a study to compare tenofovir disoproxil fumarate versus adefovir dipivoxil for the treatment of hbeag-positive chronic hepatitis b

Conditions: Chronic Hepatitis B

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.


Eligibility 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.

Keywords: tenofovir adefovir hepatitis b hbeag positive