Rademikibart Treatment for Moderate-to-Severe Uncontrolled Asthma: A Phase 2B Randomized Clinical Trial.

Abstract

<b>Rationale:</b> Rademikibart (formerly CBP-201) is an IL-4Rα-targeting antibody. <b>Objectives:</b> We sought to evaluate rademikibart in adults with moderate-to-severe, persistent, uncontrolled asthma. <b>Methods:</b> In this global Phase 2b trial, 322 patients were randomized 1:1:1 to two rademikibart groups (150 mg or 300 mg every other week, after a 600-mg loading dose) or a placebo group; rademikibart or placebo was administered subcutaneously for 24 weeks. <b>Measurements and Main Results:</b> Prebronchodilator (trough) forced expiratory volume in 1 second (FEV₁) at Week 12 (primary endpoint) improved with rademikibart at 150 mg and 300 mg: Least squares mean changes (95% confidence interval), above placebo, were 140 ml (44-236 ml; <i>P</i> = 0.005) and 189 ml (92-286 ml; <i>P</i> < 0.001), respectively. Prebronchodilator (trough) FEV₁ improvements occurred rapidly during Week 1, were sustained through Week 24, and were greatest in patients with high baseline blood eosinophils (patients with ⩾300 eosinophils/ml experienced placebo-adjusted FEV₁ improvement at Week 24 of 420 ml [95% confidence interval =  239-600 ml] in the 300-mg group). Rapid and sustained statistically significant improvements were also observed in percent predicted FEV₁ and Asthma Control Questionnaire score across 24 weeks. Through Week 24, proportions of patients with one or more exacerbations were 7.5% (150 mg) and 9.3% (300 mg) versus 16.7% (placebo). Eighty-eight percent of patients completed treatment. Treatment-emergent adverse events were generally similar to placebo, and no eosinophilia was observed. Injection site reactions were mostly mild. The most common treatment-emergent adverse events (10-12% of patients) were cough, coronavirus disease (COVID-19), and dyspnea. <b>Conclusions:</b> Rapid and sustained improvements in lung function and asthma control were gained across 24 weeks of rademikibart therapy. Clinical trial registered with www.clinicaltrials.gov (NCT04773678).