P102 Safety evaluation from an ongoing randomized, double-blind, multiple-ascending dose phase Ib study of enpatoran versus placebo in patients with active systemic or cutaneous lupus erythematosus (SLE/CLE)

• Published in: Lupus science & medicine Vol. 11; no. Suppl 1; pp. A113 - A114
• Main Authors: Wenzel, Joerg, Abramova, Nadezda, Weinelt, Dominika, Denis, Deborah, Roy, Sanjeev, Witte, Torsten
• Format: Journal Article
• Language: English
• Published: London Lupus Foundation of America 14.03.2024; BMJ Publishing Group LTD; BMJ Publishing Group
• Subjects: Lupus; Poster Presentations
• ISSN: 2053-8790
• DOI: 10.1136/lupus-2024-el.156

ObjectiveEnpatoran, a highly selective and potent toll-like receptor 7/8 inhibitor that has glucocorticoid-sparing potential, suppressed disease activity in mouse models of SLE and was well tolerated by healthy participants and patients with COVID-19 pneumonia. The objective was to evaluate safety data from the ongoing phase Ib study of enpatoran in SLE/CLE.MethodsThis randomized, double-blind, two-part phase Ib study of oral enpatoran versus placebo in patients with SLE (≥1 clinical manifestation by Systemic Lupus Erythematosus Disease Activity Index 2000 and/or Cutaneous Lupus Erythematosus Disease Area and Severity Index-A [CLASI-A] ≥6) or CLE (CLASI-A ≥6) is ongoing (NCT04647708). Part A includes 3 dose-escalating cohorts (25, 50, 100 mg twice daily [BID] versus placebo). Part B has 1 cohort (150 mg BID versus placebo). Enrollment is complete. In each cohort, patients were randomized 3:1 to enpatoran or placebo. The 12-week treatment period was extended to 24 weeks for the 100 and 150 mg BID cohorts. All cohorts have a 2-week safety follow-up period. This analysis is based on blinded data (cut-off 10 August 2023).Results25 patients were randomized to enpatoran or placebo: 20 completed treatment; 3 discontinued treatment (not due to safety reasons); treatment is ongoing for 2 patients. Overall, 12 patients reported ≥1 treatment-emergent adverse event (TEAE). Most TEAEs were mild (n=19) or moderate (n=8) in severity. There was one Grade 4 laboratory abnormality of decreased lymphocyte count; the patient had no clinical signs/symptoms and continued treatment after a short interruption. Four TEAEs were considered treatment related. There were no serious TEAEs, dose-limiting toxicities, TEAEs of special interest, life-threatening TEAEs, deaths, or clinically-significant abnormalities in electrocardiogram parameters. All electroencephalogram readings were within the normal range.ConclusionsBased on a review of blinded data, no new safety signals were identified to the cut-off date in the first clinical study of enpatoran in SLE/CLE. The phase II proof-of-concept WILLOW study is evaluating the safety and efficacy of enpatoran in a larger cohort of patients with SLE and/or CLE (NCT05162586).AcknowledgementsMerck (CrossRef Funder ID: 10.13039/100009945) sponsored the study and medical writing support by Bioscript Group.