Pharmacokinetic and Pharmacodynamic Study of IDN-6556 in ACLF

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)