Study of ADI-PEG 20 Versus Placebo in Subjects With NASH

Inclusion Criteria:

1. Males and non-lactating, pregnancy test negative females between 18 - 80 years ofage with biopsy proven F1 - F4 (compensated cirrhosis, Child-Pugh A, score ≤6) NASH.Limit F1 fibrosis to ≤ 20% of total subject population.

2. Willingness to use appropriate contraceptive measures throughout study treatment andfor 90 days thereafter (see Appendix A).

3. Body mass index (BMI) > 23 kg/m2

4. Must have confirmation of ≥ 5 % liver fat content on MRI-PDFF at screening.

5. Biopsy-proven NASH confirmed by a central pathologist. Must have had a liver biopsyeither during the screening period or a historical biopsy conducted within the last 6 months prior to pre-screening with fibrosis stage 1 to 4 (F score, F1-F4) and anon-alcoholic fatty liver disease (NAFLD) activity score (NAS) of ≥ 4 with at leasta score of 1 in each of the following NAS components:

6. Steatosis (scored 0 to 3),

7. Ballooning degeneration (scored 0 to 2), and

8. Lobular inflammation (scored 0 to 3).

9. Must have no evidence of worsening of ALT and AST (within 50%) measurements within 2months prior to screening (-8 weeks) visits.

10. Screening laboratory parameters, as determined by the central laboratory:

11. Estimated glomerular filtration rate (eGFR) ≥ 60 mL/min, as calculated by theCockcroft- Gault equation;

12. HbA1c ≤ 9.5% (or serum fructosamine ≤ 381 μmol if HbA1c is unable to beresulted);

13. Hemoglobin ≥ 11 g/dL;

14. INR ≤ 1.3, unless due to therapeutic anticoagulation;

15. Direct bilirubin ≤ 0.5 mg/dL;

16. Total bilirubin ≤ 1.3 x upper limit of normal (ULN), unless due to an alternateetiology such as Gilbert's syndrome or hemolytic anemia;

17. Creatinine kinase < 3 x ULN;

18. Platelet count ≥ 150,000/μL;

19. Serum triglyceride level ≤ 500 mg/dL;

20. ALT < 6 x ULN;

21. AST < 6 x ULN;

22. ALP < 2 x ULN.

23. FibroScan® measurement > 7.0 kPa and < 20.0 kPa.

24. Subjects on non-insulin dependent diabetic, weight loss, or lipid-modifyingmedication(s) must be on stable dose(s) for at least 3 months prior to thediagnostic liver biopsy through randomization.

25. Subjects on vitamin E and pioglitazone must maintain a stable dosage before thediagnostic liver biopsy and during the study period.

Exclusion Criteria:

1. Weight gain or loss > 5% in the 3 months prior to randomization or > 10% in the 6months prior to screening.

2. Type 1 and insulin-dependent Type 2 diabetes.

3. Poorly controlled hypertension (blood pressure [BP] > 160/100 mmHg).

4. Prior history of decompensated liver disease including ascites, hepaticencephalopathy (HE), or variceal bleeding.

5. Chronic hepatitis B virus (HBV) infection (hepatitis B surface antigen [HBsAg]positive.

6. Chronic hepatitis C virus (HCV) infection (HCV antibody [Ab] and HCV ribonucleicacid [RNA] positive). Subjects cured of HCV infection less than 1 year prior (basedon date of RNA polymerase chain reaction [PCR] negative confirmation followingconclusion of treatment) to the screening visit are not eligible.

7. Prior or planned (during the study period) bariatric surgery (e.g., gastroplasty,roux-en-Y gastric bypass), surgery reversal or removal of intragastric balloon > 2years prior to enrollment would be eligible.

8. Other causes of liver disease based on medical history and/or centralized review ofliver histology, including but not limited to alcoholic liver disease, autoimmunedisorders (e.g., primary biliary cholangitis [PBC], primary sclerosing cholangitis [PSC], autoimmune hepatitis), drug-induced hepatotoxicity, Wilson disease,clinically significant iron overload, or alpha-1-antitrypsin deficiency requiringtreatment.

9. History of liver transplantation.

10. Subjects with primary cancer, including co-existent second malignancy, with theexception of primary solid tumor with no known active disease present in the opinionof the Investigator which will not affect subject outcome in the setting of currentdiagnosis.

11. Alcohol intake above an average limit of 2 drinks per day for women and 3 drinks perday for men. An alcoholic drink is defined as 12 ounces of regular beer, which isusually about 5% alcohol, 5 ounces of wine, which is typically about 12% alcohol,and 1.5 ounces of distilled spirits, which is about 40% alcohol.

12. Human immunodeficiency virus (HIV) infection.

13. Unstable cardiovascular disease in the 6 months prior to screening.

14. Life expectancy less than 2 years.

15. Use of any investigational medication within 30 days or within 5 half-lives of theinvestigational medication, whichever is longer, prior to screening and throughoutthe study is prohibited.

16. Subjects with a history of (12 months prior to baseline) or current use ofprescription drugs associated with liver steatosis (e.g., methotrexate, amiodarone,high-dose estrogen, tamoxifen, systemic steroids, anabolic steroids, valproic acid)should be excluded. However, subjects currently using silymarin should maintaintheir current dosage throughout the trial period.

17. Contraindication of magnetic resonance imaging. These include but are not limited todevices or metal foreign bodies, such as Pacemaker, defibrillator or wires otherthan sternal wires, metallic foreign body in the eye, "triggerfish" contact lens,gastric reflux device, and insulin pumps.

18. MELD score >12

19. Subjects with esophageal or gastric varices with recent bleeding episodes (within 1year).