A Phase II Dose Response Study in Japan in Chronic Hepatitis B

Study Overview
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Brief Summary
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To demonstrate the dose response of entecavir in Japanese patients as measured by HBV DNA levels by PCR (log10 copies/mL) at Week 22

Official Title
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A Phase II Study in Japan of the Safety and Antiviral Activity of Entecavir (BMS-200475) vs Lamivudine in Adults With Chronic Hepatitis B Infection

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: Positive for HBsAg OR, negative for IgM core antibody and confirmation of chronic hepatitis B on liver biopsy, Positive for HBeAg OR negative for HBeAg with positive HBeAb, Documented HBV Viremia on 2 or more occasions: Viremia on sample drawn AND HBV DNA of ≥ 40 MEq/mL by Quantiplex assay at the screening visit

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 75 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Entecavir (0.01 mg)<br> | Drug: Entecavir<br>* Capsule, P.O., 0.01, 0.1 or 0.5 mg, once daily for 24 weeks<br>* Other names: BMS-200475;|
| Experimental: Entecavir (0.1 mg)<br> | Drug: Entecavir<br>* Capsule, P.O., 0.01, 0.1 or 0.5 mg, once daily for 24 weeks<br>* Other names: BMS-200475;|
| Experimental: Entecavir (0.5 mg)<br> | Drug: Entecavir<br>* Capsule, P.O., 0.01, 0.1 or 0.5 mg, once daily for 24 weeks<br>* Other names: BMS-200475;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean change from baseline in HBV DNA levels as measured by by PCR (log10 copies/mL) |  | at Week 22 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of clinical adverse events and discontinuations due to adverse events in each entecavir group in comparison to lamivudine |  | Through Week 24 (end of dosing) plus 5 days | 
| Incidence of laboratory abnormalities in each entecavir group in comparison to lamivudine |  | Through Week 24 (end of dosing) plus 5 days | 
| HBV DNA as measured by PCR (log10 copies/mL) at Week 22 [to demonstrate non-inferiority of at least one dose of entecavir as compared with lamivudine] |  | Week 22 | 
| Proportion of subjects in each treatment group who achieve HBV DNA reduced by ≥2 log10 and/or below the limit of quantification (LOQ) (<400 copies/mL) as measured by PCR assay |  | Week 12, Week 22 | 
| Proportion of subjects in each treatment group who achieve HBV DNA below the limit of detection (0.7 MEq/mL) of the Quantiplex branched DNA hybridization assay (Quantiplex assay) |  | Week 22 | 
| Proportion of subjects in each treatment group who achieve normalization of ALT (ALT <1.25 x UKN) |  | Week 22 | 
| Proportion of subjects in each treatment group who achieve loss of HBeAg at Week 22 among HBeAg-positive subjects at baseline |  | Baseline, Week 22 | 
| Proportion of subjects in each treatment group who achieve seroconversion at Week 22 among of HBeAg-positive subjects at baseline |  | Week 22 | 
| Proportion of HBeAg-positive subjects at baseline who achieve responder status (defined as: HBV DNA <0.7 MEq/mL by the Quantiplex assay; loss of HBeAg and normal serum ALT) |  | Week 22 | 
| Proportion of HBeAg-negative subjects at baseline who achieve responder status (defined as HBV DNA <0.7 MEq/mL by the Quantiplex assay and normal serum ALT) |  | Week 22 | 
| Incidence of genotypic resistance of HBV isolates in subjects who have a ε 1 log10 increase in HBV DNA as measured by PCR assay after achieving the lowest value while on study drug |  | Through Week 24 | 
| Relationship of HBV isolates (genotypes A, B, C etc) at baseline compared to response |  | Week 22 |