Chronic Hepatitis B
Conditions
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
Interventions
DRUGEntecavir
Tablet, P.O. 0.5, 1 mg, once daily
Sponsors
Bristol-Myers Squibb
Study design
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| 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
| Measure | Time frame |
|---|---|
| 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 |
| 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 |
| 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 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 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 |
| 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 |
Countries
Japan
Outcome results
None listed