LT F-up Study 16-20 Yrs After Vaccine Dose of Hepatitis B With/Without HBIg in Newborns to HBeAg+ Mothers

Study Overview
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Brief Summary
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To evaluate the persistence of anti-HBs antibodies up to 16, 17, 18, 19 and 20 years after administration of the first dose of the study vaccine. The Protocol Posting has been updated in order to comply with the FDA Amendment Act, Sep 2007. No additional subjects will be recruited during this long-term follow-up study and no vaccine will be administered.

Detailed Description
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The primary study was to evaluate the reactogenicity, immunogenicity and protective efficacy of a hepatitis B vaccine in healthy neonates of HBeAg positive mothers if administered with or without a dose of HBIg at birth. The current study describes the long term follow up of these subjects between Y16 and 20 after primary vaccination.

Official Title
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Comparative Study of the Immunogenicity and Protective Efficacy of GlaxoSmithKline Biologicals' Rec-DNA Hepatitis B Vaccine With or Without Hepatitis B Immunoglobulins (HBIg) in Newborns of HBeAg+ Mothers.

Conditions
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Hepatitis B

Intervention / Treatment
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* Biological: Engerix™ -B
* Biological: Hepatitis B immunoglobulin (HBIg)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects who had received at least one dose of the study vaccine in the primary study Written informed consent obtained from each subject before each blood sampling visit Exclusion Criteria: None

Ages Eligible for Study
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Minimum Age: 16 Years
Maximum Age: 20 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: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Engerix 4D + HBIg Group<br>Subjects received Engerix™ (hepatitis B vaccine [HBV]) at Month 0, 1, 6 and 60 with hepatitis B immunoglobulins (HBIg) administered concomitantly at birth in the opposite arm. | Biological: Engerix™ -B<br>* 3 (Groups A and C) or 4 (Groups B and D) intramuscular injections during the primary study<br>Biological: Hepatitis B immunoglobulin (HBIg)<br>* 1 intramuscular injections at birth (primary study)<br>|
| Experimental: Engerix 3D + HBIg Group<br>Subjects received Engerix™ (hepatitis B vaccine [HBV]) at Month 0, 1, and 6 with hepatitis B immunoglobulins (HBIg) administered concomitantly at birth in the opposite arm. | Biological: Engerix™ -B<br>* 3 (Groups A and C) or 4 (Groups B and D) intramuscular injections during the primary study<br>Biological: Hepatitis B immunoglobulin (HBIg)<br>* 1 intramuscular injections at birth (primary study)<br>|
| Experimental: Engerix 4D<br>Subjects received Engerix™ (hepatitis B vaccine [HBV]) at Month 0, 1, 6 and 60. | Biological: Engerix™ -B<br>* 3 (Groups A and C) or 4 (Groups B and D) intramuscular injections during the primary study<br>|
| Experimental: Engerix 3D Group<br>Subjects received Engerix™ (hepatitis B vaccine [HBV]) at Month 0, 1, and 6. | Biological: Engerix™ -B<br>* 3 (Groups A and C) or 4 (Groups B and D) intramuscular injections during the primary study<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentration as Measured by Enzyme-Linked Immunosorbent Assay (ELISA). | Concentrations given as GMC expressed as milli-international unit per millilitre (mIU/mL). Note: At Year 15 and 16, a commercial ELISA was used. From Year 17 to Year 20, anti-HBs antibody concentrations were tested with a validated in-house assay with cut-off 3.3mIU/mL. | At Years 15, 16, 17, 18, 19 and 20 | 
| Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentration as Measured by ChemiLuminescence ImmunoAssay (CLIA). | Concentrations given as GMC expressed as milli-international unit per millilitre (mIU/mL). Note: There was a change of assay kit at Year 19 time-point, thus for the sake of bridging, blood samples corresponding to Year 19 were re-tested with new CLIA. At Year 19 and 20, anti-HBs antibody concentrations tested with the CLIA with cut-off 6.2 mIU/mL. | At Years 19 and 20 | 
| Number of Subjects With Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentrations Above Pre-defined Cut-off Values Enzyme-Linked Immunosorbent Assay (ELISA). | Anti-hepatitis B surface antigen (anti-HBs) antibody cut-off values assessed include 1.0 and 10 mIU/mL. | At Years 15, 16, 17, 18, 19 and 20 | 
| Adjusted Number of Subjects With Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentrations Above Pre-defined Cut-off Values as Measured by ChemiLuminescence ImmunoAssay (CLIA) | Anti-hepatitis B surface antigen (anti-HBs) antibody cut-off values assessed include 1.0 and 10 mIU/mL. Note: Missing CLIA anti-HBs concentrations, for subjects with ELISA results available, are estimated by multiple imputations and GMCs and number of subjects were adjusted for these imputations. | At Years 19 and 20 | 
| Number of Subjects With Positive Results for Serological Markers for Hepatitis B Infection | Serological markers for hepatitis B infection assessed are hepatitis B surface antigen (HBsAg), antibodies to hepatitis B core antigen (anti-HBc), hepatitis B e antigen (HBeAg) and antibodies to hepatitis B e antigen (anti-HBe). | At Years 15, 16, 17, 18, 19 and 20 | 
| Number of Subjects With Different Hepatitis B Infection Statuses | Categories hepatitis B (HB) infection: Chronic infection: HBsAg and anti-HBc pos (pos) in more than two consecutive samples False positive: single HB marker (HBsAg, HBeAg, anti-HBc) pos + all other markers negative (neg) in one sample. Consecutive time points all neg. Possible subclinical breakthrough infection: One or more HB markers pos in one or more consecutive samples. Isolated natural booster: >4-fold increase of anti-HBs concentrations if <100 mIU/mL at previous sample OR >2- fold increase of anti-HBs concentrations if >=100 mIU/mL at previous sample + other markers neg | Over the entire follow up period (Final assessment of clinical significance was analyzed after the Year 20 time point) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hepatitis B immunoglobulin, Hepatitis B antibody persistence