Entecavir Plus Tenofovir Combination in Subjects With Multi-drug Resistant Chronic Hepatitis B Virus Infection

• Status: Unknown status
• Trial end date: 2014-04-01
• Target enrollment: 0
• Participant gender: All

Summary

Entecavir(ETV) plus Tenofovir Disoproxil Fumarate(TDF) combination will show effective antiviral activity and prevent further development of antiviral resistance in hepatitis B e antigen(HBeAg)-positive or -negative Chronic Hepatitis B(CHB) patients who experienced multidrug resistance

All subjects will orally take investigational drugs once daily for 48 weeks. All subjects will be assessed at baseline, Week 4, 12, 24, 36 and 48. Evaluations at each visit will include vital signs, physical examinations, laboratory tests and HBV DNA levels. They were also questioned about adverse events and concomitant medications. At baseline and every six months thereafter, serum will be assayed for HBV serology. Genotypic analysis will be performed at baseline and 48 weeks.

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

Details

• Lead Sponsor: Yonsei University
• Collaborators: Bristol-Myers Squibb; Seoul St. Mary's Hospital; The Catholic University of Korea
• Treatments: Entecavir; Tenofovir

Criteria

Inclusion Criteria:

1. ≥ 20 years of age

2. History of HBsAg positive for more than 6 months

3. Subject who has a history of genotypic resistance to NAs from two different classes A

4. Detectable HBV DNA (≥ 60 IU/mL) while on any rescue treatment regimen for at least 24 weeks

5. HBeAg-positive and -negative

6. Compensated liver disease (Child-Pugh A)

7. Signed written informed consent after being instructed about the objective and procedure of the clinical study

Exclusion Criteria:

1. Subjects with Alanine Aminotransferase(ALT) > 10xUpper Limit of normal(ULN)

2. Co-infected with hepatitis C virus(HCV) or HIV

3. Pregnant or lactating woman

4. Subject who needs long-term administration of drugs including immunosuppressive agents, agents related to high risk in the hepatic/renal toxicity, agents influencing renal excretion

5. History of liver transplantation or planned for liver transplantation

6. Subject who was diagnosed malignant tumor and has been receiving chemotherapy

7. Subject who has hepatocellular carcinoma(HCC) history or who shows potential HCC finding such as suspicious region in the radiologic exam(abdominal US or CT) or serum Alpha Feto Protein(AFP) elevation

8. Renal Insufficiency (CLcr < 50ml/min based on Cockcroft-Gault equation considering weight, ages and serum creatinine)

9. Patient who has a liver disease other than chronic hepatitis B (e.g. hemochromatosis, Wilson's disease, alcoholic liver disease, nonalcoholic fatty liver disease, alpha 1-antitrypsin deficiency etc.)

10. Subject who has a history of hypersensitivity to study drug or its ingredients

11. Subject who is involved in other clinical trial within 60 days prior to study entry

12. Subject who the investigator deems inappropriate to participate in this study