Effects of Pegylated Interferon Alfa-2b and Ribavirin After Orthotopic Liver Transplantation in Subjects With Chronic Hepatitis C Recurrence (P04590AM3)(COMPLETED)

Study Overview
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Brief Summary
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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.

Official Title
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PROTECT - Pegylated Interferon Alfa-2b and Ribavirin After Orthotopic Liver Transplantation: Efficacy and Safety in Hepatitis C Recurrence Therapy

Conditions
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Liver Transplantation, Hepatitis C, Chronic, Liver Cirrhosis

Intervention / Treatment
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* Drug: Combination of (a) pegylated interferon alfa-2b and (b) rebetol


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PEG-Intron plus Rebetol (RBV)<br>PEG-Intron plus RBV treatment for up to 48 weeks with 24-week follow up. SCH 54031 PEG-Intron 1.5 ug/kg SC per week plus SCH 18908 REBETOL twice daily (BID) PO with food, dosed as followed: Weeks 1 and 2, RBV Dose 400 mg (2 capsules, 1 AM and 1 PM). At the end of Weeks 2 and 4 of Treatment (tx), a complete blood count (CBC) was performed. An increase in RBV dose was permitted only if the hemoglobin was >10 g/dL. At Weeks 3 and 4, RBV dose was 800 mg (4 capsules, 2 AM and 2 PM). From Weeks 5 to 48, RBV doses could be increased based on subject body weight. For subjects weighing <65 kg, maximum dose of RBV was to be 800 mg (4 capsules, 2 AM and 2 PM), for subjects weighing 65-85 kg, max dose of RBV was 1000 mg/day (5 capsules, 2 AM and 3 PM), for subjects weighing >85 kg, max dose of RBV was 1200 mg/day, 6 capsules, 3 AM and 3 PM). | Drug: Combination of (a) pegylated interferon alfa-2b and (b) rebetol<br>* 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<br>* Other names: (b) SCH 18908, Rebetol;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| A Sustained Virologic Response (SVR), Defined as a Plasma HCV RNA Level Below the Lower Level of Quantitation (LLQ) at 24 Weeks Post-treatment | Number of participants with SVR at 24-week follow up after treatment with PEG-Intron and Ribavirin in post-orthotopic liver transplant recipients with recurrent HCV. | 24 weeks after completion of up to 48 weeks of therapy |