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

Study Overview
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Brief Summary
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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
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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.

Official Title
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Safety, Tolerability and Efficacy Study of a Caspase Inhibitor, IDN-6556, in Patients Undergoing Orthotopic Liver Transplantation (OLT)

Conditions
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Liver Transplantation, Hepatitis, Cholestasis, Carcinoma, Hepatocellular

Intervention / Treatment
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* Drug: IDN-6556
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 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: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Donor organ placebo and Recipient placebo<br> | Drug: Placebo<br> <br> |
| Active Comparator: Donor organ: IDN-6556 (15μg/ml), Recipient: Placebo<br> | Drug: IDN-6556<br> <br> Drug: Placebo<br> <br> |
| Active Comparator: Donor organ: IDN-6556 (5 μg/ml), Recipient: IDN-6556 0.5 mg/kg<br> | Drug: IDN-6556<br> <br> |
| Active Comparator: Donor organ: IDN-6556(15 μg/ml), Recipient: IDN-6556 0.5 mg/kg<br> | Drug: IDN-6556<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Liver Transplantation