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

Chronic Hepatitis B Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01037062
• Other study ID #: AI463-060
• Status: Completed
• Phase: Phase 2
• First received: December 17, 2009
• Last updated: January 24, 2011
• Start date: December 2003
• Est. completion date: December 2006

Study information

• Verified date: December 2009
• Source: Bristol-Myers Squibb
• Contact: n/a
• Is FDA regulated: No
• Health authority: Japan: Pharmaceuticals and Medical Devices Agency
• Study type: Interventional

Clinical Trial 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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 282
• Est. completion date: December 2006
• Est. primary completion date: December 2006
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 20 Years and older

Eligibility

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 Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Chronic Hepatitis B
• Hepatitis
• Hepatitis A
• Hepatitis B
• Hepatitis B, Chronic
• Hepatitis, Chronic

Intervention

Drug:
• Entecavir
Tablet, P.O. 0.5, 1 mg, once daily

Locations

Country	Name	City	State
Japan	Local Institution	Aichi-Gun	Aichi
Japan	Local Institution	Akashi-Shi	Hyogo
Japan	Local Institution	Asahikawa-Shi	Hokkaido
Japan	Local Institution	Chiba-Shi	Chiba
Japan	Local Institution	Fukuoka-Shi	Fukuoka
Japan	Local Institution	Fukuyama-Shi	Hiroshima
Japan	Local Institution	Gifu-Shi	Gifu
Japan	Local Institution	Hiroshima City	Hiroshima
Japan	Local Institution	Hiroshima-Shi	Hiroshima
Japan	Local Institution	Iruma-Gun	Saitama
Japan	Local Institution	Kawachinagano-Shi	Osaka
Japan	Local Institution	Kumamoto-Shi	Kumamoto
Japan	Local Institution	Kurashiki-Shi	Okayama
Japan	Local Institution	Kurume	Fukuoka
Japan	Local Institution	Kyoto
Japan	Local Institution	Matsumoto City	Nagano
Japan	Local Institution	Minato-Ku	Tokyo
Japan	Local Institution	Mitoyo-Gun	Kagawa
Japan	Local Institution	Miyazaki-Gun	Miyazaki
Japan	Local Institution	Morioka-Shi	Iwate
Japan	Local Institution	Musashino-Shi	Tokyo
Japan	Local Institution	Nagasaki City	Nagasaki
Japan	Local Institution	Nagoya	Aichi
Japan	Local Institution	Nagoya-Shi	Aichi
Japan	Local Institution	Nagoya-Shi	Aichi
Japan	Local Institution	Nakakoma-Gun	Yamanashi
Japan	Local Institution	Niigata
Japan	Local Institution	Ogaki-Shi	Gifu
Japan	Local Institution	Oita-Gun	Oita
Japan	Local Institution	Okayama-Shi	Okayama
Japan	Local Institution	Okayama-Shi	Okayama
Japan	Local Institution	Okayama-Shi	Okayama
Japan	Local Institution	Omura-Shi	Nagasaki
Japan	Local Institution	Onsen-Gun	Ehime
Japan	Local Institution	Osaka
Japan	Local Institution	Osaka-Shi	Osaka
Japan	Local Institution	Sakai-Shi	Osaka
Japan	Local Institution	Sapporo-Shi	Hokkaido
Japan	Local Institution	Sapporo-Shi	Hokkaido
Japan	Local Institution	Sendai	Miyagi
Japan	Local Institution	Shinjuku-Ku	Tokyo
Japan	Local Institution	Shinjuku-Ku	Tokyo
Japan	Local Institution	Shinjuku-Ku	Tokyo
Japan	Local Institution	Suita-Shi	Osaka
Japan	Local Institution	Takamatsu-City	Kagawa
Japan	Local Institution	Tokyo
Japan	Local Institution	Tsuyama-Shi	Okayama
Japan	Local Institution	Ube-Shi	Yamaguchi

Sponsors (1)

Lead Sponsor	Collaborator
Bristol-Myers Squibb

Country where clinical trial is conducted

Japan, 

References & Publications (2)

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. — View 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-naïve 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	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	Yes
Secondary	Incidence of laboratory abnormalities of of entecavir for each cohort		Week 2, 4, 6, 8, 10, 12, 16, 20 and 24 post dosing	Yes
Secondary	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	No
Secondary	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	No
Secondary	Proportion of subjects with abnormal ALT at baseline who achieve normalization of serum ALT at Week 48		Day 1, Week 48	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	Proportion of subjects who achieved Complete Response during therapy, who have sustained Complete Response for 24 weeks after stopping drug		24 Week post dosing	No
Secondary	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	No
Secondary	NChanges in liver histology as assessed by the New Inuyama Classification for histological assessment of chronic hepatitis		Week 48 & Week 96	No
Secondary	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	No

External Links

•   BMS Clinical Trials Disclosure
•   For FDA Safety Alerts and Recalls refer to the following link: http://www.fda.gov/MEDWATCH/safety.htm
•   Investigator Inquiry form