A 12-Week Safety Assessment of Rilzabrutinib in Patients With Chronic Spontaneous Urticaria From the RILECSU Phase 2 Dose-Ranging Study
Moshe Ben-Shoshan1; Davide Dondi2*; Fernando Valenzuela3; Marcus Maurer4; Iris Sun5; Jessica Gereige6; Leda Mannent7; Remco Diab8
Introduction & Objectives:
Rilzabrutinib (SAR444671) is an oral, reversible, covalent Bruton’s tyrosine kinase inhibitor (BTKi). We report the safety analysis of the RILECSU phase 2 study in adults with moderate-to-severe CSU randomised to rilzabrutinib or placebo during the double-blind 12-week period.
Materials & Methods:
RILECSU (NCT05107115) is a 52-week phase 2 study comprising a 12-week, randomised, double-blind, placebo-controlled, dose-ranging efficacy and safety period followed by a 40-week open-label extension period. Participants (N=160) were symptomatic adults (≥18 to 80 years) with moderate to severe CSU whose disease was not adequately controlled with H1 antihistamine treatment. They were randomised 1:1:1:1 to rilzabrutinib 400 mg (QPM; n=38; BID; n=41; TID; n=41), or matching placebo (n=40). Safety assessments included adverse events (AEs), serious AEs (SAEs) and AEs of special interest (AESIs), physical exams, vital signs, electrocardiograms (ECGs), and laboratory parameters.
Results:
AEs occurring at a higher frequency with rilzabrutinib than placebo included diarrhoea, nausea, and headache; the majority reported as mild (Table). The incidence of SAEs was low (n=1 placebo; n=2 TID), and severe AEs occurred at the same incidence across all rilzabrutinib dosing groups and placebo group. Vital signs and ECG results were similar across all groups. There were no severe/serious infections or opportunistic infections. Skin-related AEs were more frequent in placebo and rilzabrutinib QPM than in rilzabrutinib BID or TID. There was no incidence of BTKi associated cytopenia, bleeding, or atrial fibrillation among patients treated with rilzabrutinib.
Conclusion:
Rilzabrutinib showed an acceptable safety profile and was well tolerated in the 12-week double-blind period of the RILECSU dose-ranging study.
Davide Dondi