A Study to Compare Tenofovir DF Versus the Combination of Emtricitabine Plus Tenofovir DF for the Treatment of Chronic Hepatitis B in Patients With Normal Alanine Aminotransferase (ALT)
Condition: Chronic Hepatitis B
MeSH terms: Hepatitis A; Hepatitis B; Hepatitis B, Chronic; Hepatitis; Hepatitis, Chronic
Intervention: Tenofovir DF; FTC; Placebo
Intervention description: Tenofovir disoproxil fumarate (tenofovir DF) 300 mg tablet taken orally once daily; Emtricitabine (FTC) 200 mg capsule taken orally once daily; Placebo to match FTC taken once daily
Intervention MeSH terms: Tenofovir
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 126.0
Sex: All
Minimum age: 18 Years
Maximum age: 69 Years
Healthy volunteers: No
Keywords: tenofovir; monotherapy; emtricitabine; combination; hepatitis B

Summary:

      The main objective of the study was to evaluate the antiviral activity of tenofovir
      disoproxil fumarate (tenofovir DF) monotherapy versus emtricitabine (FTC) plus tenofovir DF
      combination therapy for the treatment of chronic hepatitis B (HBV) in participants in the
      immune tolerant phase of HBV infection.

      The efficacy of tenofovir DF monotherapy versus FTC plus tenofovir DF combination therapy was
      evaluated for suppression of the virus (decrease in HBV DNA), serological response
      (generation of antibodies to the virus), biochemical response (changes in liver enzymes), and
      the development of drug-resistant mutations. The safety and tolerability of both tenofovir DF
      monotherapy and FTC plus tenofovir DF were evaluated by routine monitoring for adverse events
      and changes in laboratory parameters.

      Participants were randomized in a 1:1 ratio to receive tenofovir DF monotherapy or FTC plus
      tenofovir DF. All subjects were to continue on blinded study medication until the last
      subject reached Week 192. Participants who permanently discontinued study drug (on or before
      Week 192) were followed for a 24-week treatment-free follow-up period, or until initiation of
      alternative HBV therapy, whichever occurred first. Subjects who discontinued study drug on or
      after Week 48 because of hepatitis B surface antigen (HBsAg) loss or seroconversion to
      antibody to hepatitis B surface antigen (anti-HBs), however, were to have returned for their
      regularly scheduled through Week 192 and every 16 weeks thereafter until the last subject
      reached Week 192.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Chronic HBV infection, defined as positive serum HBsAg for at least 6 months or HBsAg
             positive > 3 months and positive for immunoglobulin G antibody against hepatitis B
             core antigen

          -  18 through 69 years of age, inclusive

          -  Hepatitis B e antigen (HBeAg) positive

          -  HBV DNA ≥ 10^8 copies/mL

          -  ALT ≤ the upper limit of the normal range (ULN)

          -  Willing and able to provide written informed consent

          -  Negative serum beta-human chorionic gonadotropin (for females of childbearing
             potential only)

          -  Calculated creatinine clearance ≥ 70 mL/min

          -  Hemoglobin ≥ 10 g/dL

          -  Neutrophils ≥ 1,500/mm^3

          -  No prior oral HBV therapy (eg, nucleotide and/or nucleoside therapy or other
             investigational agents for HBV infection)

        Exclusion Criteria:

          -  Pregnant women, women who were breast feeding, or who believed they may have wished to
             become pregnant during the course of the study

          -  Males and females of reproductive potential unwilling to use an effective method of
             contraception during the study

          -  Decompensated liver disease defined as direct (conjugated) bilirubin > 1.2 x ULN,
             prothrombin time > 1.2 x ULN, platelets < 150,000/mm^3, serum albumin < 3.5 g/dL, or
             prior history of clinical hepatic decompensation (eg, ascites, jaundice,
             encephalopathy, or variceal hemorrhage)

          -  Received interferon (pegylated or not) therapy within 6 months of the screening visit

          -  Alpha-fetoprotein > 50 ng/mL

          -  Evidence of hepatocellular carcinoma

          -  Coinfection with hepatitis C virus (by serology), HIV, or hepatitis D virus

          -  Significant renal, cardiovascular, pulmonary, or neurological disease

          -  Received solid organ or bone marrow transplantation

          -  Was currently receiving therapy with immunomodulators (eg, corticosteroids, etc.),
             investigational agents, nephrotoxic agents, or agents susceptible of modifying renal
             excretion

          -  Had proximal tubulopathy

          -  Known hypersensitivity to the study drugs, the metabolites, or formulation excipients