Emricasan, a Caspase Inhibitor, for Evaluation in Subjects With Non-Alcoholic Steatohepatitis (NASH) Fibrosis

Not Recruiting

Trial ID: NCT02686762


This is a multicenter, double-blind, randomized, placebo-controlled trial involving subjects with a diagnosis of "definite NASH" with fibrosis (excluding cirrhosis) as determined by the central histopathologist. Upon successful screening, subjects will be randomized to receive either emricasan 50 mg BID or emricasan 5 mg BID or matching placebo BID.

Official Title

A Multicenter, Randomized, Double-Blind, Placebo-controlled Trial of Emricasan (IDN-6556-12), an Oral Caspase Inhibitor, in Subjects With Non-alcoholic Steatohepatitis (NASH) Fibrosis

Stanford Investigator(s)

W. Ray Kim
W. Ray Kim

Professor of Medicine (Gastroenterology and Hepatology)


Inclusion Criteria:

   1. Male or female subjects 18 years or older, able to provide written informed consent,
   and able to understand and willing to comply with the requirements of the study

   2. Histological evidence of definite NASH based on NASH CLinical Research Network (CRN)
   criteria, as confirmed by the central histopathologist, on a liver biopsy obtained no
   more than 6 months prior to Day 1

   3. NAFLD Activity Score (NAS) of 4 or greater with a score of at least 1 in each
   component of the NAS (steatosis scored 0-3, lobular inflammation scored 0-3,
   ballooning scored 0-2)

   4. Fibrosis stage 1 (limited to 20% of subjects), stage 2, or stage 3 using the NASH CRN
   Histologic Scoring System

   a. Subjects with fibrosis stage 1 must also have diabetes mellitus or metabolic

   5. Willingness to utilize effective contraception (for both males and females of
   childbearing potential) from Screening to 4 weeks after the last dose of study drug

   6. If on vitamin E or pioglitazone, subjects must have been on a stable dose for at least
   3 months prior to the biopsy (whether historical or qualifying biopsy)

Exclusion Criteria:

   1. Current or history of significant alcohol consumption, defined as more than 20 g/day
   for females and more than 30 g/day in males on average, or inability to reliably
   quantify alcohol consumption based on investigator's judgement

   2. Use of the following drugs (which may have potential hepatotoxic effects) within 6
   months prior to Day 1: amiodarone, methotrexate, tamoxifen, valproic acid, estrogens
   at doses greater than those used for hormone replacement or contraception, anabolic
   steroids, or systemic glucocorticoids for more than 4 weeks at doses greater than
   replacement doses

   3. Uncontrolled diabetes (HbA1c ≥9%) within 60 days prior to Day 1

   4. Presence of cirrhosis on liver biopsy (fibrosis stage 4 based on the central
   histopathologist reading)

   5. Hepatitis and fibrosis more likely related to etiologies other than NASH such as:

      1. alcoholic steatohepatitis

      2. autoimmune hepatitis

      3. hepatitis B virus (HBV) infection

      4. hepatitis C virus (HCV) infection

      5. primary biliary cirrhosis

      6. primary sclerosing cholangitis

      7. Wilson's disease

      8. alpha-1-antitrypsin deficiency

      9. hemochromatosis or iron overload

   10. drug-induced liver disease

   11. other biliary liver disease

   6. ALT or AST >5 times upper limit of normal (ULN) or total bilirubin >1.5 times ULN
   during screening (unless subject has elevated total bilirubin due to Gilbert's as
   documented in the medical records)

   7. Alpha-fetoprotein >200 ng/mL

   8. Hemoglobin <10 g/dL

   9. White blood cell count <2.0 x 10^3/mm3

10. Estimated creatinine clearance <30 mL/min

11. Current use of the following medications that are considered significant inhibitors of
   OATP1B1 and OATP1B3 transporters: atazanavir, cyclosporine, eltrombopag, gemfibrozil,
   indinavir, lopinavir, ritonavir, rifampin, saquinavir, simeprevir, telaprevir,
   tipranovir, or some combination of these medications

12. Symptoms of biliary colic, e.g. due to symptomatic gallstones, within the last 6
   months, unless resolved following cholecystectomy

13. Inability to safely obtain a liver biopsy

14. Known human immunodeficiency virus (HIV) infection

15. Weight loss ≥ 10% within 6 months of Day 1

16. Use of controlled substances (including inhaled or injected drugs) or non-prescribed
   use of prescription drugs within 1 year of screening to the point of interfering with
   the subject's ability to comply with study procedures and study drug administration in
   the investigator's judgement

17. History of or active malignancies, other than those successfully treated with curative
   intent and believed to be cured

18. Significant systemic or major illness other than liver disease that in the opinion of
   the investigator would preclude the subject from participating in and completing the
   study, including but not limited to acute coronary syndrome or stroke within 6 months
   of screening or major surgery within 3 months of screening

19. History or presence of clinically concerning cardiac arrhythmias, or prolongation of
   Screening (pre-treatment) QTcF interval >480 milliseconds (msec)

20. Prior or planned (during the time frame of the study) bariatric surgery

21. If female: planned or known pregnancy, positive urine or serum pregnancy test, or

22. Previous treatment with emricasan or active investigational medication in a clinical
   trial within 6 months prior to Day 1

23. Prior liver transplant


drug: Emricasan (5 mg)

drug: Emricasan (50 mg)

drug: Placebo

Not Recruiting

Contact Information

Stanford University
School of Medicine
300 Pasteur Drive
Stanford, CA 94305
Alexis Touros
(650) 721-4285