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

The primary objectives of this study are to evaluate the effect of Obeticholic Acid
treatment compared to placebo on 1) histological improvement and 2) liver-related clinical
outcomes in patients with non-cirrhotic nonalcoholic steatohepatitis (NASH) with liver
fibrosis.

Eligibility Criteria

Inclusion Criteria:

1. Histologic evidence of NASH following a liver biopsy obtained no more than 6 months
before Day 1.

2. Histologic evidence of fibrosis stage 1, stage 2 or stage 3.

3. Is either not taking or is on stable doses of :

- TZDs or vitamin E

- Therapies for diabetes

- Allowed concomitant medications

4. Stable body weight.

5. Age ≥18 years.

6. Female subjects of childbearing potential must use ≥1 effective method of
contraception during the study and until 4 weeks following the last dose of
investigational product or at study termination.

7. Must provide written informed consent and agree to comply with the study protocol.

Exclusion Criteria:

1. Current or history of significant alcohol consumption.

2. Prior or planned (during the study period) bariatric surgery or ileal resection.

3. HbA1c ≥9.0% within 60 Days before Day 1.

4. Evidence of other forms of chronic liver disease including:

- Positive test result for hepatitis B surface antigen or hepatitis C antibody

- Primary biliary cirrhosis, primary sclerosing cholangitis, autoimmune hepatitis,
or overlap syndrome

- Alcoholic liver disease

- Wilson's disease, hemochromatosis, or iron overload

- Alpha-1-antitrypsin (A1AT) deficiency

- Prior known drug-induced liver injury

- Known or suspected HCC

- History of liver transplant, current placement on a liver transplant list, or
current MELD score >12

5. Histological presence of cirrhosis.

6. Total bilirubin >1.5 mg/dL.

7. AST >10× ULN, international normalized ratio (INR) >1.3, or serum creatinine ≥1.5
mg/dL.

8. Creatinine Phospho Kinase > 5xULN

9. Platelet count <100,000/mm3.

10. LDL ≥190mg/dL and already on statin therapy.

11. Inability to safely undergo a liver biopsy.

12. History of biliary diversion.

13. Known positivity for human immunodeficiency virus infection.

14. Recent history of specific types of cardiovascular disease.

15. Other medical conditions that may diminish life expectancy to <2 years, including
known cancers.

16. Known substance abuse.

17. Pregnancy, planned pregnancy, potential for pregnancy or current or planned breast
feeding.

18. Participated in a clinical research study with any investigational product being
evaluated for the treatment of diabetes, weight loss, or NASH in the 6 months before
Day 1.

19. Received any investigational product not being evaluated for the treatment of
diabetes, weight loss, or NASH within 30 days before Day 1.

20. Previous exposure to Obeticholic Acid.

21. Mental instability or incompetence, such that the validity of informed consent or
ability to be compliant with the study, is uncertain.

22. History of known or suspected clinically significant hypersensitivity to Obeticholic
Acid or any of its components.

23. Any other condition that, in the opinion of the Investigator, would impede compliance
or hinder completion of the study

Principal Investigator

Winston Dunn, MD

Study Contact

Brian Bridges, 913-945-7830, bbridges@kumc.edu

Estimated Completion Date

Friday, October 1, 2021

ClinicalTrials.gov #

NCT02548351
07/19/2016