Journal Article

An anti-TSLP monoclonal antibody for uncontrolled CRSwNP: the DUBHE randomized clinical trial

Xian, Mu, Yang, Yucheng, Zhang, Yu, Li, Qin, Su, Lizhong, Tan, Guolin, Lan, Feng, Shen, Shen, Jiang, Luyun, Luo, Xianyang, Xiao, Zian, Liu, Feng, Yan, Bing, Qu, Shenhong, Jiang, Yan, Wang, Chengshuo, Liu, Shixi, Ye, Jing, Xu, Yu, Yan, Hongyue, Wei, Xin, Zhang, Qinna, Song, Xicheng, Yu, Shaoqing, Xue, Jinmei, Zhao, Guoqing, Xie, Yan, Yang, Guoping, Fang, Hongyan, Chen, Jianjun, Wang, Lin, Zhang, Luo, Chen, Bo, Wan, Lijia

2025

Overview

To explore the therapeutic potential of blocking thymic stromal lymphopoietin (TSLP) in patients with chronic rhinosinusitis with nasal polyps (CRSwNP), we conducted a phase 1b/2a, randomized, double-blind, placebo-controlled trial to assess the safety and efficacy of CM326, a monoclonal antibody against TSLP. We enrolled 84 eligible patients with uncontrolled CRSwNP and stratified them based on baseline tissue eosinophil count. Patients are assigned to receive CM326 220 mg ( n  = 40) or placebo ( n  = 20) every 2 weeks (Q2W) and CM326 220 mg ( n  = 20) or placebo ( n  = 4) every 4 weeks (Q4W) for 16 weeks. Subsequently, all patients continue on CM326 220 mg Q2W or Q4W for an additional 36 weeks, followed by a 12-week follow up. Primary endpoints are safety of CM326 and change from baseline in NPS at week 16 in patients with eosinophilic CRSwNP (ECRSwNP). Main secondary endpoints include the change from baseline in NPS at week 16 in non-eosinophilic CRSwNP (nonECRwNP) and pharmacodynamic markers. Throughout the 64-week study, all treatment-emergent adverse events (TEAEs) are mild or moderate. CM326 Q2W improves NPS in patients with ECRSwNP compared with placebo at week 16 (mean difference [95% CI], −1.2 [−2.3 to −0.1], P  = 0.04), with sustained benefits during the open-label and follow-up periods. Notably, peripheral blood and tissue eosinophil counts and concentrations of plasma IL-13 and IL-5 are reduced by week 16 with the treatment of CM326 Q2W versus placebo. A post-hoc analysis demonstrates that all participants with baseline TSLP > 330 fg/mL achieve a substantial reduction in NPS by week 16 with the treatment of CM326 Q2W (mean difference vs. placebo: −1.75 [95%CI, −3.06 to −0.44], P  = 0.01). Overall, CM326 is well tolerated and effective in patients with uncontrolled ECRSwNP. A baseline plasma TSLP level of 330 fg/mL may serve as a predictive marker for treatment efficacy of CM326. ClinicalTrials.gov Identifier: NCT05324137. Anti-TSLP biologics have shown promise for the clinical treatment of type 2 respiratory disease. Here the authors present a clinical trial of CM326, a monoclonal antibody against TSLP, and show the clinical effects in patients with eosinophilic chronic rhinosinusitis with nasal polyps (ECRSwNP), who present with type 2-dominant inflammation.

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
• Subject: 631/250/127/1213 / 631/250/249/2510/9 / 631/250/347 / 692/308/2779/777 / 692/699/249/2510/9 / Adult / Aged / Antibodies, Monoclonal - administration & dosage / Antibodies, Monoclonal - adverse effects / Antibodies, Monoclonal - therapeutic use / Asthma / Body mass index / Chronic Disease / Clinical trials / Comorbidity / COVID-19 / Cytokines / Cytokines - antagonists & inhibitors / Cytokines - immunology / Double-Blind Method / Drug dosages / Effectiveness / Eosinophils - drug effects / Female / Health services / Humanities and Social Sciences / Humans / Inflammation / Interleukin-13 - blood / Interleukin-5 - blood / Leukocytes (eosinophilic) / Male / Middle Aged / Monoclonal antibodies / multidisciplinary / Nasal Polyps - complications / Nasal Polyps - drug therapy / Nasal Polyps - immunology / Patients / Peripheral blood / Pharmacodynamics / Placebos / Polyps / Respiratory diseases / Rhinitis - complications / Rhinitis - drug therapy / Rhinitis - immunology / Rhinosinusitis / Science / Science (multidisciplinary) / Sinusitis - complications / Sinusitis - drug therapy / Sinusitis - immunology / Steroids / Thymic Stromal Lymphopoietin / Thymus / Treatment Outcome / Young Adult