Clinical trial NCT01020565: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Chronic Hepatitis B
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
First posted: 2009-11-25
Enrollment: 60
Sex: ALL
Minimum age (years): 20
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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


Eligibility criteria: 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

Primary outcomes:
measure: Incidence of clinical adverse events and discontinuations due to adverse events of entecavir at doses of 0.5 and 1 mg
timeFrame: Week 52 (end of dosing) plus 5 days
measure: Incidence of laboratory abnormalities of entecavir at doses of 0.5 and 1 mg for 52 weeks
timeFrame: Week 52 (end of dosing) plus 5 days
measure: Proportion of subjects with reduction in HBV DNA by ≥2 log10 or to undetectable level (<400 copies/mL) by PCR assay
timeFrame: Week 48
Secondary outcomes:
measure: Mean change from baseline in log10 HBV DNA measured by PCR assay for each entecavir dose (0.5 and 1 mg) at Week 48
timeFrame: Baseline, Week 48
measure: Proportion of subjects who achieve undetectable HBV DNA (<400 copies/mL) by PCR assay at Week 48
timeFrame: Week 48
measure: Proportion of subjects HBeAg-positive at baseline who have loss of HBeAg from serum at Week 48
timeFrame: Week 48
measure: Proportion of subjects HBeAg-positive at baseline who achieve seroconversion (loss of HBeAg and appearance of HBeAb) at Week 48
timeFrame: Week 48
measure: Proportion of subjects with abnormal ALT at baseline who achieve normalization of serum ALT (<1.25 x ULN) at Week 48
timeFrame: Week 48
measure: 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
timeFrame: Week 48
measure: 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
timeFrame: Week 48
measure: Proportion of subjects who achieve Complete Response, and remain Complete response for 24 weeks after stopping drug
timeFrame: Week 72
measure: 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
timeFrame: Baseline, Week 48
measure: Changes in liver histology as assessed by the New Inuyama Classification for histological assessment of chronic hepatitis
timeFrame: Week 52
measure: Relationship between HBV isolates (genotypes A,B,C, etc.) at baseline and antiviral activity
timeFrame: Week 48, or at end of dosing (up to Week 52)
measure: 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.
timeFrame: Week 48, or at end of dosing (up to Week 52)
measure: Mutation of HBV DNA polymerase at Week 48 from baseline
timeFrame: Baseline, Week 48
measure: Plasma concentrations of entecavir at selected time points during the treatment period
timeFrame: pre-dosing, Week 2 or 4, Week 12, Week 24 and Week 36
measure: Population pharmacokinetic assessment of entecavir developed from concentration-time data obtained from healthy subjects
timeFrame: pre-dosing, Week 2 or 4, Week 12, Week 24 and Week 36
Other outcomes:
Locations:
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References:
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.