Pilot Study of Hepatitis C Virus Entry Inhibitor (ITX 5061) in Liver Transplant Recipients

Study Overview
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Brief Summary
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This is a phase I pilot study to determine the safety and preliminary efficacy of a novel hepatitis C virus (HCV) entry inhibitor (ITX 5061) in patients with HCV infection undergoing liver transplantation.

Detailed Description
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Hepatitis C virus (HCV) infection is common and treatment options at present are limited. Recurrence of HCV infection after liver transplantation is inevitable and disease progression is rapid when compared with disease in the non-transplanted liver. Studies of ITX 5061 in vitro have shown it to be a potent inhibitor of HCV entry into hepatocytes, through blocking the interaction of the virus with scavenger receptor BI suggesting it may reduce graft re-infection rates after liver transplant. There are no studies of treatments to block host receptors for HCV and the investigators hypothesize that ITX 5061 will modulate HCV kinetics in the early phase post liver transplant.

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, Evidence of Liver Transplantation

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 years old, ≤ 65 years old Plasma HCV RNA positive at time of listing for liver transplantation Accepted for liver transplantation for any of: End-stage liver disease due to HCV infection End-stage liver disease due to HCV infection and alcohol related liver disease (ALD) HCC due to HCV Exclusion Criteria: Refusal or inability to give informed consent Viral co-infection with either hepatitis B virus (HBV) or human immunodeficiency virus (HIV) Pregnancy or breastfeeding Women, of child-bearing potential, who are not willing to practice effective contraception Men, sexually active with women of child-bearing potential, who are not willing to practice effective contraception Any situation that in the Investigator's opinion may interfere with optimal study participation Participation in any clinical study of an investigational agent within 30 days of recruitment Transplantation with a donor organ from a HCV positive individual

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Standard liver transplant care<br>Liver Transplantation as per Standard of Care | |
| Experimental: ITX 5061<br>Liver Transplantation as per Standard of Care + ITX5061 | Drug: ITX 5061<br>* ITX 5061 (150mg) pre-transplant, immediately post-transplant and daily thereafter for 1 week.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To determine the safety of ITX 5061 in liver transplant recipients | Safety will be assessed by determination of the frequency of: perioperative events: including transfusion requirements and vasopressor requirements post-operative events: including primary graft non-function, hepatic artery thrombosis, acute cellular rejection and infective complications | 90 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To determine whether treatment leads to an alteration in HCV RNA kinetics in the first week after liver transplantation | Hepatitis C virus titers will be measured at multiple times in the peri- and immediate post-operative period and kinetics assessed at 7 days after liver transplant. | One week | 
| To determine whether any change in early viral kinetics is sustained | Hepatitis C virus titers will be measured at multiple times in the post-operative period and kinetics assessed at 90 days after liver transplant. | 90 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hepatitis C virus, Entry, Scavenger receptor-BI, High density lipoprotein, Liver transplantation