Randomized Global Phase 3 Study to Evaluate the Impact on NASH With Fibrosis of Obeticholic Acid Treatment

Open to people ages 18-85

1. Histologic evidence of NASH upon central read of a liver biopsy obtained no more than 6 months before Day 1 defined by presence of all 3 key histological features of NASH according to NASH CRN criteria.

2. Histologic evidence of fibrosis stage 2 or stage 3 as defined by the NASH CRN scoring of fibrosis, or

   Histologic evidence of fibrosis stage 1a or stage 1b if accompanied by ≥1 of the following risk factors:

   • Obesity (BMI ≥30 kg/m2)
   • Type 2 diabetes diagnosed per 2013 American Diabetes Association criteria
   • ALT >1.5× upper limit of normal (ULN).
3. For subjects with a historical biopsy, is either not taking or is on stable doses of TZDs/glitazones or vitamin E for 6 months before Day 1.
4. Stable body weight.

1. Model for End-stage Liver Disease (MELD) score >12
2. ALT ≥10× ULN
3. HbA1c >9.5%
4. Total bilirubin >1.5 mg/dL
5. Evidence of other known forms of known chronic liver disease such as alcoholic liver disease, hepatitis B, hepatitis C, PBC, PSC, autoimmune hepatitis, Wilson disease, iron overload, alpha-1-antitrypsin deficiency, drug-induced liver injury, known or suspected hepatocellular carcinoma (HCC)
6. History of liver transplant, or current placement on a liver transplant list
7. Current or history of significant alcohol consumption
8. Prior or planned ileal resection, or prior or planned bariatric surgery

9. Histological presence of cirrhosis

   10. History of biliary diversion 11. Known positivity for human immunodeficiency virus infection. 12. Acute cholecystitis or acute biliary obstruction. 13. BMI >45 kg/m2