Malaria
Conditions
Keywords
Africa, Plasmodium falciparum, Malaria
Brief summary
This study is being done to assess the possibility of the potential integration of malaria vaccine into the EPI regimen. It will evaluate whether the malaria vaccine is safe and immunogenic in infants aged 6 to 10 weeks at first dose, when co-administered with other EPI vaccine antigens. The Protocol Posting has been updated in order to comply with the FDA Amendment Act, Sep 2007.
Detailed description
Two vaccination schedules will be studied, which constitutes the two alternative three dose regimens for the malaria candidate vaccine 257049 integration into EPI. The co-administered EPI vaccines include GSK Biologicals' Tritanrix™-HepB/Hiberix™, a measles vaccine (depending on the supply availability), Aventis Pasteur's Yellow Fever vaccine Stamaril™ and GSK Biologicals' Oral Polio vaccine Polio Sabin™. Tuberculosis vaccine (Bacillus of Calmette and Guerin, BCG) will be administered according to national medical practice and will not be administered as part of this protocol, but will be documented.
Interventions
BIOLOGICALGSK 257049
GlaxoSmithKline (GSK) Biologicals' candidate Plasmodium falciparum malaria vaccine
BIOLOGICALTritanrix™ HepB/Hib
GSK Biologicals' re-constituted diphtheria, tetanus, pertussis, hepatitis B vaccine (Tritanrix™ HepB) and Haemophilus influenzae type B vaccine (Hiberix™)
BIOLOGICALRouvax™
Aventis Pasteur's attenuated measles vaccine.
BIOLOGICALStamaril™
Aventis Pasteur's attenuated yellow fever vaccine.
BIOLOGICALPolio Sabin™
GSK Biologicals' oral polio virus vaccine
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
* A male or female infant between 6 and 10 weeks of age at the time of first vaccination. * Signed or thumb-printed informed consent obtained from the parent(s)/guardian(s) of the child. Where parent(s)/guardian(s) are illiterate, the consent form will be countersigned by a witness. * Subjects who have received one previous dose of OPV and BCG. * Subjects who are born after a normal gestation period (between 36 and 42 weeks).
Exclusion criteria
* Acute disease at the time of enrolment. * Serious acute or chronic illness determined by clinical or physical examination and laboratory screening tests. * Laboratory screening tests out of range, specifically: ALT and creatinine above acceptable limit; Hemoglobin, Platelet count and Total white cell count below acceptable limit. * Previous vaccination with diphtheria, tetanus, pertussis (whole-cell or acellular), Hemophilus influenzae type b or hepatitis B vaccines. * BCG administration within one week of proposed administration of a study vaccine. * OPV administration within four weeks of proposed administration of a study vaccine. * Planned administration/administration of a vaccine not foreseen by the study protocol within 30 days of the first dose of vaccine(s). * Use of any investigational or non-registered drug or vaccine within 30 days preceding the first dose of study vaccine, or planned use during the study period. * Administration of immunoglobulins, blood transfusions or other blood products since birth to the first dose of study vaccine or planned administration during the study period. * Chronic administration (defined as more than 14 days) of immunosuppressants or other immune-modifying drugs within six months prior to the first vaccine dose. * Simultaneous participation in any other clinical trial. * Twins (to avoid misidentification). * Maternal death. * History of allergic reactions (significant IgE-mediated events) or anaphylaxis to previous immunizations. * History of allergic disease or reactions likely to be exacerbated by any component of the vaccine. * Any other findings that the investigator feels would increase the risk of having an adverse outcome from participation in the trial.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects With Serious Adverse Events (SAEs). | From Month 0 to Month 8 | SAEs were defined as medical occurrences that resulted in death, were life threatening, required hospitalization or prolongation of hospitalization or resulted in disability/incapacity. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Concentrations of Anti-diphtheria (Anti-D) and Anti-tetanus (Anti-T) Antibodies. | At Month 3 | Anti-D and Anti-T antibody concentrations were expressed as geometric mean concentrations (GMCs) in international unit per milliliter (IU/mL). The seroprotection assay cut-off was 0.1 IU/mL. |
| Number of Subjects With Serious Adverse Events (SAEs). | From Month 8 to Month 19 | SAEs were defined as medical occurrences that resulted in death, were life threatening, required hospitalization or prolongation of hospitalization or resulted in disability/incapacity. |
| Concentrations of Anti-polyribosyl Ribitol Phosphate (Anti-PRP) Antibodies. | At Month 3 | Anti-PRP antibody concentrations were expressed as geometric mean concentrations (GMCs) in microgram per milliliter (µg/mL). The seroprotection assay cut-off was 0.15 µg/mL. |
| Titers for Antibodies Against Poliomyelitis Types 1, 2 and 3 (Anti-Polio 1, 2 and 3 Antibodies). | At Month 3 | Anti-Polio 1, 2 and 3 antibody titers were expressed as geometric mean titers (GMTs). The seroprotection assay cut-off was 8. |
| Concentrations of Anti-Bordetella Pertussis Toxin (Anti-BPT) Antibodies. | At Month 3 | Anti-BPT antibodies were measured by enzyme-linked immunosorbent assay (ELISA). Concentrations were expressed as geometric mean concentrations (GMCs) in ELISA unit per milliliter (EL.U/mL). The seropositivity assay cut-off was 15 EL.U/mL. |
| Concentrations of Antibodies Against Hepatitis B (Anti-HB Antibodies). | At Months 0, 1, 3 and 7. | Anti-HB antibody concentrations were expressed as geometric mean concentrations (GMCs) in milli-international unit per milliliter (mIU/mL). The seroprotection assay cut-off was 10 mIU/mL. This outcome only covers results for the GSK 257049 1 Group. |
| Titers for Anti-yellow Fever Antibodies. | At Months 7 and 8. | Anti-yellow fever antibody titers were expressed as geometric mean titers (GMTs). The seroprotection assay cut-off was 10. The analysis was only performed on subjects from the GSK 257049 2 and Tritanrix™ HepB/Hiberix™ groups. The analysis was only performed on subjects from the GSK 257049 2 and Tritanrix™ HepB/Hiberix™ groups. |
| Concentrations of Anti-circumsporozoite Protein (Anti-CS) Antibodies. | At Months 0, 1, 3 and 7. | Anti-CS antibody antibodies were measured by enzyme-linked immunosorbent assay (ELISA). Concentrations were expressed as geometric mean concentrations (GMCs) in ELISA unit per milliliter (EL.U/mL). The seropositivity assay cut-off was 0.5 EL.U/mL. This outcome only covers results for the GSK 257049 1 Group. |
| Number of Subjects With Solicited Local Symptoms. | During the 7-day (Days 0-6) follow-up period after any vaccination with the Tritanrix™ HepB/Hib, Rouvax™, GSK 257049 and Stamaril™ vaccines. | Assessed solicited local symptoms were pain and swelling at injection site following vaccination with each of the following study vaccines administered intramuscularly, e. a. the Tritanrix™ HepB/Hib, Rouvax™, GSK 257049 and Stamaril™ vaccines. The numbers of subjects with each of the assessed solicited local symptoms reported were tabulated for each vaccine administered, separately. |
| Number of Subjects With Solicited General Symptoms. | During the 7-day (Days 0-6) follow-up period after any vaccination | Assessed solicited general symptoms were drowsiness, fever \[axillary temperature equal or above (≥) 37.5 degrees Celsius (°C)\], irritability and loss of appetite following any vaccination with any of the study vaccines, e. a. the Tritanrix™ HepB/Hib, Rouvax™, GSK 257049, Stamaril™ and Polio Sabin™ vaccines. |
| Number of Subjects With Unsolicited Adverse Events (AEs) | During the 30-day (Days 0-29) follow-up period after any vaccination | An unsolicited AE is any AE (i.e. any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with use of a medicinal product, whether or not considered related to the medicinal product) reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for solicited symptoms. Unsolicited AEs were assessed following vaccination with any of the study vaccines, e. a. the Tritanrix™ HepB/Hib, Rouvax™, GSK 257049, Stamaril™ and Polio Sabin™ vaccines. |
| Concentrations of Anti-measles Antibodies. | At Months 7 and 8. | Anti-measles antibody concentrations were expressed as geometric mean concentrations (GMCs) in milli-international unit per milliliter (mIU/mL). The seropositivity assay cut-off was 150 mIU/mL. The analysis was only performed on subjects from the GSK 257049 2 and Tritanrix™ HepB/Hiberix™ groups. |
Countries
Gabon, Ghana, Tanzania
Participant flow
Pre-assignment details
The study comprised a vaccination phase (Months 0-8) and a follow-up phase (Months 8-19). The Stamaril™ vaccine was not part of the EPI Tanzanian vaccination schedule at study planning. Hence this vaccine was not administered to subjects from Tanzania.
Participants by arm
| Arm | Count |
|---|---|
| GSK 257049 1 Group Subjects aged 6 to 10 weeks at the time of first vaccination received 3 doses of Tritanrix™ HepB/Hib, Polio Sabin™ and GSK 257049 vaccines at Months 0, 1 and 2, and a single dose of Rouvax™ and Stamaril™ vaccines at Month 7.
The GSK 257049 and Tritanrix™ HepB/Hib vaccines were administered intramuscularly in the left and right antero-lateral thigh, respectively. Rouvax™ and Stamaril™ were administered intramuscularly in the left and right arm respectively. Polio Sabin™ was administered orally. The Stamaril™ vaccine was not administered to subjects from Tanzania as this vaccine was not foreseen at the time to be introduced to the EPI vaccination schedule in Tanzania. | 170 |
| GSK 257049 2 Group Subjects aged 6 to 10 weeks at the time of first vaccination received 3 doses of Tritanrix™ HepB/Hib and Polio Sabin™ at Months 0, 1 and 2, 3 doses of GSK 257049 vaccine at Months 0, 1 and 7, and a single dose of Rouvax™ and Stamaril™ at Month 7. The GSK 257049 and Tritanrix™ HepB/Hib vaccines were administered intramuscularly in the left and right antero-lateral thigh, respectively. Rouvax™ and Stamaril™ were administered intramuscularly in the left and right arm respectively. Polio Sabin™ was administered orally. Stamaril™ was not administered to subjects from Tanzania as this vaccine was not foreseen at the time to be introduced to the EPI vaccination schedule in Tanzania. | 170 |
| Tritanrix™ HepB/Hiberix™ Group Subjects aged 6 to 10 weeks at the time of first vaccination received 3 doses of Tritanrix™ HepB/Hib and Polio Sabin™ at Months 0, 1 and 2, and a single dose of Rouvax™ and Stamaril™ at Month 7. The GSK 257049 and Tritanrix™ HepB/Hib vaccines were administered intramuscularly in the left and right antero-lateral thigh, respectively. Rouvax™ and Stamaril™ were administered intramuscularly in the left and right arm respectively. Polio Sabin™ was administered orally. The Stamaril™ vaccine was not administered to subjects from Tanzania as this vaccine was not foreseen at the time to be introduced to the EPI vaccination schedule in Tanzania. | 171 |
| Total | 511 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Death | 0 | 1 | 3 |
| Overall Study | Lost to Follow-up | 14 | 10 | 13 |
| Overall Study | Other | 0 | 0 | 1 |
| Overall Study | Physician Decision | 0 | 0 | 2 |
| Overall Study | Withdrawal by Subject | 5 | 3 | 4 |
Baseline characteristics
| Characteristic | GSK 257049 1 Group | GSK 257049 2 Group | Tritanrix™ HepB/Hiberix™ Group | Total |
|---|---|---|---|---|
| Age, Continuous | 7.0 Weeks STANDARD_DEVIATION 0.97 | 7.1 Weeks STANDARD_DEVIATION 1.05 | 7.0 Weeks STANDARD_DEVIATION 0.97 | 7.0 Weeks STANDARD_DEVIATION 1 |
| Region of Enrollment Gabon | 73 Subjects | 73 Subjects | 74 Subjects | 220 Subjects |
| Region of Enrollment Ghana | 27 Subjects | 27 Subjects | 27 Subjects | 81 Subjects |
| Region of Enrollment Tanzania | 70 Subjects | 70 Subjects | 70 Subjects | 210 Subjects |
| Sex: Female, Male Female | 90 Participants | 84 Participants | 78 Participants | 252 Participants |
| Sex: Female, Male Male | 80 Participants | 86 Participants | 93 Participants | 259 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 169 / 170 | 169 / 170 | 171 / 171 |
| serious Total, serious adverse events | 57 / 170 | 47 / 170 | 49 / 171 |
Outcome results
Primary
Number of Subjects With Serious Adverse Events (SAEs).
SAEs were defined as medical occurrences that resulted in death, were life threatening, required hospitalization or prolongation of hospitalization or resulted in disability/incapacity.
Time frame: From Month 0 to Month 8
Population: The analysis was performed on the Total Vaccinated cohort, which included all vaccinated subjects.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| GSK 257049 1 Group | Number of Subjects With Serious Adverse Events (SAEs). | 38 subjects |
| GSK 257049 2 Group | Number of Subjects With Serious Adverse Events (SAEs). | 28 subjects |
| Tritanrix™ HepB/Hiberix™ Group | Number of Subjects With Serious Adverse Events (SAEs). | 33 subjects |
Secondary
Concentrations of Antibodies Against Hepatitis B (Anti-HB Antibodies).
Anti-HB antibody concentrations were expressed as geometric mean concentrations (GMCs) in milli-international unit per milliliter (mIU/mL). The seroprotection assay cut-off was 10 mIU/mL. This outcome only covers results for the GSK 257049 1 Group.
Time frame: At Months 0, 1, 3 and 7.
Population: The analysis was performed on the According-to-Protocol cohort for immunogenicity, which included all evaluable subjects (i.e. those meeting all eligibility criteria, complying with the procedures defined in the protocol, with no elimination criteria during the study) for whom data concerning immunogenicity endpoint measures were available.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| GSK 257049 1 Group | Concentrations of Antibodies Against Hepatitis B (Anti-HB Antibodies). | Anti-HB, Month 0 [N=145] | 12.5 mIU/mL |
| GSK 257049 1 Group | Concentrations of Antibodies Against Hepatitis B (Anti-HB Antibodies). | Anti-HB, Month 1 [N=133] | 173.4 mIU/mL |
| GSK 257049 1 Group | Concentrations of Antibodies Against Hepatitis B (Anti-HB Antibodies). | Anti-HB, Month 3 [N=130] | 1355.7 mIU/mL |
| GSK 257049 1 Group | Concentrations of Antibodies Against Hepatitis B (Anti-HB Antibodies). | Anti-HB, Month 7 [N=137] | 1555.5 mIU/mL |
Secondary
Concentrations of Antibodies Against Hepatitis B (Anti-HB Antibodies).
Anti-HB antibody concentrations were expressed as geometric mean concentrations (GMCs) in milli-international unit per milliliter (mIU/mL). The seroprotection assay cut-off was 10 mIU/mL. This outcome only covers results for the Tritanrix™ HepB/Hiberix™ Group.
Time frame: At Months 0, 3, 7 and 8.
Population: The analysis was performed on the According-to-Protocol cohort for immunogenicity, which included all evaluable subjects (i.e. those meeting all eligibility criteria, complying with the procedures defined in the protocol, with no elimination criteria during the study) for whom data concerning immunogenicity endpoint measures were available.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| GSK 257049 1 Group | Concentrations of Antibodies Against Hepatitis B (Anti-HB Antibodies). | Anti-HB, Month 3 [N=126] | 338.0 mIU/mL |
| GSK 257049 1 Group | Concentrations of Antibodies Against Hepatitis B (Anti-HB Antibodies). | Anti-HB, Month 0 [N=143] | 8.7 mIU/mL |
| GSK 257049 1 Group | Concentrations of Antibodies Against Hepatitis B (Anti-HB Antibodies). | Anti-HB, Month 7 [N=131] | 159.9 mIU/mL |
| GSK 257049 1 Group | Concentrations of Antibodies Against Hepatitis B (Anti-HB Antibodies). | Anti-HB, Month 8 [N=133] | 162.4 mIU/mL |
Secondary
Concentrations of Antibodies Against Hepatitis B (Anti-HB Antibodies).
Anti-HB antibody concentrations were expressed as geometric mean concentrations (GMCs) in milli-international unit per milliliter (mIU/mL). The seroprotection assay cut-off was 10 mIU/mL. This outcome only covers results for the GSK 257049 2 Group.
Time frame: At Months 0, 3, 7 and 8.
Population: The analysis was performed on the According-to-Protocol cohort for immunogenicity, which included all evaluable subjects (i.e. those meeting all eligibility criteria, complying with the procedures defined in the protocol, with no elimination criteria during the study) for whom data concerning immunogenicity endpoint measures were available.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| GSK 257049 1 Group | Concentrations of Antibodies Against Hepatitis B (Anti-HB Antibodies). | Anti-HB, Month 0 [N=131] | 9.6 mIU/mL |
| GSK 257049 1 Group | Concentrations of Antibodies Against Hepatitis B (Anti-HB Antibodies). | Anti-HB, Month 3 [N=119] | 651.2 mIU/mL |
| GSK 257049 1 Group | Concentrations of Antibodies Against Hepatitis B (Anti-HB Antibodies). | Anti-HB, Month 7 [N=126] | 1133.1 mIU/mL |
| GSK 257049 1 Group | Concentrations of Antibodies Against Hepatitis B (Anti-HB Antibodies). | Anti-HB, Month 8 [N=125] | 59813.5 mIU/mL |
Secondary
Concentrations of Anti-Bordetella Pertussis Toxin (Anti-BPT) Antibodies.
Anti-BPT antibodies were measured by enzyme-linked immunosorbent assay (ELISA). Concentrations were expressed as geometric mean concentrations (GMCs) in ELISA unit per milliliter (EL.U/mL). The seropositivity assay cut-off was 15 EL.U/mL.
Time frame: At Month 3
Population: The analysis was performed on the According-to-Protocol cohort for immunogenicity, which included all evaluable subjects (i.e. those meeting all eligibility criteria, complying with the procedures defined in the protocol, with no elimination criteria during the study) for whom data concerning immunogenicity endpoint measures were available.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| GSK 257049 1 Group | Concentrations of Anti-Bordetella Pertussis Toxin (Anti-BPT) Antibodies. | 85.3 EL.U/mL |
| GSK 257049 2 Group | Concentrations of Anti-Bordetella Pertussis Toxin (Anti-BPT) Antibodies. | 104.4 EL.U/mL |
| Tritanrix™ HepB/Hiberix™ Group | Concentrations of Anti-Bordetella Pertussis Toxin (Anti-BPT) Antibodies. | 106.5 EL.U/mL |
Secondary
Concentrations of Anti-circumsporozoite Protein (Anti-CS) Antibodies.
Anti-CS antiibodies were measured by enzyme-linked immunosorbent assay (ELISA). Concentrations were expressed as geometric mean concentrations (GMCs) in ELISA unit per milliliter (EL.U/mL). The seropositivity assay cut-off was 0.5 EL.U/mL. This outcome only covers results for the GSK 257049 2 Group.
Time frame: At Months 0, 3, 7 and 8.
Population: The analysis was performed on the According-to-Protocol cohort for immunogenicity, which included all evaluable subjects (i.e. those meeting all eligibility criteria, complying with the procedures defined in the protocol, with no elimination criteria during the study) for whom data concerning immunogenicity endpoint measures were available.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| GSK 257049 1 Group | Concentrations of Anti-circumsporozoite Protein (Anti-CS) Antibodies. | Anti-CS, Month 0 [N=141] | 0.4 EL.U/mL |
| GSK 257049 1 Group | Concentrations of Anti-circumsporozoite Protein (Anti-CS) Antibodies. | Anti-CS, Month 7 [N=127] | 6.1 EL.U/mL |
| GSK 257049 1 Group | Concentrations of Anti-circumsporozoite Protein (Anti-CS) Antibodies. | Anti-CS, Month 3 [N=121] | 57.7 EL.U/mL |
| GSK 257049 1 Group | Concentrations of Anti-circumsporozoite Protein (Anti-CS) Antibodies. | Anti-CS, Month 8 [N=127] | 107.8 EL.U/mL |
Secondary
Concentrations of Anti-circumsporozoite Protein (Anti-CS) Antibodies.
Anti-CS antibodies were measured by Enzyme-linked immunosorbent assay (ELISA). Concentrations were expressed as geometric mean concentrations (GMCs) in ELISA unit per milliliter (EL.U/mL). The seropositivity assay cut-off was 0.5 EL.U/mL. This outcome only covers results for the Tritanrix™ HepB/Hiberix™ Group.
Time frame: At Months 0, 3, 7 and 8.
Population: The analysis was performed on the According-to-Protocol cohort for immunogenicity, which included all evaluable subjects (i.e. those meeting all eligibility criteria, complying with the procedures defined in the protocol, with no elimination criteria during the study) for whom data concerning immunogenicity endpoint measures were available.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| GSK 257049 1 Group | Concentrations of Anti-circumsporozoite Protein (Anti-CS) Antibodies. | Anti-CS, Month 0 [N=156] | 0.4 EL.U/mL |
| GSK 257049 1 Group | Concentrations of Anti-circumsporozoite Protein (Anti-CS) Antibodies. | Anti-CS, Month 3 [N=129] | 0.3 EL.U/mL |
| GSK 257049 1 Group | Concentrations of Anti-circumsporozoite Protein (Anti-CS) Antibodies. | Anti-CS, Month 7 [N=132] | 0.3 EL.U/mL |
| GSK 257049 1 Group | Concentrations of Anti-circumsporozoite Protein (Anti-CS) Antibodies. | Anti-CS, Month 8 [N=135] | 0.3 EL.U/mL |
Secondary
Concentrations of Anti-circumsporozoite Protein (Anti-CS) Antibodies.
Anti-CS antibody antibodies were measured by enzyme-linked immunosorbent assay (ELISA). Concentrations were expressed as geometric mean concentrations (GMCs) in ELISA unit per milliliter (EL.U/mL). The seropositivity assay cut-off was 0.5 EL.U/mL. This outcome only covers results for the GSK 257049 1 Group.
Time frame: At Months 0, 1, 3 and 7.
Population: The analysis was performed on the According-to-Protocol cohort for immunogenicity, which included all evaluable subjects (i.e. those meeting all eligibility criteria, complying with the procedures defined in the protocol, with no elimination criteria during the study) for whom data concerning immunogenicity endpoint measures were available.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| GSK 257049 1 Group | Concentrations of Anti-circumsporozoite Protein (Anti-CS) Antibodies. | Anti-CS, Month 0 [N=153] | 0.4 EL.U/mL |
| GSK 257049 1 Group | Concentrations of Anti-circumsporozoite Protein (Anti-CS) Antibodies. | Anti-CS, Month 2 [N=137] | 86.6 EL.U/mL |
| GSK 257049 1 Group | Concentrations of Anti-circumsporozoite Protein (Anti-CS) Antibodies. | Anti-CS, Month 3 [N=131] | 190.3 EL.U/mL |
| GSK 257049 1 Group | Concentrations of Anti-circumsporozoite Protein (Anti-CS) Antibodies. | Anti-CS, Month 7 [N=137] | 35.3 EL.U/mL |
Secondary
Concentrations of Anti-diphtheria (Anti-D) and Anti-tetanus (Anti-T) Antibodies.
Anti-D and Anti-T antibody concentrations were expressed as geometric mean concentrations (GMCs) in international unit per milliliter (IU/mL). The seroprotection assay cut-off was 0.1 IU/mL.
Time frame: At Month 3
Population: The analysis was performed on the According-to-Protocol cohort for immunogenicity, which included all evaluable subjects (i.e. those meeting all eligibility criteria, complying with the procedures defined in the protocol, with no elimination criteria during the study) for whom data concerning immunogenicity endpoint measures were available.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| GSK 257049 1 Group | Concentrations of Anti-diphtheria (Anti-D) and Anti-tetanus (Anti-T) Antibodies. | Anti-D | 1.0 IU/mL |
| GSK 257049 1 Group | Concentrations of Anti-diphtheria (Anti-D) and Anti-tetanus (Anti-T) Antibodies. | Anti-T | 2.8 IU/mL |
| GSK 257049 2 Group | Concentrations of Anti-diphtheria (Anti-D) and Anti-tetanus (Anti-T) Antibodies. | Anti-D | 1.1 IU/mL |
| GSK 257049 2 Group | Concentrations of Anti-diphtheria (Anti-D) and Anti-tetanus (Anti-T) Antibodies. | Anti-T | 2.6 IU/mL |
| Tritanrix™ HepB/Hiberix™ Group | Concentrations of Anti-diphtheria (Anti-D) and Anti-tetanus (Anti-T) Antibodies. | Anti-D | 1.4 IU/mL |
| Tritanrix™ HepB/Hiberix™ Group | Concentrations of Anti-diphtheria (Anti-D) and Anti-tetanus (Anti-T) Antibodies. | Anti-T | 3.7 IU/mL |
Secondary
Concentrations of Anti-measles Antibodies.
Anti-measles antibody concentrations were expressed as geometric mean concentrations (GMCs) in milli-international unit per milliliter (mIU/mL). The seropositivity assay cut-off was 150 mIU/mL. The analysis was only performed on subjects from the GSK 257049 2 and Tritanrix™ HepB/Hiberix™ groups.
Time frame: At Months 7 and 8.
Population: The analysis was performed on the According-to-Protocol cohort for immunogenicity, which included all evaluable subjects (i.e. those meeting all eligibility criteria, complying with the procedures defined in the protocol, with no elimination criteria during the study) for whom data concerning immunogenicity endpoint measures were available.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| GSK 257049 1 Group | Concentrations of Anti-measles Antibodies. | Anti-measles, Month 7 [N=112;120] | 75.0 mIU/mL |
| GSK 257049 1 Group | Concentrations of Anti-measles Antibodies. | Anti-measles, Month 8 [N=119;122] | 76.2 mIU/mL |
| GSK 257049 2 Group | Concentrations of Anti-measles Antibodies. | Anti-measles, Month 7 [N=112;120] | 1295.2 mIU/mL |
| GSK 257049 2 Group | Concentrations of Anti-measles Antibodies. | Anti-measles, Month 8 [N=119;122] | 1299.0 mIU/mL |
Secondary
Concentrations of Anti-polyribosyl Ribitol Phosphate (Anti-PRP) Antibodies.
Anti-PRP antibody concentrations were expressed as geometric mean concentrations (GMCs) in microgram per milliliter (µg/mL). The seroprotection assay cut-off was 0.15 µg/mL.
Time frame: At Month 3
Population: The analysis was performed on the According-to-Protocol cohort for immunogenicity, which included all evaluable subjects (i.e. those meeting all eligibility criteria, complying with the procedures defined in the protocol, with no elimination criteria during the study) for whom data concerning immunogenicity endpoint measures were available.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| GSK 257049 1 Group | Concentrations of Anti-polyribosyl Ribitol Phosphate (Anti-PRP) Antibodies. | 13.3 µg/mL |
| GSK 257049 2 Group | Concentrations of Anti-polyribosyl Ribitol Phosphate (Anti-PRP) Antibodies. | 15.7 µg/mL |
| Tritanrix™ HepB/Hiberix™ Group | Concentrations of Anti-polyribosyl Ribitol Phosphate (Anti-PRP) Antibodies. | 18.6 µg/mL |
Secondary
Number of Subjects With Serious Adverse Events (SAEs).
SAEs were defined as medical occurrences that resulted in death, were life threatening, required hospitalization or prolongation of hospitalization or resulted in disability/incapacity.
Time frame: From Month 0 to Month 19
Population: The analysis was performed on the Total Vaccinated cohort, which included all vaccinated subjects.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| GSK 257049 1 Group | Number of Subjects With Serious Adverse Events (SAEs). | 57 subjects |
| GSK 257049 2 Group | Number of Subjects With Serious Adverse Events (SAEs). | 47 subjects |
| Tritanrix™ HepB/Hiberix™ Group | Number of Subjects With Serious Adverse Events (SAEs). | 49 subjects |
Secondary
Number of Subjects With Serious Adverse Events (SAEs).
SAEs were defined as medical occurrences that resulted in death, were life threatening, required hospitalization or prolongation of hospitalization or resulted in disability/incapacity.
Time frame: From Month 8 to Month 19
Population: The analysis was performed on the Total Vaccinated cohort, which included all vaccinated subjects.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| GSK 257049 1 Group | Number of Subjects With Serious Adverse Events (SAEs). | 28 subjects |
| GSK 257049 2 Group | Number of Subjects With Serious Adverse Events (SAEs). | 24 subjects |
| Tritanrix™ HepB/Hiberix™ Group | Number of Subjects With Serious Adverse Events (SAEs). | 27 subjects |
Secondary
Number of Subjects With Solicited General Symptoms.
Assessed solicited general symptoms were drowsiness, fever \[axillary temperature equal or above (≥) 37.5 degrees Celsius (°C)\], irritability and loss of appetite following any vaccination with any of the study vaccines, e. a. the Tritanrix™ HepB/Hib, Rouvax™, GSK 257049, Stamaril™ and Polio Sabin™ vaccines.
Time frame: During the 7-day (Days 0-6) follow-up period after any vaccination
Population: The Total Vaccinated cohort included all vaccinated subjects whose symptom sheet was completed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| GSK 257049 1 Group | Number of Subjects With Solicited General Symptoms. | Drowsiness | 82 subjects |
| GSK 257049 1 Group | Number of Subjects With Solicited General Symptoms. | Fever (axillary temperature ≥ 37.5°C) | 102 subjects |
| GSK 257049 1 Group | Number of Subjects With Solicited General Symptoms. | Loss of appetite | 68 subjects |
| GSK 257049 1 Group | Number of Subjects With Solicited General Symptoms. | Irritability | 124 subjects |
| GSK 257049 2 Group | Number of Subjects With Solicited General Symptoms. | Loss of appetite | 83 subjects |
| GSK 257049 2 Group | Number of Subjects With Solicited General Symptoms. | Drowsiness | 97 subjects |
| GSK 257049 2 Group | Number of Subjects With Solicited General Symptoms. | Fever (axillary temperature ≥ 37.5°C) | 95 subjects |
| GSK 257049 2 Group | Number of Subjects With Solicited General Symptoms. | Irritability | 131 subjects |
| Tritanrix™ HepB/Hiberix™ Group | Number of Subjects With Solicited General Symptoms. | Fever (axillary temperature ≥ 37.5°C) | 75 subjects |
| Tritanrix™ HepB/Hiberix™ Group | Number of Subjects With Solicited General Symptoms. | Irritability | 118 subjects |
| Tritanrix™ HepB/Hiberix™ Group | Number of Subjects With Solicited General Symptoms. | Loss of appetite | 70 subjects |
| Tritanrix™ HepB/Hiberix™ Group | Number of Subjects With Solicited General Symptoms. | Drowsiness | 72 subjects |
Secondary
Number of Subjects With Solicited Local Symptoms.
Assessed solicited local symptoms were pain and swelling at injection site following vaccination with each of the following study vaccines administered intramuscularly, e. a. the Tritanrix™ HepB/Hib, Rouvax™, GSK 257049 and Stamaril™ vaccines. The numbers of subjects with each of the assessed solicited local symptoms reported were tabulated for each vaccine administered, separately.
Time frame: During the 7-day (Days 0-6) follow-up period after any vaccination with the Tritanrix™ HepB/Hib, Rouvax™, GSK 257049 and Stamaril™ vaccines.
Population: The Total Vaccinated cohort included all vaccinated subjects whose symptom sheet was completed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| GSK 257049 1 Group | Number of Subjects With Solicited Local Symptoms. | Pain - GSK 257049 [N=170;170;0] | 126 subjects |
| GSK 257049 1 Group | Number of Subjects With Solicited Local Symptoms. | Swelling - GSK 257049 [N=170;170;0] | 28 subjects |
| GSK 257049 1 Group | Number of Subjects With Solicited Local Symptoms. | Swelling - Tritanrix™ HepB/Hib [N=170;170;171] | 47 subjects |
| GSK 257049 1 Group | Number of Subjects With Solicited Local Symptoms. | Swelling - Rouvax™ [N=163;161;159] | 20 subjects |
| GSK 257049 1 Group | Number of Subjects With Solicited Local Symptoms. | Pain - Tritanrix™ HepB/Hib [N=170;170;171] | 127 subjects |
| GSK 257049 1 Group | Number of Subjects With Solicited Local Symptoms. | Swelling - Stamaril™ [N=95;94;94] | 0 subjects |
| GSK 257049 1 Group | Number of Subjects With Solicited Local Symptoms. | Pain - Stamaril™ [N=95;94;94] | 2 subjects |
| GSK 257049 1 Group | Number of Subjects With Solicited Local Symptoms. | Pain - Rouvax™ [N=163;161;159] | 52 subjects |
| GSK 257049 2 Group | Number of Subjects With Solicited Local Symptoms. | Pain - Stamaril™ [N=95;94;94] | 7 subjects |
| GSK 257049 2 Group | Number of Subjects With Solicited Local Symptoms. | Pain - Tritanrix™ HepB/Hib [N=170;170;171] | 133 subjects |
| GSK 257049 2 Group | Number of Subjects With Solicited Local Symptoms. | Swelling - Tritanrix™ HepB/Hib [N=170;170;171] | 68 subjects |
| GSK 257049 2 Group | Number of Subjects With Solicited Local Symptoms. | Pain - GSK 257049 [N=170;170;0] | 116 subjects |
| GSK 257049 2 Group | Number of Subjects With Solicited Local Symptoms. | Pain - Rouvax™ [N=163;161;159] | 54 subjects |
| GSK 257049 2 Group | Number of Subjects With Solicited Local Symptoms. | Swelling - GSK 257049 [N=170;170;0] | 44 subjects |
| GSK 257049 2 Group | Number of Subjects With Solicited Local Symptoms. | Swelling - Rouvax™ [N=163;161;159] | 21 subjects |
| GSK 257049 2 Group | Number of Subjects With Solicited Local Symptoms. | Swelling - Stamaril™ [N=95;94;94] | 1 subjects |
| Tritanrix™ HepB/Hiberix™ Group | Number of Subjects With Solicited Local Symptoms. | Swelling - Tritanrix™ HepB/Hib [N=170;170;171] | 68 subjects |
| Tritanrix™ HepB/Hiberix™ Group | Number of Subjects With Solicited Local Symptoms. | Swelling - Stamaril™ [N=95;94;94] | 0 subjects |
| Tritanrix™ HepB/Hiberix™ Group | Number of Subjects With Solicited Local Symptoms. | Pain - GSK 257049 [N=170;170;0] | NA subjects |
| Tritanrix™ HepB/Hiberix™ Group | Number of Subjects With Solicited Local Symptoms. | Pain - Rouvax™ [N=163;161;159] | 47 subjects |
| Tritanrix™ HepB/Hiberix™ Group | Number of Subjects With Solicited Local Symptoms. | Swelling - Rouvax™ [N=163;161;159] | 16 subjects |
| Tritanrix™ HepB/Hiberix™ Group | Number of Subjects With Solicited Local Symptoms. | Pain - Stamaril™ [N=95;94;94] | 2 subjects |
| Tritanrix™ HepB/Hiberix™ Group | Number of Subjects With Solicited Local Symptoms. | Pain - Tritanrix™ HepB/Hib [N=170;170;171] | 140 subjects |
| Tritanrix™ HepB/Hiberix™ Group | Number of Subjects With Solicited Local Symptoms. | Swelling - GSK 257049 [N=170;170;0] | NA subjects |
Secondary
Number of Subjects With Unsolicited Adverse Events (AEs)
An unsolicited AE is any AE (i.e. any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with use of a medicinal product, whether or not considered related to the medicinal product) reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for solicited symptoms. Unsolicited AEs were assessed following vaccination with any of the study vaccines, e. a. the Tritanrix™ HepB/Hib, Rouvax™, GSK 257049, Stamaril™ and Polio Sabin™ vaccines.
Time frame: During the 30-day (Days 0-29) follow-up period after any vaccination
Population: The analysis was performed on the Total Vaccinated cohort, which included all vaccinated subjects.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| GSK 257049 1 Group | Number of Subjects With Unsolicited Adverse Events (AEs) | 160 subjects |
| GSK 257049 2 Group | Number of Subjects With Unsolicited Adverse Events (AEs) | 161 subjects |
| Tritanrix™ HepB/Hiberix™ Group | Number of Subjects With Unsolicited Adverse Events (AEs) | 164 subjects |
Secondary
Titers for Antibodies Against Poliomyelitis Types 1, 2 and 3 (Anti-Polio 1, 2 and 3 Antibodies).
Anti-Polio 1, 2 and 3 antibody titers were expressed as geometric mean titers (GMTs). The seroprotection assay cut-off was 8.
Time frame: At Month 3
Population: The analysis was performed on the According-to-Protocol cohort for immunogenicity, which included all evaluable subjects (i.e. those meeting all eligibility criteria, complying with the procedures defined in the protocol, with no elimination criteria during the study) for whom data concerning immunogenicity endpoint measures were available.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| GSK 257049 1 Group | Titers for Antibodies Against Poliomyelitis Types 1, 2 and 3 (Anti-Polio 1, 2 and 3 Antibodies). | Anti-Polio 3 [N=135;125;133] | 123.5 titers |
| GSK 257049 1 Group | Titers for Antibodies Against Poliomyelitis Types 1, 2 and 3 (Anti-Polio 1, 2 and 3 Antibodies). | Anti-Polio 2 [N=135;124;131] | 494.0 titers |
| GSK 257049 1 Group | Titers for Antibodies Against Poliomyelitis Types 1, 2 and 3 (Anti-Polio 1, 2 and 3 Antibodies). | Anti-Polio 1 [N=136;125;131] | 463.6 titers |
| GSK 257049 2 Group | Titers for Antibodies Against Poliomyelitis Types 1, 2 and 3 (Anti-Polio 1, 2 and 3 Antibodies). | Anti-Polio 3 [N=135;125;133] | 148.7 titers |
| GSK 257049 2 Group | Titers for Antibodies Against Poliomyelitis Types 1, 2 and 3 (Anti-Polio 1, 2 and 3 Antibodies). | Anti-Polio 1 [N=136;125;131] | 485.5 titers |
| GSK 257049 2 Group | Titers for Antibodies Against Poliomyelitis Types 1, 2 and 3 (Anti-Polio 1, 2 and 3 Antibodies). | Anti-Polio 2 [N=135;124;131] | 563.2 titers |
| Tritanrix™ HepB/Hiberix™ Group | Titers for Antibodies Against Poliomyelitis Types 1, 2 and 3 (Anti-Polio 1, 2 and 3 Antibodies). | Anti-Polio 2 [N=135;124;131] | 406.8 titers |
| Tritanrix™ HepB/Hiberix™ Group | Titers for Antibodies Against Poliomyelitis Types 1, 2 and 3 (Anti-Polio 1, 2 and 3 Antibodies). | Anti-Polio 1 [N=136;125;131] | 500.0 titers |
| Tritanrix™ HepB/Hiberix™ Group | Titers for Antibodies Against Poliomyelitis Types 1, 2 and 3 (Anti-Polio 1, 2 and 3 Antibodies). | Anti-Polio 3 [N=135;125;133] | 205.1 titers |
Secondary
Titers for Anti-yellow Fever Antibodies.
Anti-yellow fever antibody titers were expressed as geometric mean titers (GMTs). The seroprotection assay cut-off was 10. The analysis was only performed on subjects from the GSK 257049 2 and Tritanrix™ HepB/Hiberix™ groups. The analysis was only performed on subjects from the GSK 257049 2 and Tritanrix™ HepB/Hiberix™ groups.
Time frame: At Months 7 and 8.
Population: The analysis was performed on the According-to-Protocol cohort for immunogenicity, which included all evaluable subjects (i.e. those meeting all eligibility criteria, complying with the procedures defined in the protocol, with no elimination criteria during the study) for whom data concerning immunogenicity endpoint measures were available.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| GSK 257049 1 Group | Titers for Anti-yellow Fever Antibodies. | Anti-yellow fever, Month 7 [N=41;62] | 5.3 titers |
| GSK 257049 1 Group | Titers for Anti-yellow Fever Antibodies. | Anti-yellow fever, Month 8 [N=46;64] | 172.2 titers |
| GSK 257049 2 Group | Titers for Anti-yellow Fever Antibodies. | Anti-yellow fever, Month 7 [N=41;62] | 5.9 titers |
| GSK 257049 2 Group | Titers for Anti-yellow Fever Antibodies. | Anti-yellow fever, Month 8 [N=46;64] | 183.4 titers |