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<bold>Introduction:</bold> Rilzabrutinib is an oral, selective, reversible, covalent Bruton tyrosine kinase inhibitor. Nominally significant improvements in Asthma Control Questionnaire (ACQ-5) scores at Week 12 were previously reported with rilzabrutinib vs placebo despite complete ICS/LABA withdrawal. <bold>Aim:</bold> Evaluate the impact of rilzabrutinib on ACQ-5 components. <bold>Methods:</bold> This was a phase 2, double-blind, 2-staggered-cohort study evaluating the efficacy and safety of rilzabrutinib (SAR444671; <ext-link>NCT05104892</ext-link>). A total of 196 adult participants with poorly controlled moderate-to-severe asthma on ICS/LABA therapy were randomized to rilzabrutinib 800 mg (N=32) or placebo (N=32) and rilzabrutinib 1200 mg (N=64) or placebo (N=68) for 12 weeks, added to medium-to-high-dose ICS/LABA, which was gradually withdrawn starting at Week 4. Asthma control was assessed with the ACQ-5. <bold>Results:</bold> Improvements were observed with rilzabrutinib across all ACQ-5 components at Week 12, including frequency of nighttime awakenings (least squares means difference vs placebo: rilzabrutinib 800 mg: -0.39, P=.1778; rilzabrutinib 1200 mg: -0.36, P=.0598), early morning symptoms (800 mg: -0.70, P=.0192; 1200 mg: -0.40, P=.0494), limitation of activities (800 mg: -0.58, P=.0391; 1200 mg: -0.60, P=.0020), shortness of breath (800 mg: -0.66, P=.0116; 1200 mg: -0.59, P=.0039) and wheezing (800 mg: -0.60, P=.0500; 1200 mg: -0.58, P=.0078). As early as Week 2, improvements across all ACQ-5 components were observed with rilzabrutinib vs placebo and sustained until Week 12 despite ICS/LABA withdrawal. <bold>Conclusions:</bold> Rilzabrutinib demonstrated clinically meaningful improvement in all asthma control components compared with placebo over 12 weeks.