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

Durect

Status and phase: Completed; Phase 2

Conditions: Alcoholic Hepatitis

Treatments: Drug: DUR-928 90 mg; Drug: Placebo+ Standard of Care (SOC); Drug: DUR-928 30 mg

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT04563026

C928-011

Details and patient eligibility

About

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).

Enrollment: 307 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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307 participants in 3 patient groups, including a placebo group

DUR-928 (larsucosterol, 30 mg)

Experimental group

Treatment:

Drug: DUR-928 30 mg

DUR-928 (larsucosterol, 90 mg)

Experimental group

Treatment:

Drug: DUR-928 90 mg

(Placebo) Sterile Water for Injection

Placebo Comparator group

Treatment:

Drug: Placebo+ Standard of Care (SOC)