Hepatitis B, Hepatitis A
Conditions
Keywords
TWINRIX™ ADULT, 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 after subjects received their first dose of a 3 dose primary 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 11-15.
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 with 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 in the course of this extension 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™
Intramuscular injection, 3 doses
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Subjects who had consented to participate in the long-term follow-up studies at the previous long-term blood sampling time points * Written informed consent will have been obtained from each subject. before the blood sampling visit of each year.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects With Anti-hepatitis A (Anti-HAV) Antibody Concentrations Equal to or Above Cut-off Value | Years 11, 12, 13, 14 and 15 | Cut-off value was defined as 15 milli-international units per milliliter (mIU/mL). This was considered as seropositivity. |
| Number of Subjects With Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentrations Equal to or Above Cut-off Values | Years 11, 12, 13, 14 and 15 | Cut-off values were defined 3.3 mIU/mL for the in-house anti-HBs assay and 6.2 mIU/mL for the ChemiLuminescence ImmunoAssay, which was also considered as seropositivity, and 10 mIU/mL. |
| Anti-HAV and Anti-HBs Antibody Concentrations | Years 11, 12, 13, 14 and 15 | Concentrations are expressed as geometric mean concentrations (GMCs) in mIU/mL. The laboratory assay was changed from Year 13 to Year 14 to in-house ELISA and at Year 15 to CLIA for anti-HBs GMCs.Thus for the sake of bridging, blood samples corresponding to Year 14 previously tested with ELISA were re-tested with CLIA (Year 14\*). |
| Anti-HBs Antibody Concentrations | at Year 11, pre-additional vaccine, after additional dose of Engerix | Subjects who lost seroprotective concentrations for anti-HBs (\< 10 mIU/mL) at any of the LT follow-up timepoints received an additional dose of Engerix after year 15. Two subjects were eligible for this after Year 11. 3.29 in the table means a concentration of \< 3.3 mIU/mL. As the concentration was calculated per subject no mean concentration was calculated and also no measure of dispersion. |
| Number of Subjects, Receiving an Additional Vaccination of Engerix, With an Anamnestic Response | 30 days post additional dose of Engerix | Anamnestic response was assessed in subjects receiving an additional vaccine dose of Engerix. Two subjects were found eligible at Year 11 for this additional vaccine dose. Anamnestic response was defined as: * post-additional vaccination anti-HBs concentration \>= 10 mIU/mL in subject seronegative before additional dose. * 4-fold increase post-additional dose compared to pre-additional vaccine time point. |
| Number of Subjects With Solicited Local and General Symptoms Assessed | During the 4-day follow-up period after additional vaccination with Engerix | Solicited local symptoms were pain, redness and swelling. Solicited general symptoms were fatigue, fever, gastrointestinal, headache. |
| Number of Subjects With Unsolicited Symptoms | During the 30-day follow-up period after additional Engerix vaccination | Unsolicited AE covers any AE 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. |
| Number of Subjects With Serious Adverse Events (SAEs) | During the 30-day follow-up period after additional Engerix vaccination | SAEs assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization, result in disability/incapacity or are a congenital anomaly/birth defect in the offspring of a study subject |
| Number of Subjects With Serious Adverse Events (SAEs) Determined by the Investigator to Have a Causal Relationship to Primary Vaccination or Due to Lack of Vaccine Efficacy | up to Year 11, 12, 13, 14, 15 | SAEs assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization, result in disability/incapacity or are a congenital anomaly/birth defect in the offspring of a study subject. |
Countries
Belgium
Participant flow
Pre-assignment details
Subjects who came back at a follow-up, did not necessarily come back at an earlier timepoint. Therefore amount of subjects who completed the previous timepoint does not always correspond with amount of subjects who entered follow-up. As Year 15 has enrolled the most subjects, baseline measures are given for Year 15, to be as complete as possible.
Participants by arm
| Arm | Count |
|---|---|
| Twinrix Group Subjects who were vaccinated with either Lot 1, Lot 2 or Lot 3 of Twinrix in the primary study according to a 0, 1, 6-Month schedule | 50 |
| Total | 50 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Year 15 | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Twinrix Group |
|---|---|
| Age, Continuous | 34.4 Years STANDARD_DEVIATION 2.66 |
| Sex: Female, Male Female | 39 Participants |
| Sex: Female, Male Male | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 2 / 2 |
| serious Total, serious adverse events | 0 / 50 |
Outcome results
Primary
Anti-HAV and Anti-HBs Antibody Concentrations
Concentrations are expressed as geometric mean concentrations (GMCs) in mIU/mL. The laboratory assay was changed from Year 13 to Year 14 to in-house ELISA and at Year 15 to CLIA for anti-HBs GMCs.Thus for the sake of bridging, blood samples corresponding to Year 14 previously tested with ELISA were re-tested with CLIA (Year 14\*).
Time frame: Years 11, 12, 13, 14 and 15
Population: Analysis was performed on the long-term (LT) According-To-Protocol (ATP) cohort for immunogenicity, which included subjects who returned at a particular blood sampling timepoint, were in the ATP immunogenicity cohort in the primary study and for whom serology results were available for that particular timepoint.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Twinrix Group | Anti-HAV and Anti-HBs Antibody Concentrations | Year 11 anti-HAV | 680.3 mIU/mL |
| Twinrix Group | Anti-HAV and Anti-HBs Antibody Concentrations | Year 12 anti-HAV | 602.7 mIU/mL |
| Twinrix Group | Anti-HAV and Anti-HBs Antibody Concentrations | Year 13 anti-HAV | 601.5 mIU/mL |
| Twinrix Group | Anti-HAV and Anti-HBs Antibody Concentrations | Year 14 anti-HAV | 524.7 mIU/mL |
| Twinrix Group | Anti-HAV and Anti-HBs Antibody Concentrations | Year 15 anti-HAV | 610.7 mIU/mL |
| Twinrix Group | Anti-HAV and Anti-HBs Antibody Concentrations | Year 11 anti-HBs | 458.9 mIU/mL |
| Twinrix Group | Anti-HAV and Anti-HBs Antibody Concentrations | Year 12 anti-HBs | 475.8 mIU/mL |
| Twinrix Group | Anti-HAV and Anti-HBs Antibody Concentrations | Year 13 anti-HBs | 163.3 mIU/mL |
| Twinrix Group | Anti-HAV and Anti-HBs Antibody Concentrations | Year 14 anti-HBs | 149.1 mIU/mL |
| Twinrix Group | Anti-HAV and Anti-HBs Antibody Concentrations | Year 14* anti-HBs | 242.8 mIU/mL |
| Twinrix Group | Anti-HAV and Anti-HBs Antibody Concentrations | Year 15 anti-HBs | 210.9 mIU/mL |
Primary
Anti-HBs Antibody Concentrations
Subjects who lost seroprotective concentrations for anti-HBs (\< 10 mIU/mL) at any of the LT follow-up timepoints received an additional dose of Engerix after year 15. Two subjects were eligible for this after Year 11. 3.29 in the table means a concentration of \< 3.3 mIU/mL. As the concentration was calculated per subject no mean concentration was calculated and also no measure of dispersion.
Time frame: at Year 11, pre-additional vaccine, after additional dose of Engerix
Population: Analysis was performed on the long-term (LT) Total Vaccinated Cohort in subjects who were eligible for an additional dose. This included all subjects who had received at least one dose of the study vaccine in the primary study and who returned for the blood sampling timepoint and who had serology results for anti-HAV and anti-HBs available.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Twinrix Group | Anti-HBs Antibody Concentrations | subject 1 Year 11 | 3.29 mIU/mL |
| Twinrix Group | Anti-HBs Antibody Concentrations | subject 2 Year 11 | 3.29 mIU/mL |
| Twinrix Group | Anti-HBs Antibody Concentrations | subject 1 before additional dose | 3.29 mIU/mL |
| Twinrix Group | Anti-HBs Antibody Concentrations | subject 2 before additional dose | 14.5 mIU/mL |
| Twinrix Group | Anti-HBs Antibody Concentrations | subject 1 after additional dose | 6548.1 mIU/mL |
| Twinrix Group | Anti-HBs Antibody Concentrations | subject 2 after additional dose | 554.0 mIU/mL |
Primary
Number of Subjects, Receiving an Additional Vaccination of Engerix, With an Anamnestic Response
Anamnestic response was assessed in subjects receiving an additional vaccine dose of Engerix. Two subjects were found eligible at Year 11 for this additional vaccine dose. Anamnestic response was defined as: * post-additional vaccination anti-HBs concentration \>= 10 mIU/mL in subject seronegative before additional dose. * 4-fold increase post-additional dose compared to pre-additional vaccine time point.
Time frame: 30 days post additional dose of Engerix
Population: Analysis was performed on the long-term (LT) Total Vaccinated Cohort in subjects who were eligible for an additional dose. This included all subjects who had received at least one dose of the study vaccine in the primary study and who returned for the blood sampling timepoint and who had serology results for anti-HAV and anti-HBs available.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Twinrix Group | Number of Subjects, Receiving an Additional Vaccination of Engerix, With an Anamnestic Response | 2 Participants |
Primary
Number of Subjects With Anti-hepatitis A (Anti-HAV) Antibody Concentrations Equal to or Above Cut-off Value
Cut-off value was defined as 15 milli-international units per milliliter (mIU/mL). This was considered as seropositivity.
Time frame: Years 11, 12, 13, 14 and 15
Population: Analysis was performed on the long-term (LT) According-To-Protocol (ATP) cohort for immunogenicity, which included subjects who returned at a particular blood sampling timepoint, were in the ATP immunogenicity cohort in the primary study and for whom serology results were available for that particular timepoint.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Twinrix Group | Number of Subjects With Anti-hepatitis A (Anti-HAV) Antibody Concentrations Equal to or Above Cut-off Value | Year 11 | 25 Participants |
| Twinrix Group | Number of Subjects With Anti-hepatitis A (Anti-HAV) Antibody Concentrations Equal to or Above Cut-off Value | Year 12 | 28 Participants |
| Twinrix Group | Number of Subjects With Anti-hepatitis A (Anti-HAV) Antibody Concentrations Equal to or Above Cut-off Value | Year 13 | 23 Participants |
| Twinrix Group | Number of Subjects With Anti-hepatitis A (Anti-HAV) Antibody Concentrations Equal to or Above Cut-off Value | Year 14 | 24 Participants |
| Twinrix Group | Number of Subjects With Anti-hepatitis A (Anti-HAV) Antibody Concentrations Equal to or Above Cut-off Value | Year 15 | 31 Participants |
Primary
Number of Subjects With Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentrations Equal to or Above Cut-off Values
Cut-off values were defined 3.3 mIU/mL for the in-house anti-HBs assay and 6.2 mIU/mL for the ChemiLuminescence ImmunoAssay, which was also considered as seropositivity, and 10 mIU/mL.
Time frame: Years 11, 12, 13, 14 and 15
Population: Analysis was performed on the long-term (LT) According-To-Protocol (ATP) cohort for immunogenicity, which included subjects who returned at a particular blood sampling timepoint, were in the ATP immunogenicity cohort in the primary study and for whom serology results were available for that particular timepoint.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Twinrix Group | Number of Subjects With Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentrations Equal to or Above Cut-off Values | Year 11 3.3 mIU/mL | 23 Participants |
| Twinrix Group | Number of Subjects With Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentrations Equal to or Above Cut-off Values | Year 12 3.3 mIU/mL | 25 Participants |
| Twinrix Group | Number of Subjects With Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentrations Equal to or Above Cut-off Values | Year 13 3.3 mIU/mL | 20 Participants |
| Twinrix Group | Number of Subjects With Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentrations Equal to or Above Cut-off Values | Year 14 3.3 mIU/mL | 21 Participants |
| Twinrix Group | Number of Subjects With Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentrations Equal to or Above Cut-off Values | Year 14 6.2 mIU/mL | 21 Participants |
| Twinrix Group | Number of Subjects With Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentrations Equal to or Above Cut-off Values | Year 15 6.2 mIU/mL | 28 Participants |
| Twinrix Group | Number of Subjects With Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentrations Equal to or Above Cut-off Values | Year 11 10 mIU/mL | 23 Participants |
| Twinrix Group | Number of Subjects With Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentrations Equal to or Above Cut-off Values | Year 12 10 mIU/mL | 25 Participants |
| Twinrix Group | Number of Subjects With Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentrations Equal to or Above Cut-off Values | Year 13 10 mIU/mL | 20 Participants |
| Twinrix Group | Number of Subjects With Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentrations Equal to or Above Cut-off Values | Year 14 10 mIU/mL | 21 Participants |
| Twinrix Group | Number of Subjects With Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentrations Equal to or Above Cut-off Values | Year 15 10 mIU/mL | 28 Participants |
Primary
Number of Subjects With Serious Adverse Events (SAEs)
SAEs assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization, result in disability/incapacity or are a congenital anomaly/birth defect in the offspring of a study subject
Time frame: During the 30-day follow-up period after additional Engerix vaccination
Population: Analysis was performed on the long-term (LT) Total Vaccinated Cohort in subjects who were eligible for an additional dose. This included all subjects who had received at least one dose of the study vaccine in the primary study and who returned for the blood sampling timepoint and who had serology results for anti-HAV and anti-HBs available.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Twinrix Group | Number of Subjects With Serious Adverse Events (SAEs) | 0 Participants |
Primary
Number of Subjects With Serious Adverse Events (SAEs) Determined by the Investigator to Have a Causal Relationship to Primary Vaccination or Due to Lack of Vaccine Efficacy
SAEs assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization, result in disability/incapacity or are a congenital anomaly/birth defect in the offspring of a study subject.
Time frame: up to Year 11, 12, 13, 14, 15
Population: Analysis was performed on the long-term (LT) Total Vaccinated Cohort, this included all subjects who had received at least one dose of the study vaccine in the primary study and who returned for the blood sampling time-point and who had serology results for anti-HAV and anti-HBs available.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Twinrix Group | Number of Subjects With Serious Adverse Events (SAEs) Determined by the Investigator to Have a Causal Relationship to Primary Vaccination or Due to Lack of Vaccine Efficacy | Year 11 | 0 Participants |
| Twinrix Group | Number of Subjects With Serious Adverse Events (SAEs) Determined by the Investigator to Have a Causal Relationship to Primary Vaccination or Due to Lack of Vaccine Efficacy | Year 12 | 0 Participants |
| Twinrix Group | Number of Subjects With Serious Adverse Events (SAEs) Determined by the Investigator to Have a Causal Relationship to Primary Vaccination or Due to Lack of Vaccine Efficacy | Year 13 | 0 Participants |
| Twinrix Group | Number of Subjects With Serious Adverse Events (SAEs) Determined by the Investigator to Have a Causal Relationship to Primary Vaccination or Due to Lack of Vaccine Efficacy | Year 14 | 0 Participants |
| Twinrix Group | Number of Subjects With Serious Adverse Events (SAEs) Determined by the Investigator to Have a Causal Relationship to Primary Vaccination or Due to Lack of Vaccine Efficacy | Year 15 | 0 Participants |
Primary
Number of Subjects With Solicited Local and General Symptoms Assessed
Solicited local symptoms were pain, redness and swelling. Solicited general symptoms were fatigue, fever, gastrointestinal, headache.
Time frame: During the 4-day follow-up period after additional vaccination with Engerix
Population: Analysis was performed on the long-term (LT) Total Vaccinated Cohort in subjects who were eligible for an additional dose. This included all subjects who had received at least one dose of the study vaccine in the primary study and who returned for the blood sampling timepoint and who had serology results for anti-HAV and anti-HBs available.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Twinrix Group | Number of Subjects With Solicited Local and General Symptoms Assessed | Gastrointestinal | 1 Participants |
| Twinrix Group | Number of Subjects With Solicited Local and General Symptoms Assessed | Pain | 0 Participants |
| Twinrix Group | Number of Subjects With Solicited Local and General Symptoms Assessed | Redness | 0 Participants |
| Twinrix Group | Number of Subjects With Solicited Local and General Symptoms Assessed | Swelling | 0 Participants |
| Twinrix Group | Number of Subjects With Solicited Local and General Symptoms Assessed | Fatigue | 1 Participants |
| Twinrix Group | Number of Subjects With Solicited Local and General Symptoms Assessed | Fever | 0 Participants |
| Twinrix Group | Number of Subjects With Solicited Local and General Symptoms Assessed | Headache | 0 Participants |
Primary
Number of Subjects With Unsolicited Symptoms
Unsolicited AE covers any AE 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.
Time frame: During the 30-day follow-up period after additional Engerix vaccination
Population: Analysis was performed on the long-term (LT) Total Vaccinated Cohort in subjects who were eligible for an additional dose. This included all subjects who had received at least one dose of the study vaccine in the primary study and who returned for the blood sampling timepoint and who had serology results for anti-HAV and anti-HBs available.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Twinrix Group | Number of Subjects With Unsolicited Symptoms | 1 Participants |