A Study to Compare Tenofovir Disoproxil Fumarate Versus Adefovir Dipivoxil for the Treatment of HBeAg-Positive Chronic Hepatitis B
Condition: Chronic Hepatitis B
MeSH terms: Hepatitis A; Hepatitis B; Hepatitis B, Chronic; Hepatitis; Hepatitis, Chronic
Intervention: TDF; ADV; TDF placebo; ADV placebo; FTC/TDF
Intervention description: 300 mg tablet administered orally once daily; 10 mg tablet administered orally once daily; Tablet administered orally once daily; Tablet administered orally once daily; 200/300 mg fixed-dose combination (FDC) tablet administered orally once daily
Intervention MeSH terms: Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Adefovir dipivoxil
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 266.0
Sex: All
Minimum age: 18 Years
Maximum age: 69 Years
Healthy volunteers: No
Keywords: tenofovir; adefovir; hepatitis B; HBeAg Positive

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.