Adefovir Dipivoxil For The Treatment Of Chinese Compensated Chronic Hepatitis B(CHB)Patients
Condition: Chronic Hepatitis B
MeSH terms: Hepatitis A; Hepatitis B; Hepatitis B, Chronic; Hepatitis; Hepatitis, Chronic
Intervention: adefovir dipivoxil
Intervention description: adefovir dipivoxil once daily one tablet 10mg orally
Intervention MeSH terms: Adefovir; Adefovir dipivoxil
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 1470.0
Sex: All
Minimum age: 16 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: adefovir dipivoxil; compensated; chronic hepatitis B; Chinese

Summary:

      This 48-week open-label study of local manufactured adefovir dipivoxil Tablet evaluates the
      efficacy and safety of adefovir 10mg once daily in Chinese subjects with compensated CHB.
      Primary endpoint is proportion of subjects achieving HBV DNA undetectable (<=1000 copies/mL
      by by Roche COBAS AMPLICOR HBV MONITOR Test) at week 48. Approximately 1250 patients will be
      recruited in 30 study centers in China. The subjects are offered 48 weeks of open label
      adefovir dipivoxil treatment, with assessments every three months, after with is a 12-week
      post study treatment follow-up prior to study completion.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Male or female subjects aged 18-65 years inclusive

          -  Documented chronic hepatitis B infection determined by the presence of serum HBsAg for
             a least 6 months

          -  Serum HBV DNA ≥105 copies/ml for HBeAg positive subjects or ≥104 copies/ml for HBeAg
             negative subjects (Real-time PCR, LLQ=1000cp/ml) at study screening (within 2 weeks
             before baseline), respectively.

          -  ALT value ≥2 times the upper limit of normal (ULN) at the time of screening, as
             determined using laboratory ranges and documented ALT abnormal within 6 month prior
             the study screening.

          -  Compensated liver disease with the following laboratory and clinical parameters study
             screening:

          -  prothrombin time ≤ 2 seconds above normal direct bilirubin

          -  Albumin≥35g/L

          -  Total bilirubin ≤2.5mg/dL (≤ 43 µmol/L) or normal direct bilirubin

          -  No history of variceal bleeding

          -  No history of encephalopathy

          -  No history of ascites

          -  Willing and able to undergo two liver biopsies (prior to dosing, and after 48 weeks of
             therapy; only apply to subjects who are enrolled to the sites where liver biopsy is
             required).

          -  Agree not to participate in any other investigational trials or to undertake other HBV
             systemic antiviral regimens during participation in this study

        Exclusion Criteria:

        A subject will not be eligible for inclusion in this study if any of the following criteria
        apply:

          -  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, may not limit to, renal, cardiac,
             pulmonary, vascular, neurogenic, digestive, metabolic (diabetes, thyroid disorders,
             adrenal disease), immunodeficiency disorders, active infection or cancer.

          -  Documented evidence of active liver disease due to other causes including

          -  co-infection hepatitis C (HCV), Subjects who are anti-HCV positive and in whom HCV RNA
             is undetectable are considered to be HCV seropositive and will not be eligible

          -  co-infection with hepatitis delta (HDV)

          -  co-infection with HIV

          -  autoimmune hepatitis (antinuclear antibody titre>1:160)

          -  Alanine aminotransferase(ALT) > 10 times ULN at screening or history of acute
             exacerbation leading to transient decompensation

          -  Serum alpha fetoprotein (AFP) >50 ng/mL.

          -  Hepatocellular carcinoma as evidenced by one of the following:

          -  suspicious foci on ultrasound or radiological examination

          -  where no positive ultrasound finding, but serum alpha-fetoprotein > 100ng/ml

          -  Adequate renal function defined as serum creatinine >1.5 mg/dL (>130 µmol/L)

          -  Adequate hematological function defined as:

          -  Absolute neutrophil count <1 x 10³/mm³ (1 x 10^9/L)

          -  Platelets<80 x 10³/mm³ (80 x 10^9/L); platelets<100 x 10³/mm³ (100 x 10^9/L)

          -  Hemoglobin<12g/dL (120 g/L)(males) or <10 g/dL (100 g/L) (females)

          -  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.

          -  Use of immunosuppressive therapy, immunomodulatory therapy (including interferon or
             thymosin), systemic cytotoxic agents within the previous 6 months or during the study.

          -  Use of chronic anti-viral agents(e.g. lamivudine, adefovir dipivoxil, entecavir,
             famciclovir, tenofovir, FTC, ganciclovir, DAPD, LfMA, HBIg, etc.), Chinese herbal
             medicines known to have activity against HBV within the previous 3 months or during
             the study; use of agents with effect of ALT reduction (e.g. schisandra agents) during
             the study.

          -  Received nephrotoxic drugs (e.g., aminoglycosides, amphotericin B, vancomycin,
             cidofovir, foscarnet, cis-platinum, pentamidine etc.) or competitors of renal
             excretion (e.g., probenecid within 2 months prior to study screening or the
             expectation that patient will receive any of these during the course of the study.

          -  Received hepatotoxic drugs (e.g., anabolic steroids, ketaconazole, itraconazole,
             isoniazid, rifampin, rifabutin) within 2 months prior to study screening or expected
             to receive these during the course of the study.

          -  Previous (or planned) participation in an investigational trial involving
             administration of investigational compound within 2 months prior to the study
             screening.