Entecavir for Chronic Hepatitis B Patients With Persistently Normal ALT

• Status: Unknown status
• Trial end date: 2015-05-01
• Target enrollment: 0
• Participant gender: All

Summary

Entecavir (ETV) has shown superior ability to suppress hepatitis B virus (HBV) replication, histology improvement as well as low rate of emergence of resistant mutants. Out of range of clinical recommendations for treatment of chronic hepatitis B (CHB), chronic HBV carriers with persistently normal ALT and viral load more than 10^5 copies/mL have progression of liver disease during long-term follow-up. In addition, certain proportions of these patients do have significant inflammation and fibrosis in liver histology. This study will be able to identify who are at risk of liver disease progression and evaluate efficacy of ETV regarding improvement of liver histology during short-term (1-year) and long-term ETV treatment (3-year).

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: National Cheng-Kung University Hospital
• Treatments: Entecavir

Criteria

Inclusion Criteria:

1. Male and female subjects aged between 18 and 65 year-old with history of chronic hepatitis B virus infection;

2. Detectable HBsAg at screening and for at least 24 weeks prior to screening or detectable HBsAg for < 24 week and negative for IgM core antibody and confirmation of chronic hepatitis on liver biopsy;

3. ALT should be within normal range in recent one year and at least twice, which are at least 3 month apart;

4. Normal ALT at screening;

5. Screening HBV DNA of more than 10^5 copies/mL by Roche AmplicorTM PCR assay performed by the central laboratory;

6. Evidence of chronic hepatitis on liver biopsy (Knodell HAI Score >= 4) performed ≤ 52 weeks prior to randomization;

7. All women of childbearing potential must have a negative serum or urine pregnancy test.

Exclusion Criteria:

1. Coinfection with human immunodeficiency virus (HIV), hepatitis C virus (HCV), or hepatitis D virus (HDV);

2. Other forms of liver disease e.g., alcoholic, autoimmune, biliary disease;

3. Patients with evidence of decompensation of liver disease;

4. Therapy with interferon, thymosin alpha or antiviral agents with activity against hepatitis B (e.g., adefovir, famciclovir, lamivudine, and telbivudine) within 24 weeks of randomization into this study;

5. More than 12 weeks of prior therapy with nucleoside or nucleotide analogue antiviral agents with activity against hepatitis B (e.g., adefovir, famciclovir lamivudine, and telbivudine);

6. Prior therapy with entecavir;

7. Known history of allergy to nucleoside analogues;

8. Hemoglobin < 10.0 g/dL;

9. Platelet count < 75,000/mm3;

10. Absolute neutrophil count< 1500 cells/mm3;

11. Creatinine > 1.5mg/dL (133 μmol/L);

12. Anti-nuclear antibody (ANA) titer > l :160 unless attributable to non-hepatic disease.