Pharmacokinetic and Pharmacodynamic Study of IDN-6556 in ACLF
Condition: Acute on Chronic Hepatic Failure; Acute Liver Failure; Liver Cirrhosis; Acute Alcoholic Hepatitis
MeSH terms: Hepatitis; Liver Cirrhosis; Liver Failure; Hepatic Insufficiency; Hepatitis, Alcoholic; Liver Failure, Acute; Fibrosis
Intervention: IDN-6556; Placebo
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 23.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Liver Failure; Cirrhosis; Alcoholic Hepatitis

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.
    

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)