Effects of Telbivudine and Tenofovir Disproxil Fumarate on the Kinetics of Hepatitis B Virus DNA in Chronic Hepatitis B (CHB)

• Status: Completed
• Trial end date: 2010-03-01
• Target enrollment: 0
• Participant gender: All

Summary

The purpose of this study is to compare the safety, tolerability and effectiveness of 12 weeks of treatment with telbivudine 600 mg daily plus tenofovir DF 300 mg once daily (QD) taken together versus tenofovir DF 300 mg once daily (QD) or versus telbivudine 600 mg monotherapy daily (QD). This is an open-labeled, active controlled, viral kinetics study which means the subjects and study doctor will know what study drug subjects have been assigned. This study is open to male and female subjects, <40 years of age, who have been infected with HBV for at least 6 months and have not received oral treatment for HBV.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: The University of Hong Kong
• Collaborator: Novartis Pharmaceuticals
• Treatments: Telbivudine; Tenofovir

Criteria

Inclusion Criteria:

Patients must meet all of the following inclusion criteria at screening to be eligible for participation in this study.

1. Chronic HBV infection, defined as positive serum HBsAg for at least 6 months, or HBsAg positive > 3 months and negative for IgM anti-HBc and positive for IgG anti-HBc

2. Age < 40 years old

3. HBeAg positive

4. HBV DNA ≥ 10^7 copies/mL by Abbott real-time PCR

5. ALT ≤ 1 ULN

6. Willing and able to provide written informed consent

7. Negative serum β-HCG (for females of childbearing potential only)

8. Calculated creatinine clearance ≥ 70 mL/min by the following formula: (140 - age in years) x (body weight [kg]) / (72) x (serum creatinine [mg/dl]) [Note: multiply estimated rate by 0.85 for women]

9. Hemoglobin ≥ 10 g/dL

10. Neutrophils ≥ 1,500 /mm^3

11. No prior oral HBV therapy (e.g., nucleotide and/or nucleoside therapy or other investigational agents for HBV infection)

12. Is willing and able to comply with the study drug regimen and all other study procedures and requirements

13. Is willing and able to provide written informed consent before any study assessment is perform.

Exclusion Criteria:

Patients will be excluded from the study for any of the criteria:

1. Decompensated liver disease defined as direct (conjugated) bilirubin > 1.2 × ULN, PT > 1.2 × ULN, platelets < 150,000/mm3, serum albumin < 3.5 g/dL, or prior history of clinical hepatic decompensation (e.g. ascites, jaundice, encephalopathy, variceal hemorrhage).

2. Received interferon (pegylated or not) therapy within 6 months of the screening visit

3. α-fetoprotein > 50 ng/mL

4. Evidence of hepatocellular carcinoma (HCC)

5. Co-infection with HCV (by serology), HIV, or HDV.

6. Significant renal, cardiovascular, pulmonary, or neurological disease.

7. Received solid organ or bone marrow transplantation.

8. Is currently receiving therapy with immunomodulators (e.g., corticosteroids, etc.), investigational agents, nephrotoxic agents, or agents susceptible of modifying renal excretion.

9. Has proximal tubulopathy.

10. Use of other investigational drugs at the time of enrollment, or within 30 days

11. History of hypersensitivity to any of the study drugs or to drugs of similar chemical classes

12. Is pregnant or breastfeeding. Women of childbearing potential must have a negative serum β - HCG during Screening.

13. Is a women of child-bearing potential (WOCBP), defined as all women physiologically capable of becoming pregnant, including women whose career, lifestyle, or sexual orientation precludes intercourse with a male partner and women whose partners have been sterilized by vasectomy or other means, UNLESS they meet the following definition of post-menopausal: 12 months of natural (spontaneous) amenorrhea or 6 months of spontaneous amenorrhea with serum FSH levels >40 mIU/m or 6 weeks post surgical bilateral oophorectomy with or without hysterectomy OR are using one or more of the following acceptable methods of contraception: surgical sterilization (e.g., bilateral tubal ligation, vasectomy), hormonal contraception (implantable, patch, oral), and double-barrier methods (any double combination of: IUD, male or female condom with spermicidal gel, diaphragm, sponge, cervical cap).

14. Patient has any other concurrent medical or social condition likely to preclude compliance with the schedule of evaluations in the protocol, or likely to confound the efficacy or safety observations of the study.

15. Patient is currently abusing alcohol or illicit drugs, or has a history of alcohol abuse or illicit substance abuse within the preceding two years. Please refer to Appendix 3.

16. Patient has a medical condition that requires prolonged or frequent use of systemic acyclovir or famciclovir. Please refer to Appendix 1.