Study of Hepatitis C Virus (HCV) Entry Inhibitor in Liver Transplant Recipients With HCV Infection

Study Overview
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Brief Summary
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This study will test the safety and tolerability of HCV Entry Inhibitor ITX 5061 in Liver Transplant Recipients with Hepatitis C infection. The investigators hypothesize that ITX 5061 oral monotherapy will be safe in adults during and after liver transplantation and that therapy will also inhibit HCV infection of newly transplanted livers in adults with prior HCV infection.

Detailed Description
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All subjects will receive 28 days of ITX 5061 beginning at the time of transplant. Dosing of ITX 5061 is as follows: Day of Transplant prior to surgery: ITX 5061 300 mg Day of Transplant following surgery: ITX 5061 300 mg Post-Operative Days 1-6: ITX 5061 300 mg Post-Operative Days 7-27: ITX 5061 150 mg Subjects will be monitored for HCV RNA levels, HDL cholesterol and ITX 5061 drug concentration levels. A liver biopsy will be performed at 6 months post-transplant to assess for histological signs of HCV recurrence.

Official Title
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Phase I Study of Hepatitis C Virus (HCV) Entry Inhibitor (ITX 5061) in Liver Transplant Recipients With HCV Infection

Conditions
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Hepatitis C Infection

Intervention / Treatment
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* Drug: ITX 5061


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18-72 Patients accepted onto waiting list for liver transplantation for HCV related liver disease and receiving a deceased donor liver allograft HCV RNA (+) at time of listing for transplantation. All HCV genotypes will be eligible Patients with HCC and those receiving hepatitis B core (+) donor livers will be eligible Standard immunosuppression protocol with tacrolimus, corticosteroid taper, and mycophenolate mofetil Exclusion Criteria: Viral co-infection (HBV/HIV) Receipt of a HCV (+) donor allograft Patients undergoing retransplantation for recurrent HCV Multivisceral transplantation Patients receiving anti-viral therapy at the time of LT Live donor liver transplantation

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 72 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: Prevention
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ITX 5061<br>Subjects will receive ITX 5061 for 28 days beginning at the time of liver transplantation for hepatitis C virus. 300mg will be administered on the day of surgery and for one week post transplant, followed by 150mg for an additional 21 days. | Drug: ITX 5061<br>* 300 mg given orally beginning at the time of liver transplantation and for 1 week post-transplant followed by 150 mg orally for an additional 21 days.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of HCV recurrence post-transplant | We hypothesize that ITX 5061 oral monotherapy will be safe in adults during and after liver transplantation and will inhibit HCV infection of newly transplanted livers in adults with prior HCV infection. The number of treated subjects who are infected at 28 days post-transplant will be compared to the historical control rate (95%). | 28 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in serum HCV RNA | To determine the change in serum HCV RNA from study entry to end of dosing (28 days) and 3 month follow up | 3 months after transplant | 
| Levels of ITX 5061 | To assess trough levels of plasma ITX 5061 throughout the dosing period | 28 days | 
| Viral dynamics of serum HCV RNA | To characterize the viral dynamics of serum HCV RNA levels during the first 24 hours post-transplant | 24 hours post-transplant | 
| Potential changes in plasma HCV E2 | To characterize potential changes in plasma HCV E2 (HCV envelope protein) regions in the setting of ITX 5061 administration | 28 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hepatitis C Virus Infection, Liver Transplantation