Efficacy and safety of XKH004, a novel dual interleukin-17A/F inhibitory monoclonal antibody, in active ankylosing spondylitis: A 52-week phase 3 randomized study
Year: 2026
Type: article
Study designs: Randomized Controlled Trial, Clinical Trial
Abstract: Ankylosing spondylitis (AS) is an immune-mediated spondyloarthropathy with unmet clinical needs. We conducted a superiority, phase 3, multicenter, randomized, double-blind, placebo-controlled trial to evaluate the efficacy and safety of XKH004, a humanized monoclonal antibody targeting interleukin-17A/F in active AS. Of 489 screened patients with inadequate response to conventional therapy, 166 were excluded based on predefined criteria. The remaining 323 eligible patients were randomized 1:1 via a centralized interactive web-response system to receive subcutaneous XKH004 160 mg every 4 weeks or placebo until week 16. All patients completed a 52-week follow-up period, comprising 44 weeks of open-label XKH004 treatment followed by an 8-week safety follow-up. Participants and investigators were blinded to treatment allocation. Efficacy analyses utilized the Cochran–Mantel–Haenszel test. The primary endpoint was Assessment of SpondyloArthritis international Society 40 (ASAS40) response at week 16; secondary endpoints included ASAS20/50, Bath Ankylosing Spondylitis Disease Activity Index, Bath Ankylosing Spondylitis Functional Index, Ankylosing Spondylitis Quality of Life, and Ankylosing Spondylitis Disease Activity Score. At week 16, ASAS40 response was achieved by 45.4% with XKH004 ( n = 161) vs 19.4% with placebo ( n = 162; absolute difference, 95% confidence interval, 15.47–35.02; P < 0.001), with efficacy in the XKH004 group sustaining and further improving to 66.2% by week 52. Serious adverse events occurred in 1.2% and 2.5% of patients in the XKH004 and placebo groups, respectively. Overall, XKH004 was well tolerated and induced rapid, sustained improvements, supporting its potential as a novel therapeutic option for active AS. The trial was registered in the China Drug Experiment database (CTR20232310) and ClinicalTrials.gov (NCT07498634) and supported by the National Natural Science Foundation of China, National Key Research and Development Project, Shanghai Municipal Key Clinical Specialty, and Shanghai Science and Technology Development Funds.
Source: hLife
Authors: Ling Zhou, Ran Yan, Songying Ye, Juan Zhao, Xiaofei Shi, Guixiu Shi, Shujie Li, Yanfei Chen, Hui Luo, Yongtao Chen, Rui Wu, Jinying Lin, Zhenyu Jiang, Lingyun Sun, Jiankang Hu, Xiaomei Li, Zhenchun Zhang, Yi Zhao, Jian Xu, Xiaoping Hong, Lei Zhou, Lingli Dong, Guohua Yuan, Huaxiang Wu, Qian Xing, Yongjun Mei, Xiaoxia Wang, Yang Li, Rong Mu, Wei Wei, Zunfang Xu, Shudian Lin, Min Yang, Qingchun Huang, Qiong Fu, Wei Gou, Hongbin Li, Lijun Wu, Xiaodan Kong, Jian Wu, Jianguo You, Ke Ren, Li Guo, Chen Dong, Huji Xu
Institutions: Second Military Medical University, Shanghai Changzheng Hospital, First Affiliated Hospital of Henan University of Science and Technology, First Affiliated Hospital of Xiamen University, West China Medical Center of Sichuan University, West China Hospital of Sichuan University, First Hospital of Lanzhou University, Xiangya Hospital Central South University, First Affiliated Hospital of Nanchang University, The People's Hospital of Guangxi Zhuang Autonomous Region, First Hospital of Jilin University, Nanjing Drum Tower Hospital, Nanjing University, Jiangxi Pingxiang People's Hospital, University of Science and Technology of China, Anhui Provincial Hospital, Linyi People's Hospital, Capital Medical University, Xuan Wu Hospital of the Capital Medical University, First Affiliated Hospital of Kunming Medical University, ShenZhen People’s Hospital, Huazhong University of Science and Technology, Affiliated Hospital of North Sichuan Medical College, Second Affiliated Hospital of Zhejiang University, Zhejiang University, Qingdao Municipal Hospital, First Affiliated Hospital of Bengbu Medical College, Shanxi Medical University, Second Hospital of Shanxi Medical University, Guangdong Provincial People's Hospital, Peking University Third Hospital, Tianjin Medical University General Hospital, People's Hospital of Cangzhou, Hainan General Hospital, Nanfang Hospital, Southern Medical University, Guangdong Provincial Hospital of Chinese Medicine, Shanghai Jiao Tong University, Renji Hospital, Second Affiliated Hospital of Dalian Medical University, People's Hospital of Xinjiang Uygur Autonomous Region, Inner Mongolia Medical University, First Affiliated Hospital of Soochow University, Beijing Kanova Biopharmaceutical, Co. Ltd (China), Westlake University
Language: English
Subfield: Rheumatology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,300
Funders: Shanghai Science and Technology Development Foundation, Shanghai Municipal Health Commission, National Natural Science Foundation of China, Ministry of Science and Technology of the People's Republic of China, Science and Technology Commission of Shanghai Municipality, National Key Research and Development Program of China
OpenAlex ID: W7211931211