An Open Label, Multi Centre Phase IV Study of Adefovir Dipivoxil in Korean Patients With Chronic Hepatitis B (CHB)
Condition: Hepatitis B, Chronic
MeSH terms: Hepatitis A; Hepatitis B; Hepatitis B, Chronic; Hepatitis
Intervention: Adefor dipivoxil
Intervention description: All enrolled subjects were enrolled to adefovir dipivoxil arm.
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 104.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      Objective(s) The primary study objective is to assess the antiviral effect of 12 weeks of
      adefovir dipivoxil treatment in Korean patients with chronic hepatitis B and compensated
      liver disease. The secondary study objectives are to assess the antiviral effect, clinical
      benefit and safety of 52 weeks of adefovir dipivoxil treatment.

      Endpoint(s) The primary efficacy endpoint is "Mean log10 reduction in serum HBV DNA level
      from baseline to Week 12".

      The secondary efficacy endpoints include (a) the proportion of patients achieving serum ALT
      normalization at Week 52, (b) other assessments of antiviral effects (the proportion of
      patients achieving HBV DNA no less than 300 copies per mL at Week 52), (c)HBeAg loss, HBeAg
      seroconversion, HBsAg loss and HBsAg seroconversion, (d)the proportion of patients achieving
      serum ALT normalization at Week 12.

      Study Design This is an open label, multi centre phase IV study for Korean patients with
      chronic hepatitis B and compensated liver disease, assessing the antiviral effect of 12 weeks
      treatment of Adefovir dipivoxil as a primary objective and antiviral effect, clinical benefit
      and safety of 52 weeks treatment as secondary objectives.

      Patients will be screened for eligibility criteria and the baseline visit for the treatment
      initiation should occur no more than 4 weeks after screening. Total treatment period will be
      52 weeks and patients will return to the clinic for assessments as scheduled during treatment
      period. After the 52 week study period, it is likely that the patient will benefit from
      continued treatment with commercial adefovir. If in the investigator's clinical judgement
      this is the case, the investigator should ensure that a routine prescription is available in
      a timely manner, and that no unnecessary interruption in treatment occurs.

      Study Population A minimum of 100 male or female Korean patients more than 18 years of age
      with HBeAg positive chronic hepatitis B and compensated liver disease who meet the
      eligibility criteria will be enrolled.

      Study Assessments and Procedures

      Potential patients will be screened prior to study entry and eligible patients who have given
      their consent will have further baseline assessments. Following the screening, the first
      doses of study medications will be given at baseline and patients will return to the clinic
      for assessment as scheduled during treatment period. Patients who discontinue treatment
      prematurely will be followed up every 4 weeks for 12 weeks following the withdrawal visit.
      The following key assessment and or measurement will be made at one or more visits during the
      study. (See section 14.1 Appendix 1. Time and event schedule):

        -  Pregnancy test (females of child-bearing potential only)

        -  Haematology and serum chemistry profile including prothrombin time(PT) and AFP

        -  HBV DNA (Roche COBAS AMPLICOR HBV MONITOR Test, LLOD 300 copies per ml)

        -  Hepatitis B markers: HBeAg(Anti HBe will be tested if HBeAg is negative), HBsAg(Anti HBs
           will be tested if HBsAg is negative) Investigational Product(s) Adefovir dipivoxil 10mg
           tablets will be supplied by GlaxoSmithKline and presented as a white to off white, round
           tablets, packaged in the bottle containing 30 tablets
    

Eligibility criteria:

        Inclusion Criteria:

        A subject will be eligible for inclusion in this study only if all of the following
        criteria apply:

          1. Age more than 18 years

          2. HBV Serology Presence of HBsAg for at least 6 months Presence of HBeAg at the time of
             screening Positive HBV DNA plasma assay with screening value at the time of screening

        4. Evidence of at least one elevated serum alanine amonotransferase (ALT) levels greater
        than 2 times (inclusive) the upper limit of the normal range (ULN) in the previous 6
        months.

        serum ALT levels greater than 2 times (inclusive) the ULN at screening visit. 5.
        Availability and willingness of subject to provide written informed consent.

        Exclusion Criteria:

        A subject will not be eligible for inclusion in this study if any of the following criteria
        apply:

          1. Use of immunosuppressive therapy requiring use of more than 5mg of prednisone(or
             equivalent) per day, immunomodulatory therapy (including interferon or thymosin ) or
             systemic cytotoxic agents within previous 6 months or during the study

          2. Previous or current lamivudine or adefovir dipivoxil therapy or antiviral therapy with
             agents demonstrating potential anti-HBV activity

          3. Clinical signs of decompensated liver disease at screening according to the protocol

          4. Serum creatinine over 1.5mg per dL

          5. Alanine aminotransferase (ALT) over 10 times ULN at screening or history of acute
             exacerbation leading to transient decompensation

          6. Serum Amylase and/or lipase over 2 times ULN

          7. Inadequate haematological function

          8. Anti-HBe or Anti-HBs positive subjects

          9. Hepatocellular carcinoma as evidenced by the protocol

         10. Documented evidence of active liver disease

         11. Any serious or active medical or psychiatric illnesses other than hepatitis B which,
             in the opinion of the investigator, would interfere with patient treatment, assessment
             or compliance with the protocol. This would include any uncontrolled clinically
             significant renal, cardiac, pulmonary, vascular, neurogenic, digestive, metabolic
             (diabetes, thyroid disorders, adrenal disease), immunodeficiency disorders or cancer.

         12. Active alcohol or drug abuse or history of alcohol or drug abuse considered by the
             investigator to be sufficient to hinder compliance with treatment, participation in
             the study or interpretation of results.

         13. Planned for liver transplantation or previous liver transplantation

         14. Receipt of any investigational drug within within 3 months prior to screening.

         15. Therapy with nephrotoxic drugs or competitors of renal excretion within 2 months prior
             to study screening or the expectation that patient will receive any of these during
             the course of the study.

         16. History of hypersensitivity to nucleoside and/or nucleotide analogues.

         17. Inability to comply with study requirements as determined by the study investigator.