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

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

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.

Study Overview

• Status: Terminated
• Conditions: Hepatitis C Infection
• Intervention / Treatment: Drug: ITX 5061

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Anticipated): 10
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10029
      • Mount Sinai School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 72 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: ITX 5061; 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; 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Schiano, Thomas D., MD
• Collaborators: iTherX Pharmaceuticals Inc.
• Investigators: Principal Investigator: Thomas D Schiano, MD, Icahn School of Medicine at Mount Sinai

Publications and helpful links

General Publications

• Sulkowski MS, Kang M, Matining R, Wyles D, Johnson VA, Morse GD, Amorosa V, Bhattacharya D, Coughlin K, Wong-Staal F, Glesby MJ; AIDS Clinical Trials Group A5277 Protocol Team. Safety and antiviral activity of the HCV entry inhibitor ITX5061 in treatment-naive HCV-infected adults: a randomized, double-blind, phase 1b study. J Infect Dis. 2014 Mar 1;209(5):658-67. doi: 10.1093/infdis/jit503. Epub 2013 Sep 16.

Study record dates

Study Major Dates

• Study Start: March 1, 2012
• Primary Completion (ACTUAL): April 1, 2018
• Study Completion (ACTUAL): April 1, 2018

Study Registration Dates

• First Submitted: February 15, 2012
• First Submitted That Met QC Criteria: March 20, 2012
• First Posted (ESTIMATE): March 22, 2012

Study Record Updates

• Last Update Posted (ACTUAL): April 18, 2018
• Last Update Submitted That Met QC Criteria: April 16, 2018
• Last Verified: April 1, 2018

More Information

Terms related to this study

• Keywords: Liver Transplantation; Hepatitis C Virus Infection
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; RNA Virus Infections; Virus Diseases; Blood-Borne Infections; Disease Attributes; Liver Diseases; Flaviviridae Infections; Hepatitis, Viral, Human; Enterovirus Infections; Picornaviridae Infections; Infections; Communicable Diseases; Hepatitis; Hepatitis A; Hepatitis C
• Other Study ID Numbers: HSM 12-00045; 12-0123 (OTHER: Mount Sinai GCO)