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

• Status: Not yet recruiting
• Trial end date: 2023-12-31
• Target enrollment: 0
• Participant gender: All

Summary

The purpose of this trial is to assess dose related safety, early efficacy, pharmacokinetics and pharmacodynamics of INT-787 in patients with severe alcohol-associated hepatitis (sAH).

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Intercept Pharmaceuticals

Criteria

Inclusion Criteria:

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

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

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

2. Serum total bilirubin >3.0 mg/dL

3. AST ≥50 U/L

4. AST/ALT ratio ≥1.5

5. Maddrey's Discriminant Factor (MDF) ≥32 and ≤60

6. MELD-Na score 18 to 25 (inclusive)

3. Onset of jaundice within 8 weeks from the time of admission to the hospital

4. Up to and not more than 7 days since admission to the hospital

5. Female subjects must be postmenopausal, surgically sterile, or, if premenopausal (and not surgically sterile), be prepared to use ≥1 highly effective method of contraception during the study and for 90 days after the last dose of 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 contraceptive associated with inhibition of ovulation:

• Oral

• Intravaginal

• Transdermal

• Progesterone-only hormonal contraception associated with inhibition of ovulation:

• Oral

• Injectable

• Implantable

• Sexual abstinence, if in line with the preferred and usual lifestyle of the subject (where true abstinence is defined as refraining from heterosexual contact intercourse during the entire period of risk associated with study treatments).

6. Male subjects who are sexually active with female partners of childbearing potential must agree to use a condom with spermicide and to use one other approved method of highly effective contraception from the time of investigational product administration for at least 90 days after the dose of investigational product as listed in Inclusion Criteria #5

7. Male subjects must refrain from sperm donation from Screening through at least 90 days following the last dose of investigational product

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

9. Subjects must agree to participate in an alcohol use disorder program during the study period, as recommended by the local institution's addiction medicine specialists, including post-hospitalization

Exclusion Criteria:

1. Subjects taking systemic corticosteroids or products containing obeticholic acid in the 30 days prior to Screening, up to and including randomization

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

3. Cessation of alcohol consumption for ≥2 months before Day 1

4. AST or ALT >400 U/L

5. MDF <32 or >60 at Screening

6. MELD-Na score <18 or >25 at Screening (confirmed by repeat labs within 48 hours)

7. Other causes of liver disease including chronic hepatitis B (hepatitis B surface antigen [HBsAg] positive), chronic hepatitis C virus (HCV) RNA positive, acetaminophen hepatotoxicity, biliary obstruction, and autoimmune liver disease

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

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

10. Untreated sepsis (e.g., has not initiated appropriate medical treatment for infection and/or septic shock)

11. Known positivity for human immunodeficiency virus infection

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

13. Kidney injury defined as a serum creatinine >133 μmol/L (>1.5 mg/dL) confirmed by repeat testing within 48 hours or the requirement for renal replacement therapy

14. Portal vein thrombosis

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

16. Severe associated disease (e.g., cardiac failure, acute myocardial infarction, severe cardiac arrhythmias, severe pulmonary disease, neurologic disease)

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

18. Positive urine drug screen (amphetamines, barbiturates, benzodiazepines, cocaine, and opiates) except tetrahydrocannabinol or in the setting of documented prescription medications (e.g., opiates, benzodiazepines, amphetamines, barbiturates), including medications prescribed as part of in-patient management. Subjects being treated for alcohol withdrawal may be exempt, if verified by the Medical Monitor.

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

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

21. Any other condition or clinical laboratory result that, in the opinion of the Investigator, might confound the results, or would impede compliance or hinder completion of the study

22. Received a positive Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) test result within 4 weeks of Screening or a SARS-CoV-2 vaccination within 2 weeks of Screening