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

Merck Sharp & Dohme (MSD)

Status and phase: Completed; Phase 3

Conditions: Liver Transplantation; Hepatitis C, Chronic; Liver Cirrhosis

Treatments: Drug: Combination of (a) pegylated interferon alfa-2b and (b) rebetol

Study type: Interventional

Funder types: Industry

Identifiers

NCT00378599

P04590

Details and patient eligibility

About

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.

Enrollment: 125 patients

Sex: All

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

---

125 participants in 1 patient group

PEG-Intron plus Rebetol (RBV)

Experimental group

Description:

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).

Treatment:

Drug: Combination of (a) pegylated interferon alfa-2b and (b) rebetol