Antiviral Efficacy of Switching to ETV Plus TDF

• Status: Unknown status
• Trial end date: 2014-05-01
• Target enrollment: 0
• Participant gender: All

Summary

Switching to Entecavir(ETV) plus Tenofovir Disoproxil Fumarate(TDF) combination will result in faster and greater antiviral activity and lower rates of resistance emergence over maintaining Lamivudine(LAM)/Telbivudine(LdT)+Adefovir(ADV) combination in partial responders to LAM/LdT+ADV rescue therapy.

Earlier switching to combination with the most potent regimen will be more effective to achieve virologic response(VR) and prevent further resistance emergence.

All subjects will orally take assigned drugs once daily for 48 weeks. All subjects will be assessed at baseline and every three months thereafter. Evaluations at each visit will include vital signs, physical examinations, laboratory tests, HBV DNA levels and adverse events. 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; Chonbuk National University Hospital; Hallym University Medical Center; Kyungpook National University; Kyungpook National University Hospital; Pusan National University Hospital; Seoul St. Mary's Hospital; Soonchunhyang University Hospital; The Catholic University of Korea
• Treatments: Adefovir; Adefovir dipivoxil; Antiviral Agents; Entecavir; Lamivudine; Telbivudine; Tenofovir

Criteria

Inclusion Criteria:

1. ≥ 20 years of age

2. History of HBsAg positive for more than 6 months

3. History of genotypic resistance to LAM or LdT (YMDDm)

4. Partial responder (HBV DNA ≥ 60 IU/mL) currently receiving antiviral combination rescue therapy for at least 24 weeks of treatment with LAM+ADV or LdT+ADV

5. Hepatitis B e Antigen(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. History of genotypic resistance to ADV

2. Most previous treatment of other than LAM+ADV and LdT+ADV

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

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

5. Pregnant or lactating woman

6. 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

7. History of liver transplantation or planned for liver transplantation

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

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

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

11. Subject 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.)

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

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

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