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

• ClinicalTrials.gov Identifier: NCT04563026
• Recruitment Status: Recruiting
• First Posted: September 24, 2020
• Last Update Posted: February 2, 2021
• Sponsor: Durect
• Collaborator: CTI Clinical Trial and Consulting Services
• Information provided by (Responsible Party): Durect

Study Description

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).

Condition or disease	Intervention/treatment	Phase
Alcoholic Hepatitis	Drug: DUR-928 30 mg; Drug: DUR-928 90 mg; Drug: Placebo+ Standard of Care (SOC)	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 300 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: This is a Phase 2b randomized, double-blind, placebo-controlled, multi-arm, multi-center, parallel design trial.
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: 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
• Actual Study Start Date: January 22, 2021
• Estimated Primary Completion Date: September 2023
• Estimated Study Completion Date: September 2023

Arms and Interventions

Arm	Intervention/treatment
Experimental: DUR-928 (30 mg)	Drug: DUR-928 30 mg; IV infusion
Experimental: DUR-928 (90 mg)	Drug: DUR-928 90 mg; IV infusion
Placebo Comparator: (Placebo) Sterile Water for Injection	Drug: Placebo+ Standard of Care (SOC); IV infusion

Outcome Measures

Primary Outcome Measures :

1. 90-day mortality between active group/s and placebo (SOC) group [ Time Frame: Day 90 ]

Secondary Outcome Measures :

1. 28-day mortality between the treatment groups [ Time Frame: Day 28 ]
2. Occurrence of adverse events or laboratory abnormalities [ Time Frame: Day 1 to Day 90 ]
   Percentage of Participants with Treatment-Emergent (TE) Adverse Events (AE), Serious AEs (SAE), AEs Leading to Premature Study Drug Discontinuation, and Common Terminology Criteria for Adverse Events (CTCAE) Grade 3 or 4 Laboratory Abnormalities within 90 days of dosing
3. Lille score at Day 7 after the initiation of study drug treatment between the treatment groups [ Time Frame: Day 7 ]
4. MELD score at Day 28 after the initiation of study drug treatment between the treatment groups [ Time Frame: Day 28 ]
5. ICU days at Day 28 [ Time Frame: Day 1 to Day 28 ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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. Judgment regarding daily and long-term alcohol use and onset of jaundice will be made by the site investigator.

4. Serum chemistry (as determined by local laboratory):

   • Serum total bilirubin > 3.0 mg/dL
   • 50 < AST < 400 IU/L
   • ALT < 400 IU/L
   • AST/ALT > 1.5
5. Maddrey's discriminant function ≥ 32 assuming a control prothrombin time of 12 seconds
6. Model for End-stage Liver Disease (MELD) score: 21-30
7. When the diagnosis of AH remains in question, a liver biopsy (if clinically feasible and that subject has no contra-indications) will be required. Historical biopsy is allowed.
8. Subjects must agree to use effective methods to prevent pregnancy while participating in the study.
9. Subjects must agree to participate in an alcohol abstinence support program recommended by the local institution's addiction specialists

Exclusion Criteria:

1. Subjects taking corticosteroids for a duration exceeding 7 days in the 30 days prior to screening
2. Subjects experiencing alcohol withdrawal symptoms or treatment with Clinical Institute Withdrawal Assessment for Alcohol (CIWA) protocol
3. Active infection. Subjects who are febrile with leukocytosis are also excluded, even if there is no localizing diagnosis of infection.
4. Serum creatinine >2.5 mg/dL or eGFR < 60 mL/min/1.73 m2
5. Subjects with acute kidney injury (AKl) or Hepatorenal syndrome
6. Subjects undergoing continuous veno-venous hemodialysis (CVVH)
7. Uncontrolled active gastrointestinal bleeding
8. Refractory ascites
9. Liver biopsy (if carried out) with findings not compatible with AH
10. Stage ≥3 hepatic encephalopathy by West Haven criteria
11. Any severe concomitant cardiovascular, renal, endocrine, pulmonary, psychiatric disorder, or multi-organ failure
12. Other concomitant cause(s) of liver disease
13. Any active malignancies other than curatively treated skin cancer (basal cell or squamous cell carcinomas) or any other malignancy diagnosed within the last five years
14. Positive Urine Drug Screen (amphetamines, barbiturates, benzodiazepines, cocaine and opiates) except THC and prescription medications
15. Existing or intended pregnancy or breast feeding
16. Participation in another interventional clinical trial within 30 days of Screening
17. History of organ transplantation, other than a corneal transplant
18. 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

Contacts and Locations

Contacts

Contact: Christina Blevins, BS; 408-777-1417; christina.blevins@durect.com

Contact: Deborah Scott, MS; 408-777-1417; deborah.scott@durect.com

Locations

United States, California

Site 01; Not yet recruiting

Coronado, California, United States, 92118

United States, Georgia

Site 02; Recruiting

Atlanta, Georgia, United States, 30309

United States, Illinois

Site 09; Not yet recruiting

Chicago, Illinois, United States, 60611

Site 03; Recruiting

Chicago, Illinois, United States, 60612

United States, Indiana

Site 07; Recruiting

Indianapolis, Indiana, United States, 46202

United States, Maryland

Site 10; Not yet recruiting

Baltimore, Maryland, United States, 21201

United States, Michigan

Site 06; Recruiting

Detroit, Michigan, United States, 48202

United States, New Jersey

Site 04; Recruiting

Newark, New Jersey, United States, 07103

United States, New York

Site 08; Recruiting

Manhasset, New York, United States, 11030

United States, Texas

Site 11; Not yet recruiting

Dallas, Texas, United States, 75203

United States, Virginia

Site 05; Recruiting

Richmond, Virginia, United States, 23226

Sponsors and Collaborators

Durect

CTI Clinical Trial and Consulting Services

Investigators

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

More Information

• Responsible Party: Durect
• ClinicalTrials.gov Identifier: NCT04563026
• Other Study ID Numbers: C928-011
• First Posted: September 24, 2020
• Last Update Posted: February 2, 2021
• Last Verified: February 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Durect:

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

Additional relevant MeSH terms:

Hepatitis A; Hepatitis; Hepatitis, Alcoholic; Liver Diseases; Digestive System Diseases; Hepatitis, Viral, Human; Virus Diseases; Enterovirus Infections; Picornaviridae Infections; RNA Virus Infections; Liver Diseases, Alcoholic; Alcohol-Induced Disorders; Alcohol-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders