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

NCT05639543 | Terminated Phase 2 DMC FDA Drug

• 1 other identifier: 787-201
• Study Type: interventional
• Target: 67
• Locations: 3 countries
• Sites: 29

Brief Summary

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

Conditions

Alcohol Associated Hepatitis

Keywords

Severe Alcohol associated Hepatitis (sAH); Alcoholic Hepatitis (AH); Hepatitis; Alcoholic

Outcome Measures

Primary Outcomes (1)

• Lille model response based on Lille score by treatment group

  The Lille score response rate will be analyzed as a categorical variable. Participants with Lille score \<0.45 will be counted as responders and those with Lille score ≥0.45 will be counted as non-responders.

  Day 7

Secondary Outcomes (5)

• Change from baseline in the Model for End-Stage Liver Disease (MELD) score at 28-days by treatment group

  Baseline and at Day 28

• Change from Baseline in total bilirubin

  Baseline and at Day 7, 14, 21, 28, 56 and 84

• Difference in 28-day, 56-day, and 84-day all-cause mortality or liver transplantation (TFS) between INT-787 and placebo

  Day 28, 56, 84

• Number of participants with treatment emergent adverse events (TEAEs), serious adverse events (SAEs) and treatment emergent adverse event of special interest (AESIs)

  During the study period, up to 12 weeks

• Number of participants reporting infectious adverse events by System organ class (SOC)/ preferred term by treatment group

  During the study period, up to 12 weeks

Study Arms (2)

INT-787

ACTIVE COMPARATOR

Participants will be randomized to receive INT-787 (in Dose Escalation Cohorts \[Cohorts 1 through 4\] and Extension Phase Cohorts \[Cohorts 5 and 6\])

Drug: INT-787

Placebo

PLACEBO COMPARATOR

Participants will be randomized to receive matching placebo

Drug: Placebo

Interventions

INT-787 DRUG

Blinded Study Drug

INT-787

Placebo DRUG

Placebo

Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Males or females aged 18 to 65 years (inclusive)
• Clinical diagnosis of sAH based on all the following:
• History of ongoing 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
• Serum total bilirubin \>3.0 mg/dL
• Aspartate aminotransferase (AST) ≥50 U/L
• AST/Aspartate aminotransferase (ALT) ratio ≥1.5
• Onset of jaundice within prior 8 weeks
• Cohort 1 through Cohort 4: Maddrey's Discriminant Factor (mDF) ≥32 and ≤70
• Cohort 5 and Cohort 6: mDF ≥32
• Cohort 1 through Cohort 4: MELD score ≥18 to ≤25 (inclusive) and Cohort 5 and Cohort 6: MELD score ≥21 to ≤30
• Female participants must be postmenopausal, surgically sterile, or, if premenopausal (and not surgically sterile), be prepared to use ≥1 highly effective method of contraception from the initiation of Screening 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

You may not qualify if:

• Participants taking products containing obeticholic acid in the 30 days prior to randomization
• Participants taking \>2 doses of systemic corticosteroids within 30 days prior to randomization.
• Participants who have been inpatient at a referral hospital for \>7 days prior to transfer.
• Pregnancy, planned pregnancy, potential for pregnancy (e.g., unwillingness to use effective birth control during the study), or current or planned breast feeding.
• Abstinence from alcohol consumption for \>2 months before Day 1.
• AST or ALT \>400 U/L.
• Cohort 1 through Cohort 4: mDF \<32 or \>70.
• Cohort 5 and Cohort 6: mDF \<32
• Cohort 1 through Cohort 4: MELD score \<18 or \>25.
• Cohort 5 and Cohort 6: MELD \<21 or \>30
• Other causes of liver disease including chronic hepatitis B (hepatitis B surface antigen \[HBsAg\] positive), chronic hepatitis C virus (HCV) RNA positive, drug-induced liver injury (DILI), biliary obstruction, and autoimmune liver disease.
• Current or previous history of hepatocellular carcinoma (HCC)
• History of liver transplantation or currently listed for liver transplant

Sponsors & Collaborators

• Intercept Pharmaceuticals: lead

Study Sites (29)

University of California, San Francisco-Fresno

Fresno, California, 93701, United States

Location

Stanford Healthcare

Palo Alto, California, 94305, United States

Location

UC Davis Medical Center

Sacramento, California, 95817, United States

Location

Clinical Translational Research Site

Miami, Florida, 33136, United States

Location

Tampa General Medical Group

Tampa, Florida, 33606, United States

Location

Rush University Medical Center

Chicago, Illinois, 60612, United States

Location

Mercy Medical Center

Baltimore, Maryland, 21202, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

UMass Memorial Medical Center

Worcester, Massachusetts, 01655, United States

Location

Henry Ford Health System

Detroit, Michigan, 48202, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Northwell Health Center for Liver Disease and Transplantation

Manhasset, New York, 11030, United States

Location

Columbia University Medical Center/New York Presbyterian Hospital

New York, New York, 10032, United States

Location

Hospital of the University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

Vanderbilt Digestive Disease Center

Nashville, Tennessee, 37232, United States

Location

The Liver Institute at Methodist Dallas Medical Center

Dallas, Texas, 75203, United States

Location

Baylor College of Medicine

Houston, Texas, 77030, United States

Location

University of Utah Hospital

Salt Lake City, Utah, 84132, United States

Location

VCU Health Clinical Research Services Unit

Richmond, Virginia, 23298, United States

Location

CHU Angers

Angers, 49933, France

Location

Hopital Beaujon

Clichy, 92118, France

Location

Hopital Claude Huriez

Lille, 59037, France

Location

Hopital Pitie Salpetriere

Paris, 75013, France

Location

Hopital Rangueil

Toulouse, 31059, France

Location

Cambridge University NHS Foundation Trust

Cambridge, United Kingdom

Location

Royal Free Hospital

London, NW3 2QG, United Kingdom

Location

Imperial College Healthcare NHS Trust

London, United Kingdom

Location

University Hospitals Plymouth NHS Trust

Plymouth, United Kingdom

Location

MeSH Terms

Conditions

Hepatitis, Alcoholic; Hepatitis

Condition Hierarchy (Ancestors)

Liver Diseases; Digestive System Diseases; Liver Diseases, Alcoholic; Alcohol-Induced Disorders; Alcohol-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 9, 2022
• First Posted: December 6, 2022
• Study Start: December 15, 2022
• Primary Completion: February 10, 2026
• Study Completion: February 10, 2026
• Last Updated: May 5, 2026

Record last verified: 2026-04

Locations

US (20); GB (4); FR (5)