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

April 30, 2026 updated by: Intercept Pharmaceuticals

A Phase 2a, Randomized, Double-Blind, Placebo-Controlled, Multicenter, Dose-Escalation, Proof-of-Concept Study Evaluating the Safety, Tolerability, Efficacy and Pharmacokinetics of INT-787 in Subjects With Severe Alcohol Associated Hepatitis

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).

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Detailed Description

This is a Phase 2a, randomized, double-blind, placebo-controlled, dose-escalation, proof-of-concept study to evaluate the safety, tolerability, efficacy, and PK of INT-787 in participants, initially admitted to the hospital, with severe alcohol-associated hepatitis (sAH). The study aims to demonstrate and provide rationale for the selection of optimal dose(s) of INT-787 in the target population of participants with sAH. INT-787 will be evaluated for safety and tolerability prior to dose escalation. Overall efficacy, compared to placebo, will be assessed for each dose cohort.

Additionally, PK measurements at various study timepoints will allow the Sponsor to better understand the systemic exposure of INT-787 and the relationship between exposure and efficacy and safety. Such insights in participants with more advanced liver disease will provide valuable information for future clinical trials of INT-787.

The placebo-treated participants will provide important natural history information on outcomes in this participant population with sAH treated with supportive care. The placebo-treated participants within cohorts are meant to blind the study drug administration while the data across dose cohorts will be used in the overall analysis.

Study Type

Interventional

Enrollment (Actual)

67

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Angers, France, 49933
        • CHU Angers
      • Clichy, France, 92118
        • Hôpital Beaujon
      • Lille, France, 59037
        • Hôpital Claude Huriez
      • Paris, France, 75013
        • Hôpital Pitié Salpêtrière
      • Toulouse, France, 31059
        • Hôpital Rangueil
  • United Kingdom
      • Cambridge, United Kingdom
        • Cambridge University NHS Foundation Trust
      • London, United Kingdom, NW3 2QG
        • Royal Free Hospital
      • London, United Kingdom
        • Imperial College Healthcare NHS Trust
      • Plymouth, United Kingdom
        • University Hospitals Plymouth NHS Trust
  • United States
    • California
      • Fresno, California, United States, 93701
        • University of California, San Francisco-Fresno
      • Palo Alto, California, United States, 94305
        • Stanford Healthcare
      • Sacramento, California, United States, 95817
        • UC Davis Medical Center
    • Florida
      • Miami, Florida, United States, 33136
        • Clinical Translational Research Site
      • Tampa, Florida, United States, 33606
        • Tampa General Medical Group
    • Illinois
      • Chicago, Illinois, United States, 60612
        • Rush University Medical Center
    • Maryland
      • Baltimore, Maryland, United States, 21202
        • Mercy Medical Center
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • Beth Israel Deaconess Medical Center
      • Worcester, Massachusetts, United States, 01655
        • UMass Memorial Medical Center
    • Michigan
      • Detroit, Michigan, United States, 48202
        • Henry Ford Health System
    • Minnesota
      • Rochester, Minnesota, United States, 55905
        • Mayo Clinic
    • New York
      • Manhasset, New York, United States, 11030
        • Northwell Health Center for Liver Disease and Transplantation
      • New York, New York, United States, 10032
        • Columbia University Medical Center/New York Presbyterian Hospital
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • Hospital of the University of Pennsylvania
    • South Carolina
      • Charleston, South Carolina, United States, 29425
        • Medical University of South Carolina
    • Tennessee
      • Nashville, Tennessee, United States, 37232
        • Vanderbilt Digestive Disease Center
    • Texas
      • Dallas, Texas, United States, 75203
        • The Liver Institute at Methodist Dallas Medical Center
      • Houston, Texas, United States, 77030
        • Baylor College of Medicine
    • Utah
      • Salt Lake City, Utah, United States, 84132
        • University of Utah Hospital
    • Virginia
      • Richmond, Virginia, United States, 23298
        • VCU Health Clinical Research Services Unit

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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 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
    2. Serum total bilirubin >3.0 mg/dL
    3. Aspartate aminotransferase (AST) ≥50 U/L
    4. AST/Aspartate aminotransferase (ALT) ratio ≥1.5
    5. Onset of jaundice within prior 8 weeks
    6. Cohort 1 through Cohort 4: Maddrey's Discriminant Factor (mDF) ≥32 and ≤70
    7. Cohort 5 and Cohort 6: mDF ≥32
  3. Cohort 1 through Cohort 4: MELD score ≥18 to ≤25 (inclusive) and Cohort 5 and Cohort 6: MELD score ≥21 to ≤30

  4. 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
      • Intravaginal
      • Transdermal

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

      • Oral
      • Injectable
      • Implantable
    • Sexual abstinence: When in line with the preferred and usual lifestyle of the participant, is defined as avoiding all types of activity that could result in conception (pregnancy) from the initiation of Screening and until at least 90 days after the last dose of investigational product

Exclusion Criteria:

  1. Participants taking products containing obeticholic acid in the 30 days prior to randomization
  2. Participants taking >2 doses of systemic corticosteroids within 30 days prior to randomization.
  3. Participants who have been inpatient at a referral hospital for >7 days prior to transfer.
  4. Pregnancy, planned pregnancy, potential for pregnancy (e.g., unwillingness to use effective 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. Cohort 1 through Cohort 4: mDF <32 or >70.
  8. Cohort 5 and Cohort 6: mDF <32
  9. Cohort 1 through Cohort 4: MELD score <18 or >25.
  10. Cohort 5 and Cohort 6: MELD <21 or >30
  11. 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.
  12. Current or previous history of hepatocellular carcinoma (HCC)
  13. History of liver transplantation or currently listed for liver transplant

Note: Additional protocol defined Inclusion/Exclusion criteria apply.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Single Group Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: Placebo
Participants will be randomized to receive matching placebo
Drug: Placebo
Placebo
Active Comparator: INT-787
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
Blinded Study Drug

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Lille model response based on Lille score by treatment group
Time Frame: Day 7
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of participants with treatment emergent adverse events (TEAEs), serious adverse events (SAEs) and treatment emergent adverse event of special interest (AESIs)
Time Frame: During the study period, up to 12 weeks
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
Time Frame: During the study period, up to 12 weeks
During the study period, up to 12 weeks
Change from baseline in the Model for End-Stage Liver Disease (MELD) score at 28-days by treatment group
Time Frame: Baseline and at Day 28
The MELD scoring system is used to assess the severity of liver disease in participants in the setting of alcohol-associated hepatitis. The MELD score is derived from the participant's serum total bilirubin, serum creatinine, and international normalized ratio (INR). The MELD score ranges from 6 to 40 with higher scores indicating more severe liver disease and a worse outcome.
Baseline and at Day 28
Change from Baseline in total bilirubin
Time Frame: Baseline and at Day 7, 14, 21, 28, 56 and 84
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
Time Frame: Day 28, 56, 84
Day 28, 56, 84

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Intercept Pharmaceuticals

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 15, 2022

Primary Completion (Actual)

February 10, 2026

Study Completion (Actual)

February 10, 2026

Study Registration Dates

First Submitted

November 9, 2022

First Submitted That Met QC Criteria

November 28, 2022

First Posted (Actual)

December 6, 2022

Study Record Updates

Last Update Posted (Actual)

May 5, 2026

Last Update Submitted That Met QC Criteria

April 30, 2026

Last Verified

April 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 787-201

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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