Clinical trial NCT01037166: Study in Japan of the Safety And Antiviral Activity in Adults With Chronic Hepatitis B Current Lamivudine Therapy
Official title: A Phase II Study in Japan of the Safety And Antiviral Activity of Entecavir (BMS-200475) in Adults With Chronic Hepatitis B With Incomplete Response to Current Lamivudine Therapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Chronic Hepatitis B
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
First posted: 2009-12-21
Enrollment: 84
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 are to demonstrate that entecavir has antiviral activity undetectable HBV DNA measured, the Roche AmplicorTM PCR at Week 48, and to assess the safety and the pharmacokinetic of entecavir in Japanese patients with hepatitis B who have an incomplete response to current lamivudine therapy


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. Patient who have received lamivudine therapy for 24 weeks or more, or patient who have documented YMDD mutation or other lamivudine-resistant mutation while on lamivudine
  3. Documented HBV Viremia ≥ 10\*5: copies/mL
* ALT in the range of 1.3 to 10 x ULN
* Subjects must have well-compensated liver disease a) value

Exclusion Criteria:

-

Primary outcomes:
measure: To assess the safety (the incidence of clinical adverse events and discontinuations due to adverse events)
timeFrame: Week 52 (end of dosing) plus 5 days
measure: To assess the proportion of subjects with reduction in HBV DNA by ≥ 2 log10 or to undetectable level (< 400 copies/mL)
timeFrame: at Week 48
Secondary outcomes:
measure: Mean change from baseline in the log*10* 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 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 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:
city: Aichi-Gun
country: Japan
facility: Local Institution
state: Aichi
city: Nagoya-Shi
country: Japan
facility: Local Institution
state: Aichi
city: Nagoya
country: Japan
facility: Local Institution
state: Aichi
city: Chiba-Shi
country: Japan
facility: Local Institution
state: Chiba
city: Kurume
country: Japan
facility: Local Institution
state: Fukuoka
city: Ogaki-Shi
country: Japan
facility: Local Institution
state: Gifu
city: Asahikawa-Shi
country: Japan
facility: Local Institution
state: Hokkaido
city: Sapporo-Shi
country: Japan
facility: Local Institution
state: Hokkaido
city: Akashi-Shi
country: Japan
facility: Local Institution
state: Hyogo
city: Morioka-Shi
country: Japan
facility: Local Institution
state: Iwate
city: Sendai
country: Japan
facility: Local Institution
state: Miyagi
city: Okayama-Shi
country: Japan
facility: Local Institution
state: Okayama
city: Minato-Ku
country: Japan
facility: Local Institution
state: Tokyo
city: Musashino-Shi
country: Japan
facility: Local Institution
state: Tokyo
city: Shinjuku-Ku
country: Japan
facility: Local Institution
state: Tokyo
city: Kyoto
country: Japan
facility: Local Institution
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References:
citation: Suzuki F, Toyoda J, Katano Y, Sata M, Moriyama M, Imazeki F, Kage M, Seriu T, Omata M, Kumada H. Efficacy and safety of entecavir in lamivudine-refractory patients with chronic hepatitis B: randomized controlled trial in Japanese patients. J Gastroenterol Hepatol. 2008 Sep;23(9):1320-6. doi: 10.1111/j.1440-1746.2008.05455.x. Epub 2008 Jun 28.