Article Text

Download PDFPDF

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)
  1. Joerg Wenzel1,
  2. Nadezda Abramova2,
  3. Dominika Weinelt2,
  4. Deborah Denis3,
  5. Sanjeev Roy4 and
  6. Torsten Witte5
  1. 1Dept. of Dermatology and Allergy, University Hospital of Bonn, Bonn, Germany
  2. 2Global Patient Safety, Merck Healthcare KGaA, Darmstadt, Germany
  3. 3Global Clinical Development, EMD Serono Research and Development Institute, Inc., Billerica, MA, USA, an affiliate of Merck KGaA
  4. 4Global Clinical Development, Ares Trading SA, Eysins, Switzerland, an affiliate of Merck KGaA, Darmstadt, Germany
  5. 5Dept. of Rheumatology and Immunology, Hannover Medical School, Germany

Abstract

Objective Enpatoran, 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.

Methods This 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).

Results 25 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.

Conclusions Based 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).

Acknowledgements Merck (CrossRef Funder ID: 10.13039/100009945) sponsored the study and medical writing support by Bioscript Group.

http://creativecommons.org/licenses/by-nc/4.0/

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/ .

Statistics from Altmetric.com

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.