[PDF][PDF] Safety, Pharmacokinetics, & Efficacy Signals of Larsucosterol (DUR-928) in Alcohol-associated Hepatitis
T Hassanein, CJ McClain, V Vatsalya… - Official journal of the …, 2022 - journals.lww.com
T Hassanein, CJ McClain, V Vatsalya, LL Stein, SL Flamm, P Martin, MC Cave, M Mitchell Jr…
Official journal of the American College of Gastroenterology| ACG, 2022•journals.lww.comBackground: This study is to evaluate safety and pharmacokinetics (PK) of larsucosterol
(DUR-928 or 25HC3S) in subjects with alcohol-associated hepatitis (AH), a devastating
acute illness without FDA-approved therapies. Method: This Phase 2a, multicenter, open-
label, dose escalation study evaluated safety, PK, and efficacy signals of larsucosterol in 19
clinically diagnosed AH subjects. Based on MELD (Model for End-stage Liver Disease)
score, 7 subjects were considered to have moderate AH and 12 to have severe AH. All …
(DUR-928 or 25HC3S) in subjects with alcohol-associated hepatitis (AH), a devastating
acute illness without FDA-approved therapies. Method: This Phase 2a, multicenter, open-
label, dose escalation study evaluated safety, PK, and efficacy signals of larsucosterol in 19
clinically diagnosed AH subjects. Based on MELD (Model for End-stage Liver Disease)
score, 7 subjects were considered to have moderate AH and 12 to have severe AH. All …
Abstract
Background:
This study is to evaluate safety and pharmacokinetics (PK) of larsucosterol (DUR-928 or 25HC3S) in subjects with alcohol-associated hepatitis (AH), a devastating acute illness without FDA-approved therapies.
Method:
This Phase 2a, multicenter, open-label, dose escalation study evaluated safety, PK, and efficacy signals of larsucosterol in 19 clinically diagnosed AH subjects. Based on MELD (Model for End-stage Liver Disease) score, 7 subjects were considered to have moderate AH and 12 to have severe AH. All subjects received 1 or 2 intravenous (IV) infusions (72 hours apart) of larsucosterol at a dose of 30, 90, or 150mg, and were followed for 28 days. Efficacy signals from a subgroup of severe AH subjects were compared with two matched arms of severe AH subjects treated with standard of care (SOC), including corticosteroids (CS), from a contemporaneous study.
Results:
All 19 larsucosterol-treated subjects survived the 28-day study. Fourteen (74%) of all subjects including 8 (67%) of the severe AH subjects were discharged≤ 72 hours after receiving a single infusion. There were no drug-related serious adverse events (SAEs) nor early terminations due to the treatment. PK profiles were not affected by disease severity. Biochemical parameters improved in most subjects. Serum bilirubin levels declined notably from baseline to Day7 and Day28, and MELD scores were reduced at Day28. The efficacy signals compared favorably with two matched groups treated with SOC. Lille scores at Day7 were< 0.45 in 16 of the 18 (89%) subjects with Day7 samples. Lille scores from 8 severe AH subjects who received 30 or 90mg larsucosterol (doses used in Phase 2b trial) were statistically significantly lower (p< 0.01) than those severe AH subjects treated with SOC from the contemporaneous study.
Conclusion:
Larsucosterol was well tolerated at all 3 doses in AH subjects without safety concerns. Data from this pilot study showed promising efficacy signals in AH subjects. Larsucosterol is being evaluated in a Phase 2b multicenter, randomized, double-blinded, placebo-controlled (AHFIRM) trial.
Lippincott Williams & Wilkins