Long-Term Immune Persistence of GSK Biologicals' Combined Hepatitis A & B Vaccine Injected According to a 0,1,6 Month Schedule

Study Overview
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Brief Summary
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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
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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.

Official Title
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Long-Term Persistence Follow-up Study to Evaluate the Immune Persistence of GSK Biologicals' Combined Hepatitis A / Hepatitis B Vaccine in Healthy Adult Volunteers

Conditions
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Hepatitis B, Hepatitis A

Intervention / Treatment
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* Biological: Twinrix™ adult


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Twinrix Group<br>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. | Biological: Twinrix™ adult<br>* Intramuscular administration<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Anti-hepatitis A Virus (Anti-HAV) Antibody Concentration | Concentrations given as geometric mean concentration (GMC) expressed as milli-international unit per millilitre (mIU/mL). | At Years 11, 12, 13, 14, and 15 after the first vaccine dose of the 3-dose primary vaccination | 
| 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. | During the 4-day (Day 0-3) follow-up period after additional HBV vaccination | 
| 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. | At Years 11, 12, 13, 14, and 15 after the first vaccine dose of the 3-dose primary vaccination | 
| 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. | At Years 11, 12, 13, 14, and 15 after the first vaccine dose of the 3-dose primary vaccination | 
| 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) | At Years 11, 12, 13, 14, and 15 after the first vaccine dose of the 3-dose primary vaccination | 
| 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) | At Years 11, 12, 13, 14, and 15 after the first vaccine dose of the 3-dose primary vaccination | 
| 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. | During the follow-up period after additional vaccination (minimum 30 days) | 
| 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. | Before the additional dose and 1 month after the additional dose | 
| 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. | During the 4-day (Day 0-3) follow-up period after additional HBV vaccination | 
| 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. | During the 30-day follow-up period after additional vaccination | 
| 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. | At Years 11, 12, 13, 14, and 15 after the first vaccine dose of the 3-dose primary vaccination | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Combined Hepatitis A and B vaccine, Hepatitis A, Hepatitis B