A Study in Japan of the Safety and Antiviral Activity With Chronic Hepatitis B Infection

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

The objectives of this study are to demonstrate that entecavir has antiviral activity with undetectable at Week 48, and to assess the safety and the pharmacokinetic in Japanese patients given entecavir at each dose of 0.1 and 0.5 mg for 52 weeks

Study Overview

• Status: Completed
• Conditions: Chronic Hepatitis B
• Intervention / Treatment: Drug: Entecavir

• Study Type: Interventional
• Enrollment (Anticipated): 60
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Documentation of chronic hepatitis B infection by ALL of the following:

  1. Positive for HBsAg OR, negative for IgM core antibody and confirmation of chronic hepatitis B on liver biopsy
  2. Positive for HBeAg OR negative for HBeAg
  3. Documented HBV Viremia on 2 or more occasions and at screening visit: Viremia on sample drawn AND HBV DNA of ≥ 10*5* copies/mL by PCR assay at the screening visit
• ALT in the range of 1.3 to 10 x ULN

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Entecavir (0.1 mg)	Drug: Entecavir; Tablet, P.O., 0.1 OR 0.5 mg, once daily, 52 weeks; Other Names: Baraclude; BMS-200475
Experimental: Entecavir (0.5 mg)	Drug: Entecavir; Tablet, P.O., 0.1 OR 0.5 mg, once daily, 52 weeks; Other Names: Baraclude; BMS-200475

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Incidence of clinical adverse events and discontinuations due to adverse events of entecavir at doses of 0.5 and 1 mg	Week 52 (end of dosing) plus 5 days
Incidence of laboratory abnormalities of entecavir at doses of 0.5 and 1 mg for 52 weeks	Week 52 (end of dosing) plus 5 days
Proportion of subjects with reduction in HBV DNA by ≥2 log10 or to undetectable level (<400 copies/mL) by PCR assay	Week 48

Secondary Outcome Measures

Outcome Measure	Time Frame
Mean change from baseline in log10 HBV DNA measured by PCR assay for each entecavir dose (0.5 and 1 mg) at Week 48	Baseline, Week 48
Proportion of subjects who achieve undetectable HBV DNA (<400 copies/mL) by PCR assay at Week 48	Week 48
Proportion of subjects HBeAg-positive at baseline who have loss of HBeAg from serum at Week 48	Week 48
Proportion of subjects HBeAg-positive at baseline who achieve seroconversion (loss of HBeAg and appearance of HBeAb) at Week 48	Week 48
Proportion of subjects with abnormal ALT at baseline who achieve normalization of serum ALT (<1.25 x ULN) at Week 48	Week 48
Proportion of subjects HBeAg-positive at baseline who have Complete Response [undetectable HBV DNA levels by PCR assay, negative for HBeAg and normal serum ALT] at Week 48	Week 48
Proportion of subjects HBeAg-negative at baseline who have Complete Response [undetectable HBV DNA levels by PCR assay, remain negative for HBeAg and normal serum ALT] at Week 48	Week 48
Proportion of subjects who achieve Complete Response, and remain Complete response for 24 weeks after stopping drug	Week 72
Proportion of subjects w/ histological improvement in liver (improvement in necroinflammatory score (≥2 points decrease, Knodell HAI3 score) & no worsening of fibrosis (≥1 point increase, Knodell fibrosis score) at Wk 48 liver biopsy compared to baseline	Baseline, Week 48
Changes in liver histology as assessed by the New Inuyama Classification for histological assessment of chronic hepatitis	Week 52
Relationship between HBV isolates (genotypes A,B,C, etc.) at baseline and antiviral activity	Week 48, or at end of dosing (up to Week 52)
Incidence of resistance mutations of HBV isolates in subjects who have a rise in HBV DNA (by ≥1 log above the nadir for that subject) while on study drug.	Week 48, or at end of dosing (up to Week 52)
Mutation of HBV DNA polymerase at Week 48 from baseline	Baseline, Week 48
Plasma concentrations of entecavir at selected time points during the treatment period	pre-dosing, Week 2 or 4, Week 12, Week 24 and Week 36
Population pharmacokinetic assessment of entecavir developed from concentration-time data obtained from healthy subjects	pre-dosing, Week 2 or 4, Week 12, Week 24 and Week 36

Collaborators and Investigators

• Sponsor: Bristol-Myers Squibb

Publications and helpful links

General Publications

• Kobashi H, Takaguchi K, Ikeda H, Yokosuka O, Moriyama M, Imazeki F, Kage M, Seriu T, Omata M, Sakaguchi K, Shiratori Y. Efficacy and safety of entecavir in nucleoside-naive, chronic hepatitis B patients: phase II clinical study in Japan. J Gastroenterol Hepatol. 2009 Feb;24(2):255-61. doi: 10.1111/j.1440-1746.2008.05593.x.

Study record dates

Study Major Dates

• Study Start: February 1, 2003
• Primary Completion (Actual): February 1, 2005
• Study Completion (Actual): February 1, 2005

Study Registration Dates

• First Submitted: November 24, 2009
• First Submitted That Met QC Criteria: November 24, 2009
• First Posted (Estimate): November 25, 2009

Study Record Updates

• Last Update Posted (Estimate): August 6, 2010
• Last Update Submitted That Met QC Criteria: August 4, 2010
• Last Verified: June 1, 2010

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Hepatitis, Viral, Human; Hepadnaviridae Infections; DNA Virus Infections; Enterovirus Infections; Picornaviridae Infections; Hepatitis B; Hepatitis; Hepatitis A; Hepatitis B, Chronic; Hepatitis, Chronic; Anti-Infective Agents; Antiviral Agents; Entecavir
• Other Study ID Numbers: AI463-053