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

Alcoholic Hepatitis Clinical Trial

— AHFIRM  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04563026
• Other study ID #: C928-011
• Status: Completed
• Phase: Phase 2
• Start date: January 22, 2021
• Est. completion date: September 6, 2023

Study information

• Verified date: February 2024
• Source: Durect
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 307
• Est. completion date: September 6, 2023
• Est. primary completion date: September 6, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Alcoholic Hepatitis
• Hepatitis
• Hepatitis A
• Hepatitis, Alcoholic

Intervention

Drug:
• DUR-928 30 mg
IV infusion
• DUR-928 90 mg
IV infusion
• Placebo+ Standard of Care (SOC)
IV infusion

Locations

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

Sponsors (2)

Lead Sponsor	Collaborator
Durect	CTI Clinical Trial and Consulting Services

Countries where clinical trial is conducted

United States,  Australia,  Austria,  Belgium,  France,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Difference in 90-day mortality or liver transplant between IV DUR-928, 30 mg or 90 mg, and placebo.		Day 90
Secondary	Difference in 90-day mortality between IV DUR-928, 30 mg or 90 mg, and placebo.		Day 90
Secondary	Difference in 28-day mortality or liver transplant between IV DUR-928, 30 mg or 90 mg, and placebo.		Day 28
Secondary	Difference in 28-day mortality between IV DUR-928, 30 mg or 90 mg, and placebo.		Day 28