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.

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