 An anti-TSLP monoclonal antibody for uncontrolled CRSwNP: the DUBHE randomized clinical trialMu Xian,
Feng Lan,
Bing Yan,
Shen Shen,
Shixi Liu,
Lijia Wan,
Xicheng Song,
Luyun Jiang,
Yan Jiang,
Jinmei Xue,
Jianjun Chen,
Lizhong Su,
Jing Ye,
Yucheng Yang,
Hongyan Fang,
Guolin Tan,
Qinna Zhang,
Shenhong Qu,
Xin Wei,
Xianyang Luo,
Yu Xu,
Shaoqing Yu,
Zian Xiao,
Feng Liu,
Qin Li,
Yu Zhang,
Yan Xie,
Lin Wang,
Guoping Yang,
Hongyue Yan,
Guoqing Zhao,
Bo Chen,
Chengshuo Wang () and
Luo Zhang ()
Nature Communications, 2025, vol. 16, issue 1, 1-10 Abstract: 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. Date: 2025 Downloads: (external link) Related works: Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-63682-x Ordering information: This journal article can be ordered from DOI: 10.1038/s41467-025-63682-x Access Statistics for this article Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie More articles in Nature Communications from Nature |
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