Overview

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