A Study of IDN-6556 in Subjects With Liver Cirrhosis

NCT ID: NCT02230670

Last Updated: 2017-07-05

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 87 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-08-31
• Study Completion Date: 2016-01-31

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.

Conditions

Liver Cirrhosis; Hepatic Cirrhosis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

IDN-6556

25 mg BID of IDN-6556

Group Type: EXPERIMENTAL

IDN-6556

Intervention Type: DRUG

25 mg BID

Placebo

Placebo BID

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Interventions

IDN-6556

25 mg BID

Intervention Type: DRUG

Placebo

Intervention Type: DRUG

Other Intervention Names

emricasan; PF-03491390

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Conatus Pharmaceuticals Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Dave Hagerty, MD

Role: STUDY_CHAIR

Conatus Pharmaceuticals Inc.

Locations

University of Alabama at Birmingham

Birmingham, Alabama, United States

Scripps Clinic

La Jolla, California, United States

Loma Linda University Medical Center

Loma Linda, California, United States

Cedar-Sinai Medical Center

Los Angeles, California, United States

Univeristy of California, San Diego

San Diego, California, United States

California Pacific Medical Center

San Francisco, California, United States

University of Florida

Gainesville, Florida, United States

University of Miami

Miami, Florida, United States

Piedmont Atlanta Hospital

Atlanta, Georgia, United States

University of Chicago

Chicago, Illinois, United States

Loyola University Medical Cente

Maywood, Illinois, United States

Indiana University

Indianapolis, Indiana, United States

University of Louisville

Louisville, Kentucky, United States

Henry Ford Hospital

Detroit, Michigan, United States

Rutgers New Jersey Medical School

Newark, New Jersey, United States

North Shore University Hospital

Manhasset, New York, United States

NYU Medical Center

New York, New York, United States

Mt. Sinai School of Medicine

New York, New York, United States

University of Cincinnati Physicians Company, LLC

Cincinnati, Ohio, United States

University of Pennsylvania

Philadelphia, Pennsylvania, United States

Einstein Healthcare Network

Philadelphia, Pennsylvania, United States

Baylor All Saints Medical Center

Fort Worth, Texas, United States

Baylor College of Medicine

Houston, Texas, United States

Baylor St. Luke's Medical Center

Houston, Texas, United States

UT Health Science Center at Houston

Houston, Texas, United States

University of Utah Hospital

Salt Lake City, Utah, United States

Bon Secours Mary Immaculate Hospital

Newport News, Virginia, United States

Bon Secours St. Mary's Hospital of Richmond, Inc.

Richmond, Virginia, United States

Countries

United States

References

Frenette CT, Morelli G, Shiffman ML, Frederick RT, Rubin RA, Fallon MB, Cheng JT, Cave M, Khaderi SA, Massoud O, Pyrsopoulos N, Park JS, Robinson JM, Yamashita M, Spada AP, Chan JL, Hagerty DT. Emricasan Improves Liver Function in Patients With Cirrhosis and High Model for End-Stage Liver Disease Scores Compared With Placebo. Clin Gastroenterol Hepatol. 2019 Mar;17(4):774-783.e4. doi: 10.1016/j.cgh.2018.06.012. Epub 2018 Jun 18.

Reference Type: DERIVED

PMID: 29913280 (View on PubMed)

Other Identifiers

IDN-6556-10

Identifier Type: -

Identifier Source: org_study_id