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

Phase 2
Completed
Conditions
Alcoholic Hepatitis
Interventions
Drug: DUR-928 30 mg
Drug: Placebo+ Standard of Care (SOC)
Drug: DUR-928 90 mg
Registration Number
NCT04563026
Lead Sponsor
Durect
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).

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
307
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 & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
DUR-928 (larsucosterol, 30 mg)DUR-928 30 mg-
(Placebo) Sterile Water for InjectionPlacebo+ Standard of Care (SOC)-
DUR-928 (larsucosterol, 90 mg)DUR-928 90 mg-
Primary Outcome Measures
NameTimeMethod
Difference in 90-day mortality or liver transplant between IV DUR-928, 30 mg or 90 mg, and placebo.Day 90
Secondary Outcome Measures
NameTimeMethod
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

Trial Locations

Locations (68)

Stanford University Medical Center

🇺🇸

Stanford, California, United States

Mount Sinai Hospital

🇺🇸

New York, New York, United States

Yale University School of Medicine

🇺🇸

New Haven, Connecticut, United States

New York-Presbyterian - Weill Cornell Medical Center

🇺🇸

New York, New York, United States

Universitair Ziekenhuis Antwerpen (UZA)

🇧🇪

Edegem, Belgium

Hôpital St Joseph

🇫🇷

Marseille, France

Université libre de Bruxelles (ULB) - Hôpital Erasme

🇧🇪

Brussels, Belgium

Bon Secours Liver Institute of Richmond

🇺🇸

Richmond, Virginia, United States

Sir Charles Gairdner Hospital

🇦🇺

Nedlands, Western Australia, Australia

Nepean Hospital

🇦🇺

Kingswood, New South Wales, Australia

Landeskrankenhaus (LKH) - Universitätsklinikum Graz

🇦🇹

Graz, Austria

Virginia Commonwealth University Medical Center

🇺🇸

Richmond, Virginia, United States

Eastern Health - Box Hill Hospital

🇦🇺

Box Hill, Victoria, Australia

Keck Hospital of University of Southern California (USC)

🇺🇸

Los Angeles, California, United States

Loyola University Medical Center

🇺🇸

Maywood, Illinois, United States

University of Maryland Medical Center

🇺🇸

Baltimore, Maryland, United States

Methodist Dallas Medical Center

🇺🇸

Dallas, Texas, United States

Cedars-Sinai Medical Center

🇺🇸

Los Angeles, California, United States

Piedmont Atlanta Hospital

🇺🇸

Atlanta, Georgia, United States

Massachusetts General Hospital

🇺🇸

Boston, Massachusetts, United States

University of Minnesota Medical School

🇺🇸

Minneapolis, Minnesota, United States

Northwestern Memorial Hospital

🇺🇸

Chicago, Illinois, United States

Rush University Medical Center

🇺🇸

Chicago, Illinois, United States

University of Chicago Medical Center

🇺🇸

Chicago, Illinois, United States

Richard Roudebush VA Hospital

🇺🇸

Indianapolis, Indiana, United States

Johns Hopkins Hospital

🇺🇸

Baltimore, Maryland, United States

Tufts Medical Center

🇺🇸

Boston, Massachusetts, United States

Rutgers-New Jersey Medical School

🇺🇸

Newark, New Jersey, United States

Northwell Health - North Shore University Hospital

🇺🇸

Manhasset, New York, United States

Cleveland Clinic

🇺🇸

Cleveland, Ohio, United States

Baylor Scott and White Health

🇺🇸

Dallas, Texas, United States

Parkland Memorial Hospital

🇺🇸

Dallas, Texas, United States

Baylor College of Medicine Medical Center

🇺🇸

Houston, Texas, United States

Houston Methodist Hospital

🇺🇸

Houston, Texas, United States

Harborview Medical Center - University of Washington

🇺🇸

Seattle, Washington, United States

Royal Prince Alfred Hospital

🇦🇺

Camperdown, New South Wales, Australia

Barts Health NHS Trust - The Royal London Hospital

🇬🇧

London, England, United Kingdom

King's College Hospital NHS Foundation Trust

🇬🇧

London, England, United Kingdom

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

🇬🇧

London, England, United Kingdom

University Hospitals Plymouth NHS Trust - Derriford Hospital

🇬🇧

Plymouth, England, United Kingdom

Utah Health - The University of Utah Hospital

🇺🇸

Salt Lake City, Utah, United States

University of Alabama at Birmingham (UAB) Hospital

🇺🇸

Birmingham, Alabama, United States

Mayo Clinic Hospital

🇺🇸

Phoenix, Arizona, United States

Henry Ford Hospital

🇺🇸

Detroit, Michigan, United States

Hospices Civils de Lyon - Hôpital de la Croix-Rousse

🇫🇷

Lyon, France

Southern California Research Center

🇺🇸

Coronado, California, United States

University of California San Francisco (UCSF) Medical Center

🇺🇸

San Francisco, California, United States

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

🇺🇸

Charleston, South Carolina, United States

University of Texas Southwestern Medical Center

🇺🇸

Dallas, Texas, United States

Royal Perth Hospital

🇦🇺

Perth, Western Australia, Australia

Flinders Medical Centre

🇦🇺

Bedford Park, South Australia, Australia

Royal Free London NHS Foundation Trust Hospital

🇬🇧

London, United Kingdom

Tulane Medical Center

🇺🇸

New Orleans, Louisiana, United States

MedStar Health - MedStar Georgetown University Hospital

🇺🇸

Washington, District of Columbia, United States

Atrium Health

🇺🇸

Charlotte, North Carolina, United States

University of New Mexico (UNM) Hospital

🇺🇸

Albuquerque, New Mexico, United States

Doctors Hospital at Renaissance (DHR)

🇺🇸

Edinburg, Texas, United States

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

🇺🇸

Kansas City, Missouri, United States

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

🇫🇷

Besançon, France

University of Texas Southwestern (Clements University Hospital)

🇺🇸

Dallas, Texas, United States

Royal Adelaide Hospital

🇦🇺

Adelaide, South Australia, Australia

University of Virginia (UVA) Health - University Hospital

🇺🇸

Charlottesville, Virginia, United States

Mater Health - Mater Hospital Brisbane

🇦🇺

South Brisbane, Queensland, Australia

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

🇫🇷

Lille, France

University of California Davis (UC Davis) Medical Center

🇺🇸

Sacramento, California, United States

University of Louisville

🇺🇸

Louisville, Kentucky, United States

University of Nebraska Medical Center (UNMC)

🇺🇸

Omaha, Nebraska, United States

Washington University School of Medicine

🇺🇸

Saint Louis, Missouri, United States

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