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

Primary Purpose

Liver Cirrhosis, Hepatic Cirrhosis

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
IDN-6556
Placebo
Sponsored by
Conatus Pharmaceuticals Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Liver Cirrhosis focused on measuring Liver Cirrhosis, Hepatic Cirrhosis

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept 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

Sites / Locations

  • University of Alabama at Birmingham
  • Scripps Clinic
  • Loma Linda University Medical Center
  • Cedar-Sinai Medical Center
  • Univeristy of California, San Diego
  • California Pacific Medical Center
  • University of Florida
  • University of Miami
  • Piedmont Atlanta Hospital
  • University of Chicago
  • Loyola University Medical Cente
  • Indiana University
  • University of Louisville
  • Henry Ford Hospital
  • Rutgers New Jersey Medical School
  • North Shore University Hospital
  • NYU Medical Center
  • Mt. Sinai School of Medicine
  • University of Cincinnati Physicians Company, LLC
  • University of Pennsylvania
  • Einstein Healthcare Network
  • Baylor All Saints Medical Center
  • Baylor College of Medicine
  • Baylor St. Luke's Medical Center
  • UT Health Science Center at Houston
  • University of Utah Hospital
  • Bon Secours Mary Immaculate Hospital
  • Bon Secours St. Mary's Hospital of Richmond, Inc.

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

IDN-6556

Placebo

Arm Description

25 mg BID of IDN-6556

Placebo BID

Outcomes

Primary Outcome Measures

Change From Baseline at Month 3 in cCK18/M30
Baseline, Month 3, and change between for cCK18/M30
Change From Baseline at Month 3 in cCK18/M30
Data was log-transformed for analysis purposes

Secondary Outcome Measures

Change From Baseline to Month 3 in MELD Score
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.

Full Information

First Posted
August 28, 2014
Last Updated
June 6, 2017
Sponsor
Conatus Pharmaceuticals Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT02230670
Brief Title
A Study of IDN-6556 in Subjects With Liver Cirrhosis
Acronym
LC
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

2. Study Status

Record Verification Date
June 2017
Overall Recruitment Status
Completed
Study Start Date
August 2014 (undefined)
Primary Completion Date
January 2016 (Actual)
Study Completion Date
January 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Conatus Pharmaceuticals Inc.

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Liver Cirrhosis, Hepatic Cirrhosis
Keywords
Liver Cirrhosis, Hepatic Cirrhosis

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
87 (Actual)

8. Arms, Groups, and Interventions

Arm Title
IDN-6556
Arm Type
Experimental
Arm Description
25 mg BID of IDN-6556
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo BID
Intervention Type
Drug
Intervention Name(s)
IDN-6556
Other Intervention Name(s)
emricasan, PF-03491390
Intervention Description
25 mg BID
Intervention Type
Drug
Intervention Name(s)
Placebo
Primary Outcome Measure Information:
Title
Change From Baseline at Month 3 in cCK18/M30
Description
Baseline, Month 3, and change between for cCK18/M30
Time Frame
3 months
Title
Change From Baseline at Month 3 in cCK18/M30
Description
Data was log-transformed for analysis purposes
Time Frame
3 months
Secondary Outcome Measure Information:
Title
Change From Baseline to Month 3 in MELD Score
Description
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.
Time Frame
3 Months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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: 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) 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Dave Hagerty, MD
Organizational Affiliation
Conatus Pharmaceuticals
Official's Role
Study Chair
Facility Information:
Facility Name
University of Alabama at Birmingham
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35233
Country
United States
Facility Name
Scripps Clinic
City
La Jolla
State/Province
California
ZIP/Postal Code
92037
Country
United States
Facility Name
Loma Linda University Medical Center
City
Loma Linda
State/Province
California
ZIP/Postal Code
92354
Country
United States
Facility Name
Cedar-Sinai Medical Center
City
Los Angeles
State/Province
California
ZIP/Postal Code
90048
Country
United States
Facility Name
Univeristy of California, San Diego
City
San Diego
State/Province
California
ZIP/Postal Code
92093
Country
United States
Facility Name
California Pacific Medical Center
City
San Francisco
State/Province
California
ZIP/Postal Code
94115
Country
United States
Facility Name
University of Florida
City
Gainesville
State/Province
Florida
ZIP/Postal Code
32610
Country
United States
Facility Name
University of Miami
City
Miami
State/Province
Florida
ZIP/Postal Code
33136
Country
United States
Facility Name
Piedmont Atlanta Hospital
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30309
Country
United States
Facility Name
University of Chicago
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60637
Country
United States
Facility Name
Loyola University Medical Cente
City
Maywood
State/Province
Illinois
ZIP/Postal Code
60153
Country
United States
Facility Name
Indiana University
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202
Country
United States
Facility Name
University of Louisville
City
Louisville
State/Province
Kentucky
ZIP/Postal Code
40202
Country
United States
Facility Name
Henry Ford Hospital
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48202
Country
United States
Facility Name
Rutgers New Jersey Medical School
City
Newark
State/Province
New Jersey
ZIP/Postal Code
07103
Country
United States
Facility Name
North Shore University Hospital
City
Manhasset
State/Province
New York
ZIP/Postal Code
11030
Country
United States
Facility Name
NYU Medical Center
City
New York
State/Province
New York
ZIP/Postal Code
10016
Country
United States
Facility Name
Mt. Sinai School of Medicine
City
New York
State/Province
New York
ZIP/Postal Code
10029
Country
United States
Facility Name
University of Cincinnati Physicians Company, LLC
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45267
Country
United States
Facility Name
University of Pennsylvania
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Facility Name
Einstein Healthcare Network
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19141
Country
United States
Facility Name
Baylor All Saints Medical Center
City
Fort Worth
State/Province
Texas
ZIP/Postal Code
76104
Country
United States
Facility Name
Baylor College of Medicine
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Baylor St. Luke's Medical Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
UT Health Science Center at Houston
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
University of Utah Hospital
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84132
Country
United States
Facility Name
Bon Secours Mary Immaculate Hospital
City
Newport News
State/Province
Virginia
ZIP/Postal Code
23602
Country
United States
Facility Name
Bon Secours St. Mary's Hospital of Richmond, Inc.
City
Richmond
State/Province
Virginia
ZIP/Postal Code
23226
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
29913280
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.
Results Reference
derived

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A Study of IDN-6556 in Subjects With Liver Cirrhosis

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