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

Study Overview
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Brief Summary
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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).

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

Conditions
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Alcoholic Hepatitis

Intervention / Treatment
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* Drug: DUR-928 30 mg
* Drug: DUR-928 90 mg
* Drug: Placebo+ Standard of Care (SOC)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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 50 < 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. Exclusion Criteria: 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. History of organ transplantation, other than a corneal transplant. 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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: This is a Phase 2b randomized, double-blind, placebo-controlled, multi-arm, multi-center, parallel design trial.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: DUR-928 (larsucosterol, 30 mg)<br> | Drug: DUR-928 30 mg<br>* IV infusion<br>|
| Experimental: DUR-928 (larsucosterol, 90 mg)<br> | Drug: DUR-928 90 mg<br>* IV infusion<br>|
| Placebo Comparator: (Placebo) Sterile Water for Injection<br> | Drug: Placebo+ Standard of Care (SOC)<br>* IV infusion<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Difference in 90-day mortality or liver transplant between IV DUR-928, 30 mg or 90 mg, and placebo. |  | Day 90 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Alcoholic Hepatitis, acute alcoholic liver disease, progressive inflammatory liver injury