Clinical trial NCT02686762 (phase 2, status: completed)
Conditions: non-alcoholic steatohepatitis, fibrosis, liver diseases
ICD codes: K75.81, K74.01, K74.02, E84.9, J84.10, J84.112, K13.5, K74.00, K76.9, K71.8, K70.9, K71.9, K75.9, P78.84, Q44.6
Drugs: emricasan (5 mg), emricasan (50 mg), placebo
SMILES: C[C@H](NC(=O)C(=O)NC1=CC=CC=C1C(C)(C)C)C(=O)N[C@@H](CC(O)=O)C(=O)COC1=C(F)C(F)=CC(F)=C1F, C[C@H](NC(=O)C(=O)NC1=CC=CC=C1C(C)(C)C)C(=O)N[C@@H](CC(O)=O)C(=O)COC1=C(F)C(F)=CC(F)=C1F, CN1C(=O)C=C(N2CCC[C@@H](N)C2)N(CC2=C(C=CC=C2)C#N)C1=O
Eligibility criteria:

        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
             syndrome

          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
             lactating/breastfeeding

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

         23. Prior liver transplant