Back to resultsA Study in Japan of the Safety and Antiviral Activity With Chronic Hepatitis B Infection
Primary Purpose
Chronic Hepatitis B
Status
Completed
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
Entecavir
Sponsored by
About this trial
This is an interventional treatment trial for Chronic Hepatitis B
Eligibility Criteria
Inclusion Criteria:
Documentation of chronic hepatitis B infection by ALL of the following:
- 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
- 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
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Entecavir (0.1 mg)
Entecavir (0.5 mg)
Arm Description
Outcomes
Primary Outcome Measures
Incidence of clinical adverse events and discontinuations due to adverse events of entecavir at doses of 0.5 and 1 mg
Incidence of laboratory abnormalities of entecavir at doses of 0.5 and 1 mg for 52 weeks
Proportion of subjects with reduction in HBV DNA by ≥2 log10 or to undetectable level (<400 copies/mL) by PCR assay
Secondary Outcome Measures
Mean change from baseline in log10 HBV DNA measured by PCR assay for each entecavir dose (0.5 and 1 mg) at Week 48
Proportion of subjects who achieve undetectable HBV DNA (<400 copies/mL) by PCR assay at Week 48
Proportion of subjects HBeAg-positive at baseline who have loss of HBeAg from serum at Week 48
Proportion of subjects HBeAg-positive at baseline who achieve seroconversion (loss of HBeAg and appearance of HBeAb) at Week 48
Proportion of subjects with abnormal ALT at baseline who achieve normalization of serum ALT (<1.25 x ULN) at 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
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
Proportion of subjects who achieve Complete Response, and remain Complete response for 24 weeks after stopping drug
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
Changes in liver histology as assessed by the New Inuyama Classification for histological assessment of chronic hepatitis
Relationship between HBV isolates (genotypes A,B,C, etc.) at baseline and antiviral activity
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.
Mutation of HBV DNA polymerase at Week 48 from baseline
Plasma concentrations of entecavir at selected time points during the treatment period
Population pharmacokinetic assessment of entecavir developed from concentration-time data obtained from healthy subjects
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01020565
Brief Title
A Study in Japan of the Safety and Antiviral Activity With Chronic Hepatitis B Infection
Official Title
A Phase II Study in Japan of the Safety and Antiviral Activity of Entecavir (BMS-200475) in Adults With Chronic Hepatitis B Infection
Study Type
Interventional
2. Study Status
Record Verification Date
June 2010
Overall Recruitment Status
Completed
Study Start Date
February 2003 (undefined)
Primary Completion Date
February 2005 (Actual)
Study Completion Date
February 2005 (Actual)
3. Sponsor/Collaborators
Name of the Sponsor
Bristol-Myers Squibb
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
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
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Hepatitis B
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
60 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Entecavir (0.1 mg)
Arm Type
Experimental
Arm Title
Entecavir (0.5 mg)
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Entecavir
Other Intervention Name(s)
Baraclude, BMS-200475
Intervention Description
Tablet, P.O., 0.1 OR 0.5 mg, once daily, 52 weeks
Primary Outcome Measure Information:
Title
Incidence of clinical adverse events and discontinuations due to adverse events of entecavir at doses of 0.5 and 1 mg
Time Frame
Week 52 (end of dosing) plus 5 days
Title
Incidence of laboratory abnormalities of entecavir at doses of 0.5 and 1 mg for 52 weeks
Time Frame
Week 52 (end of dosing) plus 5 days
Title
Proportion of subjects with reduction in HBV DNA by ≥2 log10 or to undetectable level (<400 copies/mL) by PCR assay
Time Frame
Week 48
Secondary Outcome Measure Information:
Title
Mean change from baseline in log10 HBV DNA measured by PCR assay for each entecavir dose (0.5 and 1 mg) at Week 48
Time Frame
Baseline, Week 48
Title
Proportion of subjects who achieve undetectable HBV DNA (<400 copies/mL) by PCR assay at Week 48
Time Frame
Week 48
Title
Proportion of subjects HBeAg-positive at baseline who have loss of HBeAg from serum at Week 48
Time Frame
Week 48
Title
Proportion of subjects HBeAg-positive at baseline who achieve seroconversion (loss of HBeAg and appearance of HBeAb) at Week 48
Time Frame
Week 48
Title
Proportion of subjects with abnormal ALT at baseline who achieve normalization of serum ALT (<1.25 x ULN) at Week 48
Time Frame
Week 48
Title
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
Time Frame
Week 48
Title
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
Time Frame
Week 48
Title
Proportion of subjects who achieve Complete Response, and remain Complete response for 24 weeks after stopping drug
Time Frame
Week 72
Title
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
Time Frame
Baseline, Week 48
Title
Changes in liver histology as assessed by the New Inuyama Classification for histological assessment of chronic hepatitis
Time Frame
Week 52
Title
Relationship between HBV isolates (genotypes A,B,C, etc.) at baseline and antiviral activity
Time Frame
Week 48, or at end of dosing (up to Week 52)
Title
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.
Time Frame
Week 48, or at end of dosing (up to Week 52)
Title
Mutation of HBV DNA polymerase at Week 48 from baseline
Time Frame
Baseline, Week 48
Title
Plasma concentrations of entecavir at selected time points during the treatment period
Time Frame
pre-dosing, Week 2 or 4, Week 12, Week 24 and Week 36
Title
Population pharmacokinetic assessment of entecavir developed from concentration-time data obtained from healthy subjects
Time Frame
pre-dosing, Week 2 or 4, Week 12, Week 24 and Week 36
10. Eligibility
Sex
All
Minimum Age & Unit of Time
20 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Documentation of chronic hepatitis B infection by ALL of the following:
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
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Bristol-Myers Squibb
Organizational Affiliation
Bristol-Myers Squibb
Official's Role
Study Director
12. IPD Sharing Statement
Citations:
PubMed Identifier
19215336
Citation
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.
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A Study in Japan of the Safety and Antiviral Activity With Chronic Hepatitis B Infection
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