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

Inclusion Criteria:

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.

Exclusion Criteria:

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