Hepatitis A, Hepatitis B
Conditions
Keywords
Combined Hepatitis A and B vaccine, Hepatitis A, Hepatitis B
Brief summary
The aim of this study is to evaluate the long-term persistence of hepatitis A and B antibodies at Years 11, 12, 13, 14 and 15 years after subjects received their first dose of a 3 dose vaccination schedule of combined hepatitis A/hepatitis B vaccine. The Protocol Posting has been updated in order to comply with the FDA Amendment Act, Sep 2007. This protocol posting deals with objectives & outcome measures of the extension phase at year 11 to 15.
Detailed description
This is a long-term follow-up study at Years 11, 12, 13, 14 and 15 after primary vaccination with GSK Biologicals' hepatitis A/hepatitis B vaccine (three-dose schedule, 3 different lots). To evaluate the long-term antibody persistence, volunteers will be bled at Years 11, 12, 13, 14 and 15 after the first vaccine dose of the primary vaccination course to determine their anti-HAV and anti-HBs antibody concentrations. No additional subjects will be recruited during the course of this long-term study. If a subject has become seronegative for anti-HAV antibodies or lost anti-HBs seroprotection concentrations at the long-term blood sampling time point (i.e. Years 11, 12, 13, 14 or 15), he/ she will be offered an additional vaccine dose.
Interventions
BIOLOGICALTwinrix™ adult
Intramuscular administration
Sponsors
GlaxoSmithKline
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Subjects participating in this study should have received three-dose primary vaccination with combined hepatitis A/hepatitis B vaccine in the primary study. * Written informed consent will be obtained from each subject before the blood sampling visit of each year
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Anti-hepatitis A Virus (Anti-HAV) Antibody Concentration | At Years 11, 12, 13, 14, and 15 after the first vaccine dose of the 3-dose primary vaccination | Concentrations given as geometric mean concentration (GMC) expressed as milli-international unit per millilitre (mIU/mL). |
| Number of Subjects Reporting Any and Grade 3 Solicited Local Symptoms. | During the 4-day (Day 0-3) follow-up period after additional HBV vaccination | Solicited local symptoms assessed include pain, redness and swelling. Any was defined as occurrence of the specified solicited local symptom regardless of its intensity. Grade 3 pain was defined as pain that prevented normal everyday activities. Grade 3 swelling was greater than 100 millimeters (mm) i.e. \>100mm. |
| Number of Subjects Seropositive for Anti-HAV Antibodies | At Years 11, 12, 13, 14, and 15 after the first vaccine dose of the 3-dose primary vaccination | A seropositive subject was defined as a vaccinated subject who had a anti-HAV antibody titres ≥ 33 mIU/ml. |
| Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentration | At Years 11, 12, 13, 14, and 15 after the first vaccine dose of the 3-dose primary vaccination | Concentrations given as GMC expressed as mIU/mL. NOTE: There was a change of assay kit at Year 15 time-point, thus for the sake of bridging, blood samples corresponding to Year 14 were re-tested with ChemiLuminescence ImmunoAssay (CLIA). From Year 11 to Year 14, anti-HBs antibody concentrations were tested with ELISA with cut-off of 3.3 mIU/mL while, Year 14\* onwards, anti-HBs antibody concentrations were tested with the CLIA with cut-off of 6.2 mIU/mL. |
| Number of Subjects Seropositive for Anti-HB Antibodies | At Years 11, 12, 13, 14, and 15 after the first vaccine dose of the 3-dose primary vaccination | A seropositive subject was defined as a vaccinated subject who had anti-HB antibody titres ≥ 1 mIU/mL. NOTE: There was a change of assay kit at Year 15 time-point, thus for the sake of bridging, blood samples corresponding to Year 14 were re-tested with ChemiLuminescence ImmunoAssay (CLIA) |
| Number of Subjects Seroprotected for Anti-HBs Antibodies. | At Years 11, 12, 13, 14, and 15 after the first vaccine dose of the 3-dose primary vaccination | A seroprotected subject was defined as a subjects with the anti-HBs titres ≥ 10 mIU/mL. NOTE: There was a change of assay kit at Year 15 time-point, thus for the sake of bridging, blood samples corresponding to Year 14 were re-tested with ChemiLuminescence ImmunoAssay (CLIA) |
| Number of Subjects Reporting Serious Adverse Events (SAE) | During the follow-up period after additional vaccination (minimum 30 days) | A SAE was defined as any untoward medical occurrence that: resulted in death, was life threatening, required hospitalization or prolongation of hospitalization, resulted in disability/incapacity or was a congenital anomaly/birth defect in the offspring of a study subject. Any was defined as occurrence of any symptom regardless of intensity grade or relation to vaccination and related was an event assessed by the investigator as causally related to the study vaccination. |
| Anti-Hepatitis B Surface Antigen (Anti-HBs) Antibody Concentration | Before the additional dose and 1 month after the additional dose | Concentrations given as GMC expressed as mIU/mL. If a subject became seronegative (\< 10 mIU/mL) at any of the long-term blood sampling timepoint, he/she was offered an additional vaccine dose. |
| Number of Subjects Reporting Any Solicited General Symptoms. | During the 4-day (Day 0-3) follow-up period after additional HBV vaccination | Solicited general symptoms assessed included fatigue, headache, malaise, nausea, vomiting and fever. Any was defined as any solicited general symptom reported irrespective of intensity and relationship to vaccination. |
| Number of Subjects Reporting Unsolicited Adverse Events (AE) | During the 30-day follow-up period after additional 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. |
| Number of Subjects Reporting Serious Adverse Events (SAEs) | At Years 11, 12, 13, 14, and 15 after the first vaccine dose of the 3-dose primary vaccination | A SAE was defined as any untoward medical occurrence that: resulted in death, was life threatening, required hospitalization or prolongation of hospitalization, resulted in disability/incapacity or was a congenital anomaly/birth defect in the offspring of a study subject. Any was defined as occurrence of any symptom regardless of intensity grade or relation to vaccination and related was an event assessed by the investigator as causally related to the study vaccination. |
Countries
Belgium
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Twinrix Group Subjects who received 2 doses of Twinrix™ (lot A, B or C) in the primary study.
As lot to lot consistency was assessed during the primary study, the 3 groups (lot A, B or C) were pooled into the Twinrix Group for data analyses during the long term follow-up | 51 |
| Total | 51 |
Baseline characteristics
| Characteristic | Twinrix Group |
|---|---|
| Age, Continuous | 36.4 years STANDARD_DEVIATION 5.65 |
| Sex: Female, Male Female | 41 Participants |
| Sex: Female, Male Male | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 1 |
| other Total, other adverse events | 1 / 1 |
| serious Total, serious adverse events | 1 / 1 |
Outcome results
Primary
Anti-hepatitis A Virus (Anti-HAV) Antibody Concentration
Concentrations given as geometric mean concentration (GMC) expressed as milli-international unit per millilitre (mIU/mL).
Time frame: At Years 11, 12, 13, 14, and 15 after the first vaccine dose of the 3-dose primary vaccination
Population: Analysis was performed on the Long Term According-to-Protocol (LT-ATP) cohort for immunogenicity, on subjects with available data for the defined timepoint
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Twinrix Group | Anti-hepatitis A Virus (Anti-HAV) Antibody Concentration | Year 11 (N=33) | 369.1 mIU/mL |
| Twinrix Group | Anti-hepatitis A Virus (Anti-HAV) Antibody Concentration | Year 12 (N=33) | 323.5 mIU/mL |
| Twinrix Group | Anti-hepatitis A Virus (Anti-HAV) Antibody Concentration | Year 13 (N=32) | 293.7 mIU/mL |
| Twinrix Group | Anti-hepatitis A Virus (Anti-HAV) Antibody Concentration | Year 14 (N=30) | 298.2 mIU/mL |
| Twinrix Group | Anti-hepatitis A Virus (Anti-HAV) Antibody Concentration | Year 15 (N=29) | 274.4 mIU/mL |
Primary
Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentration
Concentrations given as GMC expressed as mIU/mL. NOTE: There was a change of assay kit at Year 15 time-point, thus for the sake of bridging, blood samples corresponding to Year 14 were re-tested with ChemiLuminescence ImmunoAssay (CLIA). From Year 11 to Year 14, anti-HBs antibody concentrations were tested with ELISA with cut-off of 3.3 mIU/mL while, Year 14\* onwards, anti-HBs antibody concentrations were tested with the CLIA with cut-off of 6.2 mIU/mL.
Time frame: At Years 11, 12, 13, 14, and 15 after the first vaccine dose of the 3-dose primary vaccination
Population: Analysis was performed on the Long Term According-to-Protocol (LT-ATP) cohort for immunogenicity, on subjects with available data for the defined timepoint
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Twinrix Group | Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentration | Year 11 (N=33) | 123.6 mIU/mL |
| Twinrix Group | Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentration | Year 12 (N=33) | 150.3 mIU/mL |
| Twinrix Group | Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentration | Year 13 (N=32) | 77.8 mIU/mL |
| Twinrix Group | Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentration | Year 14 (N=30) | 71.7 mIU/mL |
| Twinrix Group | Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentration | Year 14* (N=28) | 95.3 mIU/mL |
| Twinrix Group | Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentration | Year 15 (N=29) | 79.2 mIU/mL |
Primary
Anti-Hepatitis B Surface Antigen (Anti-HBs) Antibody Concentration
Concentrations given as GMC expressed as mIU/mL. If a subject became seronegative (\< 10 mIU/mL) at any of the long-term blood sampling timepoint, he/she was offered an additional vaccine dose.
Time frame: Before the additional dose and 1 month after the additional dose
Population: Analysis was performed on the Long Term Total cohort, on subjects who received an additional vaccine dose. Only 1 subject received an additional dose.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Twinrix Group | Anti-Hepatitis B Surface Antigen (Anti-HBs) Antibody Concentration | before additional dose at Year 12 | 9.7 mIU/mL |
| Twinrix Group | Anti-Hepatitis B Surface Antigen (Anti-HBs) Antibody Concentration | 1 month after additional dose at Year 12 | NA mIU/mL |
| Twinrix Group | Anti-Hepatitis B Surface Antigen (Anti-HBs) Antibody Concentration | before additional dose at Year 13 | 9.5 mIU/mL |
| Twinrix Group | Anti-Hepatitis B Surface Antigen (Anti-HBs) Antibody Concentration | 1 month after additional dose at Year 13 | 15022.3 mIU/mL |
Primary
Number of Subjects Reporting Any and Grade 3 Solicited Local Symptoms.
Solicited local symptoms assessed include pain, redness and swelling. Any was defined as occurrence of the specified solicited local symptom regardless of its intensity. Grade 3 pain was defined as pain that prevented normal everyday activities. Grade 3 swelling was greater than 100 millimeters (mm) i.e. \>100mm.
Time frame: During the 4-day (Day 0-3) follow-up period after additional HBV vaccination
Population: Analysis was performed on the Long Term Total cohort, on subjects who received an additional vaccine dose. Only 1 subject received an additional dose.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Twinrix Group | Number of Subjects Reporting Any and Grade 3 Solicited Local Symptoms. | Pain | 1 subjects |
| Twinrix Group | Number of Subjects Reporting Any and Grade 3 Solicited Local Symptoms. | Redness | 0 subjects |
| Twinrix Group | Number of Subjects Reporting Any and Grade 3 Solicited Local Symptoms. | Swelling | 0 subjects |
Primary
Number of Subjects Reporting Any Solicited General Symptoms.
Solicited general symptoms assessed included fatigue, headache, malaise, nausea, vomiting and fever. Any was defined as any solicited general symptom reported irrespective of intensity and relationship to vaccination.
Time frame: During the 4-day (Day 0-3) follow-up period after additional HBV vaccination
Population: Analysis was performed on the Long Term Total cohort, on subjects who received an additional vaccine dose. Only 1 subject received an additional dose.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Twinrix Group | Number of Subjects Reporting Any Solicited General Symptoms. | Any Malaise | 0 Subjects |
| Twinrix Group | Number of Subjects Reporting Any Solicited General Symptoms. | Any Nausea | 0 Subjects |
| Twinrix Group | Number of Subjects Reporting Any Solicited General Symptoms. | Any Fatigue | 0 Subjects |
| Twinrix Group | Number of Subjects Reporting Any Solicited General Symptoms. | Any Headache | 0 Subjects |
| Twinrix Group | Number of Subjects Reporting Any Solicited General Symptoms. | Any Vomiting | 0 Subjects |
| Twinrix Group | Number of Subjects Reporting Any Solicited General Symptoms. | Any Fever | 0 Subjects |
Primary
Number of Subjects Reporting Serious Adverse Events (SAE)
A SAE was defined as any untoward medical occurrence that: resulted in death, was life threatening, required hospitalization or prolongation of hospitalization, resulted in disability/incapacity or was a congenital anomaly/birth defect in the offspring of a study subject. Any was defined as occurrence of any symptom regardless of intensity grade or relation to vaccination and related was an event assessed by the investigator as causally related to the study vaccination.
Time frame: During the follow-up period after additional vaccination (minimum 30 days)
Population: Analysis was performed on the Long Term Total cohort, on subjects who received an additional vaccine dose. Only 1 subject received an additional dose.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Twinrix Group | Number of Subjects Reporting Serious Adverse Events (SAE) | 0 subjects |
| Twinrix Group (Lot B) | Number of Subjects Reporting Serious Adverse Events (SAE) | 1 subjects |
Primary
Number of Subjects Reporting Serious Adverse Events (SAEs)
A SAE was defined as any untoward medical occurrence that: resulted in death, was life threatening, required hospitalization or prolongation of hospitalization, resulted in disability/incapacity or was a congenital anomaly/birth defect in the offspring of a study subject. Any was defined as occurrence of any symptom regardless of intensity grade or relation to vaccination and related was an event assessed by the investigator as causally related to the study vaccination.
Time frame: At Years 11, 12, 13, 14, and 15 after the first vaccine dose of the 3-dose primary vaccination
Population: Analysis was performed on the LT Total Cohort that included all subjects who returned at a specified follow-up study and who belonged to the Total Cohort of the primary vaccination course.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Twinrix Group | Number of Subjects Reporting Serious Adverse Events (SAEs) | 0 Subjects |
Primary
Number of Subjects Reporting Unsolicited Adverse Events (AE)
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: During the 30-day follow-up period after additional vaccination
Population: Analysis was performed on the Long Term Total cohort, on subjects who received an additional vaccine dose. Only 1 subject received an additional dose.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Twinrix Group | Number of Subjects Reporting Unsolicited Adverse Events (AE) | 1 subjects |
Primary
Number of Subjects Seropositive for Anti-HAV Antibodies
A seropositive subject was defined as a vaccinated subject who had a anti-HAV antibody titres ≥ 33 mIU/ml.
Time frame: At Years 11, 12, 13, 14, and 15 after the first vaccine dose of the 3-dose primary vaccination
Population: Analysis was performed on the Long Term According-to-Protocol (LT-ATP) cohort for immunogenicity, on subjects with available data for the defined timepoint
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Twinrix Group | Number of Subjects Seropositive for Anti-HAV Antibodies | Year 11 (N=33) | 33 Subjects |
| Twinrix Group | Number of Subjects Seropositive for Anti-HAV Antibodies | Year 12 (N=33) | 33 Subjects |
| Twinrix Group | Number of Subjects Seropositive for Anti-HAV Antibodies | Year 13 (N=32) | 32 Subjects |
| Twinrix Group | Number of Subjects Seropositive for Anti-HAV Antibodies | Year 14 (N=30) | 30 Subjects |
| Twinrix Group | Number of Subjects Seropositive for Anti-HAV Antibodies | Year 15 (N=29) | 29 Subjects |
Primary
Number of Subjects Seropositive for Anti-HB Antibodies
A seropositive subject was defined as a vaccinated subject who had anti-HB antibody titres ≥ 1 mIU/mL. NOTE: There was a change of assay kit at Year 15 time-point, thus for the sake of bridging, blood samples corresponding to Year 14 were re-tested with ChemiLuminescence ImmunoAssay (CLIA)
Time frame: At Years 11, 12, 13, 14, and 15 after the first vaccine dose of the 3-dose primary vaccination
Population: Analysis was performed on the Long Term According-to-Protocol (LT-ATP) cohort for immunogenicity, on subjects with available data for the defined timepoint
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Twinrix Group | Number of Subjects Seropositive for Anti-HB Antibodies | YEAR 11 (N=33) | 33 Subjects |
| Twinrix Group | Number of Subjects Seropositive for Anti-HB Antibodies | YEAR 12 (N=33) | 33 Subjects |
| Twinrix Group | Number of Subjects Seropositive for Anti-HB Antibodies | YEAR 13 (N=32) | 32 Subjects |
| Twinrix Group | Number of Subjects Seropositive for Anti-HB Antibodies | YEAR 14 (N=30) | 29 Subjects |
| Twinrix Group | Number of Subjects Seropositive for Anti-HB Antibodies | Year 14* (N=28) | 27 Subjects |
| Twinrix Group | Number of Subjects Seropositive for Anti-HB Antibodies | YEAR 15 (N=29) | 28 Subjects |
Primary
Number of Subjects Seroprotected for Anti-HBs Antibodies.
A seroprotected subject was defined as a subjects with the anti-HBs titres ≥ 10 mIU/mL. NOTE: There was a change of assay kit at Year 15 time-point, thus for the sake of bridging, blood samples corresponding to Year 14 were re-tested with ChemiLuminescence ImmunoAssay (CLIA)
Time frame: At Years 11, 12, 13, 14, and 15 after the first vaccine dose of the 3-dose primary vaccination
Population: Analysis was performed on the Long Term According-to-Protocol (LT-ATP) cohort for immunogenicity, on subjects with available data for the defined timepoint
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Twinrix Group | Number of Subjects Seroprotected for Anti-HBs Antibodies. | YEAR 11 (N=33) | 33 Subjects |
| Twinrix Group | Number of Subjects Seroprotected for Anti-HBs Antibodies. | YEAR 12 (N=33) | 32 Subjects |
| Twinrix Group | Number of Subjects Seroprotected for Anti-HBs Antibodies. | YEAR 13 (N=32) | 32 Subjects |
| Twinrix Group | Number of Subjects Seroprotected for Anti-HBs Antibodies. | YEAR 14 (N=30) | 29 Subjects |
| Twinrix Group | Number of Subjects Seroprotected for Anti-HBs Antibodies. | Year 14* (N=28) | 27 Subjects |
| Twinrix Group | Number of Subjects Seroprotected for Anti-HBs Antibodies. | YEAR 15 (N=29) | 28 Subjects |