Effects of Pegylated Interferon Alfa-2b and Ribavirin After Orthotopic Liver Transplantation in Subjects With Chronic Hepatitis C Recurrence (P04590AM3)(COMPLETED)
Condition: Liver Transplantation; Hepatitis C, Chronic; Liver Cirrhosis
MeSH terms: Hepatitis A; Hepatitis C; Hepatitis C, Chronic; Hepatitis; Liver Cirrhosis; Recurrence
Intervention: Combination of (a) pegylated interferon alfa-2b and (b) rebetol
Intervention description: Powder for injection in vials and Redipen (50, 80, 120, and 150 microgram strengths), subcutaneous, dose of 1.5 micrograms/kg, weekly for up to 48 weeks
200 mg capsules, oral, weight based dose of 400-1200 mg, daily for up to 48 weeks
Intervention MeSH terms: Interferons; Interferon-alpha; Interferon alpha-2; Ribavirin; Peginterferon alfa-2b
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 125.0
Sex: All
Minimum age: 18 Years
Maximum age: 70 Years
Healthy volunteers: No

Summary:

      This is an exploratory study and is a Phase 3, single-arm, multi-center, open-label study of
      pegylated interferon alfa-2b, PEG-IFN alpha-2b (PEG-Intron) and ribavirin (RBV) to determine
      the sustained virologic response (SVR) at 24-week follow-up to 48 week in subjects after
      orthotopic liver transplantation (OLT) with chronic hepatitis C (HCV) recurrence.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Subjects must confirm that all prior medication washout times have been observed.

          -  Subject must be 18 - 70 years of age of either gender and of any race.

          -  Subject must be transplanted for end-stage hepatitis C or fulminant hepatitis C.

          -  Subject must have documented:

               -  persistent HCV viremia after OLT as defined by plasma positive for HCV RNA by
                  quantitative reverse transcription-polymerase chain reaction (RT-PCR),

               -  A liver transplant performed at least 3 months prior to screening but not more
                  than 3 years prior to screening.

          -  Subject must be on stable doses of immunosuppression for at least 1 month.

          -  Compensated liver disease with minimum hematologic, biochemical, and serologic
             criteria at the (Day 1) baseline visit.

               -  Alpha-fetoprotein value (AFP) less than or equal to 250ng/mL. If AFP greater than
                  100 ng/mL, patient will need evidence of normal liver (magnetic resonance
                  imaging) MRI and normal chest computerized tomography (CT) scan within the last 3
                  months or during the screening period.

          -  For subjects with a history of diabetes or hypertension, clearance from an
             ophthalmologist has to be obtained prior to treatment start (Day 1/Visit 2).

          -  Subjects with a history of mild depression may be considered for entry into this
             study.

          -  Female subjects cannot be pregnant or breastfeeding and must be either postmenopausal,
             surgically sterile or using 2 methods of birth control.

          -  Sexually active male subjects are practicing an acceptable, method of contraception.

          -  Contraceptive measures will be reviewed with female subjects at each visit. Dual
             methods of contraception must be used for 1 month prior to the start of treatment and
             6 months after treatment discontinuation.

          -  Pregnancy tests obtained at Screen Visit and Day 1 Visit prior to the initiation of
             treatment must be negative.

        Exclusion Criteria:

          -  Pregnant women, women who plan to become pregnant, male subjects whose partner wants
             to become pregnant, and breastfeeding women (during study and up to 6 months after
             study completion).

          -  Subject has used any investigational product within 30 days prior to Screening or is
             participating in any other clinical study.

          -  Prior treatment for chronic hepatitis C post-liver transplant, including but not
             limited to antiviral or immunomodulatory product, any interferon product, or RBV,
             either as monotherapy or in combination.

          -  Subjects with other organ transplants.

          -  Any subject who received a positive hepatitis C core antibody (HBcAb) or HCV positive
             donor liver graft.

          -  Retransplantation of the liver for rejection or graft failure.

          -  Evidence of decompensated liver disease.

          -  Known coagulopathies including hemophilia.

          -  Known hemoglobinopathies.

          -  Known glucose-6-phosphate dehydrogenase (G6PD) deficiency.

          -  Hypersensitivity to alpha interferon and/or RBV.

          -  Co-infection with hepatitis B virus (HBV) and/or human immunodeficiency virus (HIV).

          -  Evidence of active or suspected malignancy or a history of malignancy within the last
             5 years (with the exception of pre-transplant hepatocellular carcinoma histologically
             within the Milan criteria, and adequately treated basal or squamous cell carcinoma of
             the skin).

          -  Any known pre-existing medical condition that could interfere with the subject's
             participation in and completion of the study.

          -  Subject is or was a substance abuser. Subjects treated with buprenorphine (Subutex)
             who have been stable for 6 months may be included.

          -  Patients weighing over 135 kg;

        Is participating in any other clinical study(ies);

        Is allergic to or has sensitivity to the study drug or its excipients.