Study of IDN-6556 in Patients With Severe Alcoholic Hepatitis and Contraindications to Steroid Therapy
Condition: Alcoholic Hepatitis
MeSH terms: Hepatitis A; Hepatitis; Hepatitis, Alcoholic
Intervention: IDN-6556; Placebo
Intervention description: 25 mg BID for 28 days; Placebo controlled
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 5.0
Sex: All
Minimum age: 21 Years
Healthy volunteers: No
Keywords: alcoholic hepatitis

Summary:

      The main purpose of the study is to test if taking a study drug called emricasan (also known
      as IDN-6556 and PF-03491390) will affect overall patient survival after one month of
      treatment.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Able to provide written informed consent (either from patient or patient's legally
             acceptable representative), and understand and willing to comply with the requirements
             of the study

          2. Male or female patients 21 years of age or older

          3. Patients with alcoholic hepatitis defined as:

               1. History of heavy alcohol abuse use: >40 g/day in females and >60 g/day in males
                  for most days in a minimum period of 6 months

               2. Consumed alcohol within 6 weeks of entry into the study

               3. Biochemical parameters of severe disease as evidenced by MELD score >20 but <35,
                  or MELD score 35-40 if the SOFA score is <10

          4. Willingness to utilize 2 reliable forms of contraception (for both males and females
             of childbearing potential) from screening to 1 month after the completion of study
             treatment

          5. Patients with established contraindications to steroid use including but not limited
             to the following:

               1. GI bleed

               2. Active infection, including spontaneous bacterial peritonitis, based on positive
                  blood culture, urine culture, or chest x-ray (if positive, must have been on
                  antibiotics for at least 24 hours prior to study entry)

               3. Acute pancreatitis (increased lipase > 3x ULN or radiologic evidence)

               4. Positivity for hepatitis B (HBsAg+) or C virus (HCV+), and

               5. Renal failure

        Exclusion Criteria:

          1. Other or concomitant cause of liver disease as a result of:

               1. Autoimmune liver disease (positive anti-mitochondrial antibody and smooth muscle
                  antibody, positive reading on anti-nuclear antibody titer >1:160)

               2. Metabolic liver disease (abnormal ceruloplasmin levels)

               3. Vascular liver disease

               4. Drug induced liver disease Note: Concurrent viral hepatitis is not excluded.

          2. Co-infection with human immunodeficiency virus (HIV)

          3. Sepsis as evidenced by positive blood or urine culture, or pneumonia as confirmed by
             x-ray

          4. History of renal transplant and/or on dialysis at time of entry into study

          5. Inflammatory bowel disease

          6. Diagnosed or suspected systemic lupus erythematosus (SLE) and/or rheumatoid arthritis
             (RA)

          7. Hepatocellular carcinoma (HCC) at entry into the study

          8. Active non-liver malignancies other than curatively treated skin cancer (basal cell or
             squamous cell carcinomas)

          9. Active tuberculosis on chest x-ray at study entry

         10. History or presence of clinically concerning cardiac arrhythmias, or prolongation of
             screening (pre-treatment) QT or QTc interval of >480 milliseconds (msec)

         11. Significant systemic or major illness other than liver disease, including coronary
             artery disease, cerebrovascular disease, pulmonary disease, renal failure, serious
             psychiatric disease, that, in the opinion of the Investigator would preclude the
             patient from participating in and completing the study

         12. Patients requiring the use of vasopressors or inotropic support

         13. Liver biopsy, if carried out, showing findings not compatible with alcoholic hepatitis

         14. Any patient that has received any investigational drug or device within 30 days of
             dosing or who is scheduled to receive another investigational drug or device in the
             course of the study Note: Investigational drug includes any drug that is used
             off-label.

         15. If female, known pregnancy, or has a positive urine or serum pregnancy test, or
             lactating/breastfeeding

         16. If male, if partner is known to be pregnant at time of entry into study or becomes
             pregnant while patient is on study drug or up to 1 month after completion of study
             drug

         17. Appropriate candidate for corticosteroid therapy

         18. Treatment for alcohol hepatitis within 1 month of study entry with use of
             corticosteroids for >1 week or corticosteroid use at the time of entry into the study.