Anti-IL-4Rα monoclonal antibody (CM310) in patients with chronic rhinosinusitis with nasal polyps (CROWNS-2): Rationale and design of a multicenter, randomized, double-blind, placebo-controlled, parallel-group study.

ABSTRACT

Background: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a heterogeneous disease that affects a large proportion of the global population. The treatment of CRSwNP, especially eosinophilic CRSwNP (ECRSwNP), has always been of great obstacle. Our previous phase 2 trial showed that CM310, a monoclonal antibody that targets interleukin-4 receptor alpha, was both safe and effective in reducing the size of nasal polyps, improving symptom scores, and increasing the quality of life for those with severe ECRSwNP. Objective: This phase 3 trial aims to evaluate the efficacy, safety, pharmacokinetic, pharmacodynamic, and immunogenicity of CM310 in participants with CRSwNP. Result: The CROWNS-2 is a multicenter, randomized, double-blind, placebo-controlled, parallel-group, phase 3 trial. The study consisted of a screening/run-in period (up to 4 weeks), a treatment period (24-week double-blind treatment period plus 28-week maintenance period), and a safety follow-up period (8 weeks). The study planned to enroll 180 participants with CRSwNP (at least 60% of ECRSwNP) to receive CM310 300 mg/placebo every 2 weeks (Q2W) subcutaneously for a total of 12 doses in double-blind treatment period and 300 mg CM310 Q2W subcutaneously for a total of 14 doses in maintenance period. Enrolled participants continued to use mometasone furoate nasal spray throughout the study. The primary endpoints are a change from baseline in nasal polyp score and nasal congestion score at week 24 between CM310 and placebo in both ECRSwNP and CRSwNP. Conclusion: The CROWNS-2 is a multicenter, randomized, double-blind, placebo-controlled, parallel-group, phase 3 clinical study to evaluate the efficacy and safety of CM310 in patients with CRSwNP. Trial registration NCT05436275.