An Open-Label Rollover Study of Entecavir (BMS-200475) in Adults With Chronic Hepatitis B Infection

Study Overview
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Brief Summary
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To provide open-label entecavir to subjects who have completed previous blinded entecavir trials in Japan and are assessed by the investigator as likely to benefit from additional anti-hepatitis B therapy

Official Title
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An Open-Label Rollover Study of Entecavir (BMS-200475) in Adults With Chronic Hepatitis B Infection Who Have Completed Previous Phase II Studies in Japan But Who Require Further Treatment

Conditions
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Chronic Hepatitis B

Intervention / Treatment
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* Drug: Entecavir


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects who completed a previous entecavir Phase II studies (AI463047, 052 or 053); ALT ≤ 10 x upper limit of normal; Subjects must have well-compensated liver disease according to ALL of the following criteria; Prothrombin time ≤ 3 seconds prolonged compared to control value or INR ≤ 1.5 Serum albumin ≥ 3 g/dL (≥ 30 g/L) Serum bilirubin ≤ 2.5 mg/dL (≤ 42.75 μmol/L) Exclusion Criteria: Sex and Reproductive Status Exceptions Target Disease Exceptions Medical History and Concurrent Diseases

Ages Eligible for Study
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Minimum Age: 20 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Entecavir<br> | Drug: Entecavir<br>* Tablet, P.O. 0.5, 1 mg, once daily<br>* Other names: BMS-200475;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To provide open-label entecavir to subjects who have completed previous blinded entecavir trials in Japan and are assessed by the investigator as likely to benefit from additional anti-hepatitis B therapy |  | 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of clinical adverse events and discontinuations due to adverse events of entecavir for each cohort |  | Week 2, 4, 6, 8, 10, 12, 16, 20 and 24 post dosing | 
| Incidence of laboratory abnormalities of of entecavir for each cohort |  | Week 2, 4, 6, 8, 10, 12, 16, 20 and 24 post dosing | 
| Proportion of subjects HBeAg-positive at baseline who have loss of HBeAg from serum |  | Day 1, Week 12, Week 24 and every subsequent 24 week during dosing | 
| Proportion of subjects HBeAg-positive at baseline who achieve seroconversion (loss of HBeAg and appearance of HBeAb) |  | Day 1, Week 12, Week 24 and every subsequent 24 week during dosing | 
| Proportion of subjects with abnormal ALT at baseline who achieve normalization of serum ALT at Week 48 |  | Day 1, Week 48 | 
| Proportion of subjects who achieve HBV DNA levels by PCR assay less than the limit of quantification (LOQ) |  | Day 1, Week 12, 24, and subsequent 24 week during dosing | 
| Proportion of subjects positive for HBeAg at baseline who achieve HBV DNA levels by PCR assay less than LOQ, normal serum ALT, and seroconversion |  | Week 8, 16, 24 post dosing | 
| Proportion of subjects negative for HBeAg at baseline who achieve HBV DNA levels by PCR assay less than LOQ and normal ALT and remain negative for HBeAg |  | Day 1, Week 12, Week 24 and every subsequent 24 weeks during dosing | 
| Proportion of subjects who achieved Complete Response during therapy, who have sustained Complete Response for 24 weeks after stopping drug |  | 24 Week post dosing | 
| Proportion of subjects with histological improvement in the liver at Wks 48 & 96 [improvement in necroinflammatory score and no worsening of fibrosis at Wks 48 & 96 liver biopsy compared to baseline & to baseline in previous study] |  | Week 48, 96 | 
| NChanges in liver histology as assessed by the New Inuyama Classification for histological assessment of chronic hepatitis |  | Week 48 & Week 96 | 
| Incidence of genotypic changes in HBV DNA polymerase conferring resistance to entecavir in subjects with confirmed ≥1 log10 increase in HBV DNA from nadir on treatment |  | Week 2, 4, ± days, Week 8 every 4 weeks ± 7 days |