Randomized phase 2a study of TAS5315, a Bruton’s tyrosine kinase inhibitor, for chronic spontaneous urticaria

Background Chronic spontaneous urticaria (CSU) is a chronic skin disorder primarily driven by mast cell activation and basophil involvement. CSU is often associated with autoimmune mechanisms, positioning Bruton’s tyrosine kinase (BTK) inhibition as an attractive therapeutic strategy. TAS5315 is a once-daily oral inhibitor of BTK with activity against Tec tyrosine-protein kinase and IL-2-inducible T-cell kinase (ITK). This study evaluated the efficacy and safety of TAS5315 in patients with CSU inadequately responding to non-sedating second-generation H1 receptor antagonists (ns-antihistamines). Methods This Phase 2a, randomized, double-blind, parallel-group, multicenter study randomized patients (1:1:1:1:1:1) with CSU to TAS5315 4 mg, 2 mg, 1 mg, 0.5 mg, 0.25 mg, or placebo for 12 weeks. The primary endpoint was the change from baseline in Weekly Urticaria Activity Score (UAS7) at Week 12. Results Of 126 patients enrolled, all received study treatment ( n = 21 per dose group). The primary endpoint, mean changes from baseline in UAS7 at Week 12 were −17.15, −16.01, −15.19, −11.63, −17.84, and −9.06 for the TAS5315 4 mg, 2 mg, 1 mg, 0.5 mg, 0.25 mg, and placebo groups, respectively. Similar improvements were observed with TAS5315 versus placebo for other efficacy endpoints. Adverse events (AEs) were reported in over half of patients in each treatment group, and most were mild in severity. The most frequently reported AE with TAS5315 was petechiae. Conclusions Once-daily TAS5315 was well tolerated and showed promising efficacy, making it a potential treatment option for CSU patients with inadequate response to ns-antihistamines.