin™ | Number of Subjects With Any and Any Grade 3 Solicited Local Symptoms | Grade 3 Pain | 3 Participants |
| Zilbrix™ Hib + Polio Sabin™ | Number of Subjects With Any and Any Grade 3 Solicited Local Symptoms | Grade 3 Swelling | 11 Participants |
| Zilbrix™ Hib + Polio Sabin™ | Number of Subjects With Any and Any Grade 3 Solicited Local Symptoms | Any Redness | 30 Participants |
Secondary
Number of Subjects With Fever (Temperature Measured Rectally) > the Cut-off
The cut-off for the assay was \> 39.0°C.
Time frame: Within the 4-day (Days 0 to 3) follow-up periods after each vaccination, across doses and across vaccines
Population: The Total Vaccinated Cohort included all evaluable subjects.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Synflorix™ + Zilbrix™ Hib + Polio Sabin™ | Number of Subjects With Fever (Temperature Measured Rectally) > the Cut-off | 40 Participants |
| Zilbrix™ Hib + Polio Sabin™ | Number of Subjects With Fever (Temperature Measured Rectally) > the Cut-off | 13 Participants |
Secondary
Number of Subjects With Serious Adverse Events (SAEs)
Serious adverse events (SAEs) assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization or result in disability/ incapacity.
Time frame: Throughout the entire study period, from Month 0 to Month 3
Population: The Total Vaccinated Cohort included all evaluable subjects.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Synflorix™ + Zilbrix™ Hib + Polio Sabin™ | Number of Subjects With Serious Adverse Events (SAEs) | 5 Participants |
| Zilbrix™ Hib + Polio Sabin™ | Number of Subjects With Serious Adverse Events (SAEs) | 0 Participants |
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. Any was defined an incidence of an unsolicited AE regardless of intensity or relationship to study vaccination.
Time frame: Within the 31-day (Days 0-30) follow-up periods post vaccination, across doses and across vaccines
Population: The Total Vaccinated Cohort included all evaluable subjects.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Synflorix™ + Zilbrix™ Hib + Polio Sabin™ | Number of Subjects With Unsolicited Adverse Events (AEs) | 176 Participants |
| Zilbrix™ Hib + Polio Sabin™ | Number of Subjects With Unsolicited Adverse Events (AEs) | 92 Participants |
Secondary
Titers for Opsonophagocytic Activity (OPA) Against Cross-reactive Pneumococcal Serotypes
Pneumococcal serotypes assessed were cross-reactive pneumococcal serotypes 6A and 19A. Seropositivity status was defined as an opsonophagocytic activity against cross-reactive pneumococcal serotypes 6A and 19A (OPA-6A and 19A) ≥ 8.
Time frame: At Month 3, one month after the administration of the third dose of Synflorix vaccine
Population: The According-To-Protocol (ATP) cohort for immunogenicity included all evaluable subjects with available immunogenicity data. The ATP cohort for immunogenicity included subjects for whom assay results were available for antibodies against at least one study vaccine antigen component after vaccination.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Synflorix™ + Zilbrix™ Hib + Polio Sabin™ | Titers for Opsonophagocytic Activity (OPA) Against Cross-reactive Pneumococcal Serotypes | OPA-6A | 14.1 Titres |
| Synflorix™ + Zilbrix™ Hib + Polio Sabin™ | Titers for Opsonophagocytic Activity (OPA) Against Cross-reactive Pneumococcal Serotypes | OPA-19A | 11 Titres |
| Zilbrix™ Hib + Polio Sabin™ | Titers for Opsonophagocytic Activity (OPA) Against Cross-reactive Pneumococcal Serotypes | OPA-6A | 6.1 Titres |
| Zilbrix™ Hib + Polio Sabin™ | Titers for Opsonophagocytic Activity (OPA) Against Cross-reactive Pneumococcal Serotypes | OPA-19A | 4.3 Titres |
Secondary
Titers for Opsonophagocytic Activity (OPA) Against Vaccine Pneumococcal Serotypes
Pneumococcal serotypes assessed were vaccine pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F. Seropositivity status was defined as an opsonophagocytic activity against vaccine pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F (OPA-1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F) ≥ 8.
Time frame: At Month 3, one month after the administration of the third dose of Synflorix vaccine
Population: The According-To-Protocol (ATP) cohort for immunogenicity included all evaluable subjects with available immunogenicity data. The ATP cohort for immunogenicity included subjects for whom assay results were available for antibodies against at least one study vaccine antigen component after vaccination.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Synflorix™ + Zilbrix™ Hib + Polio Sabin™ | Titers for Opsonophagocytic Activity (OPA) Against Vaccine Pneumococcal Serotypes | OPA-1 | 83 Titers |
| Synflorix™ + Zilbrix™ Hib + Polio Sabin™ | Titers for Opsonophagocytic Activity (OPA) Against Vaccine Pneumococcal Serotypes | OPA-4 | 892.5 Titers |
| Synflorix™ + Zilbrix™ Hib + Polio Sabin™ | Titers for Opsonophagocytic Activity (OPA) Against Vaccine Pneumococcal Serotypes | OPA-5 | 82.7 Titers |
| Synflorix™ + Zilbrix™ Hib + Polio Sabin™ | Titers for Opsonophagocytic Activity (OPA) Against Vaccine Pneumococcal Serotypes | OPA-6B | 538.6 Titers |
| Synflorix™ + Zilbrix™ Hib + Polio Sabin™ | Titers for Opsonophagocytic Activity (OPA) Against Vaccine Pneumococcal Serotypes | OPA-7F | 2733 Titers |
| Synflorix™ + Zilbrix™ Hib + Polio Sabin™ | Titers for Opsonophagocytic Activity (OPA) Against Vaccine Pneumococcal Serotypes | OPA-9V | 1023.7 Titers |
| Synflorix™ + Zilbrix™ Hib + Polio Sabin™ | Titers for Opsonophagocytic Activity (OPA) Against Vaccine Pneumococcal Serotypes | OPA-14 | 1079.2 Titers |
| Synflorix™ + Zilbrix™ Hib + Polio Sabin™ | Titers for Opsonophagocytic Activity (OPA) Against Vaccine Pneumococcal Serotypes | OPA-18C | 617.6 Titers |
| Synflorix™ + Zilbrix™ Hib + Polio Sabin™ | Titers for Opsonophagocytic Activity (OPA) Against Vaccine Pneumococcal Serotypes | OPA-19F | 358.3 Titers |
| Synflorix™ + Zilbrix™ Hib + Polio Sabin™ | Titers for Opsonophagocytic Activity (OPA) Against Vaccine Pneumococcal Serotypes | OPA-23F | 881.8 Titers |
| Zilbrix™ Hib + Polio Sabin™ | Titers for Opsonophagocytic Activity (OPA) Against Vaccine Pneumococcal Serotypes | OPA-18C | 4.4 Titers |
| Zilbrix™ Hib + Polio Sabin™ | Titers for Opsonophagocytic Activity (OPA) Against Vaccine Pneumococcal Serotypes | OPA-1 | 5 Titers |
| Zilbrix™ Hib + Polio Sabin™ | Titers for Opsonophagocytic Activity (OPA) Against Vaccine Pneumococcal Serotypes | OPA-9V | 8.4 Titers |
| Zilbrix™ Hib + Polio Sabin™ | Titers for Opsonophagocytic Activity (OPA) Against Vaccine Pneumococcal Serotypes | OPA-4 | 4.6 Titers |
| Zilbrix™ Hib + Polio Sabin™ | Titers for Opsonophagocytic Activity (OPA) Against Vaccine Pneumococcal Serotypes | OPA-23F | 6.6 Titers |
| Zilbrix™ Hib + Polio Sabin™ | Titers for Opsonophagocytic Activity (OPA) Against Vaccine Pneumococcal Serotypes | OPA-5 | 4.5 Titers |
| Zilbrix™ Hib + Polio Sabin™ | Titers for Opsonophagocytic Activity (OPA) Against Vaccine Pneumococcal Serotypes | OPA-14 | 8.9 Titers |
| Zilbrix™ Hib + Polio Sabin™ | Titers for Opsonophagocytic Activity (OPA) Against Vaccine Pneumococcal Serotypes | OPA-6B | 5.7 Titers |
| Zilbrix™ Hib + Polio Sabin™ | Titers for Opsonophagocytic Activity (OPA) Against Vaccine Pneumococcal Serotypes | OPA-19F | 4.6 Titers |
| Zilbrix™ Hib + Polio Sabin™ | Titers for Opsonophagocytic Activity (OPA) Against Vaccine Pneumococcal Serotypes | OPA-7F | 31.5 Titers |