Long-term Immune Persistence of GSK Biologicals' Combined Hepatitis A & B Vaccine Injected According to a 0,1,6 Mth Schedule in Healthy Adults

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 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
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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 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.

Official Title
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A Double Blind Randomised, Comparative Study of the Immunogenicity and Reactogenicity of Three Different Lots of GlaxoSmithKline Biologicals' Combined Hepatitis A - Hepatitis B Vaccine When Administered in Healthy Adults

Conditions
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Hepatitis B, Hepatitis A

Intervention / Treatment
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* Biological: Twinrix™


Participation Criteria
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Eligibility Criteria
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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.

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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group A<br>Was vaccinated with Lot A in the primary study. | Biological: Twinrix™<br>* Intramuscular injection, 3 doses<br>|
| Experimental: Group B<br>Was vaccinated with Lot B in the primary study. | Biological: Twinrix™<br>* Intramuscular injection, 3 doses<br>|
| Experimental: Group C<br>Was vaccinated with Lot C in the primary study. | Biological: Twinrix™<br>* Intramuscular injection, 3 doses<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Years 11, 12, 13, 14 and 15 | 
| 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. | Years 11, 12, 13, 14 and 15 | 
| 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*). | Years 11, 12, 13, 14 and 15 | 
| 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. | at Year 11, pre-additional vaccine, after additional dose of Engerix | 
| 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. | 30 days post additional dose of Engerix | 
| 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. | During the 4-day follow-up period after additional vaccination with Engerix | 
| 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. | During the 30-day follow-up period after additional Engerix vaccination | 
| 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 | During the 30-day follow-up period after additional Engerix vaccination | 
| 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. | up to Year 11, 12, 13, 14, 15 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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TWINRIX™ ADULT, Hepatitis A, Hepatitis B