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An Open-Label Rollover Study of Entecavir (BMS-200475) in Adults With Chronic Hepatitis B Infection

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 - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Subjects who completed a previous entecavir Phase II studies (AI463047, 052 or 053);
  • ALT ≤ 10 x upper limit of normal;

  • Subjects must have well-compensated liver disease according to ALL of the following criteria;

    1. Prothrombin time ≤ 3 seconds prolonged compared to control value or INR ≤ 1.5
    2. Serum albumin ≥ 3 g/dL (≥ 30 g/L)
    3. Serum bilirubin ≤ 2.5 mg/dL (≤ 42.75 μmol/L)

Exclusion Criteria:

  • Sex and Reproductive Status Exceptions
  • Target Disease Exceptions
  • Medical History and Concurrent Diseases

Sites / Locations

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Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Entecavir

Arm Description

Outcomes

Primary Outcome Measures

To provide open-label entecavir to subjects who have completed previous blinded entecavir trials in Japan and are assessed by the investigator as likely to benefit from additional anti-hepatitis B therapy

Secondary Outcome Measures

Incidence of clinical adverse events and discontinuations due to adverse events of entecavir for each cohort
Incidence of laboratory abnormalities of of entecavir for each cohort
Proportion of subjects HBeAg-positive at baseline who have loss of HBeAg from serum
Proportion of subjects HBeAg-positive at baseline who achieve seroconversion (loss of HBeAg and appearance of HBeAb)
Proportion of subjects with abnormal ALT at baseline who achieve normalization of serum ALT at Week 48
Proportion of subjects who achieve HBV DNA levels by PCR assay less than the limit of quantification (LOQ)
Proportion of subjects positive for HBeAg at baseline who achieve HBV DNA levels by PCR assay less than LOQ, normal serum ALT, and seroconversion
Proportion of subjects negative for HBeAg at baseline who achieve HBV DNA levels by PCR assay less than LOQ and normal ALT and remain negative for HBeAg
Proportion of subjects who achieved Complete Response during therapy, who have sustained Complete Response for 24 weeks after stopping drug
Proportion of subjects with histological improvement in the liver at Wks 48 & 96 [improvement in necroinflammatory score and no worsening of fibrosis at Wks 48 & 96 liver biopsy compared to baseline & to baseline in previous study]
NChanges in liver histology as assessed by the New Inuyama Classification for histological assessment of chronic hepatitis
Incidence of genotypic changes in HBV DNA polymerase conferring resistance to entecavir in subjects with confirmed ≥1 log10 increase in HBV DNA from nadir on treatment

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
NCT01037062
Brief Title
An Open-Label Rollover Study of Entecavir (BMS-200475) in Adults With Chronic Hepatitis B Infection
Official Title
An Open-Label Rollover Study of Entecavir (BMS-200475) in Adults With Chronic Hepatitis B Infection Who Have Completed Previous Phase II Studies in Japan But Who Require Further Treatment
Study Type
Interventional

2. Study Status

Record Verification Date
December 2009
Overall Recruitment Status
Completed
Study Start Date
December 2003 (undefined)
Primary Completion Date
December 2006 (Actual)
Study Completion Date
December 2006 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor
Bristol-Myers Squibb

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
To provide open-label entecavir to subjects who have completed previous blinded entecavir trials in Japan and are assessed by the investigator as likely to benefit from additional anti-hepatitis B 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
None (Open Label)
Enrollment
282 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Entecavir
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Entecavir
Other Intervention Name(s)
Baraclude, BMS-200475
Intervention Description
Tablet, P.O. 0.5, 1 mg, once daily
Primary Outcome Measure Information:
Title
To provide open-label entecavir to subjects who have completed previous blinded entecavir trials in Japan and are assessed by the investigator as likely to benefit from additional anti-hepatitis B therapy
Time Frame
24 weeks
Secondary Outcome Measure Information:
Title
Incidence of clinical adverse events and discontinuations due to adverse events of entecavir for each cohort
Time Frame
Week 2, 4, 6, 8, 10, 12, 16, 20 and 24 post dosing
Title
Incidence of laboratory abnormalities of of entecavir for each cohort
Time Frame
Week 2, 4, 6, 8, 10, 12, 16, 20 and 24 post dosing
Title
Proportion of subjects HBeAg-positive at baseline who have loss of HBeAg from serum
Time Frame
Day 1, Week 12, Week 24 and every subsequent 24 week during dosing
Title
Proportion of subjects HBeAg-positive at baseline who achieve seroconversion (loss of HBeAg and appearance of HBeAb)
Time Frame
Day 1, Week 12, Week 24 and every subsequent 24 week during dosing
Title
Proportion of subjects with abnormal ALT at baseline who achieve normalization of serum ALT at Week 48
Time Frame
Day 1, Week 48
Title
Proportion of subjects who achieve HBV DNA levels by PCR assay less than the limit of quantification (LOQ)
Time Frame
Day 1, Week 12, 24, and subsequent 24 week during dosing
Title
Proportion of subjects positive for HBeAg at baseline who achieve HBV DNA levels by PCR assay less than LOQ, normal serum ALT, and seroconversion
Time Frame
Week 8, 16, 24 post dosing
Title
Proportion of subjects negative for HBeAg at baseline who achieve HBV DNA levels by PCR assay less than LOQ and normal ALT and remain negative for HBeAg
Time Frame
Day 1, Week 12, Week 24 and every subsequent 24 weeks during dosing
Title
Proportion of subjects who achieved Complete Response during therapy, who have sustained Complete Response for 24 weeks after stopping drug
Time Frame
24 Week post dosing
Title
Proportion of subjects with histological improvement in the liver at Wks 48 & 96 [improvement in necroinflammatory score and no worsening of fibrosis at Wks 48 & 96 liver biopsy compared to baseline & to baseline in previous study]
Time Frame
Week 48, 96
Title
NChanges in liver histology as assessed by the New Inuyama Classification for histological assessment of chronic hepatitis
Time Frame
Week 48 & Week 96
Title
Incidence of genotypic changes in HBV DNA polymerase conferring resistance to entecavir in subjects with confirmed ≥1 log10 increase in HBV DNA from nadir on treatment
Time Frame
Week 2, 4, ± days, Week 8 every 4 weeks ± 7 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
20 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Subjects who completed a previous entecavir Phase II studies (AI463047, 052 or 053); ALT ≤ 10 x upper limit of normal; Subjects must have well-compensated liver disease according to ALL of the following criteria; Prothrombin time ≤ 3 seconds prolonged compared to control value or INR ≤ 1.5 Serum albumin ≥ 3 g/dL (≥ 30 g/L) Serum bilirubin ≤ 2.5 mg/dL (≤ 42.75 μmol/L) Exclusion Criteria: Sex and Reproductive Status Exceptions Target Disease Exceptions Medical History and Concurrent Diseases
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
457-0866
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
Onsen-Gun
State/Province
Ehime
ZIP/Postal Code
791-0204
Country
Japan
Facility Name
Local Institution
City
Fukuoka-Shi
State/Province
Fukuoka
ZIP/Postal Code
814-0180
Country
Japan
Facility Name
Local Institution
City
Kurume
State/Province
Fukuoka
Country
Japan
Facility Name
Local Institution
City
Gifu-Shi
State/Province
Gifu
ZIP/Postal Code
500-8513
Country
Japan
Facility Name
Local Institution
City
Ogaki-Shi
State/Province
Gifu
ZIP/Postal Code
503-8502
Country
Japan
Facility Name
Local Institution
City
Fukuyama-Shi
State/Province
Hiroshima
ZIP/Postal Code
721-0971
Country
Japan
Facility Name
Local Institution
City
Hiroshima City
State/Province
Hiroshima
ZIP/Postal Code
734-0037
Country
Japan
Facility Name
Local Institution
City
Hiroshima-Shi
State/Province
Hiroshima
ZIP/Postal Code
730-8518
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
006-0813
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
Mitoyo-Gun
State/Province
Kagawa
ZIP/Postal Code
769-1601
Country
Japan
Facility Name
Local Institution
City
Takamatsu-City
State/Province
Kagawa
Country
Japan
Facility Name
Local Institution
City
Kumamoto-Shi
State/Province
Kumamoto
ZIP/Postal Code
860-8556
Country
Japan
Facility Name
Local Institution
City
Sendai
State/Province
Miyagi
Country
Japan
Facility Name
Local Institution
City
Miyazaki-Gun
State/Province
Miyazaki
ZIP/Postal Code
889-1692
Country
Japan
Facility Name
Local Institution
City
Matsumoto City
State/Province
Nagano
ZIP/Postal Code
390-0802
Country
Japan
Facility Name
Local Institution
City
Nagasaki City
State/Province
Nagasaki
Country
Japan
Facility Name
Local Institution
City
Omura-Shi
State/Province
Nagasaki
ZIP/Postal Code
856-0000
Country
Japan
Facility Name
Local Institution
City
Oita-Gun
State/Province
Oita
ZIP/Postal Code
879-5503
Country
Japan
Facility Name
Local Institution
City
Kurashiki-Shi
State/Province
Okayama
ZIP/Postal Code
710-8602
Country
Japan
Facility Name
Local Institution
City
Okayama-Shi
State/Province
Okayama
ZIP/Postal Code
700-0082
Country
Japan
Facility Name
Local Institution
City
Okayama-Shi
State/Province
Okayama
ZIP/Postal Code
700-8505
Country
Japan
Facility Name
Local Institution
City
Okayama-Shi
State/Province
Okayama
ZIP/Postal Code
700-8511
Country
Japan
Facility Name
Local Institution
City
Tsuyama-Shi
State/Province
Okayama
ZIP/Postal Code
708-0841
Country
Japan
Facility Name
Local Institution
City
Kawachinagano-Shi
State/Province
Osaka
ZIP/Postal Code
86-0008
Country
Japan
Facility Name
Local Institution
City
Osaka-Shi
State/Province
Osaka
ZIP/Postal Code
553-0003
Country
Japan
Facility Name
Local Institution
City
Sakai-Shi
State/Province
Osaka
ZIP/Postal Code
591-8025
Country
Japan
Facility Name
Local Institution
City
Suita-Shi
State/Province
Osaka
Country
Japan
Facility Name
Local Institution
City
Iruma-Gun
State/Province
Saitama
ZIP/Postal Code
350-0495
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
160-8582
Country
Japan
Facility Name
Local Institution
City
Shinjuku-Ku
State/Province
Tokyo
ZIP/Postal Code
162-8655
Country
Japan
Facility Name
Local Institution
City
Shinjuku-Ku
State/Province
Tokyo
ZIP/Postal Code
162-8666
Country
Japan
Facility Name
Local Institution
City
Ube-Shi
State/Province
Yamaguchi
ZIP/Postal Code
755-0067
Country
Japan
Facility Name
Local Institution
City
Nakakoma-Gun
State/Province
Yamanashi
ZIP/Postal Code
409-3821
Country
Japan
Facility Name
Local Institution
City
Kyoto
Country
Japan
Facility Name
Local Institution
City
Niigata
Country
Japan
Facility Name
Local Institution
City
Osaka
Country
Japan
Facility Name
Local Institution
City
Tokyo
ZIP/Postal Code
173-8610
Country
Japan

12. IPD Sharing Statement

Citations:
PubMed Identifier
20409606
Citation
Yokosuka O, Takaguchi K, Fujioka S, Shindo M, Chayama K, Kobashi H, Hayashi N, Sato C, Kiyosawa K, Tanikawa K, Ishikawa H, Masaki N, Seriu T, Omata M. Long-term use of entecavir in nucleoside-naive Japanese patients with chronic hepatitis B infection. J Hepatol. 2010 Jun;52(6):791-9. doi: 10.1016/j.jhep.2009.12.036. Epub 2010 Mar 24.
Results Reference
background
PubMed Identifier
20305760
Citation
Karino Y, Toyota J, Kumada H, Katano Y, Izumi N, Kobashi H, Sata M, Moriyama M, Imazeki F, Kage M, Ishikawa H, Masaki N, Seriu T, Omata M. Efficacy and resistance of entecavir following 3 years of treatment of Japanese patients with lamivudine-refractory chronic hepatitis B. Hepatol Int. 2010 Feb 6;4(1):414-22. doi: 10.1007/s12072-009-9162-x. Erratum In: Hepatol Int. 2010;4(4):789-90.
Results Reference
background

Learn more about this trial

An Open-Label Rollover Study of Entecavir (BMS-200475) in Adults With Chronic Hepatitis B Infection

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