Efficacy and safety of CM310 in severe eosinophilic chronic rhinosinusitis with nasal polyps (CROWNS-1): a multicentre, randomised, double-blind, placebo-controlled phase 2 clinical trial

BackgroundSevere eosinophilic chronic rhinosinusitis with nasal polyps (ECRSwNP) remains the most relapsed subtype of uncontrolled CRSwNP. CM310, a humanised anti-interleukin (IL)-4 receptor alpha monoclonal antibody, inhibits IL-4 and IL-13 signaling which underlying inflammation. This study aims to evaluate efficacy safety CM310 in patients severe ECRSwNP.MethodsA multicentre, randomised, double-blind, placebo-controlled phase 2 clinical trial was conducted. 56 eligible adult ECRSwNP were randomised 1:1 receive subcutaneously either (300 mg) or placebo every weeks under background therapy mometasone furoate spray (MFNS) for 16 weeks, 8 follow-up. Coprimary endpoints included changes from baseline polyp score (NPS) congestion (NCS) at week 16. Key secondary sinus Lund-Mackay CT score, change volume occupied by disease, University Pennsylvania Smell Identification Test 22-item Sino-nasal Outcome total symptom score. Safety, pharmacodynamics, type inflammation biomarkers assessed. is registered ClinicalTrials.gov, NCT04805398.FindingsBetween April 6, 2021, March 18, 2022, 27 respectively both groups completed study. Findings suggested that improved coprimary decreasing size alleviating compared placebo. Least squares (LS) mean differences (CM310 vs placebo) NPS NCS −2.1 (95% CI −2.9, −1.4; p < 0.0001) −0.9 −1.4, −0.5; 0.0001), respectively. Sinus scan revealed (LS difference [95% CI] −7.6, [−9.4, −5.8]; disease −37%, [−47%, −28%]; significantly In addition, relieved daily symptoms CRSwNP their quality life reflected improvements TSS (−2.6 −3.5, −1.6]), UPSIT (10.4 6.8, 14.0]) SNOT-22 (−19.1 −29.8, −8.5]). Compared placebo, administration reduced 2-related including serum TARC IgE, tissue eosinophils. The common adverse events upper respiratory tract infection, blood cholesterol increased, tinnitus, but none considered drug-related.InterpretationThese findings support as an effective additional treatment option standard care ECRSwNP.FundingKeyMed Biosciences (Chengdu) Limited. Severe ECRSwNP. A NCT04805398. Between drug-related. These