Safety and Efficacy Study of a Caspase Inhibitor in Patients Undergoing Liver Transplantation

Phase 2

Completed

• Conditions: Liver Transplantation; Hepatitis; Cholestasis; Carcinoma, Hepatocellular
• Interventions: Drug: Placebo; Drug: IDN-6556

• Registration Number: NCT00080236
• Lead Sponsor: Conatus Pharmaceuticals Inc.

Brief Summary

The purpose of the study is to test the safety and effectiveness of IDN-6556 in preventing liver damage that normally occurs when livers are transported before being transplanted and in the immediate post-transplant period.

Detailed Description

The occurrence of apoptosis in liver ischemia/reperfusion injury has been well characterized in animal models. In this context apoptosis has specifically been observed in sinusoidal endothelial cells and hepatocytes, and this has also been associated with an increase in activated caspase-3 in liver tissue extracts. The use of caspase inhibitors to prevent apoptosis during liver storage and transplantation may reduce ischemia/reperfusion injury and hence improve graft function after transplantation. Suppression of apoptosis by caspase inhibitors may also allow for longer ischemic times allowing organs to be transported greater distances. In addition, suppression of apoptosis may lower the risk involved in using suboptimal donor organs.

Study Timeline

• Study Start: 2003-11
• Study First Submitted: 2004-03-24
• Study First Submitted QC: 2004-03-25
• Study First Posted: 2004-03-26
• Primary Completion: 2006-01
• Study Completion: 2006-01
• Status Verified: 2012-08
• Last Update Submitted: 2012-08-08
• Last Update Posted: 2012-08-10

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 99

Inclusion Criteria

• Minimum adult age

Exclusion Criteria

• Fulminant hepatic failure (UNOS Status I patients)
• Previous liver transplantation
• Patients undergoing split liver grafts
• Extrahepatic malignancy
• If female, pregnant or lactating

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Donor organ placebo and Recipient placebo	Placebo	-
Donor organ: IDN-6556 (15μg/ml), Recipient: Placebo	IDN-6556	-
Donor organ: IDN-6556 (15μg/ml), Recipient: Placebo	Placebo	-
Donor organ: IDN-6556(15 μg/ml), Recipient: IDN-6556 0.5 mg/kg	IDN-6556	-
Donor organ: IDN-6556 (5 μg/ml), Recipient: IDN-6556 0.5 mg/kg	IDN-6556	-

Primary Outcome Measures

Name	Time	Method
Peak absolute change in alanine aminotransferase (ALT) values measured from baseline to up to 3 days post-transplantation
Peak absolute change in aspartate transaminase (AST) values measured from baseline to up to 3 days post-transplantation

Trial Locations

Locations (13)

University of Cincinnati; 🇺🇸 Cincinnati, Ohio, United States

Mayo Clinic Scottsdale; 🇺🇸 Phoenix, Arizona, United States

Mount Sinai School of Medicine; 🇺🇸 New York City, New York, United States

University of California Los Angeles; 🇺🇸 Los Angeles, California, United States

Indiana University Medical Center; 🇺🇸 Indianapolis, Indiana, United States

Tulane University Hospital and Clinic; 🇺🇸 New Orleans, Louisiana, United States

Baylor Regional Transplant Institute, Baylor University Medical Center; 🇺🇸 Dallas, Texas, United States

Mayo Clinic Rochester; 🇺🇸 Rochester, Minnesota, United States

The University of Texas Health Science Center at San Antonio; 🇺🇸 San Antonio, Texas, United States

Klinik für Viszeral- und Transplantationschirurgie Medizinische Hochschule Hannover; 🇩🇪 Hannover, Germany

Abteilung für Transplantationschirurgie Johannes Gutenberg-Universität Mainz; 🇩🇪 Mainz, Germany

University of California San Francisco; 🇺🇸 San Francisco, California, United States

Oberarzt der Klinik für Allgemein-, Viszeral- und Transplantationschirurgie Charité-Virchow; 🇩🇪 Berlin, Germany