Pharmacokinetic and Pharmacodynamic Study of IDN-6556 in ACLF

Brief Summary
The study will evaluate the pharmacokinetics, pharmacodynamics, safety and preliminary efficacy of IDN-6556 in subjects with cirrhosis of the liver who are hospitalized for more than 24 hours due to acute deterioration of liver function.
Brief Title
Pharmacokinetic and Pharmacodynamic Study of IDN-6556 in ACLF
Completion Date
Completion Date Type
Actual
Conditions
Acute on Chronic Hepatic Failure
Acute Liver Failure
Liver Cirrhosis
Acute Alcoholic Hepatitis
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 understand and comply with the requirements of the study
* Subjects with a clinical, radiological and/or histological diagnosis of cirrhosis
* Subjects having not required hospital admission within 4 weeks of screening for a complication of cirrhosis
* Subjects with an acute deterioration of liver function
* Subjects who meet one of the following criteria:

1. Subjects with renal failure (defined as creatinine ≥ 2.0 to ≤ 3.4 mg/dL)
2. Subjects with other single organ failure with i. Renal impairment (defined as an increase in creatinine of \> 0.3 mg/dL from either an established prior Baseline level or if applicable, upon admission to hospital if prior level is unavailable; for inclusion, the creatinine level must be raised above normal levels), and/or ii. Hepatic encephalopathy grade I or II
3. Subjects with two organ failures
* If a subject received steroids for alcohol-induced acute liver failure, he/she must be unresponsive to steroid therapy. Responsiveness is based on investigator discretion.
* 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 HIV
* Subjects with cirrhosis who develop decompensation at any time in the postoperative period following partial hepatectomy
* Subjects with evidence of uncontrolled infection defined as persistent bacterial culture positivity despite adequate antibiotic therapy
* Subjects with clinical evidence of disseminated intravascular coagulation
* Subjects with chronic and/or pre-existing kidney disease defined as eGFR (estimated glomerular filtration rate) of less than 30 mL/min for 3 months or longer
* Subjects who are hypotensive (defined as mean arterial pressure \<70 mmHg) or require the use of inotropic support
* Subjects with evidence of significant and/or uncontrolled bleeding
* Subjects requiring mechanical ventilation
* 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
* Subjects previously exposed to IDN-6556
* History or presence of clinically concerning cardiac arrhythmias, or prolongation of Screening (pre-treatment) QT or QTc interval of \> 480 milliseconds (msec)
Inclusion 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 understand and comply with the requirements of the study
* Subjects with a clinical, radiological and/or histological diagnosis of cirrhosis
* Subjects having not required hospital admission within 4 weeks of screening for a complication of cirrhosis
* Subjects with an acute deterioration of liver function
* Subjects who meet one of the following criteria:

1. Subjects with renal failure (defined as creatinine ≥ 2.0 to ≤ 3.4 mg/dL)
2. Subjects with other single organ failure with i. Renal impairment (defined as an increase in creatinine of \> 0.3 mg/dL from either an established prior Baseline level or if applicable, upon admission to hospital if prior level is unavailable; for inclusion, the creatinine level must be raised above normal levels), and/or ii. Hepatic encephalopathy grade I or II
3. Subjects with two organ failures
* If a subject received steroids for alcohol-induced acute liver failure, he/she must be unresponsive to steroid therapy. Responsiveness is based on investigator discretion.
* 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

Gender
All
Gender Based
false
Keywords
Liver Failure
Cirrhosis
Alcoholic Hepatitis
Healthy Volunteers
No
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT01937130
Org Class
Industry
Org Full Name
Conatus Pharmaceuticals Inc.
Org Study Id
IDN-6556-02
Overall Status
Terminated
Phases
Phase 2
Primary Completion Date
Primary Completion Date Type
Actual
Official Title
A Placebo-Controlled, Multicenter, Double-Blind, Randomized, Pharmacokinetic and Pharmacodynamic Trial of IDN-6556 in Subjects With Acute-on-Chronic Liver Failure
Primary Outcomes
Outcome Description
Primary endpoints for AUC_0-8, AUC_0 last, AUC_0-inf on Day 1 and Day 4 for the active treatment arms were analyzed.
Outcome Measure
Area Under the Curve (AUC)
Outcome Time Frame
28 days
Outcome Description
Primary endpoints forCmax on Day 1 and Day 4 for the active treatment arms were analyzed.
Outcome Measure
Cmax
Outcome Time Frame
28 Days
Outcome Description
Primary endpoints for tmax \& t1/2 on Day 1 and Day 4 for the active treatment arms were analyzed.
Outcome Measure
Tmax & t1/2 Parameters
Outcome Time Frame
28 Days
Secondary Outcomes
Outcome Description
Caspase-cleaved cytokeratin serum levels (CK18/M30)
Outcome Time Frame
Baseline, Day 2, Day 4, Day 7, Day 14, Day 21, and Day 28
Outcome Measure
Levels of CK18/M30
Outcome Description
Caspase full-length cytokeratin serum levels CK18/M65
Outcome Time Frame
Baseline, Day 2, Day 4, Day 7, Day 14, Day 21, and Day 28
Outcome Measure
Levels of CK18/M65
Outcome Description
Concentration of Caspase 3/7 Relative Light Units
Outcome Time Frame
Baseline, Day 2, Day 4, Day 7, Day 14, Day 21, and Day 28
Outcome Measure
Levels of Caspase 3/7 RLU
Start Date
Status Verified Date
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Harmit Kalia
Investigator Email
hkalia@montefiore.org
Investigator Phone
347-443-1783