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

Liver Cirrhosis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00378599
• Other study ID #: P04590
• Status: Completed
• Phase: Phase 3
• First received: September 18, 2006
• Last updated: April 7, 2015
• Start date: May 2006
• Est. completion date: July 2009

Study information

• Verified date: April 2015
• Source: Merck Sharp & Dohme Corp.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 125
• Est. completion date: July 2009
• Est. primary completion date: July 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 70 Years

Eligibility

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.

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hepatitis
• Hepatitis A
• Hepatitis C
• Hepatitis C, Chronic
• Liver Cirrhosis
• Liver Transplantation

Intervention

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

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme Corp.

References & Publications (1)

Gordon FD, Kwo P, Ghalib R, Crippin J, Vargas HE, Brown KA, Schiano T, Chaudhri E, Pedicone LD, Brown RS Jr. Peginterferon-a-2b and ribavirin for hepatitis C recurrence postorthotopic liver transplantation. J Clin Gastroenterol. 2012 Sep;46(8):700-8. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No