NCT03917407

DUR-928 in Patients With Alcoholic Hepatitis

U01 Pilot Trial of DUR-928 in Patients With Moderate and Severe Alcoholic Hepatitis

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 43 (actual)
• Sponsor: Craig James McClain · Academic / Other
• Sex: All
• Age: 21 Years – 67 Years
• Healthy volunteers: Not accepted

Summary

The proposed study is An Open-Label, Dose Escalation Study to Assess the Safety, and Pharmacodynamics (PD) signals of DUR 928 in Patients with AH. DUR-928 will be administered in 100 mL 5% dextrose or 0.9% sodium chloride by slow intravenous infusion over 2 hrs (50mL/h) until entire dose is given at Day 1 and Day 4. If a patient meets the hospital discharge criteria prior to the 2nd dose, the patient will receive only one dose of DUR-928 instead of 2 doses.

Detailed description

The study will be conducted in 2 Parts using a staggered parallel design. Part A will include patients with MELD scores of 11-20, and Part B will include patients with MELD of scores 21-30. Within each Part, the study will be conducted using a starting dose level of 30 mg with sequential dose escalation following review of safety results of the prior dose level by the sponsor, the principal investigators. The planned subsequent doses of DUR-928 after the starting dose are 90 mg and 150 mg. Patients with a MELD score of 21-30 (Part B) receiving the 30 mg dose level will only be enrolled once safety review of the 30 mg dose of DUR-928 in patients with MELD score 11-20 (Part A) has been completed. The subsequent dose escalation in Part B will not proceed until the sponsor, and the principal investigators, and the medical monitor complete the review of safety of the 30 mg dose level and determine it is safe to do so. At each dose level within a Part, 4 patients will be treated. If no SUSAR is observed, dose escalation to the next dose cohort within the Part will proceed. If 1 of the 4 patients demonstrates a SUSAR in a given dose level, an additional 2 patients will be treated at that dose level. If only 1 of the 6 patients demonstrates SUSAR, the next cohort of four patients will enter at the next dose level. If 6 patients are dosed and 2 or more demonstrate SUSAR at that dose level, the study will deescalate to a lower dose (but higher than the previous dose). At subsequent dose levels, the maximum tolerated dose (MTD) is defined as the dose level where no more than 1 of 6 patients experiences a SUSAR. If no SUSAR is observed, dose escalation to the next dose cohort will proceed. All patients will be followed up to Day 28 (Total duration of patient engagement is 33 days). Trial Population: Patients with AH will be enrolled at Louisville associated hospitals in the US. The target number of participants to complete the study is 24-36. During the trial, patients should receive standard of care as determined by the PI (e.g. pentoxifylline or corticosteroids).

Conditions

• Alcoholic Hepatitis

Interventions

Type	Name	Description
DRUG	DUR-928 (Moderate AH)	A total of no more than two doses of DUR-928 will be given, with 72 hrs between each dose. A second dose of the assigned study treatment (test drug) will be repeated 3 days after Dose 1 to patients who are still hospitalized. If a patient meets the discharge criteria prior to Day 4, the patient will receive only one dose of DUR 928. Patients of Part A (MELD 11-20) will follow the dose escalation procedure based on cohort; each patient will receive an intravenous infusion dose of: * Cohort 1A: 30 mg of DUR-928in 100 mL 5% dextrose or 0.9% sodium chloride administered over approximately 2 hrs via IV infusion. * Cohort 2A: 90 mg of DUR 928 in 100 mL5% dextrose or 0.9% sodium chloride administered over approximately 2 hrs via IV infusion. * Cohort 3A: 150 mg of DUR 928 in 100 mL5% dextrose or 0.9% sodium chloride administered over approximately 2 hrs via IV infusion.
DRUG	DUR-928 (Severe AH)	Dose escalation to the next cohort will be determined after review of safety, tolerability and pharmacokinetic data of the previous cohort. Dose escalation for Part B will follow the same requirements as for Part A. The dose levels for Part B are planned to be the same as Part A. Patients of Part B (MELD 21-30) will follow the dose escalation procedure based on cohort; each patient will receive an intravenous infusion dose of: * Cohort 1B: 30 mg of DUR-928 in 100 mL 5% dextrose or 0.9% sodium chloride administered over approximately 2 hrs via IV infusion. * Cohort 2B: 90 mg of DUR 928 in 100 mL5% dextrose or 0.9% sodium chloride administered over approximately 2 hrs via IV infusion. * Cohort 3B: 150 mg of DUR 928 in 100 mL5% dextrose or 0.9% sodium chloride administered over approximately 2 hrs via IV infusion More details on preparation and administration of study drug will be provided in the Investigation Product Manual for this study.

Timeline

• Start date: 2021-06-01
• Primary completion: 2023-09-24
• Completion: 2023-09-30
• First posted: 2019-04-17
• Last updated: 2023-10-18

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study