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

Phase 3

Completed

• Conditions: Hepatitis B; Hepatitis A
• Interventions: Biological: Twinrix™ adult

• Registration Number: NCT00289718
• Lead Sponsor: GlaxoSmithKline

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.

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study Start: 2004-11-01
• Primary Completion: 2005-03-02
• Study Completion: 2005-03-02
• Study First Submitted: 2006-02-09
• Study First Submitted QC: 2006-02-09
• Study First Posted: 2006-02-10
• Results First Submitted: 2010-01-11
• Results First Submitted QC: 2010-07-29
• Results First Posted: 2010-08-26
• Status Verified: 2016-11
• Last Update Submitted: 2017-09-01
• Last Update Posted: 2018-02-15

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 51

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

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Exclusion Criteria

Not provided

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Twinrix Group	Twinrix™ adult	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.

Primary Outcome Measures

Name	Time	Method
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 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.
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 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.
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.
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.
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 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.
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.

Trial Locations

Locations (1)

GSK Investigational Site; 🇧🇪 Gent, Belgium