HIS news
Phase 2 Trial of Rilzabrutinib in Antihistamine-Refractory Chronic Spontaneous Urticaria Completed
A randomized, double-blind, placebo-controlled phase 2 dose-ranging trial evaluating oral rilzabrutinib (SAR444671) in adults with moderate-to-severe chronic spontaneous urticaria inadequately controlled by H1 antihistamines has reached completion. The Sanofi-sponsored study assessed three dose levels over 12 weeks, followed by a 40-week open-label extension.
Sanofi has completed a randomized, double-blind, placebo-controlled, multicenter phase 2 trial investigating three oral dose levels of rilzabrutinib (SAR444671) versus placebo in adults aged 18 and older with moderate-to-severe chronic spontaneous urticaria (CSU) who remained symptomatic despite H1 antihistamine therapy. The 12-week, four-arm parallel-group design was intended to characterize the dose-response relationship for reductions in itch frequency and severity as well as urticaria burden.
Rilzabrutinib is an oral, covalent-reversible Bruton's tyrosine kinase (BTK) inhibitor. BTK plays a central role in IgE receptor signaling in mast cells and basophils, making it a mechanistically rational target in CSU, where aberrant mast cell activation drives whealing and pruritus. The dose-ranging design aimed to identify an optimal therapeutic dose prior to potential advancement into phase 3 development.
Following the double-blind phase, eligible participants could enroll in a 40-week open-label extension (OLE) receiving rilzabrutinib at one of two dose levels, with dose selection informed by the 12-week safety and efficacy data. Enhanced monitoring was implemented through week 24 to capture safety signals in participants receiving active drug for the first time during the OLE, with subsequent assessments at weeks 36 and 52. Full efficacy and safety results from this completed trial have not yet been publicly disclosed.
Key points
- Phase 2 dose-ranging trial of oral rilzabrutinib in moderate-to-severe CSU refractory to H1 antihistamines is now complete.
- Three active dose levels were compared against placebo over a 12-week double-blind period, with primary endpoints focused on itch and urticaria severity reduction.
- A 40-week open-label extension phase allowed continued exposure and longer-term safety characterization.
- Rilzabrutinib is a covalent-reversible BTK inhibitor targeting mast cell and basophil IgE receptor signaling pathways implicated in CSU pathogenesis.
- Efficacy and safety data from this completed Sanofi-sponsored trial have not yet been publicly reported.
Why it matters
Chronic spontaneous urticaria refractory to H1 antihistamines represents a significant unmet need, and oral BTK inhibition offers a mechanistically distinct approach compared to existing biologics such as omalizumab. Dose-ranging data from this completed trial will be critical in determining whether rilzabrutinib advances to pivotal phase 3 evaluation.