Clinical trial NCT02230670: A Study of IDN-6556 in Subjects With Liver Cirrhosis
Official title: A Multicenter, Double-Blind, Placebo Controlled Study to Evaluate the Safety, Tolerability and Efficacy of IDN-6556 in Subjects With Liver Cirrhosis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Liver Cirrhosis
Hepatic Cirrhosis
Keywords: Liver Cirrhosis
Hepatic Cirrhosis
Lead sponsor: Conatus Pharmaceuticals Inc.
Sponsor class: INDUSTRY
First posted: 2014-09-03
Enrollment: 87
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Change From Baseline at Month 3 in cCK18/M30
timeFrame: 3 months
measure: Change From Baseline at Month 3 in cCK18/M30
timeFrame: 3 months
Secondary outcomes:
measure: Change From Baseline to Month 3 in MELD Score
timeFrame: 3 Months
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: La Jolla
country: United States
facility: Scripps Clinic
state: California
city: Loma Linda
country: United States
facility: Loma Linda University Medical Center
state: California
city: Los Angeles
country: United States
facility: Cedar-Sinai Medical Center
state: California
city: San Diego
country: United States
facility: Univeristy of California, San Diego
state: California
city: San Francisco
country: United States
facility: California Pacific Medical Center
state: California
city: Gainesville
country: United States
facility: University of Florida
state: Florida
city: Miami
country: United States
facility: University of Miami
state: Florida
city: Atlanta
country: United States
facility: Piedmont Atlanta Hospital
state: Georgia
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
city: Maywood
country: United States
facility: Loyola University Medical Cente
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University
state: Indiana
city: Louisville
country: United States
facility: University of Louisville
state: Kentucky
city: Detroit
country: United States
facility: Henry Ford Hospital
state: Michigan
city: Newark
country: United States
facility: Rutgers New Jersey Medical School
state: New Jersey
city: Manhasset
country: United States
facility: North Shore University Hospital
state: New York
city: New York
country: United States
facility: NYU Medical Center
state: New York
city: New York
country: United States
facility: Mt. Sinai School of Medicine
state: New York
city: Cincinnati
country: United States
facility: University of Cincinnati Physicians Company, LLC
state: Ohio
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Philadelphia
country: United States
facility: Einstein Healthcare Network
state: Pennsylvania
city: Fort Worth
country: United States
facility: Baylor All Saints Medical Center
state: Texas
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
city: Houston
country: United States
facility: Baylor St. Luke's Medical Center
state: Texas
city: Houston
country: United States
facility: UT Health Science Center at Houston
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah Hospital
state: Utah
city: Newport News
country: United States
facility: Bon Secours Mary Immaculate Hospital
state: Virginia
city: Richmond
country: United States
facility: Bon Secours St. Mary's Hospital of Richmond, Inc.
state: Virginia
Study officials:
affiliation: Conatus Pharmaceuticals Inc.
name: Dave Hagerty, MD
role: STUDY_CHAIR
References:
citation: 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.