Clinical trial NCT04563026: A Phase 2b Study in Subjects With Alcoholic Hepatitis to Evaluate Safety and Efficacy of DUR-928 Treatment
Official title: A Randomized, Double-blind, Placebo-controlled, Phase 2b Study to Evaluate Safety and Efficacy of DUR-928 in Subjects With Alcoholic Hepatitis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Alcoholic Hepatitis
Keywords: Alcoholic Hepatitis
acute alcoholic liver disease
progressive inflammatory liver injury
Lead sponsor: Durect
Sponsor class: INDUSTRY
Collaborators: name: CTI Clinical Trial and Consulting Services
First posted: 2020-09-24
Enrollment: 307
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This is a Phase 2b randomized, double-blind, placebo-controlled, multi-arm, multi-center, parallel design trial.
Primary purpose: TREATMENT

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).


Eligibility criteria: 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.

Primary outcomes:
measure: Difference in 90-day mortality or liver transplant between IV DUR-928, 30 mg or 90 mg, and placebo.
timeFrame: Day 90
Secondary outcomes:
measure: Difference in 90-day mortality between IV DUR-928, 30 mg or 90 mg, and placebo.
timeFrame: Day 90
measure: Difference in 28-day mortality or liver transplant between IV DUR-928, 30 mg or 90 mg, and placebo.
timeFrame: Day 28
measure: Difference in 28-day mortality between IV DUR-928, 30 mg or 90 mg, and placebo.
timeFrame: Day 28
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham (UAB) Hospital
state: Alabama
city: Phoenix
country: United States
facility: Mayo Clinic Hospital
state: Arizona
city: Coronado
country: United States
facility: Southern California Research Center
state: California
city: Los Angeles
country: United States
facility: Keck Hospital of University of Southern California (USC)
state: California
city: Los Angeles
country: United States
facility: Cedars-Sinai Medical Center
state: California
city: Sacramento
country: United States
facility: University of California Davis (UC Davis) Medical Center
state: California
city: San Francisco
country: United States
facility: University of California San Francisco (UCSF) Medical Center
state: California
city: Stanford
country: United States
facility: Stanford University Medical Center
state: California
city: New Haven
country: United States
facility: Yale University School of Medicine
state: Connecticut
city: Washington
country: United States
facility: MedStar Health - MedStar Georgetown University Hospital
state: District of Columbia
city: Atlanta
country: United States
facility: Piedmont Atlanta Hospital
state: Georgia
city: Chicago
country: United States
facility: Northwestern Memorial Hospital
state: Illinois
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: Chicago
country: United States
facility: University of Chicago Medical Center
state: Illinois
city: Maywood
country: United States
facility: Loyola University Medical Center
state: Illinois
city: Indianapolis
country: United States
facility: Richard Roudebush VA Hospital
state: Indiana
city: Louisville
country: United States
facility: University of Louisville
state: Kentucky
city: New Orleans
country: United States
facility: Tulane Medical Center
state: Louisiana
city: Baltimore
country: United States
facility: University of Maryland Medical Center
state: Maryland
city: Baltimore
country: United States
facility: Johns Hopkins Hospital
state: Maryland
city: Boston
country: United States
facility: Tufts Medical Center
state: Massachusetts
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Detroit
country: United States
facility: Henry Ford Hospital
state: Michigan
city: Minneapolis
country: United States
facility: University of Minnesota Medical School
state: Minnesota
city: Kansas City
country: United States
facility: Saint Luke's Health System - Saint Luke's Hospital of Kansas City
state: Missouri
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Omaha
country: United States
facility: University of Nebraska Medical Center (UNMC)
state: Nebraska
city: Newark
country: United States
facility: Rutgers-New Jersey Medical School
state: New Jersey
city: Albuquerque
country: United States
facility: University of New Mexico (UNM) Hospital
state: New Mexico
city: Manhasset
country: United States
facility: Northwell Health - North Shore University Hospital
state: New York
city: New York
country: United States
facility: Mount Sinai Hospital
state: New York
city: New York
country: United States
facility: New York-Presbyterian - Weill Cornell Medical Center
state: New York
city: Charlotte
country: United States
facility: Atrium Health
state: North Carolina
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Charleston
country: United States
facility: Medical University of South Carolina (MUSC) Health - University Medical Center
state: South Carolina
city: Dallas
country: United States
facility: Methodist Dallas Medical Center
state: Texas
city: Dallas
country: United States
facility: Parkland Memorial Hospital
state: Texas
city: Dallas
country: United States
facility: Baylor Scott and White Health
state: Texas
city: Dallas
country: United States
facility: University of Texas Southwestern (Clements University Hospital)
state: Texas
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center
state: Texas
city: Edinburg
country: United States
facility: Doctors Hospital at Renaissance (DHR)
state: Texas
city: Houston
country: United States
facility: Baylor College of Medicine Medical Center
state: Texas
city: Houston
country: United States
facility: Houston Methodist Hospital
state: Texas
city: Salt Lake City
country: United States
facility: Utah Health - The University of Utah Hospital
state: Utah
city: Charlottesville
country: United States
facility: University of Virginia (UVA) Health - University Hospital
state: Virginia
city: Richmond
country: United States
facility: Bon Secours Liver Institute of Richmond
state: Virginia
city: Richmond
country: United States
facility: Virginia Commonwealth University Medical Center
state: Virginia
city: Seattle
country: United States
facility: Harborview Medical Center - University of Washington
state: Washington
city: Camperdown
country: Australia
facility: Royal Prince Alfred Hospital
state: New South Wales
city: Kingswood
country: Australia
facility: Nepean Hospital
state: New South Wales
city: South Brisbane
country: Australia
facility: Mater Health - Mater Hospital Brisbane
state: Queensland
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital
state: South Australia
city: Bedford Park
country: Australia
facility: Flinders Medical Centre
state: South Australia
city: Box Hill
country: Australia
facility: Eastern Health - Box Hill Hospital
state: Victoria
city: Nedlands
country: Australia
facility: Sir Charles Gairdner Hospital
state: Western Australia
city: Perth
country: Australia
facility: Royal Perth Hospital
state: Western Australia
city: Graz
country: Austria
facility: Landeskrankenhaus (LKH) - Universitätsklinikum Graz
city: Brussels
country: Belgium
facility: Université libre de Bruxelles (ULB) - Hôpital Erasme
city: Edegem
country: Belgium
facility: Universitair Ziekenhuis Antwerpen (UZA)
city: Besançon
country: France
facility: Centre Hospitalier Régional Universitaire (CHRU) Besançon - Hôpital Jean Minjoz
city: Lille
country: France
facility: Centre Hospitalier Universitaire (CHU) de Lille - Hôpital Jeanne de Flandre
city: Lyon
country: France
facility: Hospices Civils de Lyon - Hôpital de la Croix-Rousse
city: Marseille
country: France
facility: Hôpital St Joseph
city: London
country: United Kingdom
facility: Barts Health NHS Trust - The Royal London Hospital
state: England
city: London
country: United Kingdom
facility: King's College Hospital NHS Foundation Trust
state: England
city: London
country: United Kingdom
facility: Imperial College Healthcare NHS Trust - St. Mary's Hospital
state: England
city: Plymouth
country: United Kingdom
facility: University Hospitals Plymouth NHS Trust - Derriford Hospital
state: England
city: London
country: United Kingdom
facility: Royal Free London NHS Foundation Trust Hospital
Study officials:
affiliation: CTI Clinical Trial and Consulting Services
name: Robert Gordon, MD, FACS
role: STUDY_DIRECTOR
References: