A Phase 2b Study in Subjects With Alcoholic Hepatitis to Evaluate Safety and Efficacy of DUR-928 Treatment (AHFIRM)

September 3, 2024 updated by: Durect

A Randomized, Double-blind, Placebo-controlled, Phase 2b Study to Evaluate Safety and Efficacy of DUR-928 in Subjects With Alcoholic Hepatitis

This is a randomized, double-blind, placebo-controlled, phase 2b clinical Trial evaluating Safety and Efficacy of DUR-928 (an experimental medication) in Patients with Alcoholic Hepatitis (AH).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

307

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

  • Australia
    • New South Wales
      • Camperdown, New South Wales, Australia, 2050
        • Royal Prince Alfred Hospital
      • Kingswood, New South Wales, Australia, 2217
        • Nepean Hospital
    • Queensland
      • South Brisbane, Queensland, Australia, 4101
        • Mater Health - Mater Hospital Brisbane
    • South Australia
      • Adelaide, South Australia, Australia, 5000
        • Royal Adelaide Hospital
      • Bedford Park, South Australia, Australia, 5042
        • Flinders Medical Centre
    • Victoria
      • Box Hill, Victoria, Australia, 3128
        • Eastern Health - Box Hill Hospital
    • Western Australia
      • Nedlands, Western Australia, Australia, 6009
        • Sir Charles Gairdner Hospital
      • Perth, Western Australia, Australia, 6000
        • Royal Perth Hospital
  • Austria
      • Graz, Austria, 8036
        • Landeskrankenhaus (LKH) - Universitätsklinikum Graz
  • Belgium
      • Brussels, Belgium, 1070
        • Universite Libre de Bruxelles (ULB) - Hopital Erasme
      • Edegem, Belgium, 2650
        • Universitair Ziekenhuis Antwerpen (UZA)
  • France
      • Besançon, France, 25000
        • Centre Hospitalier Régional Universitaire (CHRU) Besançon - Hôpital Jean Minjoz
      • Lille, France, 59037
        • Centre Hospitalier Universitaire (CHU) de Lille - Hôpital Jeanne de Flandre
      • Lyon, France, 69004
        • Hospices Civils de Lyon - Hôpital de la Croix-Rousse
      • Marseille, France, 13008
        • Hôpital St Joseph
  • United Kingdom
      • London, United Kingdom, NW3 2QG
        • Royal Free London NHS Foundation Trust Hospital
    • England
      • London, England, United Kingdom, SE5 9RS
        • King's College Hospital NHS Foundation Trust
      • London, England, United Kingdom, E1 1FR
        • Barts Health NHS Trust - The Royal London Hospital
      • London, England, United Kingdom, W2 1NY
        • Imperial College Healthcare NHS Trust - St. Mary's Hospital
      • Plymouth, England, United Kingdom, PL6 8DH
        • University Hospitals Plymouth NHS Trust - Derriford Hospital
  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35233
        • University of Alabama at Birmingham (UAB) Hospital
    • Arizona
      • Phoenix, Arizona, United States, 85054
        • Mayo Clinic Hospital
    • California
      • Coronado, California, United States, 92118
        • Southern California Research Center
      • Los Angeles, California, United States, 90048
        • Cedars-Sinai Medical Center
      • Los Angeles, California, United States, 90033
        • Keck Hospital of University of Southern California (USC)
      • Sacramento, California, United States, 95817
        • University of California Davis (UC Davis) Medical Center
      • San Francisco, California, United States, 94143
        • University of California San Francisco (UCSF) Medical Center
      • Stanford, California, United States, 94305
        • Stanford University Medical Center
    • Connecticut
      • New Haven, Connecticut, United States, 06510
        • Yale University School of Medicine
    • District of Columbia
      • Washington, District of Columbia, United States, 20007
        • MedStar Health - MedStar Georgetown University Hospital
    • Georgia
      • Atlanta, Georgia, United States, 30309
        • Piedmont Atlanta Hospital
    • Illinois
      • Chicago, Illinois, United States, 60612
        • Rush University Medical Center
      • Chicago, Illinois, United States, 60637
        • University of Chicago Medical Center
      • Chicago, Illinois, United States, 60611
        • Northwestern Memorial Hospital
      • Maywood, Illinois, United States, 60153
        • Loyola University Medical Center
    • Indiana
      • Indianapolis, Indiana, United States, 46202
        • Richard Roudebush VA Hospital
    • Kentucky
      • Louisville, Kentucky, United States, 40202
        • University of Louisville
    • Louisiana
      • New Orleans, Louisiana, United States, 70112
        • Tulane Medical Center
    • Maryland
      • Baltimore, Maryland, United States, 21205
        • Johns Hopkins Hospital
      • Baltimore, Maryland, United States, 21201
        • University of Maryland Medical Center
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Massachusetts General Hospital
      • Boston, Massachusetts, United States, 02111
        • Tufts Medical Center
    • Michigan
      • Detroit, Michigan, United States, 48202
        • Henry Ford Hospital
    • Minnesota
      • Minneapolis, Minnesota, United States, 55455
        • University of Minnesota Medical School
    • Missouri
      • Kansas City, Missouri, United States, 64111
        • Saint Luke's Health System - Saint Luke's Hospital of Kansas City
      • Saint Louis, Missouri, United States, 63110
        • Washington University School of Medicine
    • Nebraska
      • Omaha, Nebraska, United States, 68198
        • University of Nebraska Medical Center (UNMC)
    • New Jersey
      • Newark, New Jersey, United States, 07103
        • Rutgers-New Jersey Medical School
    • New Mexico
      • Albuquerque, New Mexico, United States, 87106
        • University of New Mexico (UNM) Hospital
    • New York
      • Manhasset, New York, United States, 11030
        • Northwell Health - North Shore University Hospital
      • New York, New York, United States, 10029
        • Mount Sinai Hospital
      • New York, New York, United States, 10065
        • New York-Presbyterian - Weill Cornell Medical Center
    • North Carolina
      • Charlotte, North Carolina, United States, 28204
        • Atrium Health
    • Ohio
      • Cleveland, Ohio, United States, 44195
        • Cleveland Clinic
    • South Carolina
      • Charleston, South Carolina, United States, 29425
        • Medical University of South Carolina (MUSC) Health - University Medical Center
    • Texas
      • Dallas, Texas, United States, 75390
        • University of Texas Southwestern Medical Center
      • Dallas, Texas, United States, 75235
        • Parkland Memorial Hospital
      • Dallas, Texas, United States, 75203
        • Methodist Dallas Medical Center
      • Dallas, Texas, United States, 75246
        • Baylor Scott and White Health
      • Dallas, Texas, United States, 75390
        • University of Texas Southwestern (Clements University Hospital)
      • Edinburg, Texas, United States, 78539
        • Doctors Hospital at Renaissance (DHR)
      • Houston, Texas, United States, 77030
        • Houston Methodist Hospital
      • Houston, Texas, United States, 77030
        • Baylor College of Medicine Medical Center
    • Utah
      • Salt Lake City, Utah, United States, 84132
        • Utah Health - The University of Utah Hospital
    • Virginia
      • Charlottesville, Virginia, United States, 22908
        • University of Virginia (UVA) Health - University Hospital
      • Richmond, Virginia, United States, 23298
        • Virginia Commonwealth University Medical Center
      • Richmond, Virginia, United States, 23226
        • Bon Secours Liver Institute of Richmond
    • Washington
      • Seattle, Washington, United States, 98104
        • Harborview Medical Center - University of Washington

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 and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Able to provide written informed consent (either from subject or subject's legally acceptable representative).
  2. Onset of jaundice within prior 8 weeks.
  3. Average daily consumption of >40 (females) or >60 (males) grams of alcohol for 6 months or longer, with < 8 weeks of abstinence before the onset of jaundice.

  4. The determination of AH may be based on typical serum chemistry (as determined by local laboratory) or liver biopsy at any time during the current episode of AH:

    • Serum total bilirubin > 3.0 mg/dL
    • 50 < AST < 400 IU/L
    • ALT < 400 IU/L
    • AST/ALT > 1.5
  5. Maddrey discriminant function (MDF) ≥ 32 assuming a control prothrombin time of 12 seconds.
  6. Model for End-stage Liver Disease (MELD) score: 21-30.
  7. Liver biopsy is not required, but may be used to confirm the diagnosis of AH at the Investigator's discretion. Biopsy, if used as a diagnostic criterion, must have occurred during the current episode.
  8. Male or female subjects 18 years of age or older.
  9. Subjects must agree to use effective methods to prevent pregnancy while participating in the study.
  10. Subjects must agree to participate in an alcohol abstinence support program recommended by the local institution's addiction specialists.

Exclusion Criteria:

  1. Subjects taking systemic corticosteroids for a duration exceeding 8 days in the 30 days prior to screening.
  2. Subjects experiencing or considered at high risk for alcohol withdrawal seizures or delirium tremens.
  3. Active infection (such as spontaneous bacterial peritonitis [SBP], urinary tract infection [UTI], bacteremia, acute viral hepatitis, uncontrolled HIV, and active SARS CoV2 infection).
  4. Serum creatinine >2.5 mg/dL.
  5. Subjects undergoing continuous veno-venous hemodialysis (CVVH).
  6. Uncontrolled gastrointestinal bleeding.
  7. A history of pre-admission refractory ascites defined as more than 4 paracenteses in the previous 8 weeks despite diuretic therapy.
  8. Liver biopsy (if carried out) with findings not compatible with AH.
  9. Stage ≥3 hepatic encephalopathy by West Haven criteria.
  10. Any severe concomitant cardiovascular, renal, endocrine, pulmonary, psychiatric disorder, or multi-organ failure.
  11. Other concomitant cause(s) of liver disease.
  12. Any active malignancy or any malignancy diagnosed within the last five years other than curable skin cancer (basal cell or squamous cell carcinomas).
  13. Positive Urine Drug Screen (amphetamines, barbiturates, benzodiazepines, cocaine and opiates) except THC and prescription medications.
  14. Existing or intended pregnancy or breast feeding.
  15. Participation in another interventional clinical trial within 30 days of Screening.
  16. History of organ transplantation, other than a corneal transplant.
  17. Underlying diseases that, in the opinion of the site investigator, might be complicated or exacerbated by proposed treatments or might confound assessment of study drug.

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: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: DUR-928 (larsucosterol, 30 mg)
Drug: DUR-928 30 mg
IV infusion
Experimental: DUR-928 (larsucosterol, 90 mg)
Drug: DUR-928 90 mg
IV infusion
Placebo Comparator: (Placebo) Sterile Water for Injection
Drug: Placebo+ Standard of Care (SOC)
IV infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Difference in 90-day mortality or liver transplant between IV DUR-928, 30 mg or 90 mg, and placebo.
Time Frame: Day 90
Day 90

Secondary Outcome Measures

Outcome Measure
Time Frame
Difference in 90-day mortality between IV DUR-928, 30 mg or 90 mg, and placebo.
Time Frame: Day 90
Day 90
Difference in 28-day mortality or liver transplant between IV DUR-928, 30 mg or 90 mg, and placebo.
Time Frame: Day 28
Day 28
Difference in 28-day mortality between IV DUR-928, 30 mg or 90 mg, and placebo.
Time Frame: Day 28
Day 28

Collaborators and Investigators

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

Sponsor

Durect

Collaborators

CTI Clinical Trial and Consulting Services

Investigators

  • Study Director: Robert Gordon, MD, FACS, CTI Clinical Trial and Consulting Services

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)

January 22, 2021

Primary Completion (Actual)

September 6, 2023

Study Completion (Actual)

September 6, 2023

Study Registration Dates

First Submitted

September 18, 2020

First Submitted That Met QC Criteria

September 18, 2020

First Posted (Actual)

September 24, 2020

Study Record Updates

Last Update Posted (Estimated)

September 5, 2024

Last Update Submitted That Met QC Criteria

September 3, 2024

Last Verified

September 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • C928-011

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

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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