A Study of IDN-6556 in Subjects With Liver Cirrhosis (LC)

Conatus Pharmaceuticals

Status and phase

Completed

Phase 2

Conditions

Hepatic Cirrhosis

Liver Cirrhosis

Treatments

Drug: Placebo

Drug: IDN-6556

Study type

Interventional

Funder types

Industry

Identifiers

NCT02230670

IDN-6556-10

Details and patient eligibility

About

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.

Full 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.

Enrollment

87 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

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.

Exclusion criteria

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)
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:
1. Fibrates or statins
2. 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:
1. Systemic corticosteroids
2. Known or suspected use of illicit drugs or drugs of abuse (allowed if medically prescribed or indicated)
Concomitant pancreatitis
Active inflammatory bowel disease
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