Infections, Streptococcal
Conditions
Keywords
Pneumococcal vaccine, Immunogenicity, Primary vaccination, Safety, Pneumococcal disease
Brief summary
The purpose of the present study is to demonstrate that the changes in the manufacturing process for the commercial lot of the pneumococcal conjugate vaccine GSK1024850A have no clinical impact and that the immune responses are non-inferior to the immune responses induced by the clinical lot. The study will be conducted in Singapore and Malaysia.
Interventions
BIOLOGICALPneumococcal conjugate vaccine GSK1024850A (different lots)
Intramuscular injection, 3 doses
BIOLOGICALInfanrix hexa
Intramuscular injection, 3 doses in Malaysia and 2 doses in Singapore
BIOLOGICALInfanrix-IPV/Hib
Intramuscular injection, only for Visit 2 in Singapore
BIOLOGICALRotarix
Oral, 2 doses
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
DOUBLE (Caregiver, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
6 Weeks to 12 Weeks
Healthy volunteers
Yes
Inclusion criteria
* Male or female subjects between, and including 6-12 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. * Free of any known or suspected health problems (as established by medical history and clinical examination before entering into the study). * Born after a gestation period of \>= 36 to \<= 42 weeks.
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. * 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, poliomyelitis, hepatitis B, Haemophilus influenzae type b and/or Streptococcus pneumoniae (with the exception of vaccines where the first dose can be given within the first two weeks of life). * Planned administration/administration of a vaccine not foreseen by the study protocol during the period starting 30 days before each dose of vaccine and ending 7 days after Dose 1 and Dose 2 and 30 days after Dose 3. * History of, or intercurrent diphtheria, tetanus, pertussis, hepatitis B, poliomyelitis, H. influenzae type b and rotavirus 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. * Gastroenteritis within 7 days preceding the study vaccine administration. * Any clinically significant history of chronic gastrointestinal disease including any uncorrected congenital malformation of the gastrointestinal tract, intussusception or other medical condition determined to be serious by the investigator.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Concentrations of Antibodies Against Vaccine Components of the Pneumococcal Vaccine | One month after primary immunization (month 4) | Concentrations are given as Geometric Mean Concentrations (GMCs) in microgram per milliliter (μg/mL). Vaccine pneumococcal serotypes assessed 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 4) | Concentration was expressed as GMC in GSK's 22F enzyme-linked-immunosorbent assay (ELISA) units per milliliter (EL.U/mL). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects With Anti-pneumococcal Cross-reactive Serotype Concentrations Equal to or Above 0.20 µg/mL | One month after primary immunization (month 4) | Anti-pneumococcal cross-reactive serotypes were 6A and 19A. |
| Number of Subjects With Opsonophagocytic Activity Against Vaccine Pneumococcal Serotypes | One month after primary immunization (month 4) | Vaccine pneumococcal serotypes included 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F, and 23F. 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 With Opsonophagocytic Activity Against Cross-reactive Pneumococcal Serotypes | One month after primary immunization (month 4) | Cross-reactive pneumococcal serotypes were 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. |
| Opsonophagocytic Titers of Cross-reactive Pneumococcal Serotypes | One month after primary immunization (month 4) | Opsonophagocytic titers were expressed as GMTs. Cross-reactive pneumococcal serotypes included 6A and 19A. |
| Poliovirus Types 1, 2 and 3 Titers | One month after primary immunization (month 4) | Titers were given as Geometric Mean Titers (GMTs). |
| Concentration of Antibody Against Hepatitis B Surface Antigen (HBs) by Enzyme Linked ImmunoSorbent Assay (ELISA). | One month after primary immunization (month 4) | Concentration was given as GMC in milli international units per milliliter (mIU/mL). As a decrease in the specificity of the anti-HB 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 reanalysis. |
| Concentrations of Antibodies Against Diphteria Toxoid (DT) and Tetanus Toxoid (TT) | One month after primary immunization (month 4) | Concentrations were defined as GMCs in international units per milliter (IU/mL) |
| Occurrence of Serious Adverse Events | Following vaccination and throughout the entire study period (Month 0 to Month 4) | SAEs assessed include medical occurrences that result in death, is 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. |
| Opsonophagocytic Titers of Vaccine Pneumococcal Serotypes | One month after primary immunization (month 4) | Titers are presented as Geometric Mean Titers (GMTs). Pneumococcal serotypes included 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F. |
| Number of Subjects With Solicited Local and General Symptoms. | Within 4 days (day 0-3) after vaccination | Solicited local symptoms were pain, redness and swelling. Solicited general symptoms were drowsiness, fever, irritability, loss of appetite, diarrhoea and vomiting. |
| Concentrations of Antibodies Against Pertussis Toxoid (PT), Filamentous Haemagglutinin (FHA), Pertactin (PRN) | One month after primary immunization (month 4) | Concentrations are expressed as GMCs in EL.U/mL. |
| Concentration of Antibody Against Polyribosyl-ribitol Phosphate (PRP) | One month after primary immunization (month 4) | Concentrain was expressed as GMC in µg/mL. |
| Occurrence of Unsolicited Adverse Events | 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. |
| Concentration of Antibody Against Rotavirus Immunoglobulin A (IgA) | 3 months after primary immunization (month 4) | Concentration was expressed as GMC in units per milliliter (U/mL). |
| Number of Subjects With Anti-pneumococcal Vaccine Serotype Antibody Concentrations Equal to or Above 0.20 µg/mL | One month after primary immunization (month 4) | Vaccine pneumococcal serotypes included 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F. |
Countries
Malaysia, Singapore
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Synflorix Clinical Lot & Infanrix Group Subjects received 3 doses of the clinical lot of Synflorix TM (GSK1024850A) intramuscularly in the right thigh at 2-3-5 months of age (= study month 0, 1, 3) co-administered with a DTPa-combined vaccine (Infanrix hexa TM (at 2, 3 and 5 months of age in Malaysia or 2 and 5 months of age in Singapore) or Infanrix-IPV/Hib TM (at 3 months of age in Singapore)) intramuscularly in the left thigh and Rotarix TM orally at 2-3 months of age (= study month 0, 1). | 233 |
| Synflorix Commercial Lot & Infanrix Group Subjects received 3 doses of the commercial lot of Synflorix TM (GSK1024850A) intramuscularly in the lright thigh at 2-3-5 months of age (= study month 0, 1, 3) co-administered with a DTPa-combined vaccine (Infanrix hexa TM (at 2, 3 or 5 months of age in Malaysia or 2 and 5 months in Singapore) or Infanrix-IPV/Hib TM (at 3 months of age in Singapore)) intramuscularly in the left thigh and Rotarix TM orally at 2-3 months of age (= study month 0, 1). | 233 |
| Total | 466 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 0 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Synflorix Clinical Lot & Infanrix Group | Synflorix Commercial Lot & Infanrix Group | Total |
|---|---|---|---|
| Age, Continuous | 7.3 Weeks STANDARD_DEVIATION 1.35 | 7.2 Weeks STANDARD_DEVIATION 1.3 | 7.3 Weeks STANDARD_DEVIATION 1.32 |
| Sex: Female, Male Female | 113 Participants | 104 Participants | 217 Participants |
| Sex: Female, Male Male | 120 Participants | 129 Participants | 249 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 230 / 233 | 228 / 233 |
| serious Total, serious adverse events | 18 / 233 | 7 / 233 |
Outcome results
Primary
Concentration of Antibody Against Protein D (PD)
Concentration was expressed as GMC in GSK's 22F enzyme-linked-immunosorbent assay (ELISA) units per milliliter (EL.U/mL).
Time frame: One month after primary immunization (month 4)
Population: Analysis was performed on the According-to-Protocol cohort for immunogenicity, which included all evaluable subjects for whom immunogenicity data were available.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Synflorix Clinical Lot & Infanrix Group | Concentration of Antibody Against Protein D (PD) | 2543.6 EL.U/mL |
| Synflorix Commercial Lot & Infanrix Group | Concentration of Antibody Against Protein D (PD) | 1869.8 EL.U/mL |
Primary
Concentrations of Antibodies Against Vaccine Components of the Pneumococcal Vaccine
Concentrations are given as Geometric Mean Concentrations (GMCs) in microgram per milliliter (μg/mL). Vaccine pneumococcal serotypes assessed included 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F.
Time frame: One month after primary immunization (month 4)
Population: Analysis was performed on the According-to-Protocol cohort for immunogenicity, which included all evaluable subjects for whom immunogenicity data were available.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Synflorix Clinical Lot & Infanrix Group | Concentrations of Antibodies Against Vaccine Components of the Pneumococcal Vaccine | Anti-1 | 2.67 μg/mL |
| Synflorix Clinical Lot & Infanrix Group | Concentrations of Antibodies Against Vaccine Components of the Pneumococcal Vaccine | Anti-4 | 3.95 μg/mL |
| Synflorix Clinical Lot & Infanrix Group | Concentrations of Antibodies Against Vaccine Components of the Pneumococcal Vaccine | Anti-5 | 4.34 μg/mL |
| Synflorix Clinical Lot & Infanrix Group | Concentrations of Antibodies Against Vaccine Components of the Pneumococcal Vaccine | Anti-6B | 1.31 μg/mL |
| Synflorix Clinical Lot & Infanrix Group | Concentrations of Antibodies Against Vaccine Components of the Pneumococcal Vaccine | Anti-7 | 3.10 μg/mL |
| Synflorix Clinical Lot & Infanrix Group | Concentrations of Antibodies Against Vaccine Components of the Pneumococcal Vaccine | Anti-9V | 3.34 μg/mL |
| Synflorix Clinical Lot & Infanrix Group | Concentrations of Antibodies Against Vaccine Components of the Pneumococcal Vaccine | Anti-14 | 5.13 μg/mL |
| Synflorix Clinical Lot & Infanrix Group | Concentrations of Antibodies Against Vaccine Components of the Pneumococcal Vaccine | Anti-18C | 5.00 μg/mL |
| Synflorix Clinical Lot & Infanrix Group | Concentrations of Antibodies Against Vaccine Components of the Pneumococcal Vaccine | Anti-19F | 6.69 μg/mL |
| Synflorix Clinical Lot & Infanrix Group | Concentrations of Antibodies Against Vaccine Components of the Pneumococcal Vaccine | Anti-23F | 1.98 μg/mL |
| Synflorix Commercial Lot & Infanrix Group | Concentrations of Antibodies Against Vaccine Components of the Pneumococcal Vaccine | Anti-18C | 5.15 μg/mL |
| Synflorix Commercial Lot & Infanrix Group | Concentrations of Antibodies Against Vaccine Components of the Pneumococcal Vaccine | Anti-1 | 2.46 μg/mL |
| Synflorix Commercial Lot & Infanrix Group | Concentrations of Antibodies Against Vaccine Components of the Pneumococcal Vaccine | Anti-9V | 3.14 μg/mL |
| Synflorix Commercial Lot & Infanrix Group | Concentrations of Antibodies Against Vaccine Components of the Pneumococcal Vaccine | Anti-4 | 3.14 μg/mL |
| Synflorix Commercial Lot & Infanrix Group | Concentrations of Antibodies Against Vaccine Components of the Pneumococcal Vaccine | Anti-23F | 1.68 μg/mL |
| Synflorix Commercial Lot & Infanrix Group | Concentrations of Antibodies Against Vaccine Components of the Pneumococcal Vaccine | Anti-5 | 3.59 μg/mL |
| Synflorix Commercial Lot & Infanrix Group | Concentrations of Antibodies Against Vaccine Components of the Pneumococcal Vaccine | Anti-14 | 4.74 μg/mL |
| Synflorix Commercial Lot & Infanrix Group | Concentrations of Antibodies Against Vaccine Components of the Pneumococcal Vaccine | Anti-6B | 1.23 μg/mL |
| Synflorix Commercial Lot & Infanrix Group | Concentrations of Antibodies Against Vaccine Components of the Pneumococcal Vaccine | Anti-19F | 6.96 μg/mL |
| Synflorix Commercial Lot & Infanrix Group | Concentrations of Antibodies Against Vaccine Components of the Pneumococcal Vaccine | Anti-7 | 3.20 μg/mL |
Secondary
Concentration of Antibody Against Hepatitis B Surface Antigen (HBs) by Enzyme Linked ImmunoSorbent Assay (ELISA).
Concentration was given as GMC in milli international units per milliliter (mIU/mL). As a decrease in the specificity of the anti-HB 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 reanalysis.
Time frame: One month after primary immunization (month 4)
Population: Analysis was performed on the According-to-Protocol cohort for immunogenicity, which included all evaluable subjects for whom immunogenicity data were available.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Synflorix Clinical Lot & Infanrix Group | Concentration of Antibody Against Hepatitis B Surface Antigen (HBs) by Enzyme Linked ImmunoSorbent Assay (ELISA). | 1521.2 mIU/mL |
| Synflorix Commercial Lot & Infanrix Group | Concentration of Antibody Against Hepatitis B Surface Antigen (HBs) by Enzyme Linked ImmunoSorbent Assay (ELISA). | 2114.1 mIU/mL |
Secondary
Concentration of Antibody Against Polyribosyl-ribitol Phosphate (PRP)
Concentrain was expressed as GMC in µg/mL.
Time frame: One month after primary immunization (month 4)
Population: Analysis was performed on the According-to-Protocol cohort for immunogenicity, which included all evaluable subjects for whom immunogenicity data were available.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Synflorix Clinical Lot & Infanrix Group | Concentration of Antibody Against Polyribosyl-ribitol Phosphate (PRP) | 9.745 µg/mL |
| Synflorix Commercial Lot & Infanrix Group | Concentration of Antibody Against Polyribosyl-ribitol Phosphate (PRP) | 6.387 µg/mL |
Secondary
Concentration of Antibody Against Rotavirus Immunoglobulin A (IgA)
Concentration was expressed as GMC in units per milliliter (U/mL).
Time frame: 3 months after primary immunization (month 4)
Population: Analysis was performed on the According-to-Protocol cohort for immunogenicity, which included all evaluable subjects for whom immunogenicity data were available.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Synflorix Clinical Lot & Infanrix Group | Concentration of Antibody Against Rotavirus Immunoglobulin A (IgA) | 141.1 U/mL |
| Synflorix Commercial Lot & Infanrix Group | Concentration of Antibody Against Rotavirus Immunoglobulin A (IgA) | 114.8 U/mL |
Secondary
Concentrations of Antibodies Against Diphteria Toxoid (DT) and Tetanus Toxoid (TT)
Concentrations were defined as GMCs in international units per milliter (IU/mL)
Time frame: One month after primary immunization (month 4)
Population: Analysis was performed on the According-to-Protocol cohort for immunogenicity, which included all evaluable subjects for whom immunogenicity data were available.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Synflorix Clinical Lot & Infanrix Group | Concentrations of Antibodies Against Diphteria Toxoid (DT) and Tetanus Toxoid (TT) | Anti-DT | 3.317 IU/mL |
| Synflorix Clinical Lot & Infanrix Group | Concentrations of Antibodies Against Diphteria Toxoid (DT) and Tetanus Toxoid (TT) | Anti-TT | 4.879 IU/mL |
| Synflorix Commercial Lot & Infanrix Group | Concentrations of Antibodies Against Diphteria Toxoid (DT) and Tetanus Toxoid (TT) | Anti-DT | 3.353 IU/mL |
| Synflorix Commercial Lot & Infanrix Group | Concentrations of Antibodies Against Diphteria Toxoid (DT) and Tetanus Toxoid (TT) | Anti-TT | 4.476 IU/mL |
Secondary
Concentrations of Antibodies Against Pertussis Toxoid (PT), Filamentous Haemagglutinin (FHA), Pertactin (PRN)
Concentrations are expressed as GMCs in EL.U/mL.
Time frame: One month after primary immunization (month 4)
Population: Analysis was performed on the According-to-Protocol cohort for immunogenicity, which included all evaluable subjects for whom immunogenicity data were available.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Synflorix Clinical Lot & Infanrix Group | Concentrations of Antibodies Against Pertussis Toxoid (PT), Filamentous Haemagglutinin (FHA), Pertactin (PRN) | Anti-PT | 46.5 EL.U/mL |
| Synflorix Clinical Lot & Infanrix Group | Concentrations of Antibodies Against Pertussis Toxoid (PT), Filamentous Haemagglutinin (FHA), Pertactin (PRN) | Anti-FHA | 179.2 EL.U/mL |
| Synflorix Clinical Lot & Infanrix Group | Concentrations of Antibodies Against Pertussis Toxoid (PT), Filamentous Haemagglutinin (FHA), Pertactin (PRN) | Anti-PRN | 142.1 EL.U/mL |
| Synflorix Commercial Lot & Infanrix Group | Concentrations of Antibodies Against Pertussis Toxoid (PT), Filamentous Haemagglutinin (FHA), Pertactin (PRN) | Anti-PT | 45.4 EL.U/mL |
| Synflorix Commercial Lot & Infanrix Group | Concentrations of Antibodies Against Pertussis Toxoid (PT), Filamentous Haemagglutinin (FHA), Pertactin (PRN) | Anti-FHA | 186.2 EL.U/mL |
| Synflorix Commercial Lot & Infanrix Group | Concentrations of Antibodies Against Pertussis Toxoid (PT), Filamentous Haemagglutinin (FHA), Pertactin (PRN) | Anti-PRN | 128.3 EL.U/mL |
Secondary
Number of Subjects With Anti-pneumococcal Cross-reactive Serotype Concentrations Equal to or Above 0.20 µg/mL
Anti-pneumococcal cross-reactive serotypes were 6A and 19A.
Time frame: One month after primary immunization (month 4)
Population: Analysis was performed on the According-to-Protocol cohort for immunogenicity, which included all evaluable subjects for whom immunogenicity data were available.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Synflorix Clinical Lot & Infanrix Group | Number of Subjects With Anti-pneumococcal Cross-reactive Serotype Concentrations Equal to or Above 0.20 µg/mL | Anti-6A | 152 Participants |
| Synflorix Clinical Lot & Infanrix Group | Number of Subjects With Anti-pneumococcal Cross-reactive Serotype Concentrations Equal to or Above 0.20 µg/mL | Anti-19A | 135 Participants |
| Synflorix Commercial Lot & Infanrix Group | Number of Subjects With Anti-pneumococcal Cross-reactive Serotype Concentrations Equal to or Above 0.20 µg/mL | Anti-6A | 132 Participants |
| Synflorix Commercial Lot & Infanrix Group | Number of Subjects With Anti-pneumococcal Cross-reactive Serotype Concentrations Equal to or Above 0.20 µg/mL | Anti-19A | 119 Participants |
Secondary
Number of Subjects With Anti-pneumococcal Vaccine Serotype Antibody Concentrations Equal to or Above 0.20 µg/mL
Vaccine pneumococcal serotypes included 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F.
Time frame: One month after primary immunization (month 4)
Population: Analysis was performed on the According-to-Protocol cohort for immunogenicity, which included all evaluable subjects for whom immunogenicity data were available.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Synflorix Clinical Lot & Infanrix Group | Number of Subjects With Anti-pneumococcal Vaccine Serotype Antibody Concentrations Equal to or Above 0.20 µg/mL | Anti-1 | 219 Participants |
| Synflorix Clinical Lot & Infanrix Group | Number of Subjects With Anti-pneumococcal Vaccine Serotype Antibody Concentrations Equal to or Above 0.20 µg/mL | Anti-4 | 219 Participants |
| Synflorix Clinical Lot & Infanrix Group | Number of Subjects With Anti-pneumococcal Vaccine Serotype Antibody Concentrations Equal to or Above 0.20 µg/mL | Anti-5 | 218 Participants |
| Synflorix Clinical Lot & Infanrix Group | Number of Subjects With Anti-pneumococcal Vaccine Serotype Antibody Concentrations Equal to or Above 0.20 µg/mL | Anti-6B | 211 Participants |
| Synflorix Clinical Lot & Infanrix Group | Number of Subjects With Anti-pneumococcal Vaccine Serotype Antibody Concentrations Equal to or Above 0.20 µg/mL | Anti-7F | 218 Participants |
| Synflorix Clinical Lot & Infanrix Group | Number of Subjects With Anti-pneumococcal Vaccine Serotype Antibody Concentrations Equal to or Above 0.20 µg/mL | Anti-9V | 219 Participants |
| Synflorix Clinical Lot & Infanrix Group | Number of Subjects With Anti-pneumococcal Vaccine Serotype Antibody Concentrations Equal to or Above 0.20 µg/mL | Anti-14 | 218 Participants |
| Synflorix Clinical Lot & Infanrix Group | Number of Subjects With Anti-pneumococcal Vaccine Serotype Antibody Concentrations Equal to or Above 0.20 µg/mL | Anti-18C | 219 Participants |
| Synflorix Clinical Lot & Infanrix Group | Number of Subjects With Anti-pneumococcal Vaccine Serotype Antibody Concentrations Equal to or Above 0.20 µg/mL | Anti-19F | 218 Participants |
| Synflorix Clinical Lot & Infanrix Group | Number of Subjects With Anti-pneumococcal Vaccine Serotype Antibody Concentrations Equal to or Above 0.20 µg/mL | Anti-23F | 215 Participants |
| Synflorix Commercial Lot & Infanrix Group | Number of Subjects With Anti-pneumococcal Vaccine Serotype Antibody Concentrations Equal to or Above 0.20 µg/mL | Anti-18C | 217 Participants |
| Synflorix Commercial Lot & Infanrix Group | Number of Subjects With Anti-pneumococcal Vaccine Serotype Antibody Concentrations Equal to or Above 0.20 µg/mL | Anti-1 | 218 Participants |
| Synflorix Commercial Lot & Infanrix Group | Number of Subjects With Anti-pneumococcal Vaccine Serotype Antibody Concentrations Equal to or Above 0.20 µg/mL | Anti-9V | 218 Participants |
| Synflorix Commercial Lot & Infanrix Group | Number of Subjects With Anti-pneumococcal Vaccine Serotype Antibody Concentrations Equal to or Above 0.20 µg/mL | Anti-4 | 218 Participants |
| Synflorix Commercial Lot & Infanrix Group | Number of Subjects With Anti-pneumococcal Vaccine Serotype Antibody Concentrations Equal to or Above 0.20 µg/mL | Anti-23F | 212 Participants |
| Synflorix Commercial Lot & Infanrix Group | Number of Subjects With Anti-pneumococcal Vaccine Serotype Antibody Concentrations Equal to or Above 0.20 µg/mL | Anti-5 | 218 Participants |
| Synflorix Commercial Lot & Infanrix Group | Number of Subjects With Anti-pneumococcal Vaccine Serotype Antibody Concentrations Equal to or Above 0.20 µg/mL | Anti-14 | 218 Participants |
| Synflorix Commercial Lot & Infanrix Group | Number of Subjects With Anti-pneumococcal Vaccine Serotype Antibody Concentrations Equal to or Above 0.20 µg/mL | Anti-6B | 204 Participants |
| Synflorix Commercial Lot & Infanrix Group | Number of Subjects With Anti-pneumococcal Vaccine Serotype Antibody Concentrations Equal to or Above 0.20 µg/mL | Anti-19F | 217 Participants |
| Synflorix Commercial Lot & Infanrix Group | Number of Subjects With Anti-pneumococcal Vaccine Serotype Antibody Concentrations Equal to or Above 0.20 µg/mL | Anti-7F | 217 Participants |
Secondary
Number of Subjects With Opsonophagocytic Activity Against Cross-reactive Pneumococcal Serotypes
Cross-reactive pneumococcal serotypes were 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 4)
Population: Analysis was performed on the According-to-Protocol cohort for immunogenicity, which included all evaluable subjects for whom immunogenicity data were available.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Synflorix Clinical Lot & Infanrix Group | Number of Subjects With Opsonophagocytic Activity Against Cross-reactive Pneumococcal Serotypes | Opsono-6A | 173 Participants |
| Synflorix Clinical Lot & Infanrix Group | Number of Subjects With Opsonophagocytic Activity Against Cross-reactive Pneumococcal Serotypes | Opsono-19A | 83 Participants |
| Synflorix Commercial Lot & Infanrix Group | Number of Subjects With Opsonophagocytic Activity Against Cross-reactive Pneumococcal Serotypes | Opsono-6A | 171 Participants |
| Synflorix Commercial Lot & Infanrix Group | Number of Subjects With Opsonophagocytic Activity Against Cross-reactive Pneumococcal Serotypes | Opsono-19A | 75 Participants |
Secondary
Number of Subjects With Opsonophagocytic Activity Against Vaccine Pneumococcal Serotypes
Vaccine pneumococcal serotypes included 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F, and 23F. 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 4)
Population: Analysis was performed on the According-to-Protocol cohort for immunogenicity, which included all evaluable subjects for whom immunogenicity data were available.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Synflorix Clinical Lot & Infanrix Group | Number of Subjects With Opsonophagocytic Activity Against Vaccine Pneumococcal Serotypes | Opsono-1 | 185 Participants |
| Synflorix Clinical Lot & Infanrix Group | Number of Subjects With Opsonophagocytic Activity Against Vaccine Pneumococcal Serotypes | Opsono-4 | 207 Participants |
| Synflorix Clinical Lot & Infanrix Group | Number of Subjects With Opsonophagocytic Activity Against Vaccine Pneumococcal Serotypes | Opsono-5 | 204 Participants |
| Synflorix Clinical Lot & Infanrix Group | Number of Subjects With Opsonophagocytic Activity Against Vaccine Pneumococcal Serotypes | Opsono-6B | 196 Participants |
| Synflorix Clinical Lot & Infanrix Group | Number of Subjects With Opsonophagocytic Activity Against Vaccine Pneumococcal Serotypes | Opsono-7F | 206 Participants |
| Synflorix Clinical Lot & Infanrix Group | Number of Subjects With Opsonophagocytic Activity Against Vaccine Pneumococcal Serotypes | Opsono-9V | 207 Participants |
| Synflorix Clinical Lot & Infanrix Group | Number of Subjects With Opsonophagocytic Activity Against Vaccine Pneumococcal Serotypes | Opsono-14 | 208 Participants |
| Synflorix Clinical Lot & Infanrix Group | Number of Subjects With Opsonophagocytic Activity Against Vaccine Pneumococcal Serotypes | Opsono-18C | 202 Participants |
| Synflorix Clinical Lot & Infanrix Group | Number of Subjects With Opsonophagocytic Activity Against Vaccine Pneumococcal Serotypes | Opsono-19F | 202 Participants |
| Synflorix Clinical Lot & Infanrix Group | Number of Subjects With Opsonophagocytic Activity Against Vaccine Pneumococcal Serotypes | Opsono-23F | 207 Participants |
| Synflorix Commercial Lot & Infanrix Group | Number of Subjects With Opsonophagocytic Activity Against Vaccine Pneumococcal Serotypes | Opsono-18C | 199 Participants |
| Synflorix Commercial Lot & Infanrix Group | Number of Subjects With Opsonophagocytic Activity Against Vaccine Pneumococcal Serotypes | Opsono-1 | 189 Participants |
| Synflorix Commercial Lot & Infanrix Group | Number of Subjects With Opsonophagocytic Activity Against Vaccine Pneumococcal Serotypes | Opsono-9V | 208 Participants |
| Synflorix Commercial Lot & Infanrix Group | Number of Subjects With Opsonophagocytic Activity Against Vaccine Pneumococcal Serotypes | Opsono-4 | 203 Participants |
| Synflorix Commercial Lot & Infanrix Group | Number of Subjects With Opsonophagocytic Activity Against Vaccine Pneumococcal Serotypes | Opsono-23F | 206 Participants |
| Synflorix Commercial Lot & Infanrix Group | Number of Subjects With Opsonophagocytic Activity Against Vaccine Pneumococcal Serotypes | Opsono-5 | 203 Participants |
| Synflorix Commercial Lot & Infanrix Group | Number of Subjects With Opsonophagocytic Activity Against Vaccine Pneumococcal Serotypes | Opsono-14 | 207 Participants |
| Synflorix Commercial Lot & Infanrix Group | Number of Subjects With Opsonophagocytic Activity Against Vaccine Pneumococcal Serotypes | Opsono-6B | 191 Participants |
| Synflorix Commercial Lot & Infanrix Group | Number of Subjects With Opsonophagocytic Activity Against Vaccine Pneumococcal Serotypes | Opsono-19F | 200 Participants |
| Synflorix Commercial Lot & Infanrix Group | Number of Subjects With Opsonophagocytic Activity Against Vaccine Pneumococcal Serotypes | Opsono-7F | 208 Participants |
Secondary
Number of Subjects With Solicited Local and General Symptoms.
Solicited local symptoms were pain, redness and swelling. Solicited general symptoms were drowsiness, fever, irritability, loss of appetite, diarrhoea and vomiting.
Time frame: Within 4 days (day 0-3) after vaccination
Population: Analysis was performed on the Total Vaccinated Cohort, which inlcuded all vaccinated subjects.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Synflorix Clinical Lot & Infanrix Group | Number of Subjects With Solicited Local and General Symptoms. | Redness | 149 Participants |
| Synflorix Clinical Lot & Infanrix Group | Number of Subjects With Solicited Local and General Symptoms. | Irritability | 168 Participants |
| Synflorix Clinical Lot & Infanrix Group | Number of Subjects With Solicited Local and General Symptoms. | Drowsiness | 151 Participants |
| Synflorix Clinical Lot & Infanrix Group | Number of Subjects With Solicited Local and General Symptoms. | Loss of appetite | 127 Participants |
| Synflorix Clinical Lot & Infanrix Group | Number of Subjects With Solicited Local and General Symptoms. | Swelling | 133 Participants |
| Synflorix Clinical Lot & Infanrix Group | Number of Subjects With Solicited Local and General Symptoms. | Diarrhoea | 53 Participants |
| Synflorix Clinical Lot & Infanrix Group | Number of Subjects With Solicited Local and General Symptoms. | Fever | 193 Participants |
| Synflorix Clinical Lot & Infanrix Group | Number of Subjects With Solicited Local and General Symptoms. | Vomiting | 44 Participants |
| Synflorix Clinical Lot & Infanrix Group | Number of Subjects With Solicited Local and General Symptoms. | Pain | 162 Participants |
| Synflorix Commercial Lot & Infanrix Group | Number of Subjects With Solicited Local and General Symptoms. | Vomiting | 46 Participants |
| Synflorix Commercial Lot & Infanrix Group | Number of Subjects With Solicited Local and General Symptoms. | Pain | 157 Participants |
| Synflorix Commercial Lot & Infanrix Group | Number of Subjects With Solicited Local and General Symptoms. | Redness | 142 Participants |
| Synflorix Commercial Lot & Infanrix Group | Number of Subjects With Solicited Local and General Symptoms. | Swelling | 124 Participants |
| Synflorix Commercial Lot & Infanrix Group | Number of Subjects With Solicited Local and General Symptoms. | Drowsiness | 136 Participants |
| Synflorix Commercial Lot & Infanrix Group | Number of Subjects With Solicited Local and General Symptoms. | Fever | 175 Participants |
| Synflorix Commercial Lot & Infanrix Group | Number of Subjects With Solicited Local and General Symptoms. | Irritability | 171 Participants |
| Synflorix Commercial Lot & Infanrix Group | Number of Subjects With Solicited Local and General Symptoms. | Loss of appetite | 121 Participants |
| Synflorix Commercial Lot & Infanrix Group | Number of Subjects With Solicited Local and General Symptoms. | Diarrhoea | 54 Participants |
Secondary
Occurrence of Serious Adverse Events
SAEs assessed include medical occurrences that result in death, is 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 vaccination and throughout the entire study period (Month 0 to Month 4)
Population: Analysis was performed on the Total Vaccinated Cohort, which included all vaccinated subjects.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Synflorix Clinical Lot & Infanrix Group | Occurrence of Serious Adverse Events | 18 subjects |
| Synflorix Commercial Lot & Infanrix Group | Occurrence of Serious Adverse Events | 7 subjects |
Secondary
Occurrence of Unsolicited Adverse Events
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.
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 (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Synflorix Clinical Lot & Infanrix Group | Occurrence of Unsolicited Adverse Events | 88 Participants |
| Synflorix Commercial Lot & Infanrix Group | Occurrence of Unsolicited Adverse Events | 96 Participants |
Secondary
Opsonophagocytic Titers of Cross-reactive Pneumococcal Serotypes
Opsonophagocytic titers were expressed as GMTs. Cross-reactive pneumococcal serotypes included 6A and 19A.
Time frame: One month after primary immunization (month 4)
Population: Analysis was performed on the According-to-Protocol cohort for immunogenicity, which included all evaluable subjects for whom immunogenicity data were available.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Synflorix Clinical Lot & Infanrix Group | Opsonophagocytic Titers of Cross-reactive Pneumococcal Serotypes | Opsono-6A | 230.8 titer |
| Synflorix Clinical Lot & Infanrix Group | Opsonophagocytic Titers of Cross-reactive Pneumococcal Serotypes | Opsono-19A | 18.1 titer |
| Synflorix Commercial Lot & Infanrix Group | Opsonophagocytic Titers of Cross-reactive Pneumococcal Serotypes | Opsono-6A | 173.7 titer |
| Synflorix Commercial Lot & Infanrix Group | Opsonophagocytic Titers of Cross-reactive Pneumococcal Serotypes | Opsono-19A | 15.1 titer |
Secondary
Opsonophagocytic Titers of Vaccine Pneumococcal Serotypes
Titers are presented as Geometric Mean Titers (GMTs). Pneumococcal serotypes included 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F.
Time frame: One month after primary immunization (month 4)
Population: Analysis was performed on the According-to-Protocol cohort for immunogenicity, which included all evaluable subjects for whom immunogenicity data were available.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Synflorix Clinical Lot & Infanrix Group | Opsonophagocytic Titers of Vaccine Pneumococcal Serotypes | Opsono-1 | 128.9 titer |
| Synflorix Clinical Lot & Infanrix Group | Opsonophagocytic Titers of Vaccine Pneumococcal Serotypes | Opsono-4 | 698.3 titer |
| Synflorix Clinical Lot & Infanrix Group | Opsonophagocytic Titers of Vaccine Pneumococcal Serotypes | Opsono-5 | 127.9 titer |
| Synflorix Clinical Lot & Infanrix Group | Opsonophagocytic Titers of Vaccine Pneumococcal Serotypes | Opsono-6B | 870.7 titer |
| Synflorix Clinical Lot & Infanrix Group | Opsonophagocytic Titers of Vaccine Pneumococcal Serotypes | Opsono-7F | 3905.8 titer |
| Synflorix Clinical Lot & Infanrix Group | Opsonophagocytic Titers of Vaccine Pneumococcal Serotypes | Opsono-9V | 1800.0 titer |
| Synflorix Clinical Lot & Infanrix Group | Opsonophagocytic Titers of Vaccine Pneumococcal Serotypes | Opsono-14 | 1521.0 titer |
| Synflorix Clinical Lot & Infanrix Group | Opsonophagocytic Titers of Vaccine Pneumococcal Serotypes | Opsono-18C | 533.5 titer |
| Synflorix Clinical Lot & Infanrix Group | Opsonophagocytic Titers of Vaccine Pneumococcal Serotypes | Opsono-19F | 689.6 titer |
| Synflorix Clinical Lot & Infanrix Group | Opsonophagocytic Titers of Vaccine Pneumococcal Serotypes | Opsono-23F | 2716.7 titer |
| Synflorix Commercial Lot & Infanrix Group | Opsonophagocytic Titers of Vaccine Pneumococcal Serotypes | Opsono-18C | 383.9 titer |
| Synflorix Commercial Lot & Infanrix Group | Opsonophagocytic Titers of Vaccine Pneumococcal Serotypes | Opsono-1 | 122.1 titer |
| Synflorix Commercial Lot & Infanrix Group | Opsonophagocytic Titers of Vaccine Pneumococcal Serotypes | Opsono-9V | 1851.3 titer |
| Synflorix Commercial Lot & Infanrix Group | Opsonophagocytic Titers of Vaccine Pneumococcal Serotypes | Opsono-4 | 609.3 titer |
| Synflorix Commercial Lot & Infanrix Group | Opsonophagocytic Titers of Vaccine Pneumococcal Serotypes | Opsono-23F | 2379.5 titer |
| Synflorix Commercial Lot & Infanrix Group | Opsonophagocytic Titers of Vaccine Pneumococcal Serotypes | Opsono-5 | 98.6 titer |
| Synflorix Commercial Lot & Infanrix Group | Opsonophagocytic Titers of Vaccine Pneumococcal Serotypes | Opsono-14 | 1485.8 titer |
| Synflorix Commercial Lot & Infanrix Group | Opsonophagocytic Titers of Vaccine Pneumococcal Serotypes | Opsono-6B | 619.2 titer |
| Synflorix Commercial Lot & Infanrix Group | Opsonophagocytic Titers of Vaccine Pneumococcal Serotypes | Opsono-19F | 573.5 titer |
| Synflorix Commercial Lot & Infanrix Group | Opsonophagocytic Titers of Vaccine Pneumococcal Serotypes | Opsono-7F | 3585.7 titer |
Secondary
Poliovirus Types 1, 2 and 3 Titers
Titers were given as Geometric Mean Titers (GMTs).
Time frame: One month after primary immunization (month 4)
Population: Analysis was performed on the According-to-Protocol cohort for immunogenicity, which included all evaluable subjects for whom immunogenicity data were available.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Synflorix Clinical Lot & Infanrix Group | Poliovirus Types 1, 2 and 3 Titers | Anti-Polio 1 | 313.8 titer |
| Synflorix Clinical Lot & Infanrix Group | Poliovirus Types 1, 2 and 3 Titers | Anti-Polio 2 | 278.7 titer |
| Synflorix Clinical Lot & Infanrix Group | Poliovirus Types 1, 2 and 3 Titers | Anti-Polio 3 | 408.8 titer |
| Synflorix Commercial Lot & Infanrix Group | Poliovirus Types 1, 2 and 3 Titers | Anti-Polio 1 | 328.7 titer |
| Synflorix Commercial Lot & Infanrix Group | Poliovirus Types 1, 2 and 3 Titers | Anti-Polio 2 | 229.1 titer |
| Synflorix Commercial Lot & Infanrix Group | Poliovirus Types 1, 2 and 3 Titers | Anti-Polio 3 | 449.4 titer |