Clinical trial NCT01292824: Pilot Study of Hepatitis C Virus Entry Inhibitor (ITX 5061) in Liver Transplant Recipients
Official title: Phase I Study of Hepatitis C Virus (HCV) Entry Inhibitor (ITX 5061) in Liver Transplant Recipients With HCV Infection
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Hepatitis C
Evidence of Liver Transplantation
Keywords: Hepatitis C virus
Entry
Scavenger receptor-BI
High density lipoprotein
Liver transplantation
Lead sponsor: University of Birmingham
Sponsor class: OTHER
Collaborators: name: University Hospital Birmingham
name: National Institute for Health Research, United Kingdom
First posted: 2011-02-10
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: To determine the safety of ITX 5061 in liver transplant recipients
timeFrame: 90 days
Secondary outcomes:
measure: To determine whether treatment leads to an alteration in HCV RNA kinetics in the first week after liver transplantation
timeFrame: One week
measure: To determine whether any change in early viral kinetics is sustained
timeFrame: 90 days
Other outcomes:
Locations:
city: Birmingham
country: United Kingdom
facility: University Hospital Birmingham
state: West Midlands
Study officials:
affiliation: University of Birmingham
name: David J Mutimer, FRCP
role: PRINCIPAL_INVESTIGATOR
References:
citation: Syder AJ, Lee H, Zeisel MB, Grove J, Soulier E, Macdonald J, Chow S, Chang J, Baumert TF, McKeating JA, McKelvy J, Wong-Staal F. Small molecule scavenger receptor BI antagonists are potent HCV entry inhibitors. J Hepatol. 2011 Jan;54(1):48-55. doi: 10.1016/j.jhep.2010.06.024. Epub 2010 Aug 21.
citation: Rowe IA, Tully DC, Armstrong MJ, Parker R, Guo K, Barton D, Morse GD, Venuto CS, Ogilvie CB, Hedegaard DL, McKelvy JF, Wong-Staal F, Allen TM, Balfe P, McKeating JA, Mutimer DJ. Effect of scavenger receptor class B type I antagonist ITX5061 in patients with hepatitis C virus infection undergoing liver transplantation. Liver Transpl. 2016 Mar;22(3):287-97. doi: 10.1002/lt.24349.