Acute-on-Chronic Liver Failure
Conditions
Sponsors
Conatus Pharmaceuticals Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. 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 2. Subjects with a clinical, radiological and/or histological diagnosis of cirrhosis 3. Subjects having not required hospital admission within 4 weeks of screening for a complication of cirrhosis Note: A variceal hemorrhage requiring hospitalization within 4 weeks of screening is acceptable if it did not result in further complications. 4. Subjects with an acute deterioration of liver function Note: Acute deterioration is defined as a decompensating event or illness (including but not limited to alcohol use, GI hemorrhage, etc.) of = 6 weeks’ duration on a background of chronic liver disease. 5. Subjects who meet one of the following criteria: a) Subjects with renal failure (defined as creatinine = 2.0 to = 3.4 mg/dL) b) 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 c) Subjects with two organ failures Note: If hospitalized, assessments for organ failure can be made at hospital admission (or after the subject has been treated for any precipitating event). Organ failure is defined as follows: Liver: bilirubin = 12.0 mg/dL Kidney: creatinine = 2.0 to = 3.4 mg/dL Cerebral: hepatic encephalopathy grade III or IV Coagulation: INR = 1.7 Lung and Circulatory failures are not defined due to the likely need for mechanical ventilation and inotropic support, respectively (see exclusion criteria). 6. 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. Note: Dose and duration of steroid therapy prior to determining responsiveness is to be defined by the treating physician. 7. 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 Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 50 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 10
Exclusion criteria
Exclusion criteria: 1. Known infection with HIV 2. Subjects with cirrhosis who develop decompensation at any time in the postoperative period following partial hepatectomy 3. Subjects with evidence of uncontrolled infection defined as persistent bacterial culture positivity despite adequate antibiotic therapy 4. Subjects with clinical evidence of disseminated intravascular coagulation 5. 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 6. Subjects who are hypotensive (defined as mean arterial pressure 480 milliseconds (msec) 12. If female: known pregnancy, or has a positive urine or serum pregnancy test, or is lactating/breastfeeding
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary end point(s): IDN-6556 Pharmacokinetic Evaluation, Pharmacodynamic Evaluation ; Main Objective: To assess the pharmacokinetics and pharmacodynamics of IDN-6556 in subjects with Acute-on-Chronic Liver Failure (ACLF). ; Secondary Objective: To assess the safety of IDN-6556 in subjects with ACLF. To evaluate the clinical outcomes following treatment with IDN-6556. ; Timepoint(s) of evaluation of this end point: PK - Day 1: pre-dose and 0.5, 1, 2, 3, 4, 5, 8, and 12 hours post-dose; Day 4: Up to 8 hours if hospitalized, following Day 1 scheme (If not hospitalized, no PK samples taken); Single sample on date of discharge from hospital or Day 28. PD – Day 1, 2, 3-7, 8-14, 15-21, 22-28, and 28/EOT. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Safety Assessment, Clinical Outcomes ;Timepoint(s) of evaluation of this end point: Screening, Day 1, 2, 3-7, 8-14, 15-21, 22-28, and 28/EOT | — |
Countries
United Kingdom, United States
Contacts
Public ContactClinical Operations
Conatus Pharmaceuticals, Inc.
Outcome results
None listed