Iberdomide in patients with systemic lupus erythematosus: a randomised, double-blind, placebo-controlled, ascending-dose, phase 2a study

作者：Richard Furie, Douglas R. Hough, Allison Gaudy, Ying Ye, Shimon Korish, Nikolay Delev, Michael Weiswasser, Xiaojiang Zhan, Peter Schäfer, Victoria P. Werth · 发表于：Lupus Science & Medicine · 年份：2022 · DOI：10.1136/lupus-2021-000581 · 被引用次数：37 · 研究领域：Systemic Lupus Erythematosus Research、Protein Degradation and Inhibitors、Platelet Disorders and Treatments

OBJECTIVE: To evaluate safety, pharmacokinetics, pharmacodynamics and efficacy of iberdomide in patients with SLE. Iberdomide is a high-affinity cereblon ligand that targets the hematopoietic transcription factors Ikaros and Aiolos for proteasomal degradation. METHODS: A 12-week, multicentre, double-blind, placebo-controlled, dose-escalation study in active SLE was followed by a 2-year, open-label active treatment extension phase (ATEP) (NCT02185040). In the dose-escalation phase, adults with active SLE were randomised to oral placebo or iberdomide (0.3 mg every other day, 0.3 mg once daily, 0.6 mg and 0.3 mg alternating once daily, or 0.6 mg once daily). Primary endpoints were safety and tolerability. RESULTS: The dose-escalation phase enrolled 42 patients, with 33 completing this phase and 17 patients enrolling into the ATEP. In the dose-escalation phase, the most common treatment-emergent adverse events (TEAEs; iberdomide/placebo groups) were nausea (20.6%/12.5%), diarrhoea (17.6%/12.5%) and upper respiratory tract infection (11.8%/12.5%). Most TEAEs were mild or moderate in severity and more common in the highest dose groups in both study phases. In the dose-escalation phase, Physician's Global Assessment and Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) activity scores improved relative to baseline and placebo in all iberdomide groups, with a trend toward continued score improvements in the ATEP. In the dose-escalation phase, iberdomide treatment ...