Infections, Meningococcal
Conditions
Keywords
meningococcal serogroups A and C diseases, tetanus, hepatitis B, pertussis, Haemophilus influenzae type b, meningococcal vaccine, Prophylaxis diphtheria
Brief summary
The purpose of this study is to assess the safety and reactogenicity of a booster dose of diphtheria-tetanus-whole cell pertussis-hepatitis B virus/Haemophilus influenzae type b vaccine (DTPw-HBV/Hib) at 15-18 m and to assess the immunogenicity, safety, and reactogenicity of a dose of Mencevax™ Group A, C and W135 polysaccharide meningococcal vaccine (ACW) at 24 to 30 m in primed subjects. The Protocol Posting has been updated in order to comply with the FDA Amendment Act, Sep 2007.
Detailed description
This open study will have two parallel groups based on the vaccination received in the primary study: AC primed Group: primed with Tritanrix™-HepB/Hib-MenAC vaccine and AC unprimed Group (control): primed with Tritanrix™-HepB/Hiberix™ vaccine. All subjects will receive a booster dose of Tritanrix™-HepB/Hiberix™ vaccine at 15 to 18 months of age with GSK Biological's OPV vaccine given concomitantly and a dose of Mencevax™ ACW vaccine at 24 to 30 months of age. Blood sampling will be done prior to (pre) and one month after (post) the Mencevax™ ACW vaccine administration for immunogenicity analyses. The study will last minimum 7 to maximum 16 months per subject. Mencevax™ ACWY was changed to Mencevax™ ACW throughout the posting to correct an inconsistency in the earlier version of the protocol posting and to reflect the actual situation.
Interventions
BIOLOGICALTritanrix™- HepB
One intramuscular dose during the booster vaccination study in subjects aged 15 to 18 months
BIOLOGICALHiberix™
One intramuscular dose during the booster vaccination study in subjects aged 15 to 18 months
BIOLOGICALMencevax™ ACW
One subcutaneous dose during the booster vaccination study in subjects aged 24 to 30 months
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
15 Months to 18 Months
Healthy volunteers
Yes
Inclusion criteria
* Subjects who the investigator believes that their parents/guardians can and will comply with the requirements of the protocol. * A male or female between, and including, 15 and 18 months of age at the time of vaccination. * Written informed consent obtained from the parent or guardian of the subject. * Healthy subjects as established by medical history and clinical examination before entering into the study. * Having participated in the primary vaccination study (CPMS N° 759346/007).
Exclusion criteria
* Use of any investigational or non-registered product (drug or vaccine) other than the study vaccine within 30 days preceding the vaccination, or planned use during the study period. * Chronic administration (defined as more than 14 days) of immunosuppressants or other immune-modifying drugs within six months prior to vaccination. * Planned administration/ administration of a vaccine not foreseen by the study protocol within 30 days of vaccination. * Booster vaccination against diphtheria, tetanus, pertussis, hepatitis B, Haemophilus influenzae type b (Hib) and/or meningococcal serogroups A, C or W disease, after the date of the study conclusion visit of the primary vaccination study (CPMS N° 759346/007). * History of diphtheria, tetanus, pertussis, hepatitis B, Hib and/or meningococcal serogroup A, C or W disease. * Known exposure to diphtheria, tetanus, pertussis, hepatitis B, Hib and/or meningococcal serogroup A, C or W disease. * Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination. * A family history of congenital or hereditary immunodeficiency. * History of allergic disease or reactions likely to be exacerbated by any component of the vaccines administered in the study. * Major congenital defects or serious chronic illness. * History of any neurologic disorders or seizures including febrile seizures in infancy. * Acute disease at the time of enrolment. * Axillary temperature ≥ 37.5°C at the time of vaccination. * Administration of immunoglobulins and/or any blood products within the three months preceding the vaccination or planned administration during the study period. * Anaphylactic reaction following the administration of vaccine in the primary vaccination study. * Known hypersensitivity to any component of the vaccine, or subjects having shown signs of hypersensitivity after previous administration of diphtheria, tetanus, pertussis, hepatitis B, Hib or meningococcal vaccines.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects With Serum Bactericidal Assay Against N. Meningitidis Serogroups A, C Using Rabbit Complement (rSBA-MenA,C) Antibodies | At one month post vaccination with Mencevax™ ACW vaccine (Month 25-31) | Pre-defined assay cut-off values for assessed titers were greater than or equal to (≥) 1:128. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Anti-rSBA-MenA, C, W-135 Antibody Titers | Prior to (Months 24-30) & one month after the administration of the Mencevax™ ACW vaccine (Months 25-31) | Antibody titers were expressed as geometric mean titers (GMTs). |
| Number of Subjects With Anti-polysaccharide A (Anti-PSA) and C (Anti-PSC) Antibody Concentrations Above Predefined Cut-off Values | Prior to (Months 24-30) & one month after the administration of the Mencevax™ ACW vaccine (Months 25-31) | Antibody concentrations cut-off were ≥ 0.3 and ≥2 micrograms per millilitre (µg/mL). |
| Anti-PSA and Anti-PSC Antibody Concentrations | Prior to (Months 24-30) & one month after the administration of the Mencevax™ ACW vaccine (Months 25-31 | Antibody concentrations were expressed as Geometric Mean Concentrations (GMCs). |
| Number of Subjects With Anti- Polysaccharide W (Anti-PSW) Antibody Concentrations ≥ Predefined Cut-off Values | Prior to (Months 24-30) & one month after the administration of the Mencevax™ ACW vaccine (Months 25-31) | Antibody concentrations were ≥ 0.3 µg/mL. |
| Anti-PSW Antibody Concentrations | Prior to (Months 24-30) & one month after the administration of the Mencevax™ ACW vaccine (Months 25-31) | Antibody concentrations were expressed as Geometric Mean Concentrations (GMCs). |
| Number of Subjects With Anti-hepatitis B (Anti-HBs) Antibody Concentrations ≥ Predefined Cut-off Values | Prior to (Months 24-30) the administration of the Mencevax™ ACW vaccine | Antibody concentrations cut-off were ≥ 10 milli international units per milliliter (mIU/mL). |
| Number of Subjects With rSBA-MenA,C, W-135 Antibody Titers ≥ Predefined Cut-offs | Prior to (Months 24-30) & one month after the administration of the Mencevax™ ACW vaccine (Months 25-31) | Antibody titer cut-offs were ≥ 1:8 and ≥ 1:128. |
| Number of Subjects With Vaccine Response for rSBA-Men A, C and W-135 | At one month after the administration of the Mencevax™ ACW vaccine (Months 25-31) | Vaccine response was defined as follows: for initially seronegative subjects (i.e. with rSBA titre \< 1:8 pre-vaccination), rSBA titre ≥ 1:32 post-vaccination (seroconversion), and for initially seropositive subjects (i.e. with rSBA titre ≥ 1:8 pre-vaccination), at least a 4-fold increase in rSBA titre from pre to post-vaccination. |
| Number of Subjects With Fever | During the 4-day (Days 0-3) after the administration of the Tritanrix™-HepB/Hiberix™ vaccine | Any Fever (measured rectally) = subjects with symptom, regardless of the intensity grade. |
| Number of Subjects With Solicited Local Symtoms | During the 4-Day (Days 0-3) after the administration of the Mencevax™ ACW vaccine | Assessed solicited local symptoms were: pain, redness and swelling at the injection site. Any = subjects with symptom, regardless of the intensity grade. |
| Number of Subjects With Solicited General Symptoms | During the 4-Day (Days 0-3) after the administration of the Mencevax™ ACW vaccine | Assessed solicited general symptoms were: drowsiness, fever, irritability and loss of appetite. Any = subjects with symptoms, regardless of intensity grade and casual relationship to study vaccination. |
| Number of Subjects With Unsolicited Adverse Events (AEs) | During the 31-Day (Days 0-30) after the administration of the Mencevax™ ACW vaccine | An unsolicited AE covers 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 and 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. Any was defined as the occurrence of any unsolicited AE regardless of intensity grade or relation to vaccination. |
| Number of Subjects With Serious Adverse Events (SAEs) | From Months 15-18 and up to Months 25-31 post vaccination | 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-HBs Antibody Concentrations | Prior to (Months 24-30) the administration of the Mencevax™ ACW vaccine | Antibody concentrations were expressed as Geometric Mean Concentrations (GMCs). |
Countries
South Africa
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Tritanrix-HepB/Hiberix Group Subjects vaccinated with 3 doses of Tritanrix-HepB/Hiberix vaccine in the primary study (NCT00317122), were boosted in the current study with one dose of the same vaccine at 15 to 18 months of age, intramuscularly into the anterolateral quadrant of the left thigh or upper region of the left arm. Subjects were also administered one booster dose of Mencevax ACW vaccine at 24 to 30 months of age by deep subcutaneous injection in the upper region of the left arm. | 84 |
| Tritanrix-HepB/Hiberix-Mencevax AC Group Subjects vaccinated with 3 doses of Tritanrix-HepB/Hiberix-Mencevax AC vaccine in the primary study (NCT00317122), were boosted in the current study with one dose of Tritanrix-HepB/Hiberix vaccine at 15 to 18 months of age, intramuscularly into the anterolateral quadrant of the left thigh or upper region of the left arm. Subjects were also administered one booster dose of Mencevax ACW vaccine at 24 to 30 months of age by deep subcutaneous injection in the upper region of the left arm. | 84 |
| Total | 168 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Migated/moved from study area | 1 | 0 |
| Overall Study | Withdrawal by Subject | 2 | 0 |
Baseline characteristics
| Characteristic | Tritanrix-HepB/Hiberix Group | Tritanrix-HepB/Hiberix-Mencevax AC Group | Total |
|---|---|---|---|
| Age, Continuous Months at MENCEVAX™ booster | 24.5 Months STANDARD_DEVIATION 0.92 | 24.6 Months STANDARD_DEVIATION 1.04 | 24.55 Months STANDARD_DEVIATION 0.98 |
| Age, Continuous Months at TRITANRIX™-HEPB/HIBERIX™ booster | 16.5 Months STANDARD_DEVIATION 1.02 | 16.5 Months STANDARD_DEVIATION 1.02 | 16.5 Months STANDARD_DEVIATION 1.02 |
| Sex: Female, Male Female | 45 Participants | 39 Participants | 84 Participants |
| Sex: Female, Male Male | 39 Participants | 45 Participants | 84 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 56 / 84 | 56 / 84 |
| serious Total, serious adverse events | 2 / 82 | 1 / 84 |
Outcome results
Primary
Number of Subjects With Serum Bactericidal Assay Against N. Meningitidis Serogroups A, C Using Rabbit Complement (rSBA-MenA,C) Antibodies
Pre-defined assay cut-off values for assessed titers were greater than or equal to (≥) 1:128.
Time frame: At one month post vaccination with Mencevax™ ACW vaccine (Month 25-31)
Population: The analysis were performed on the Booster ATP cohort for immunogenicity which included all evaluable subjects who received the 3 vaccine doses in the primary vaccination study, received one of the two vaccines according to the protocol in this booster study and for whom data concerning immunogenicity measures were available.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tritanrix-HepB/Hiberix Group | Number of Subjects With Serum Bactericidal Assay Against N. Meningitidis Serogroups A, C Using Rabbit Complement (rSBA-MenA,C) Antibodies | rSBA-MenA [N=65,60] | 65 Subjects |
| Tritanrix-HepB/Hiberix Group | Number of Subjects With Serum Bactericidal Assay Against N. Meningitidis Serogroups A, C Using Rabbit Complement (rSBA-MenA,C) Antibodies | rSBA-MenC [N=59,66] | 30 Subjects |
| Tritanrix-HepB/Hiberix-Mencevax AC Group | Number of Subjects With Serum Bactericidal Assay Against N. Meningitidis Serogroups A, C Using Rabbit Complement (rSBA-MenA,C) Antibodies | rSBA-MenA [N=65,60] | 59 Subjects |
| Tritanrix-HepB/Hiberix-Mencevax AC Group | Number of Subjects With Serum Bactericidal Assay Against N. Meningitidis Serogroups A, C Using Rabbit Complement (rSBA-MenA,C) Antibodies | rSBA-MenC [N=59,66] | 66 Subjects |
Secondary
Anti-HBs Antibody Concentrations
Antibody concentrations were expressed as Geometric Mean Concentrations (GMCs).
Time frame: Prior to (Months 24-30) the administration of the Mencevax™ ACW vaccine
Population: The analysis were performed on the Booster ATP cohort for immunogenicity which included all evaluable subjects who received the 3 vaccine doses in the primary vaccination study, received one of the two vaccines according to the protocol in this booster study and for whom data concerning immunogenicity measures were available.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Tritanrix-HepB/Hiberix Group | Anti-HBs Antibody Concentrations | 722.0 mIU/mL |
| Tritanrix-HepB/Hiberix-Mencevax AC Group | Anti-HBs Antibody Concentrations | 713.1 mIU/mL |
Secondary
Anti-PSA and Anti-PSC Antibody Concentrations
Antibody concentrations were expressed as Geometric Mean Concentrations (GMCs).
Time frame: Prior to (Months 24-30) & one month after the administration of the Mencevax™ ACW vaccine (Months 25-31
Population: The analysis were performed on the Booster ATP cohort for immunogenicity which included all evaluable subjects who received the 3 vaccine doses in the primary vaccination study, received one of the two vaccines according to the protocol in this booster study and for whom data concerning immunogenicity measures were available.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Tritanrix-HepB/Hiberix Group | Anti-PSA and Anti-PSC Antibody Concentrations | anti-PSA (M24-30) [N=63,61] | 0.18 µg/mL |
| Tritanrix-HepB/Hiberix Group | Anti-PSA and Anti-PSC Antibody Concentrations | anti-PSA (M25-31) [N=65,65] | 6.61 µg/mL |
| Tritanrix-HepB/Hiberix Group | Anti-PSA and Anti-PSC Antibody Concentrations | anti-PSC (M25-31) [N=65,66] | 15.70 µg/mL |
| Tritanrix-HepB/Hiberix Group | Anti-PSA and Anti-PSC Antibody Concentrations | anti-PSC (M24-30) [N=61,64] | 0.18 µg/mL |
| Tritanrix-HepB/Hiberix-Mencevax AC Group | Anti-PSA and Anti-PSC Antibody Concentrations | anti-PSC (M25-31) [N=65,66] | 35.10 µg/mL |
| Tritanrix-HepB/Hiberix-Mencevax AC Group | Anti-PSA and Anti-PSC Antibody Concentrations | anti-PSA (M25-31) [N=65,65] | 22.39 µg/mL |
| Tritanrix-HepB/Hiberix-Mencevax AC Group | Anti-PSA and Anti-PSC Antibody Concentrations | anti-PSC (M24-30) [N=61,64] | 0.35 µg/mL |
| Tritanrix-HepB/Hiberix-Mencevax AC Group | Anti-PSA and Anti-PSC Antibody Concentrations | anti-PSA (M24-30) [N=63,61] | 0.19 µg/mL |
Secondary
Anti-PSW Antibody Concentrations
Antibody concentrations were expressed as Geometric Mean Concentrations (GMCs).
Time frame: Prior to (Months 24-30) & one month after the administration of the Mencevax™ ACW vaccine (Months 25-31)
Population: The analysis were performed on the Booster ATP cohort for immunogenicity which included all evaluable subjects who received the 3 vaccine doses in the primary vaccination study, received one of the two vaccines according to the protocol in this booster study and for whom data concerning immunogenicity measures were available.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Tritanrix-HepB/Hiberix Group | Anti-PSW Antibody Concentrations | anti-PSW (M24-30) [N=61,62] | 0.15 µg/mL |
| Tritanrix-HepB/Hiberix Group | Anti-PSW Antibody Concentrations | anti-PSW (M25-31) [N=64,66] | 4.89 µg/mL |
| Tritanrix-HepB/Hiberix-Mencevax AC Group | Anti-PSW Antibody Concentrations | anti-PSW (M24-30) [N=61,62] | 0.16 µg/mL |
| Tritanrix-HepB/Hiberix-Mencevax AC Group | Anti-PSW Antibody Concentrations | anti-PSW (M25-31) [N=64,66] | 5.19 µg/mL |
Secondary
Anti-rSBA-MenA, C, W-135 Antibody Titers
Antibody titers were expressed as geometric mean titers (GMTs).
Time frame: Prior to (Months 24-30) & one month after the administration of the Mencevax™ ACW vaccine (Months 25-31)
Population: The analysis were performed on the Booster ATP cohort for immunogenicity which included all evaluable subjects who received the 3 vaccine doses in the primary vaccination study, received one of the two vaccines according to the protocol in this booster study and for whom data concerning immunogenicity measures were available.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Tritanrix-HepB/Hiberix Group | Anti-rSBA-MenA, C, W-135 Antibody Titers | rSBA-MenA (M25-31) [N=65,60] | 1871.7 Titers |
| Tritanrix-HepB/Hiberix Group | Anti-rSBA-MenA, C, W-135 Antibody Titers | rSBA-MenC (M24-30) [N=67,61] | 6.7 Titers |
| Tritanrix-HepB/Hiberix Group | Anti-rSBA-MenA, C, W-135 Antibody Titers | rSBA-MenC (M25-31) [N=59,66] | 141.3 Titers |
| Tritanrix-HepB/Hiberix Group | Anti-rSBA-MenA, C, W-135 Antibody Titers | rSBA-MenW-135 (M24-30) [N=67,63] | 11.1 Titers |
| Tritanrix-HepB/Hiberix Group | Anti-rSBA-MenA, C, W-135 Antibody Titers | rSBA-MenW-135 (M25-31) [N=64,66] | 159.4 Titers |
| Tritanrix-HepB/Hiberix Group | Anti-rSBA-MenA, C, W-135 Antibody Titers | rSBA-MenA (M24-30) [N=58,53] | 503.8 Titers |
| Tritanrix-HepB/Hiberix-Mencevax AC Group | Anti-rSBA-MenA, C, W-135 Antibody Titers | rSBA-MenW-135 (M25-31) [N=64,66] | 92.8 Titers |
| Tritanrix-HepB/Hiberix-Mencevax AC Group | Anti-rSBA-MenA, C, W-135 Antibody Titers | rSBA-MenA (M25-31) [N=65,60] | 1562.0 Titers |
| Tritanrix-HepB/Hiberix-Mencevax AC Group | Anti-rSBA-MenA, C, W-135 Antibody Titers | rSBA-MenW-135 (M24-30) [N=67,63] | 13.7 Titers |
| Tritanrix-HepB/Hiberix-Mencevax AC Group | Anti-rSBA-MenA, C, W-135 Antibody Titers | rSBA-MenC (M24-30) [N=67,61] | 50.7 Titers |
| Tritanrix-HepB/Hiberix-Mencevax AC Group | Anti-rSBA-MenA, C, W-135 Antibody Titers | rSBA-MenA (M24-30) [N=58,53] | 509.9 Titers |
| Tritanrix-HepB/Hiberix-Mencevax AC Group | Anti-rSBA-MenA, C, W-135 Antibody Titers | rSBA-MenC (M25-31) [N=59,66] | 5251.6 Titers |
Secondary
Number of Subjects With Anti-hepatitis B (Anti-HBs) Antibody Concentrations ≥ Predefined Cut-off Values
Antibody concentrations cut-off were ≥ 10 milli international units per milliliter (mIU/mL).
Time frame: Prior to (Months 24-30) the administration of the Mencevax™ ACW vaccine
Population: The analysis were performed on the Booster ATP cohort for immunogenicity which included all evaluable subjects who received the 3 vaccine doses in the primary vaccination study, received one of the two vaccines according to the protocol in this booster study and for whom data concerning immunogenicity measures were available.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tritanrix-HepB/Hiberix Group | Number of Subjects With Anti-hepatitis B (Anti-HBs) Antibody Concentrations ≥ Predefined Cut-off Values | 63 Subjects |
| Tritanrix-HepB/Hiberix-Mencevax AC Group | Number of Subjects With Anti-hepatitis B (Anti-HBs) Antibody Concentrations ≥ Predefined Cut-off Values | 65 Subjects |
Secondary
Number of Subjects With Anti-polysaccharide A (Anti-PSA) and C (Anti-PSC) Antibody Concentrations Above Predefined Cut-off Values
Antibody concentrations cut-off were ≥ 0.3 and ≥2 micrograms per millilitre (µg/mL).
Time frame: Prior to (Months 24-30) & one month after the administration of the Mencevax™ ACW vaccine (Months 25-31)
Population: The analysis were performed on the Booster ATP cohort for immunogenicity which included all evaluable subjects who received the 3 vaccine doses in the primary vaccination study, received one of the two vaccines according to the protocol in this booster study and for whom data concerning immunogenicity measures were available.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tritanrix-HepB/Hiberix Group | Number of Subjects With Anti-polysaccharide A (Anti-PSA) and C (Anti-PSC) Antibody Concentrations Above Predefined Cut-off Values | anti-PSA ≥ 0.3 µg/mL (M24-30) [N=63,61] | 8 Subjects |
| Tritanrix-HepB/Hiberix Group | Number of Subjects With Anti-polysaccharide A (Anti-PSA) and C (Anti-PSC) Antibody Concentrations Above Predefined Cut-off Values | anti-PSA ≥ 2 µg/mL (M24-30) [N=63,61] | 0 Subjects |
| Tritanrix-HepB/Hiberix Group | Number of Subjects With Anti-polysaccharide A (Anti-PSA) and C (Anti-PSC) Antibody Concentrations Above Predefined Cut-off Values | anti-PSA ≥ 0.3 µg/mL (M25-31) [N=65,65] | 62 Subjects |
| Tritanrix-HepB/Hiberix Group | Number of Subjects With Anti-polysaccharide A (Anti-PSA) and C (Anti-PSC) Antibody Concentrations Above Predefined Cut-off Values | anti-PSA ≥ 2 µg/mL (M25-31) [N=65,65] | 48 Subjects |
| Tritanrix-HepB/Hiberix Group | Number of Subjects With Anti-polysaccharide A (Anti-PSA) and C (Anti-PSC) Antibody Concentrations Above Predefined Cut-off Values | anti-PSC ≥ 0.3 µg/mL (M24-30) [N=61,64] | 6 Subjects |
| Tritanrix-HepB/Hiberix Group | Number of Subjects With Anti-polysaccharide A (Anti-PSA) and C (Anti-PSC) Antibody Concentrations Above Predefined Cut-off Values | anti-PSC ≥ 0.3 µg/mL (M25-31) [N=65,66] | 65 Subjects |
| Tritanrix-HepB/Hiberix Group | Number of Subjects With Anti-polysaccharide A (Anti-PSA) and C (Anti-PSC) Antibody Concentrations Above Predefined Cut-off Values | anti-PSC ≥ 2 µg/mL (M24-30) [N=61,64] | 2 Subjects |
| Tritanrix-HepB/Hiberix Group | Number of Subjects With Anti-polysaccharide A (Anti-PSA) and C (Anti-PSC) Antibody Concentrations Above Predefined Cut-off Values | anti-PSC ≥ 2 µg/mL (M25-31) [N=65,66] | 64 Subjects |
| Tritanrix-HepB/Hiberix-Mencevax AC Group | Number of Subjects With Anti-polysaccharide A (Anti-PSA) and C (Anti-PSC) Antibody Concentrations Above Predefined Cut-off Values | anti-PSC ≥ 2 µg/mL (M25-31) [N=65,66] | 65 Subjects |
| Tritanrix-HepB/Hiberix-Mencevax AC Group | Number of Subjects With Anti-polysaccharide A (Anti-PSA) and C (Anti-PSC) Antibody Concentrations Above Predefined Cut-off Values | anti-PSA ≥ 0.3 µg/mL (M25-31) [N=65,65] | 64 Subjects |
| Tritanrix-HepB/Hiberix-Mencevax AC Group | Number of Subjects With Anti-polysaccharide A (Anti-PSA) and C (Anti-PSC) Antibody Concentrations Above Predefined Cut-off Values | anti-PSC ≥ 0.3 µg/mL (M24-30) [N=61,64] | 33 Subjects |
| Tritanrix-HepB/Hiberix-Mencevax AC Group | Number of Subjects With Anti-polysaccharide A (Anti-PSA) and C (Anti-PSC) Antibody Concentrations Above Predefined Cut-off Values | anti-PSA ≥ 2 µg/mL (M24-30) [N=63,61] | 1 Subjects |
| Tritanrix-HepB/Hiberix-Mencevax AC Group | Number of Subjects With Anti-polysaccharide A (Anti-PSA) and C (Anti-PSC) Antibody Concentrations Above Predefined Cut-off Values | anti-PSA ≥ 0.3 µg/mL (M24-30) [N=63,61] | 10 Subjects |
| Tritanrix-HepB/Hiberix-Mencevax AC Group | Number of Subjects With Anti-polysaccharide A (Anti-PSA) and C (Anti-PSC) Antibody Concentrations Above Predefined Cut-off Values | anti-PSC ≥ 2 µg/mL (M24-30) [N=61,64] | 4 Subjects |
| Tritanrix-HepB/Hiberix-Mencevax AC Group | Number of Subjects With Anti-polysaccharide A (Anti-PSA) and C (Anti-PSC) Antibody Concentrations Above Predefined Cut-off Values | anti-PSC ≥ 0.3 µg/mL (M25-31) [N=65,66] | 66 Subjects |
| Tritanrix-HepB/Hiberix-Mencevax AC Group | Number of Subjects With Anti-polysaccharide A (Anti-PSA) and C (Anti-PSC) Antibody Concentrations Above Predefined Cut-off Values | anti-PSA ≥ 2 µg/mL (M25-31) [N=65,65] | 64 Subjects |
Secondary
Number of Subjects With Anti- Polysaccharide W (Anti-PSW) Antibody Concentrations ≥ Predefined Cut-off Values
Antibody concentrations were ≥ 0.3 µg/mL.
Time frame: Prior to (Months 24-30) & one month after the administration of the Mencevax™ ACW vaccine (Months 25-31)
Population: The analysis were performed on the Booster ATP cohort for immunogenicity which included all evaluable subjects who received the 3 vaccine doses in the primary vaccination study, received one of the two vaccines according to the protocol in this booster study and for whom data concerning immunogenicity measures were available.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tritanrix-HepB/Hiberix Group | Number of Subjects With Anti- Polysaccharide W (Anti-PSW) Antibody Concentrations ≥ Predefined Cut-off Values | anti-PSW (M24-30) [N=61,62] | 0 Subjects |
| Tritanrix-HepB/Hiberix Group | Number of Subjects With Anti- Polysaccharide W (Anti-PSW) Antibody Concentrations ≥ Predefined Cut-off Values | anti-PSW (M25-31) [N=64,66] | 64 Subjects |
| Tritanrix-HepB/Hiberix-Mencevax AC Group | Number of Subjects With Anti- Polysaccharide W (Anti-PSW) Antibody Concentrations ≥ Predefined Cut-off Values | anti-PSW (M24-30) [N=61,62] | 2 Subjects |
| Tritanrix-HepB/Hiberix-Mencevax AC Group | Number of Subjects With Anti- Polysaccharide W (Anti-PSW) Antibody Concentrations ≥ Predefined Cut-off Values | anti-PSW (M25-31) [N=64,66] | 64 Subjects |
Secondary
Number of Subjects With Fever
Any Fever (measured rectally) = subjects with symptom, regardless of the intensity grade.
Time frame: During the 4-day (Days 0-3) after the administration of the Tritanrix™-HepB/Hiberix™ vaccine
Population: The analysis was performed on the Booster Total Vaccinated Cohort which included all subjects who received at least one of the two vaccines.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tritanrix-HepB/Hiberix Group | Number of Subjects With Fever | 33 Subjects |
| Tritanrix-HepB/Hiberix-Mencevax AC Group | Number of Subjects With Fever | 29 Subjects |
Secondary
Number of Subjects With rSBA-MenA,C, W-135 Antibody Titers ≥ Predefined Cut-offs
Antibody titer cut-offs were ≥ 1:8 and ≥ 1:128.
Time frame: Prior to (Months 24-30) & one month after the administration of the Mencevax™ ACW vaccine (Months 25-31)
Population: The analysis were performed on the Booster ATP cohort for immunogenicity which included all evaluable subjects who received the 3 vaccine doses in the primary vaccination study, received one of the two vaccines according to the protocol in this booster study and for whom data concerning immunogenicity measures were available.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tritanrix-HepB/Hiberix Group | Number of Subjects With rSBA-MenA,C, W-135 Antibody Titers ≥ Predefined Cut-offs | rSBA-MenC ≥1:8 (M24-30) [N=67,61] | 10 Subjects |
| Tritanrix-HepB/Hiberix Group | Number of Subjects With rSBA-MenA,C, W-135 Antibody Titers ≥ Predefined Cut-offs | rSBA-MenC ≥1:8 (M25-31) [N=59,66] | 53 Subjects |
| Tritanrix-HepB/Hiberix Group | Number of Subjects With rSBA-MenA,C, W-135 Antibody Titers ≥ Predefined Cut-offs | rSBA-MenW-135 ≥1:8 (M24-30) [N=67,63] | 18 Subjects |
| Tritanrix-HepB/Hiberix Group | Number of Subjects With rSBA-MenA,C, W-135 Antibody Titers ≥ Predefined Cut-offs | rSBA-MenA ≥1:8 (M25-31) [N=65,60] | 65 Subjects |
| Tritanrix-HepB/Hiberix Group | Number of Subjects With rSBA-MenA,C, W-135 Antibody Titers ≥ Predefined Cut-offs | rSBA-MenW-135 ≥1:8 (M25-31) [N=64,66] | 49 Subjects |
| Tritanrix-HepB/Hiberix Group | Number of Subjects With rSBA-MenA,C, W-135 Antibody Titers ≥ Predefined Cut-offs | rSBA-MenC ≥1:128 (M24-30) [N=67,61] | 4 Subjects |
| Tritanrix-HepB/Hiberix Group | Number of Subjects With rSBA-MenA,C, W-135 Antibody Titers ≥ Predefined Cut-offs | rSBA-MenW-135 ≥1:128 (M24-30) [N=67,63] | 13 Subjects |
| Tritanrix-HepB/Hiberix Group | Number of Subjects With rSBA-MenA,C, W-135 Antibody Titers ≥ Predefined Cut-offs | rSBA-MenA ≥1:128 (M24-30) [N=58,53] | 54 Subjects |
| Tritanrix-HepB/Hiberix Group | Number of Subjects With rSBA-MenA,C, W-135 Antibody Titers ≥ Predefined Cut-offs | rSBA-MenW-135 ≥1:128 (M25-31) [N=64,66] | 45 Subjects |
| Tritanrix-HepB/Hiberix Group | Number of Subjects With rSBA-MenA,C, W-135 Antibody Titers ≥ Predefined Cut-offs | rSBA-MenA ≥1:8 (M24-30) [N=58,53] | 55 Subjects |
| Tritanrix-HepB/Hiberix-Mencevax AC Group | Number of Subjects With rSBA-MenA,C, W-135 Antibody Titers ≥ Predefined Cut-offs | rSBA-MenW-135 ≥1:128 (M25-31) [N=64,66] | 37 Subjects |
| Tritanrix-HepB/Hiberix-Mencevax AC Group | Number of Subjects With rSBA-MenA,C, W-135 Antibody Titers ≥ Predefined Cut-offs | rSBA-MenC ≥1:8 (M25-31) [N=59,66] | 66 Subjects |
| Tritanrix-HepB/Hiberix-Mencevax AC Group | Number of Subjects With rSBA-MenA,C, W-135 Antibody Titers ≥ Predefined Cut-offs | rSBA-MenA ≥1:8 (M24-30) [N=58,53] | 50 Subjects |
| Tritanrix-HepB/Hiberix-Mencevax AC Group | Number of Subjects With rSBA-MenA,C, W-135 Antibody Titers ≥ Predefined Cut-offs | rSBA-MenA ≥1:8 (M25-31) [N=65,60] | 60 Subjects |
| Tritanrix-HepB/Hiberix-Mencevax AC Group | Number of Subjects With rSBA-MenA,C, W-135 Antibody Titers ≥ Predefined Cut-offs | rSBA-MenA ≥1:128 (M24-30) [N=58,53] | 48 Subjects |
| Tritanrix-HepB/Hiberix-Mencevax AC Group | Number of Subjects With rSBA-MenA,C, W-135 Antibody Titers ≥ Predefined Cut-offs | rSBA-MenC ≥1:128 (M24-30) [N=67,61] | 27 Subjects |
| Tritanrix-HepB/Hiberix-Mencevax AC Group | Number of Subjects With rSBA-MenA,C, W-135 Antibody Titers ≥ Predefined Cut-offs | rSBA-MenW-135 ≥1:8 (M24-30) [N=67,63] | 20 Subjects |
| Tritanrix-HepB/Hiberix-Mencevax AC Group | Number of Subjects With rSBA-MenA,C, W-135 Antibody Titers ≥ Predefined Cut-offs | rSBA-MenW-135 ≥1:8 (M25-31) [N=64,66] | 44 Subjects |
| Tritanrix-HepB/Hiberix-Mencevax AC Group | Number of Subjects With rSBA-MenA,C, W-135 Antibody Titers ≥ Predefined Cut-offs | rSBA-MenW-135 ≥1:128 (M24-30) [N=67,63] | 11 Subjects |
| Tritanrix-HepB/Hiberix-Mencevax AC Group | Number of Subjects With rSBA-MenA,C, W-135 Antibody Titers ≥ Predefined Cut-offs | rSBA-MenC ≥1:8 (M24-30) [N=67,61] | 42 Subjects |
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: From Months 15-18 and up to Months 25-31 post vaccination
Population: The analysis were performed on the Booster Total Vaccinated Cohort which included all subjects who received at least one of the two vaccines.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tritanrix-HepB/Hiberix Group | Number of Subjects With Serious Adverse Events (SAEs) | 2 Subjects |
| Tritanrix-HepB/Hiberix-Mencevax AC Group | Number of Subjects With Serious Adverse Events (SAEs) | 1 Subjects |
Secondary
Number of Subjects With Solicited General Symptoms
Assessed solicited general symptoms were: drowsiness, fever, irritability and loss of appetite. Any = subjects with symptoms, regardless of intensity grade and casual relationship to study vaccination.
Time frame: During the 4-Day (Days 0-3) after the administration of the Mencevax™ ACW vaccine
Population: The analysis were performed on the Booster Total Vaccinated Cohort which included all subjects who received at least one of the two vaccines and had the symptoms sheet filled in.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tritanrix-HepB/Hiberix Group | Number of Subjects With Solicited General Symptoms | Any Drowsiness | 14 Subjects |
| Tritanrix-HepB/Hiberix Group | Number of Subjects With Solicited General Symptoms | Any Fever | 8 Subjects |
| Tritanrix-HepB/Hiberix Group | Number of Subjects With Solicited General Symptoms | Any Irritability | 15 Subjects |
| Tritanrix-HepB/Hiberix Group | Number of Subjects With Solicited General Symptoms | Any Loss of appetite | 13 Subjects |
| Tritanrix-HepB/Hiberix-Mencevax AC Group | Number of Subjects With Solicited General Symptoms | Any Loss of appetite | 18 Subjects |
| Tritanrix-HepB/Hiberix-Mencevax AC Group | Number of Subjects With Solicited General Symptoms | Any Drowsiness | 12 Subjects |
| Tritanrix-HepB/Hiberix-Mencevax AC Group | Number of Subjects With Solicited General Symptoms | Any Irritability | 12 Subjects |
| Tritanrix-HepB/Hiberix-Mencevax AC Group | Number of Subjects With Solicited General Symptoms | Any Fever | 5 Subjects |
Secondary
Number of Subjects With Solicited Local Symtoms
Assessed solicited local symptoms were: pain, redness and swelling at the injection site. Any = subjects with symptom, regardless of the intensity grade.
Time frame: During the 4-Day (Days 0-3) after the administration of the Mencevax™ ACW vaccine
Population: The analysis was performed on the Booster Total Vaccinated Cohort which included all subjects who received at least one of the two vaccines and had the symptoms sheet filled in.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tritanrix-HepB/Hiberix Group | Number of Subjects With Solicited Local Symtoms | Any Redness | 20 Subjects |
| Tritanrix-HepB/Hiberix Group | Number of Subjects With Solicited Local Symtoms | Any Swelling | 13 Subjects |
| Tritanrix-HepB/Hiberix Group | Number of Subjects With Solicited Local Symtoms | Any Pain | 21 Subjects |
| Tritanrix-HepB/Hiberix-Mencevax AC Group | Number of Subjects With Solicited Local Symtoms | Any Redness | 16 Subjects |
| Tritanrix-HepB/Hiberix-Mencevax AC Group | Number of Subjects With Solicited Local Symtoms | Any Swelling | 11 Subjects |
| Tritanrix-HepB/Hiberix-Mencevax AC Group | Number of Subjects With Solicited Local Symtoms | Any Pain | 25 Subjects |
Secondary
Number of Subjects With Unsolicited Adverse Events (AEs)
An unsolicited AE covers 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 and 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. Any was defined as the occurrence of any unsolicited AE regardless of intensity grade or relation to vaccination.
Time frame: During the 31-Day (Days 0-30) after the administration of the Mencevax™ ACW vaccine
Population: The analysis were performed on the Booster Total Vaccinated Cohort which included all subjects who received at least one of the two vaccines.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tritanrix-HepB/Hiberix Group | Number of Subjects With Unsolicited Adverse Events (AEs) | 10 Subjects |
| Tritanrix-HepB/Hiberix-Mencevax AC Group | Number of Subjects With Unsolicited Adverse Events (AEs) | 16 Subjects |
Secondary
Number of Subjects With Vaccine Response for rSBA-Men A, C and W-135
Vaccine response was defined as follows: for initially seronegative subjects (i.e. with rSBA titre \< 1:8 pre-vaccination), rSBA titre ≥ 1:32 post-vaccination (seroconversion), and for initially seropositive subjects (i.e. with rSBA titre ≥ 1:8 pre-vaccination), at least a 4-fold increase in rSBA titre from pre to post-vaccination.
Time frame: At one month after the administration of the Mencevax™ ACW vaccine (Months 25-31)
Population: The analysis were performed on the Booster ATP cohort for immunogenicity which included all evaluable subjects who received the 3 vaccine doses in the primary vaccination study, received one of the two vaccines according to the protocol in this booster study and for whom data concerning immunogenicity measures were available.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tritanrix-HepB/Hiberix Group | Number of Subjects With Vaccine Response for rSBA-Men A, C and W-135 | rSBA-MenC, Total [N=59,60] | 41 Subjects |
| Tritanrix-HepB/Hiberix Group | Number of Subjects With Vaccine Response for rSBA-Men A, C and W-135 | rSBA-MenA, Total [N=56,47] | 26 Subjects |
| Tritanrix-HepB/Hiberix Group | Number of Subjects With Vaccine Response for rSBA-Men A, C and W-135 | rSBA-MenW-135, Total [N=64,62] | 41 Subjects |
| Tritanrix-HepB/Hiberix-Mencevax AC Group | Number of Subjects With Vaccine Response for rSBA-Men A, C and W-135 | rSBA-MenA, Total [N=56,47] | 21 Subjects |
| Tritanrix-HepB/Hiberix-Mencevax AC Group | Number of Subjects With Vaccine Response for rSBA-Men A, C and W-135 | rSBA-MenC, Total [N=59,60] | 56 Subjects |
| Tritanrix-HepB/Hiberix-Mencevax AC Group | Number of Subjects With Vaccine Response for rSBA-Men A, C and W-135 | rSBA-MenW-135, Total [N=64,62] | 32 Subjects |