Clinical trial NCT01037062: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Chronic Hepatitis B
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
First posted: 2009-12-21
Enrollment: 282
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Intervention model: PARALLEL
Primary purpose: TREATMENT

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


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;

  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

Primary outcomes:
measure: 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
timeFrame: 24 weeks
Secondary outcomes:
measure: Incidence of clinical adverse events and discontinuations due to adverse events of entecavir for each cohort
timeFrame: Week 2, 4, 6, 8, 10, 12, 16, 20 and 24 post dosing
measure: Incidence of laboratory abnormalities of of entecavir for each cohort
timeFrame: Week 2, 4, 6, 8, 10, 12, 16, 20 and 24 post dosing
measure: Proportion of subjects HBeAg-positive at baseline who have loss of HBeAg from serum
timeFrame: Day 1, Week 12, Week 24 and every subsequent 24 week during dosing
measure: Proportion of subjects HBeAg-positive at baseline who achieve seroconversion (loss of HBeAg and appearance of HBeAb)
timeFrame: Day 1, Week 12, Week 24 and every subsequent 24 week during dosing
measure: Proportion of subjects with abnormal ALT at baseline who achieve normalization of serum ALT at Week 48
timeFrame: Day 1, Week 48
measure: Proportion of subjects who achieve HBV DNA levels by PCR assay less than the limit of quantification (LOQ)
timeFrame: Day 1, Week 12, 24, and subsequent 24 week during dosing
measure: Proportion of subjects positive for HBeAg at baseline who achieve HBV DNA levels by PCR assay less than LOQ, normal serum ALT, and seroconversion
timeFrame: Week 8, 16, 24 post dosing
measure: 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
timeFrame: Day 1, Week 12, Week 24 and every subsequent 24 weeks during dosing
measure: Proportion of subjects who achieved Complete Response during therapy, who have sustained Complete Response for 24 weeks after stopping drug
timeFrame: 24 Week post dosing
measure: 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]
timeFrame: Week 48, 96
measure: NChanges in liver histology as assessed by the New Inuyama Classification for histological assessment of chronic hepatitis
timeFrame: Week 48 & Week 96
measure: 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
timeFrame: Week 2, 4, ± days, Week 8 every 4 weeks ± 7 days
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-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: Onsen-Gun
country: Japan
facility: Local Institution
state: Ehime
city: Fukuoka-Shi
country: Japan
facility: Local Institution
state: Fukuoka
city: Kurume
country: Japan
facility: Local Institution
state: Fukuoka
city: Gifu-Shi
country: Japan
facility: Local Institution
state: Gifu
city: Ogaki-Shi
country: Japan
facility: Local Institution
state: Gifu
city: Fukuyama-Shi
country: Japan
facility: Local Institution
state: Hiroshima
city: Hiroshima City
country: Japan
facility: Local Institution
state: Hiroshima
city: Hiroshima-Shi
country: Japan
facility: Local Institution
state: Hiroshima
city: Asahikawa-Shi
country: Japan
facility: Local Institution
state: Hokkaido
city: Sapporo-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: Mitoyo-Gun
country: Japan
facility: Local Institution
state: Kagawa
city: Takamatsu-City
country: Japan
facility: Local Institution
state: Kagawa
city: Kumamoto-Shi
country: Japan
facility: Local Institution
state: Kumamoto
city: Sendai
country: Japan
facility: Local Institution
state: Miyagi
city: Miyazaki-Gun
country: Japan
facility: Local Institution
state: Miyazaki
city: Matsumoto City
country: Japan
facility: Local Institution
state: Nagano
city: Nagasaki City
country: Japan
facility: Local Institution
state: Nagasaki
city: Omura-Shi
country: Japan
facility: Local Institution
state: Nagasaki
city: Oita-Gun
country: Japan
facility: Local Institution
state: Oita
city: Kurashiki-Shi
country: Japan
facility: Local Institution
state: Okayama
city: Okayama-Shi
country: Japan
facility: Local Institution
state: Okayama
city: Okayama-Shi
country: Japan
facility: Local Institution
state: Okayama
city: Okayama-Shi
country: Japan
facility: Local Institution
state: Okayama
city: Tsuyama-Shi
country: Japan
facility: Local Institution
state: Okayama
city: Kawachinagano-Shi
country: Japan
facility: Local Institution
state: Osaka
city: Osaka-Shi
country: Japan
facility: Local Institution
state: Osaka
city: Sakai-Shi
country: Japan
facility: Local Institution
state: Osaka
city: Suita-Shi
country: Japan
facility: Local Institution
state: Osaka
city: Iruma-Gun
country: Japan
facility: Local Institution
state: Saitama
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: Shinjuku-Ku
country: Japan
facility: Local Institution
state: Tokyo
city: Shinjuku-Ku
country: Japan
facility: Local Institution
state: Tokyo
city: Ube-Shi
country: Japan
facility: Local Institution
state: Yamaguchi
city: Nakakoma-Gun
country: Japan
facility: Local Institution
state: Yamanashi
city: Kyoto
country: Japan
facility: Local Institution
city: Niigata
country: Japan
facility: Local Institution
city: Osaka
country: Japan
facility: Local Institution
city: Tokyo
country: Japan
facility: Local Institution
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References:
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.
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.