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

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

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

Study Overview

• Status: Completed
• Conditions: Chronic Hepatitis B
• Intervention / Treatment: Drug: Entecavir

• Study Type: Interventional
• Enrollment (Actual): 282
• Phase: Phase 2

Contacts and Locations

Study Locations

• Japan
  • Kyoto, Japan
    • Local Institution
  • Niigata, Japan
    • Local Institution
  • Osaka, Japan
    • Local Institution
  • Tokyo, Japan, 173-8610
    • Local Institution
  • Aichi
    • Aichi-Gun, Aichi, Japan, 480-1195
      • Local Institution
    • Nagoya, Aichi, Japan, 466-8550
      • Local Institution
    • Nagoya-Shi, Aichi, Japan, 467-8602
      • Local Institution
    • Nagoya-Shi, Aichi, Japan, 457-0866
      • Local Institution
  • Chiba
    • Chiba-Shi, Chiba, Japan
      • Local Institution
  • Ehime
    • Onsen-Gun, Ehime, Japan, 791-0204
      • Local Institution
  • Fukuoka
    • Fukuoka-Shi, Fukuoka, Japan, 814-0180
      • Local Institution
    • Kurume, Fukuoka, Japan
      • Local Institution
  • Gifu
    • Gifu-Shi, Gifu, Japan, 500-8513
      • Local Institution
    • Ogaki-Shi, Gifu, Japan, 503-8502
      • Local Institution
  • Hiroshima
    • Fukuyama-Shi, Hiroshima, Japan, 721-0971
      • Local Institution
    • Hiroshima City, Hiroshima, Japan, 734-0037
      • Local Institution
    • Hiroshima-Shi, Hiroshima, Japan, 730-8518
      • Local Institution
  • Hokkaido
    • Asahikawa-Shi, Hokkaido, Japan, 070-0054
      • Local Institution
    • Sapporo-Shi, Hokkaido, Japan, 060-0033
      • Local Institution
    • Sapporo-Shi, Hokkaido, Japan, 006-0813
      • Local Institution
  • Hyogo
    • Akashi-Shi, Hyogo, Japan, 673-0848
      • Local Institution
  • Iwate
    • Morioka-Shi, Iwate, Japan, 020-8505
      • Local Institution
  • Kagawa
    • Mitoyo-Gun, Kagawa, Japan, 769-1601
      • Local Institution
    • Takamatsu-City, Kagawa, Japan
      • Local Institution
  • Kumamoto
    • Kumamoto-Shi, Kumamoto, Japan, 860-8556
      • Local Institution
  • Miyagi
    • Sendai, Miyagi, Japan
      • Local Institution
  • Miyazaki
    • Miyazaki-Gun, Miyazaki, Japan, 889-1692
      • Local Institution
  • Nagano
    • Matsumoto City, Nagano, Japan, 390-0802
      • Local Institution
  • Nagasaki
    • Nagasaki City, Nagasaki, Japan
      • Local Institution
    • Omura-Shi, Nagasaki, Japan, 856-0000
      • Local Institution
  • Oita
    • Oita-Gun, Oita, Japan, 879-5503
      • Local Institution
  • Okayama
    • Kurashiki-Shi, Okayama, Japan, 710-8602
      • Local Institution
    • Okayama-Shi, Okayama, Japan, 700-0082
      • Local Institution
    • Okayama-Shi, Okayama, Japan, 700-8505
      • Local Institution
    • Okayama-Shi, Okayama, Japan, 700-8511
      • Local Institution
    • Tsuyama-Shi, Okayama, Japan, 708-0841
      • Local Institution
  • Osaka
    • Kawachinagano-Shi, Osaka, Japan, 86-0008
      • Local Institution
    • Osaka-Shi, Osaka, Japan, 553-0003
      • Local Institution
    • Sakai-Shi, Osaka, Japan, 591-8025
      • Local Institution
    • Suita-Shi, Osaka, Japan
      • Local Institution
  • Saitama
    • Iruma-Gun, Saitama, Japan, 350-0495
      • Local Institution
  • Tokyo
    • Minato-Ku, Tokyo, Japan, 105-0001
      • Local Institution
    • Musashino-Shi, Tokyo, Japan, 180-0023
      • Local Institution
    • Shinjuku-Ku, Tokyo, Japan, 160-8582
      • Local Institution
    • Shinjuku-Ku, Tokyo, Japan, 162-8666
      • Local Institution
    • Shinjuku-Ku, Tokyo, Japan, 162-8655
      • Local Institution
  • Yamaguchi
    • Ube-Shi, Yamaguchi, Japan, 755-0067
      • Local Institution
  • Yamanashi
    • Nakakoma-Gun, Yamanashi, Japan, 409-3821
      • Local Institution

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Entecavir	Drug: Entecavir; Tablet, P.O. 0.5, 1 mg, once daily; Other Names: Baraclude; BMS-200475

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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	24 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Incidence of clinical adverse events and discontinuations due to adverse events of entecavir for each cohort	Week 2, 4, 6, 8, 10, 12, 16, 20 and 24 post dosing
Incidence of laboratory abnormalities of of entecavir for each cohort	Week 2, 4, 6, 8, 10, 12, 16, 20 and 24 post dosing
Proportion of subjects HBeAg-positive at baseline who have loss of HBeAg from serum	Day 1, Week 12, Week 24 and every subsequent 24 week during dosing
Proportion of subjects HBeAg-positive at baseline who achieve seroconversion (loss of HBeAg and appearance of HBeAb)	Day 1, Week 12, Week 24 and every subsequent 24 week during dosing
Proportion of subjects with abnormal ALT at baseline who achieve normalization of serum ALT at Week 48	Day 1, Week 48
Proportion of subjects who achieve HBV DNA levels by PCR assay less than the limit of quantification (LOQ)	Day 1, Week 12, 24, and subsequent 24 week during dosing
Proportion of subjects positive for HBeAg at baseline who achieve HBV DNA levels by PCR assay less than LOQ, normal serum ALT, and seroconversion	Week 8, 16, 24 post dosing
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	Day 1, Week 12, Week 24 and every subsequent 24 weeks during dosing
Proportion of subjects who achieved Complete Response during therapy, who have sustained Complete Response for 24 weeks after stopping drug	24 Week post dosing
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]	Week 48, 96
NChanges in liver histology as assessed by the New Inuyama Classification for histological assessment of chronic hepatitis	Week 48 & Week 96
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	Week 2, 4, ± days, Week 8 every 4 weeks ± 7 days

Collaborators and Investigators

• Sponsor: Bristol-Myers Squibb

Publications and helpful links

General Publications

• 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.
• 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.

Study record dates

Study Major Dates

• Study Start: December 1, 2003
• Primary Completion (Actual): December 1, 2006
• Study Completion (Actual): December 1, 2006

Study Registration Dates

• First Submitted: December 17, 2009
• First Submitted That Met QC Criteria: December 17, 2009
• First Posted (Estimate): December 21, 2009

Study Record Updates

• Last Update Posted (Estimate): January 31, 2011
• Last Update Submitted That Met QC Criteria: January 24, 2011
• Last Verified: December 1, 2009

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Hepatitis, Viral, Human; Hepadnaviridae Infections; DNA Virus Infections; Enterovirus Infections; Picornaviridae Infections; Hepatitis B; Hepatitis; Hepatitis A; Hepatitis B, Chronic; Hepatitis, Chronic; Anti-Infective Agents; Antiviral Agents; Entecavir
• Other Study ID Numbers: AI463-060