Stapokibart for moderate-to-severe seasonal allergic rhinitis: a randomized phase 3 trial

Seasonal allergic rhinitis (SAR) places a significant socioeconomic burden, particularly on individuals with poorly managed recurrent and severe symptoms despite standard-of-care treatment. Stapokibart, a humanized monoclonal antibody that targets the interleukin (IL)-4 receptor subunit alpha, inhibits its interaction with both IL-4 and IL-13 in type 2 inflammation. Here we aim to assess the efficacy and safety of stapokibart as an add-on therapy in adults with moderate-to-severe SAR. The study was a phase 3 multicenter, randomized, double-blind, placebo-controlled clinical trial with 108 patients diagnosed with moderate-to-severe SAR and having baseline blood eosinophil counts ≥300 cells μl<sup>-1</sup>. Participants were randomized (1:1) to receive 600 mg (loading dose) to 300 mg stapokibart subcutaneously or a placebo every 2 weeks for 4 weeks. The primary endpoint was mean change from baseline in daily reflective total nasal symptom score (rTNSS) over the first 2 weeks. Multiplicity-tested secondary endpoints included changes in rTNSS over 4 weeks, reflective total ocular symptom score and Rhinoconjunctivitis Quality of Life Questionnaire score over 2 weeks and 4 weeks. Compared with the placebo, stapokibart led to a significant improvement in the mean change from baseline in daily rTNSS during the 2-week (least-squares mean difference, -1.3; 95% confidence interval, -2.0 to -0.6; P = 0.0008) and 4-week (least-squares mean difference, -1.7; 95% confidence interval, -2.5 to -0.8; P = 0.0002) treatments. Stapokibart significantly improved the multiplicity-tested secondary endpoints. Treatment-emergent adverse events were comparable between the groups. Pharmacodynamics and exploratory analyses indicated that the observed improvements in outcomes during pollen season may be attributed to the reduction of type 2 inflammation in response to stapokibart treatment. The results of this trial show that pollen seasonal administration of stapokibart improved both nasal and ocular symptoms and quality of life in patients with moderate-to-severe SAR. ClinicalTrials.gov registration: NCT05908032 .

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Publication Details

Journal
Nature Medicine
Published
2025-04-04
DOI
https://doi.org/10.1038/s41591-025-03651-5
Citations
28
Primary Topic
Allergic Rhinitis and Sensitization
Type
article
Field-Weighted Citation Impact
45.42

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article

Stapokibart for moderate-to-severe seasonal allergic rhinitis: a randomized phase 3 trial

Zhendong Xu, Xiaoyong Ren, Ruixia Ma, Jingyun Li et al.
28 citations
Nature Medicine
Allergic Rhinitis and Sensitization
45.42
article

Stapokibart for moderate-to-severe seasonal allergic rhinitis: a randomized phase 3 trial

Zhendong Xu, Xiaoyong Ren, Ruixia Ma, Jingyun Li, Zhimin Xing, Fang Quan, Chengshuo Wang, Luo Zhang, Jing Pan, Bing Yan, Feng Yan, Jinmei Xue, Xiaoqiu Chen, Yi Yang, Jixiang Liu, Xiaoping Gao, Yusheng Wang, Wenwen Liu, Weiwei Liu, Yuan Zhang, Bo Chen, Feng Shi, Zhiwei Cao, Xian Li, Guoqing Zhao, Hongyue Yan, Menglin Wang, Yue Sun, Xicheng Song, Xuezhong Li, Shi Li
article en
28 citations

Abstract

Seasonal allergic rhinitis (SAR) places a significant socioeconomic burden, particularly on individuals with poorly managed recurrent and severe symptoms despite standard-of-care treatment. Stapokibart, a humanized monoclonal antibody that targets the interleukin (IL)-4 receptor subunit alpha, inhibits its interaction with both IL-4 and IL-13 in type 2 inflammation. Here we aim to assess the efficacy and safety of stapokibart as an add-on therapy in adults with moderate-to-severe SAR. The study was a phase 3 multicenter, randomized, double-blind, placebo-controlled clinical trial with 108 patients diagnosed with moderate-to-severe SAR and having baseline blood eosinophil counts ≥300 cells μl<sup>-1</sup>. Participants were randomized (1:1) to receive 600 mg (loading dose) to 300 mg stapokibart subcutaneously or a placebo every 2 weeks for 4 weeks. The primary endpoint was mean change from baseline in daily reflective total nasal symptom score (rTNSS) over the first 2 weeks. Multiplicity-tested secondary endpoints included changes in rTNSS over 4 weeks, reflective total ocular symptom score and Rhinoconjunctivitis Quality of Life Questionnaire score over 2 weeks and 4 weeks. Compared with the placebo, stapokibart led to a significant improvement in the mean change from baseline in daily rTNSS during the 2-week (least-squares mean difference, -1.3; 95% confidence interval, -2.0 to -0.6; P = 0.0008) and 4-week (least-squares mean difference, -1.7; 95% confidence interval, -2.5 to -0.8; P = 0.0002) treatments. Stapokibart significantly improved the multiplicity-tested secondary endpoints. Treatment-emergent adverse events were comparable between the groups. Pharmacodynamics and exploratory analyses indicated that the observed improvements in outcomes during pollen season may be attributed to the reduction of type 2 inflammation in response to stapokibart treatment. The results of this trial show that pollen seasonal administration of stapokibart improved both nasal and ocular symptoms and quality of life in patients with moderate-to-severe SAR. ClinicalTrials.gov registration: NCT05908032 .

Nature MedicineVol. 31(7)
Beijing Tongren Hospital (CN), Union Hospital (HK), Shanxi Medical University (CN), Capital Medical University (CN), Jilin University (CN), Chinese Academy of Medical Sciences & Peking Union Medical College (CN), Peking University (CN), Chengdu Medical College (CN), National Medical Products Administration (CN), Yuhuangding Hospital (CN), Yinchuan First People's Hospital (CN), Cangzhou Central Hospital (CN), Beijing Luhe Hospital Affiliated to Capital Medical University (CN), Shandong Provincial Hospital (CN), Beijing Hospital (CN), First Affiliated Hospital of Xi'an Jiaotong University (CN), Peking University People's Hospital (CN), First Hospital of Jilin University (CN), First Hospital of Shanxi Medical University (CN), Baotou Central Hospital (CN), Ningxia Medical University (CN), Second Affiliated Hospital of Xi'an Jiaotong University (CN), Second Hospital of Shanxi Medical University (CN), Ningxia Medical University General Hospital (CN), Ministry of Education (TW), Central Hospital of Zibo (CN), Beijing Center for Disease Prevention and Control (CN), Qilu Hospital of Shandong University (CN), Ministry of Education and Child Care (CA), China Medical University (CN)
National Natural Science Foundation of China
Openalex Percentile: Top 0%
Allergic Rhinitis and Sensitization
45.42
DOIOpen Access PDFOpenAlex
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