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

Rationale: Rademikibart (formerly CBP-201) is an IL-4Rα-targeting antibody.

Objectives: To evaluate rademikibart in adults with moderate-to-severe, persistent, uncontrolled asthma.

Methods: In this global phase 2b trial (NCT04773678), 322 patients were randomized 1:1:1 to two rademikibart groups (150 mg or 300 mg every other week, following a 600 mg loading dose) or placebo, administered subcutaneously, for 24 weeks.

Measurements And Main Results: Prebronchodilator (trough) forced expiratory volume in the first second of expiration (FEV) at Week 12 (primary endpoint) improved with rademikibart 150 mg and 300 mg: least squares mean changes (95% CI), above placebo, were +140 mL (+44-236 mL; p=0.005) and +189 mL (+92-286 mL; p<0.001), respectively. Prebronchodilator trough FEV improvements occurred rapidly during Week 1, were sustained through Week 24, and greatest in patients with high baseline blood eosinophils (patients with ≥300 eosinophils/mL experienced placebo-adjusted FEV improvement at Week 24 of +420 mL [95% CI, +239-600 mL] in the 300 mg group). Rapid and sustained statistically significant improvements were also observed in percent predicted FEV and Asthma Control Questionnaire score across 24 weeks. Through Week 24, proportions of patients with ≥1 exacerbation were 7.5% (150 mg) and 9.3% (300 mg) vs 16.7% (placebo). 88% of patients completed treatment. Treatment-emergent adverse events (TEAEs) were generally similar to placebo, and no eosinophilia was observed. Injection site reactions were mostly mild. The most common TEAEs (10-12% of patients) were cough, COVID-19, and dyspnea.

Conclusions: Rapid and sustained improvements in lung function and asthma control were gained across 24 weeks of rademikibart therapy. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/). Clinical trial registration available at www.

Clinicaltrials: gov, ID: NCT04773678.