Clinical trial NCT00378599: Effects of Pegylated Interferon Alfa-2b and Ribavirin After Orthotopic Liver Transplantation in Subjects With Chronic Hepatitis C Recurrence (P04590AM3)(COMPLETED)
Official title: PROTECT - Pegylated Interferon Alfa-2b and Ribavirin After Orthotopic Liver Transplantation: Efficacy and Safety in Hepatitis C Recurrence Therapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Liver Transplantation
Hepatitis C, Chronic
Liver Cirrhosis
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2006-09-20
Enrollment: 125
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

Primary outcomes:
measure: A Sustained Virologic Response (SVR), Defined as a Plasma HCV RNA Level Below the Lower Level of Quantitation (LLQ) at 24 Weeks Post-treatment
timeFrame: 24 weeks after completion of up to 48 weeks of therapy
Secondary outcomes:
Other outcomes:
Locations:
Study officials:
References:
citation: Gordon FD, Kwo P, Ghalib R, Crippin J, Vargas HE, Brown KA, Schiano T, Chaudhri E, Pedicone LD, Brown RS Jr. Peginterferon-alpha-2b and ribavirin for hepatitis C recurrence postorthotopic liver transplantation. J Clin Gastroenterol. 2012 Sep;46(8):700-8. doi: 10.1097/MCG.0b013e31825833be.