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

NCT04563026 | Completed Phase 2 DMC FDA Drug

• 1 other identifier: C928-011
• Study Type: interventional
• Target: 307
• Locations: 5 countries
• Sites: 60

Brief Summary

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).

Conditions

Alcoholic Hepatitis

Keywords

Alcoholic Hepatitis; acute alcoholic liver disease; progressive inflammatory liver injury

Outcome Measures

Primary Outcomes (1)

• Difference in 90-day mortality or liver transplant between IV DUR-928, 30 mg or 90 mg, and placebo.

  Day 90

Secondary Outcomes (3)

• Difference in 90-day mortality between IV DUR-928, 30 mg or 90 mg, and placebo.

  Day 90

• Difference in 28-day mortality or liver transplant between IV DUR-928, 30 mg or 90 mg, and placebo.

  Day 28

• Difference in 28-day mortality between IV DUR-928, 30 mg or 90 mg, and placebo.

  Day 28

Study Arms (3)

DUR-928 (larsucosterol, 30 mg)

EXPERIMENTAL

Drug: DUR-928 30 mg

DUR-928 (larsucosterol, 90 mg)

EXPERIMENTAL

Drug: DUR-928 90 mg

(Placebo) Sterile Water for Injection

PLACEBO COMPARATOR

Drug: Placebo+ Standard of Care (SOC)

Interventions

DUR-928 30 mg DRUG

IV infusion

DUR-928 (larsucosterol, 30 mg)

DUR-928 90 mg DRUG

IV infusion

DUR-928 (larsucosterol, 90 mg)

Placebo+ Standard of Care (SOC) DRUG

IV infusion

(Placebo) Sterile Water for Injection

Eligibility Criteria

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

You may qualify if:

• Able to provide written informed consent (either from subject or subject's legally acceptable representative).
• Onset of jaundice within prior 8 weeks.
• 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.
• 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
• \< AST \< 400 IU/L
• ALT \< 400 IU/L
• AST/ALT \> 1.5
• Maddrey discriminant function (MDF) ≥ 32 assuming a control prothrombin time of 12 seconds.
• Model for End-stage Liver Disease (MELD) score: 21-30.
• 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.
• Male or female subjects 18 years of age or older.
• Subjects must agree to use effective methods to prevent pregnancy while participating in the study.
• Subjects must agree to participate in an alcohol abstinence support program recommended by the local institution's addiction specialists.

You may not qualify if:

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

Sponsors & Collaborators

• Durect: lead
• CTI Clinical Trial and Consulting Services: collaborator

Study Sites (68)

University of Alabama at Birmingham (UAB) Hospital

Birmingham, Alabama, 35233, United States

Location

Mayo Clinic Hospital

Phoenix, Arizona, 85054, United States

Location

Southern California Research Center

Coronado, California, 92118, United States

Location

Keck Hospital of University of Southern California (USC)

Los Angeles, California, 90033, United States

Location

Cedars-Sinai Medical Center

Los Angeles, California, 90048, United States

Location

University of California Davis (UC Davis) Medical Center

Sacramento, California, 95817, United States

Location

University of California San Francisco (UCSF) Medical Center

San Francisco, California, 94143, United States

Location

Stanford University Medical Center

Stanford, California, 94305, United States

Location

Yale University School of Medicine

New Haven, Connecticut, 06510, United States

Location

MedStar Health - MedStar Georgetown University Hospital

Washington D.C., District of Columbia, 20007, United States

Location

Piedmont Atlanta Hospital

Atlanta, Georgia, 30309, United States

Location

Northwestern Memorial Hospital

Chicago, Illinois, 60611, United States

Location

Rush University Medical Center

Chicago, Illinois, 60612, United States

Location

University of Chicago Medical Center

Chicago, Illinois, 60637, United States

Location

Loyola University Medical Center

Maywood, Illinois, 60153, United States

Location

Richard Roudebush VA Hospital

Indianapolis, Indiana, 46202, United States

Location

University of Louisville

Louisville, Kentucky, 40202, United States

Location

Tulane Medical Center

New Orleans, Louisiana, 70112, United States

Location

University of Maryland Medical Center

Baltimore, Maryland, 21201, United States

Location

Johns Hopkins Hospital

Baltimore, Maryland, 21205, United States

Location

Tufts Medical Center

Boston, Massachusetts, 02111, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Henry Ford Hospital

Detroit, Michigan, 48202, United States

Location

University of Minnesota Medical School

Minneapolis, Minnesota, 55455, United States

Location

Saint Luke's Health System - Saint Luke's Hospital of Kansas City

Kansas City, Missouri, 64111, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

University of Nebraska Medical Center (UNMC)

Omaha, Nebraska, 68198, United States

Location

Rutgers-New Jersey Medical School

Newark, New Jersey, 07103, United States

Location

University of New Mexico (UNM) Hospital

Albuquerque, New Mexico, 87106, United States

Location

Northwell Health - North Shore University Hospital

Manhasset, New York, 11030, United States

Location

Mount Sinai Hospital

New York, New York, 10029, United States

Location

New York-Presbyterian - Weill Cornell Medical Center

New York, New York, 10065, United States

Location

Atrium Health

Charlotte, North Carolina, 28204, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

Medical University of South Carolina (MUSC) Health - University Medical Center

Charleston, South Carolina, 29425, United States

Location

Methodist Dallas Medical Center

Dallas, Texas, 75203, United States

Location

Parkland Memorial Hospital

Dallas, Texas, 75235, United States

Location

Baylor Scott and White Health

Dallas, Texas, 75246, United States

Location

University of Texas Southwestern (Clements University Hospital)

Dallas, Texas, 75390, United States

Location

University of Texas Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

Doctors Hospital at Renaissance (DHR)

Edinburg, Texas, 78539, United States

Location

Baylor College of Medicine Medical Center

Houston, Texas, 77030, United States

Location

Houston Methodist Hospital

Houston, Texas, 77030, United States

Location

Utah Health - The University of Utah Hospital

Salt Lake City, Utah, 84132, United States

Location

University of Virginia (UVA) Health - University Hospital

Charlottesville, Virginia, 22908, United States

Location

Bon Secours Liver Institute of Richmond

Richmond, Virginia, 23226, United States

Location

Virginia Commonwealth University Medical Center

Richmond, Virginia, 23298, United States

Location

Harborview Medical Center - University of Washington

Seattle, Washington, 98104, United States

Location

Royal Prince Alfred Hospital

Camperdown, New South Wales, 2050, Australia

Location

Nepean Hospital

Kingswood, New South Wales, 2217, Australia

Location

Mater Health - Mater Hospital Brisbane

South Brisbane, Queensland, 4101, Australia

Location

Royal Adelaide Hospital

Adelaide, South Australia, 5000, Australia

Location

Flinders Medical Centre

Bedford Park, South Australia, 5042, Australia

Location

Eastern Health - Box Hill Hospital

Box Hill, Victoria, 3128, Australia

Location

Sir Charles Gairdner Hospital

Nedlands, Western Australia, 6009, Australia

Location

Royal Perth Hospital

Perth, Western Australia, 6000, Australia

Location

Landeskrankenhaus (LKH) - Universitätsklinikum Graz

Graz, 8036, Austria

Location

Université libre de Bruxelles (ULB) - Hôpital Erasme

Brussels, 1070, Belgium

Location

Universitair Ziekenhuis Antwerpen (UZA)

Edegem, 2650, Belgium

Location

Centre Hospitalier Régional Universitaire (CHRU) Besançon - Hôpital Jean Minjoz

Besançon, 25000, France

Location

Centre Hospitalier Universitaire (CHU) de Lille - Hôpital Jeanne de Flandre

Lille, 59037, France

Location

Hospices Civils de Lyon - Hôpital de la Croix-Rousse

Lyon, 69004, France

Location

Hôpital St Joseph

Marseille, 13008, France

Location

Barts Health NHS Trust - The Royal London Hospital

London, England, E1 1FR, United Kingdom

Location

King's College Hospital NHS Foundation Trust

London, England, SE5 9RS, United Kingdom

Location

Imperial College Healthcare NHS Trust - St. Mary's Hospital

London, England, W2 1NY, United Kingdom

Location

University Hospitals Plymouth NHS Trust - Derriford Hospital

Plymouth, England, PL6 8DH, United Kingdom

Location

Royal Free London NHS Foundation Trust Hospital

London, NW3 2QG, United Kingdom

Location

Related Publications (1)

• Shiffman M, Da B, Goel A, Kwong A, Stein L, Moreno C, Nicoll A, Mehta A, Louvet A, Flamm S, Pyrsopoulos N, Satapathy S, Kuo A, Ganger D, Aloman C, Strasser SI, Tse E, Russo MW, Rockey D, Gray M, Mitchell M, Thursz M, Krebs W, Scott D, Blevins C, Ellis D, Brown J, Sussman N, Lin W. Larsucosterol for the Treatment of Alcohol-Associated Hepatitis. NEJM Evid. 2025 Feb;4(2):EVIDoa2400243. doi: 10.1056/EVIDoa2400243. Epub 2025 Jan 28.

  PMID: 39873544 DERIVED

MeSH Terms

Conditions

Hepatitis, Alcoholic

Condition Hierarchy (Ancestors)

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

Study Officials

• Robert Gordon, MD, FACS

  CTI Clinical Trial and Consulting Services

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: This is a Phase 2b randomized, double-blind, placebo-controlled, multi-arm, multi-center, parallel design trial.

Study Record Dates

• First Submitted: September 18, 2020
• First Posted: September 24, 2020
• Study Start: January 22, 2021
• Primary Completion: September 6, 2023
• Study Completion: September 6, 2023
• Last Updated: September 5, 2024

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will not share

Locations

AU (1); BE (2); US (48); FR (4); GB (5)