Clinical trial NCT01909401: Pilot Study With Peginterferon, Ribavirin, and Boceprevir Prior to Transplantation to Clear Virus in Hepatitis C Genotype 1 Infected Individuals Undergoing Orthotopic Liver Transplantation
Official title: Pilot Study With Peginterferon, Ribavirin, and Boceprevir Prior to Transplantation to Clear Virus in Hepatitis C Genotype 1 Infected Individuals Undergoing Orthotopic Liver Transplantation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: EARLY_PHASE1
Conditions: Liver Transplantation
Keywords: Liver Transplantation
Lead sponsor: Indiana University
Sponsor class: OTHER
Collaborators: name: Merck Sharp & Dohme LLC
First posted: 2013-07-26
Enrollment: 1
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Currently, there is no treatment standard for use of anti-HCV (hepatitic C virus) medications for those preparing for a liver transplant. The purpose of this study is to determine whether those individuals who require liver transplantation for Hepatitis C, genotype I, who are undergoing liver transplantation may successfully get rid of their virus before the transplant by taking three medicines, peginterferon, ribavirin, and boceprevir, up until the time of the liver transplant surgery. If successful, the Hepatitis C virus will not re-infect the new liver that they receive and they will not require therapy for Hepatitis C after liver transplantation. This study involves the use of peginterferon alfa-2b, ribavirin, and boceprevir, all of which are approved for the treatment of genotype I Hepatitis C.

Hypothesis: The addition of boceprevir to peginterferon alfa-2b and ribavirin in patients with Hepatitis C genotype 1 with or without hepatocellular carcinoma undergoing orthotopic liver transplantation will lead to rapid HCV RNA clearance of genotype I infected individuals. Transplantation with anhepatic boceprevir will prevent reinfection of the new transplanted graft and prevent graft infection posttransplantation.

Detailed description: Subject Patient Inclusion Criteria: Men and women age 18 to 70 inclusive, patients with genotype I Hepatitis C who are listed for orthotopic liver transplantation (OLT) will be enrolled. Those with hepatocellular carcinoma with or without treatment of hepatoma may also be included. The MELD score for enrollment will be capped at 16. Patients must have medically controlled ascites and those who have moderate or poorly controlled ascites will be excluded.

Treatment Plan: Fifteen patients with chronic genotype I Hepatitis C will be enrolled. All patients will begin with peginterferon and ribavirin for 4 weeks with the addition of boceprevir after Week 4 until orthotopic liver transplantation. The dose of interferon will be peginterferon 1.0 mcg/kg with weight-based ribavirin (600-1200 mg) with boceprevir 800 mg TID (three times per day) until OLT. All patients will be listed for orthotopic liver transplantation. HCV RNA will be measured monthly. When they are called in for transplant, they will take their last dose of ribavirin just prior to going to operating room. Patients will undergo orthotopic liver transplantation under standard protocol by Indiana University. They will receive by Dobhoff boceprevir 800 tid for 3 doses post transplantation. Virologic failure will be HCV RNA \> 100 I.U. at Week 12.

Eligibility criteria: Inclusion Criteria:

* Men and women age 18-70
* Patients must be genotype I HCV-infected individuals with cirrhosis undergoing orthotopic liver transplantation.
* Those with hepatocellular carcinoma with or without treatment of hepatoma may also be included.
* The MELD score for enrollment will be capped at 16.
* Patients must have medically controlled ascites and those who have moderate or poorly controlled ascites will be excluded.

Inclusion Laboratory Values

ALT (alanine aminotransferase) \< 250 IU/L, AST (Aspartate aminotransferase ) \< 250 IU/L, total bilirubin \< 3 mg/dl, creatinine clearance \> 45 ml by MDRD (Modification of Diet in Renal Disease), albumin \> 2.8 g/dl, hemoglobin \> 11, white count \> 2.0 X103, absolute neutrophil count 1.5 X103, platelet count \> 50,000.

Women of childbearing potential and male patients with sexual female partner who is of childbearing potential should use two acceptable methods of contraception.

Exclusion Criteria:

-

Primary outcomes:
measure: Number of individuals who can remain HCV RNA undetected 6 months post orthotopic liver transplant after receiving peginterferon, ribavirin, and boceprevir.
timeFrame: 6 months post orthotopic liver transplant
Secondary outcomes:
measure: Safety and efficacy of peginterferon, ribavirin, and boceprevir in patients with genotype I undergoing orthotopic liver transplant for cirrhosis and/or hepatocellular carcinoma.
timeFrame: 6 months post orthotopic liver transplant
Other outcomes:
Locations:
city: Indianapolis
country: United States
facility: Indiana University School of Medicine - IUHealth-University Hospital
state: Indiana
Study officials:
affiliation: Indiana University
name: Paul Y Kwo, MD
role: PRINCIPAL_INVESTIGATOR
References: