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

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.

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Publication Details

Journal
Nature Communications
Published
2025-09-29
DOI
https://doi.org/10.1038/s41467-025-63682-x
Citations
4
Primary Topic
Sinusitis and nasal conditions
Type
article
Field-Weighted Citation Impact
7.39

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article

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

Bing Yan, Chengshuo Wang, Yan Jiang, Luo Zhang et al.
4 citations
Nature Communications
Sinusitis and nasal conditions
7.39
article

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

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

Abstract

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.

Nature CommunicationsVol. 16(1)
Qingdao University (CN), Tongji University (CN), Beijing Tongren Hospital (CN), Union Hospital (HK), Central South University (CN), Nanchang University (CN), Shanxi Medical University (CN), Yangtze University (CN), Capital Medical University (CN), Chinese Academy of Medical Sciences & Peking Union Medical College (CN), Chengdu Medical College (CN), Sichuan University (CN), Yuhuangding Hospital (CN), Wuhan University (CN), First Affiliated Hospital of Xiamen University (CN), West China Hospital of Sichuan University (CN), Capital Institute of Pediatrics (CN), Beijing Luhe Hospital Affiliated to Capital Medical University (CN), The People's Hospital of Guangxi Zhuang Autonomous Region (CN), Affiliated Hospital of Qingdao University (CN), First Hospital of Shanxi Medical University (CN), Wangjing Hospital of China Academy of Chinese Medical Sciences (CN), Hainan General Hospital (CN), The Affiliated Yongchuan Hospital of Chongqing Medical University (CN), Second Hospital of Shanxi Medical University (CN), Renmin Hospital of Wuhan University (CN), Second Xiangya Hospital of Central South University (CN), Third Xiangya Hospital (CN), Tongji Hospital (CN), First People's Hospital of Chongqing (CN), First Affiliated Hospital of Nanchang University (CN), Hangzhou Medical College (CN), Huazhong University of Science and Technology (CN), Chengdu University of Traditional Chinese Medicine (CN), Hainan Medical University (CN), Shandong Institute of Business and Technology (CN), Chongqing Medical University (CN)
Capital Medical University
Openalex Percentile: Top 2%
Sinusitis and nasal conditions
7.39
DOIOpen Access PDFOpenAlex
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