Telbivudine Versus Entecavir in Reducing Serum HBsAg Levels in Patients With HBeAg-positive Chronic Hepatitis B
Condition: Chronic Viral Hepatitis B Without Delta-agent
MeSH terms: Hepatitis A; Hepatitis B; Hepatitis B, Chronic; Hepatitis
Study type: Interventional
Phase: Phase 3

Summary: 
      The goal of chronic hepatitis B (CHB) treatment is complete and permanent eradication of
      hepatitis B virus (HBV) from patient's body, which is best represented by serum HBsAg loss
      accompanied by undetectable serum HBV DNA level.

      While the most recently approved nucleos(t)ide analogues (NA) have marked antiviral potency
      and can induce HBV DNA undetectability in the majority of patients through prolonged
      treatment, NA need to be given long term, almost indefinitely, in most cases because they
      suppress HBV DNA only during therapy. For example, even after HBeAg-loss by a potent NA,
      suppression of serum HBV DNA to undetectable level is sustained only in about 23%-37% at 24
      weeks off treatment. Thus, continuous therapy with NA until HBsAg clearance remains necessary
      in a majority of cases.

      The recent availability of commercial quantitative assays of serum hepatitis B surface
      antigen (HBsAg) has enabled quantitative HBsAg to be used as a biomarker for prognosis and
      treatment response in CHB. It has been suggested that HBsAg decline during lamivudine or
      entecavir therapy is slower and less pronounced compared to interferon treatment, despite a
      higher effect on HBV DNA suppression. Based on HBsAg kinetics, it has been estimated that the
      predicted median time to HBsAg loss in patients treated with lamivudine or entecavir is more
      than 30 years. Thus, treatment that can induce rapid decline of HBsAg would have clear
      advantage in reducing the treatment duration required to achieve HBsAg-loss.

      Interestingly, in a recent preliminary study, 24-weeks of treatment with telbivudine has
      induced HBsAg decline as comparable to pegylated interferon treatment. Although there has
      been no head-to-head trial comparing NAs in inducing HBsAg decline, previous studies
      consistently suggested that the decline of HBsAg is greater during telbivudine treatment
      compared with lamivudine or entecavir.

      Thus, in this clinical trial, the investigators will investigate whether telbivudine is more
      effective in inducing HBsAg decline compared with entecavir in HBeAg-positive CHB patients
      who have achieved undetectable serum HBV DNA by preceding entecavir treatment.
    

Detailed description: 
      A single-center randomized active-controlled open-label superiority trial

        -  Patients will be randomly assigned 1:1 to receive telbivudine (600 mg/day) or ongoing
           entecavir (0.5 mg/day) for 48 weeks.

        -  Eligible patients will be randomized using blocks of permuted treatment assignments
           after stratification by HBsAg level (1,000 IU/mL-5,000 IU/mL and ≥5,000 IU/mL IU/mL) and
           by entecavir treatment duration (1 year-2 year, ≥2 year).

        -  Because over 98% of Korean patients with CHB have HBV genotype C,9 HBV genotype will not
           determined or be regarded as a stratification factor.

        -  There will be no interruption in entecavir therapy before randomization.

        -  Patients' treatment information will be retrospectively collected during entecavir
           treatment phase as well (DNA change, HBeAg status, HBsAg titre, ALT, and treatment
           duration. etc)

        -  Patients will be screened within 4 weeks before randomization to determine study
           eligibility.
    

Intervention name(s): Telbivudine; Entecavir
Intervention type(s): Drug; Drug
Intervention description(s): Telbivudine 600 mg Daily Oral; Entecavir 0.5 mg Daily Oral
Other intervention name(s): Sebivo; Baraclude
Intervention MeSH terms: Entecavir; Telbivudine
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: HBeAg-positive