Tenofovir Versus Adefovir for the Treatment of HBeAg Positive Chronic Hepatitis B

Protocol: 
GS-US-174-0103
Phase: 
III

A Randomized, DoubleBlind, Controlled Evaluation of Tenofovir DF versus Adefovir Dipivoxil for the Treatment of HBeAg Positive Chronic Hepatitis B

This study is designed to evaluate the safety and antiviral activity of tenofovir disoproxil fumarate (TDF, tenofovir DF) compared to adefovir dipivoxil (ADV) for the treatment of HBeAg-positive chronic hepatitis B. Participants will receive either TDF or the approved hepatitis B therapy ADV. After 48 weeks all participants will be switched to open-label TDF.

Trial Website: https://clinicaltrials.gov/show/NCT00116805

Are you Eligible? (Inclusion Criteria)

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

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

Specialty Area(s)

Trial Location

NYP/Columbia
New York, NY 10032
United States