A Study to Compare Tenofovir Disoproxil Fumarate Versus Adefovir Dipivoxil for the Treatment of HBeAg-Negative 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: 382.0
Sex: All
Minimum age: 18 Years
Maximum age: 69 Years
Healthy volunteers: No
Keywords: tenofovir; adefovir; hepatitis B virus; HBeAg Negative

Summary:

      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.
    

Eligibility criteria:

        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.