PegIntron Versus Adefovir in the Treatment of Chronic Hepatitis B (CHB) e Antigen Positive Patients in Taiwan (P04498/MK-4031-278)
Condition: Hepatitis B, Chronic (CHB)
MeSH terms: Hepatitis A; Hepatitis B; Hepatitis B, Chronic; Hepatitis
Intervention: Pegylated interferon alfa-2b (PegIntron); Adefovir dipivoxil (adefovir)
Intervention description: Powder for injection in vials ( 100, and 120 microgram strengths), subcutaneous, dose of 1.5 micrograms/kg, weekly for up to 24 weeks; 10 mg adefovir dipivoxil (equivalent to 5.4.5 mg adefovir) tablets, oral, dose of 1 tablet per day for up to 48 weeks
Intervention MeSH terms: Interferons; Interferon-alpha; Interferon alpha-2; Peginterferon alfa-2b; Adefovir; Adefovir dipivoxil
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 25.0
Sex: All
Minimum age: 18 Years
Maximum age: 70 Years
Healthy volunteers: No
Keywords: Hepatitis B virus; Pegylated interferon alfa-2b (PegIntron)

Summary:

      This is an open label, randomized, comparative, multi-center study. Subjects will be screened
      within 2 weeks prior to study entry to establish eligibility. Subjects who meet all the
      selection criteria will be randomly assigned 1:1 to (1) once-a-week, subcutaneous Pegylated
      interferon alfa-2b (PegIntron) (1.5 mcg/kg body weight) or (2) oral adefovir 10 mg daily. The
      treatment phase will be 24 weeks for PegIntron and 48 weeks for adefovir. All subjects
      completing the assigned treatment phase will be followed up for an additional 48 weeks for
      PegIntron and 24 weeks for adefovir as observation phase. The primary objective is to
      establish the efficacy profile of PegIntron. Secondary objectives are to compare the efficacy
      profile of PegIntron with that of adefovir, compare efficacy of PegIntron in lamivudine-naïve
      and lamivudine-experienced subjects, and to establish the safety profile of PegIntron in
      treating patients with hepatitis B e antigen (HBeAg)-positive chronic hepatitis B.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Adult male or female, 18 to 70 years of age.

          -  Documented positive serum hepatitis B surface antigen (HBsAg) for a minimum of 6
             months prior to randomization.

          -  Hepatitis B virus (HBV) replication and hepatitis documented by:

               -  Serum HBV DNA (Hepatitis B Virus Deoxyribonucleic acid) >= 10^5 copies/mL within
                  3 months prior to entry

               -  Positive serum hepatitis B e antigen (HBeAg) within 3 months prior to entry

               -  Documented presence of ALT (Alanine Aminotransferase) twice (1 month apart)
                  within 3 months prior to entry (2 to 10 folds above the upper normal level)

               -  Liver biopsy finding shows evidence of chronic hepatitis without liver cirrhosis,
                  document acceptable if no anti-HBV treatment within 1 year prior to randomization

               -  Naïve or exposed to lamivudine (3 months treatment-free interval prior to
                  randomization)

               -  Adequate renal function (creatinine within normal upper limit).

          -  Compensated liver disease with certain minimum hematological and serum biochemical
             criteria.

          -  Thyroid stimulating hormone (TSH) and free T4 within normal ranges.

          -  Negative antibody to hepatitis C and hepatitis D.

          -  Negative antibody to human immunodeficiency virus.

          -  Negative evidence for hepatocellular carcinoma by alfa-fetoprotein and ultrasound
             within 1 month prior to randomization.

        Exclusion Criteria:

          -  Women who are pregnant or nursing.

          -  Prior treatment for hepatitis with any interferon or adefovir, or other
             investigational anti-virus agents.

          -  Prior treatment for hepatitis with immunomodulatory drug within 2 years prior to
             randomization.

          -  Suspected hypersensitivity to interferon or adefovir.

          -  Liver cirrhosis.

          -  History of severe psychiatric disease, especially depression.

          -  Concurrent malignancies (including hepatocellular carcinoma).

          -  Unstable or significant cardiovascular diseases.

          -  Prolonged exposure to known hepatotoxins.

          -  History of thyroid disease poorly controlled on prescribed medication.

          -  Poorly controlled diabetes mellitus.

          -  Have suspected or confirmed significant hepatic disease from an etiology other than
             HBV.

          -  Severe renal disease or myeloid dysfunction.

          -  History of organ transplantation other than cornea and hair transplant.

          -  Any medical condition requiring chronic systemic administration of steroids.