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Study in Japan of the Safety And Antiviral Activity in Adults With Chronic Hepatitis B Current Lamivudine Therapy

Primary Purpose

Chronic Hepatitis B

Status
Completed
Phase
Phase 2
Locations
Japan
Study Type
Interventional
Intervention
Entecavir
Sponsored by
Bristol-Myers Squibb
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Chronic Hepatitis B

Eligibility Criteria

20 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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:

-

Sites / Locations

  • Local Institution
  • Local Institution
  • Local Institution
  • Local Institution
  • Local Institution
  • Local Institution
  • Local Institution
  • Local Institution
  • Local Institution
  • Local Institution
  • Local Institution
  • Local Institution
  • Local Institution
  • Local Institution
  • Local Institution
  • Local Institution

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Entecavir (0.5 mg)

Entecavir (1mg)

Arm Description

Outcomes

Primary Outcome Measures

To assess the safety (the incidence of clinical adverse events and discontinuations due to adverse events)
To assess the proportion of subjects with reduction in HBV DNA by ≥ 2 log10 or to undetectable level (< 400 copies/mL)

Secondary Outcome Measures

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
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 undetectable HBV DNA levels by PCR assay, remain negative for HBeAg and normal serum ALT at Week 48
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

First Posted
December 17, 2009
Last Updated
January 24, 2011
Sponsor
Bristol-Myers Squibb
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1. Study Identification

Unique Protocol Identification Number
NCT01037166
Brief Title
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

2. Study Status

Record Verification Date
June 2010
Overall Recruitment Status
Completed
Study Start Date
December 2002 (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 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

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
84 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Entecavir (0.5 mg)
Arm Type
Experimental
Arm Title
Entecavir (1mg)
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Entecavir
Other Intervention Name(s)
Baraclude, BMS-200475
Intervention Description
Tablet, P.O., 0.5 mg or 1mg, once daily, 52 weeks
Primary Outcome Measure Information:
Title
To assess the safety (the incidence of clinical adverse events and discontinuations due to adverse events)
Time Frame
Week 52 (end of dosing) plus 5 days
Title
To assess the proportion of subjects with reduction in HBV DNA by ≥ 2 log10 or to undetectable level (< 400 copies/mL)
Time Frame
at Week 48
Secondary Outcome Measure Information:
Title
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
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 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 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 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 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: -
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Bristol-Myers Squibb
Organizational Affiliation
Bristol-Myers Squibb
Official's Role
Study Director
Facility Information:
Facility Name
Local Institution
City
Aichi-Gun
State/Province
Aichi
ZIP/Postal Code
480-1195
Country
Japan
Facility Name
Local Institution
City
Nagoya-Shi
State/Province
Aichi
ZIP/Postal Code
467-8602
Country
Japan
Facility Name
Local Institution
City
Nagoya
State/Province
Aichi
ZIP/Postal Code
466-8550
Country
Japan
Facility Name
Local Institution
City
Chiba-Shi
State/Province
Chiba
Country
Japan
Facility Name
Local Institution
City
Kurume
State/Province
Fukuoka
Country
Japan
Facility Name
Local Institution
City
Ogaki-Shi
State/Province
Gifu
ZIP/Postal Code
503-8502
Country
Japan
Facility Name
Local Institution
City
Asahikawa-Shi
State/Province
Hokkaido
ZIP/Postal Code
070-0054
Country
Japan
Facility Name
Local Institution
City
Sapporo-Shi
State/Province
Hokkaido
ZIP/Postal Code
060-0033
Country
Japan
Facility Name
Local Institution
City
Akashi-Shi
State/Province
Hyogo
ZIP/Postal Code
673-0848
Country
Japan
Facility Name
Local Institution
City
Morioka-Shi
State/Province
Iwate
ZIP/Postal Code
020-8505
Country
Japan
Facility Name
Local Institution
City
Sendai
State/Province
Miyagi
Country
Japan
Facility Name
Local Institution
City
Okayama-Shi
State/Province
Okayama
ZIP/Postal Code
700-0082
Country
Japan
Facility Name
Local Institution
City
Minato-Ku
State/Province
Tokyo
ZIP/Postal Code
105-0001
Country
Japan
Facility Name
Local Institution
City
Musashino-Shi
State/Province
Tokyo
ZIP/Postal Code
180-0023
Country
Japan
Facility Name
Local Institution
City
Shinjuku-Ku
State/Province
Tokyo
ZIP/Postal Code
162-8666
Country
Japan
Facility Name
Local Institution
City
Kyoto
Country
Japan

12. IPD Sharing Statement

Citations:
PubMed Identifier
18554238
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.
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Study in Japan of the Safety And Antiviral Activity in Adults With Chronic Hepatitis B Current Lamivudine Therapy

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