A Study of IDN-6556 in Subjects With Liver Cirrhosis
- Registration Number
- NCT02230670
- Lead Sponsor
- Conatus Pharmaceuticals Inc.
- Brief Summary
This is a multicenter study to see if treatment with IDN-6556 can help improve the liver function of patients with liver cirrhosis with Model for End-Stage Liver Disease scores between 11-18.
- Detailed Description
Numerous studies have shown that caspase cleaved cytokeratin 18 (cCK18) is elevated in the serum of liver disease patients and has been associated with disease severity, thus associating both excessive apoptosis and caspase activity with disease. Studies have also shown that caspase cleaved cytokeratin 18 is generally elevated to an even greater degree in cirrhosis than in other liver diseases. In addition, increasing stages of cirrhosis from Child-Pugh A, Child-Pugh B to Child-Pugh C are associated with progressively higher levels of caspase cleaved cytokeratin 18. Therefore, it appears that apoptosis and caspase activity tend to correlate with the stage of cirrhosis. A caspase inhibitor like IDN-6556 could have clinical utility by reducing the rate of apoptosis in cirrhotic patients and potentially reduce the progression of disease as determined by clinical markers of progression.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 87
- Male or female subjects of minimum adult legal age (according to local laws for signing the informed consent document), able to provide written informed consent, and able to understand and willing to comply with the requirements of the study
- Clinical, radiological, or biochemical evidence of liver cirrhosis
- Model for End-Stage Liver Disease (MELD) Score of 11 to 18 during the Screening period
- Willingness to utilize two reliable forms of contraception (for both males and females of childbearing potential) from Screening to one month after the last dose of study drug.
-
Known infection with human immunodeficiency virus (HIV)
-
Auto-immune hepatitis
-
Subjects with evidence of uncontrolled infection, defined as persistent bacterial culture positivity despite adequate antibiotic therapy
-
HCV infected subjects who are receiving or plan to receive anti-viral therapy during the study
-
Untreated esophageal varices with high risk stigmata for hemorrhage
-
Variceal hemorrhage within 3 months of Screening
-
Ascites not adequately controlled on stable background medication
-
Other non-liver organ failure
-
Child-Pugh score of 10-15 (Child-Pugh C classification)
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Use of vasoactive drugs (at or within 3 months of Screening) that may impair hepatic blood flow
-
Change in dose or regimen within 3 months of Screening of:
- Fibrates or statins
- Angiotensin II receptor antagonist or angiotensin converting enzyme (ACE) inhibitor
-
Use of chronic anticoagulation therapy including but not limited to Vitamin K/Factor Xa antagonists/inhibitors
-
Use of the following drugs within 2 months of Screening:
- Systemic corticosteroids
- Known or suspected use of illicit drugs or drugs of abuse (allowed if medically prescribed or indicated)
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Concomitant pancreatitis
-
Active inflammatory bowel disease
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Diagnosed or suspected systemic lupus erythematosus (SLE) and/or rheumatoid arthritis (RA)
-
Subjects with active or history of malignancies other than hepatocellular carcinoma (HCC) within Milan criteria or curatively treated skin cancer (basal cell or squamous cell carcinomas), unless adequately treated or in complete remission for five or more years
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description IDN-6556 IDN-6556 25 mg BID of IDN-6556 Placebo Placebo Placebo BID
- Primary Outcome Measures
Name Time Method Change From Baseline at Month 3 in cCK18/M30 3 months Data was log-transformed for analysis purposes
- Secondary Outcome Measures
Name Time Method Change From Baseline to Month 3 in MELD Score 3 Months The Model for End-Stage Liver Disease (MELD) is a scoring system for assessing the severity of chronic liver disease and uses the subject's values for total bilirubin, serum creatinine, and the international normalized ratio (INR) for prothrombin time to predict survival. MELD is calculated according to the following formula:
MELD = 3.78×ln\[serum bilirubin (mg/dL)\] + 11.2×ln\[INR\] + 9.57×ln\[serum creatinine (mg/dL)\] + 6.43
MELD scores are reported as whole numbers, so the result of the equation above is rounded. Notes: If the patient has been dialyzed twice within the last 7 days, then the value for serum creatinine used should be 4.0. Any value less than one is given a value of 1 (i.e. if bilirubin is 0.8, a value of 1.0 is used) to prevent the occurrence of scores below 0 (the natural logarithm of 1 is 0, and any value below 1 would yield a negative result). The higher the MELD score the more severe the disease state.
Trial Locations
- Locations (28)
Loma Linda University Medical Center
🇺🇸Loma Linda, California, United States
University of Chicago
🇺🇸Chicago, Illinois, United States
Cedar-Sinai Medical Center
🇺🇸Los Angeles, California, United States
Univeristy of California, San Diego
🇺🇸San Diego, California, United States
University of Miami
🇺🇸Miami, Florida, United States
Baylor St. Luke's Medical Center
🇺🇸Houston, Texas, United States
UT Health Science Center at Houston
🇺🇸Houston, Texas, United States
Piedmont Atlanta Hospital
🇺🇸Atlanta, Georgia, United States
Loyola University Medical Cente
🇺🇸Maywood, Illinois, United States
Rutgers New Jersey Medical School
🇺🇸Newark, New Jersey, United States
University of Pennsylvania
🇺🇸Philadelphia, Pennsylvania, United States
Baylor College of Medicine
🇺🇸Houston, Texas, United States
Scripps Clinic
🇺🇸La Jolla, California, United States
California Pacific Medical Center
🇺🇸San Francisco, California, United States
University of Florida
🇺🇸Gainesville, Florida, United States
Indiana University
🇺🇸Indianapolis, Indiana, United States
University of Louisville
🇺🇸Louisville, Kentucky, United States
North Shore University Hospital
🇺🇸Manhasset, New York, United States
University of Cincinnati Physicians Company, LLC
🇺🇸Cincinnati, Ohio, United States
NYU Medical Center
🇺🇸New York, New York, United States
Baylor All Saints Medical Center
🇺🇸Fort Worth, Texas, United States
Mt. Sinai School of Medicine
🇺🇸New York, New York, United States
University of Utah Hospital
🇺🇸Salt Lake City, Utah, United States
Bon Secours St. Mary's Hospital of Richmond, Inc.
🇺🇸Richmond, Virginia, United States
Bon Secours Mary Immaculate Hospital
🇺🇸Newport News, Virginia, United States
Einstein Healthcare Network
🇺🇸Philadelphia, Pennsylvania, United States
University of Alabama at Birmingham
🇺🇸Birmingham, Alabama, United States
Henry Ford Hospital
🇺🇸Detroit, Michigan, United States