A Study to Compare Tenofovir Disoproxil Fumarate Versus Adefovir Dipivoxil for the Treatment of HBeAg-Positive Chronic Hepatitis B

• Status: Completed
• Trial end date: 2016-01-01
• Target enrollment: 0
• Participant gender: All

Summary

The primary objectives of this study are to compare the efficacy, safety, and tolerability of tenofovir disoproxil fumarate (TDF) versus adefovir dipivoxil (ADV) for the treatment of HBeAg-positive chronic hepatitis B. Participants will receive TDF or ADV for 48 weeks (double-blind). After 48 weeks, eligible participants switched to open-label TDF for up to 480 weeks.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Gilead Sciences
• Treatments: Adefovir; Adefovir dipivoxil; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Tenofovir

Criteria

Key Inclusion Criteria:

A patient must meet all of the following inclusion criteria to be eligible for participation in this study:

• Chronic hepatitis B virus (HBV) infection, defined as positive serum hepatitis B s-antigen (HBsAg) for more than 6 months

• 18 through 69 years of age, inclusive

• Active hepatitis B e-antigen (HBeAg) positive chronic HBV infection, with all of the following:

• HBeAg positive at screening

• Alanine aminotransferase (ALT) levels > 2 × ULN and ≤ 10 × the upper limit of the normal range (ULN)

• Serum HBV DNA > 1 million copies/mL at screening

• creatinine clearance ≥ 70 mL/min

• hemoglobin ≥ 8 g/dL

• neutrophils ≥ 1,000 /mL

• Knodell necroinflammatory score ≥ 3 and a Knodell fibrosis score < 4; however, up to 96 patients with cirrhosis, ie, a Knodell fibrosis score equal to 4, will be eligible for enrollment

• Negative serum β-human chorionic gonadotropin (hCG)

• Nucleotide naïve, ie, no prior nucleotide (TDF or ADV) therapy for > 12 weeks

• Nucleoside naïve, ie, no prior nucleoside (any nucleoside) therapy for > 12 weeks

• Willing and able to provide written informed consent

• Liver biopsy performed within 6 months of baseline and has readable biopsy slides or agrees to have a biopsy performed prior to baseline

Key Exclusion Criteria:

A patient who meets any of the following exclusion criteria is not to be enrolled in this study:

• Pregnant women, women who are breast feeding or who believe they may wish to become pregnant during the course of the study

• Males and females of reproductive potential who are unwilling to use an effective method of contraception during the study; for males, condoms should be used and for females, a barrier contraception method should be used

• Decompensated liver disease defined as conjugated bilirubin > 1.5 x ULN, prothrombin time (PT) > 1.5 x ULN, platelets < 75,000/mL, serum albumin < 3.0 g/dL, or prior history of clinical hepatic decompensation (eg, ascites, jaundice, encephalopathy, variceal hemorrhage)

• Received any nucleoside, nucleotide (TDF or ADV) or interferon (pegylated or not) therapy within 6 months prior to the pre-treatment biopsy

• Evidence of hepatocellular carcinoma (HCC), ie, α-fetoprotein >50 ng/mL

• Coinfection with hepatitis C virus (HCV), human immunodeficiency virus (HIV), or hepatitis delta virus (HDV)

• Significant renal, cardiovascular, pulmonary, or neurological disease

• Received solid organ or bone marrow transplantation

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

• Has proximal tubulopathy

Note: Other protocol defined Inclusion/Exclusion criteria may apply.