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

A Randomized, Double-Blind, Controlled Evaluation of Tenofovir DF Versus Adefovir Dipivoxil for the Treatment of Presumed Pre-Core Mutant Chronic Hepatitis B

This 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 pre-core mutant 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.

Key Inclusion Criteria:

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

• 18 through 69 years of age, inclusive.

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

  • HBeAg negative and HBeAb positive at screening
  • Alanine aminotransferase (ALT) levels > the upper limit of the normal range (ULN) and ≤ 10 x ULN
  • Serum HBV DNA > 100,000 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 120 patients with cirrhosis, ie, a Knodell fibrosis score equal to 4, will be eligible for enrollment

• Negative serum β-human chorionic gonadotropin (hCG)

• Nucleotide naive, ie, no prior nucleotide (TDF or ADV) therapy for greater than 12 weeks

• Nucleoside naive, ie, no prior nucleoside (any nucleoside) therapy for greater than 12 weeks. However, up to 120 patients with > 12 weeks prior lamivudine experience will be eligible

• Willing and able to provide written informed consent

• Had a 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:

• Pregnant women, women who are breast feeding, or women 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.
• 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)
• Coinfection with hepatitis C virus (HCV), human immunodeficiency virus (HIV), or hepatitis D 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.