FXR Effect on Severe Alcohol-Associated Hepatitis (FRESH) Study

Inclusion Criteria:

1. Males or females aged 18 to 65 years (inclusive)

2. Clinical diagnosis of sAH based on all the following:

3. History of ongoing excess alcohol (>60 g/day [male] or >40 g/day [female]) usefor ≥6 months, with <60 days of abstinence prior to the onset of jaundice

4. Serum total bilirubin >3.0 mg/dL

5. Aspartate aminotransferase (AST) ≥50 U/L

6. AST/Aspartate aminotransferase (ALT) ratio ≥1.5

7. Onset of jaundice within prior 8 weeks

8. Maddrey's Discriminant Factor (mDF) ≥32 and ≤70

9. MELD score 18 to 25 (inclusive)

10. Female participants must be postmenopausal, surgically sterile, or, if premenopausal (and not surgically sterile), be prepared to use ≥1 highly effective method ofcontraception from the initiation of Screening and for 90 days after the last doseof investigational product as follows:

• Surgical sterilization (bilateral tubal occlusion, etc.)

• Placement of an intrauterine device (IUD) or intrauterine system (e.g.,intrauterine hormone-releasing system [IUS])

• Combined (estrogen and progesterone containing) hormonal contraceptiveassociated with inhibition of ovulation:

• Oral

• Intravaginal

• Transdermal

• Progesterone-only hormonal contraception associated with inhibition ofovulation:

• Oral

• Injectable

• Implantable

• Sexual abstinence: Defined as avoiding all types of activity that could resultin conception (pregnancy) from the initiation of Screening and until at least 90 days after the last dose of investigational product

5. Male participants who are sexually active with female partners of childbearingpotential must agree to use a condom with spermicide and to use 1 other approvedmethod of highly effective contraception from the initiation of Screening and untilat least 90 days after the dose of investigational product as listed in InclusionCriteria #3.

6. Male participants must refrain from sperm donation from the initiation of Screeningand until at least 90 days after the last dose of investigational product

7. Must provide written informed consent and agree to comply with the study protocol.In participants with hepatic encephalopathy which may impair decision-making,consent will be obtained per hospital procedures (e.g., by Legally AuthorizedRepresentative).

8. Participants must agree to participate in an alcohol use disorder program during thestudy period, as recommended by the local institution's addiction medicinespecialists, including post-hospitalization

Exclusion Criteria:

1. Participants taking products containing obeticholic acid in the 30 days prior torandomization

2. Participants taking >2 doses of systemic corticosteroids within 30 days prior torandomization.

3. Participants who have been inpatient at a referral hospital for >7 days prior totransfer.

4. Pregnancy, planned pregnancy, potential for pregnancy (e.g., unwillingness to useeffective birth control during the study), or current or planned breast feeding.

5. Abstinence from alcohol consumption for >2 months before Day 1.

6. AST or ALT >400 U/L.

7. mDF <32 or >70 at Screening

8. MELD score <18 or >25 at Screening.

9. Other causes of liver disease including chronic hepatitis B (hepatitis B surfaceantigen [HBsAg] positive), chronic hepatitis C virus (HCV) RNA positive,drug-induced liver injury (DILI), biliary obstruction, and autoimmune liver disease.

10. Current or previous history of hepatocellular carcinoma (HCC)

11. History of liver transplantation or currently listed for liver transplant

12. Untreated infection (e.g., has not initiated appropriate medical treatment forinfection)

13. Known positivity for human immunodeficiency virus infection

14. Uncontrolled gastrointestinal (GI) bleeding or controlled GI bleeding that wasassociated with shock or required transfusion of more than 3 units of blood within 7days of Screening.

15. Kidney injury defined as a serum creatinine >133 μmol/L (>1.5 mg/dL) or therequirement for renal replacement therapy.

16. Portal vein thrombosis

17. Acute pancreatitis or acute gallbladder disease (e.g., cholecystitis)

18. Severe, on-going associated disease (e.g., cardiac failure, acute myocardialinfarction, severe cardiac arrhythmias, severe pulmonary disease, neurologicdisease)

19. Malignancy within the 2 years prior to Screening, with the exception of specificcancers that have been cured by surgical resection (e.g., basal cell skin cancer).Participants under evaluation for possible malignancy are not eligible.

20. Positive urine drug screen (amphetamines, barbiturates, benzodiazepines, cocaine,and opiates) except tetrahydrocannabinol or in the setting of documentedprescription medications (e.g., opiates, benzodiazepines, amphetamines,barbiturates), which also include medications prescribed as part of in-patientmanagement. Participants being treated for alcohol withdrawal may be exempt for thisreason, verify with Medical Monitor.

21. Participated in a clinical research study and received any active investigationalproduct being evaluated for the treatment of sAH within 3 months before Day 1

22. Participation in a study of another investigational medicine or device within 30days before Screening

23. Any other condition or clinical laboratory result that, in the opinion of theInvestigator, might confound the results, or would impede compliance or hindercompletion of the study