Skip to content
DraconiticResearch
Search Sources API
201,818 studies31 sourcesUpdated 6 min ago
Peer-reviewedCC BY-NC-NDhLife

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

  • Ling Zhou1
  • Ran Yan1
  • Songying Ye1
  • Juan Zhao1
  • Xiaofei Shi2
  • Guixiu Shi3
  • Shujie Li4
  • Yanfei Chen5
  • Hui Luo6
  • Yongtao Chen7
  • Rui Wu8
  • Jinying Lin9
33 more authors
  • Zhenyu Jiang10
  • Lingyun Sun11
  • Jiankang Hu12
  • Xiaomei Li13
  • Zhenchun Zhang14
  • Yi Zhao15
  • Jian Xu16
  • Xiaoping Hong17
  • Lei Zhou18
  • Lingli Dong19
  • Guohua Yuan20
  • Huaxiang Wu21
  • Qian Xing22
  • Yongjun Mei23
  • Xiaoxia Wang24
  • Yang Li25
  • Rong Mu26
  • Wei Wei27
  • Zunfang Xu28
  • Shudian Lin29
  • Min Yang30
  • Qingchun Huang31
  • Qiong Fu32
  • Wei Gou33
  • Hongbin Li34
  • Lijun Wu35
  • Xiaodan Kong36
  • Jian Wu37
  • Jianguo You38
  • Ke Ren38
  • Li Guo38
  • Chen Dong39
  • Huji Xu40
40 affiliations
  1. 1Department of Rheumatology and Immunology, National Key Laboratory for Immunity and Inflammation, Changzheng Hospital, Naval Medical University, Shanghai, China
  2. 2Department of Rheumatology and Immunology, The First Affiliated Hospital of Henan University of Science & Technology, Henan, China
  3. 3Department of Rheumatology and Immunology, The First Affiliated Hospital of Xiamen University, Fujian, China
  4. 4Department of Rheumatology and Immunology, Jining No.1 People's Hospital, Shandong, China
  5. 5Department of Rheumatology and Immunology, The First Hospital of Lanzhou University, Gansu, China
  6. 6Department of Rheumatology and Immunology, Xiangya Hospital of Central South University, Hunan, China
  7. 7Department of Rheumatology and Immunology, West China Hospital of Sichuan University, Sichuan, China
  8. 8Department of Rheumatology and Immunology, The First Affiliated Hospital of Nanchang University, Jiangxi, China
  9. 9Department of Rheumatology and Immunology, The People’s Hospital of Guangxi Zhuang Autonomous Region, Guangxi Zhuang Autonomous Region, China
  10. 10Department of Rheumatology and Immunology, The First Hospital of Jilin University, Jilin, China
  11. 11Department of Rheumatology and Immunology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Jiangsu, China
  12. 12Department of Rheumatology and Immunology, Pingxiang People's Hospital, Jiangxi, China
  13. 13Department of Rheumatology and Immunology, The First Affiliated Hospital of University of Science and Technology of China (Anhui Provincial Hospital), Anhui, China
  14. 14Department of Rheumatology and Immunology, Linyi People's Hospital, Shandong, China
  15. 15Department of Rheumatology and Immunology, Xuanwu Hospital, Capital Medical University, Beijing, China
  16. 16Department of Rheumatology and Immunology, The First Affiliated Hospital of Kunming Medical University, Yunnan, China
  17. 17Department of Rheumatology and Immunology, Shenzhen People's Hospital, Guangdong, China
  18. 18Department of Rheumatology and Immunology, Changzhou No.2 People's Hospital, Jiangsu, China
  19. 19Department of Rheumatology and Immunology, Tongji Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology, Hubei, China
  20. 20Department of Rheumatology and Immunology, Affiliated Hospital of North Sichuan Medical College, Sichuan, China
  21. 21Department of Rheumatology and Immunology, The Second Affiliated Hospital of Zhejiang University School of Medicine, Zhejiang, China
  22. 22Department of Rheumatology and Immunology, Qingdao Municipal Hospital, Shandong, China
  23. 23Department of Rheumatology and Immunology, The First Affiliated Hospital of Bengbu Medical University, Anhui, China
  24. 24Department of Rheumatology and Immunology, The Second Hospital of Shanxi Medical University, Shanxi, China
  25. 25Department of Rheumatology and Immunology, Guangdong Provincial People's Hospital, Guangdong, China
  26. 26Department of Rheumatology and Immunology, Peking University Third Hospital, Beijing, China
  27. 27Department of Rheumatology and Immunology, Tianjin Medical University General Hospital, Tianjin, China
  28. 28Department of Rheumatology and Immunology, Cangzhou People's Hospital, Hebei, China
  29. 29Department of Rheumatology and Immunology, Hainan General Hospital, Hainan, China
  30. 30Department of Rheumatology and Immunology, Nanfang Hospital of Southern Medical University, Guangdong, China
  31. 31Department of Rheumatology and Immunology, Guangdong Provincial Hospital of Traditional Chinese Medicine, Guangdong, China
  32. 32Department of Rheumatology and Immunology, Renji Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
  33. 33Department of Rheumatology and Immunology, Hebei PetroChina Central Hospital, Hebei, China
  34. 34Department of Rheumatology and Immunology, Affiliated Hospital of Inner Mongolia Medical University, Inner Mongolia Autonomous Region, China
  35. 35Department of Rheumatology and Immunology, People's Hospital of Xinjiang Uygur Autonomous Region, Xinjiang Uygur Autonomous Region, China
  36. 36Department of Rheumatology and Immunology, The Second Affiliated Hospital of Dalian Medical University, Liaoning, China
  37. 37Department of Rheumatology and Immunology, The First Affiliated Hospital of Soochow University, Jiangsu, China
  38. 38Kanova Biopharmaceutical Co., Ltd., Beijing, China
  39. 39Westlake University School of Medicine, Zhejiang, China
  40. 40Department of Rheumatology and Immunology, National Key Laboratory for Immunity and Inflammation, Changzheng Hospital, Naval Medical University, Shanghai, China; Correspondence:
Read full textPDFDOICite

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 the proportion of patients achieving an Assessment of SpondyloArthritis international Society ≥ 40% improvement (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.

Related

  1. Adalimumab-induced pustular psoriasis successfully treated with tofacitinib in a patient with ankylosing spondylitis: A brief report.
    Duygu Kurtuluş, İlkin Zindancı
    JAAD case reportsPeer-reviewedCC BYFull textGeneral medicineEurope PMCPMC
  2. GLP-1 receptor agonist initiation and newly recorded ankylosing spondylitis diagnoses in type 2 diabetes: a target trial emulation
    Yu-Chen Lu, Tzu-Hao Li, Ya-Fang Liu +1
    Scientific ReportsPeer-reviewedCC BY-NC-ND 4.0Full textEndocrinology & metabolismCrossref
  3. Ultrasound-guided Interscalene Block as a Safer Alternative to General Anesthesia in a Patient with Ankylosing Spondylitis Undergoing Proximal Humerus Fracture Fixation
    Bhagyashree Soor, Ruhi Vaid, Abhijit More
    Annals of African MedicinePeer-reviewedCC BY-NC-SA 4.0Full text1 citedSurgery & anaesthesiaPMC
  4. Case Report: Spinal cord herniation associated with ankylosing spondylitis
    Zekai Ke, Chunguang Duan
    Frontiers in surgeryPeer-reviewedCC BYFull textSurgery & anaesthesiaEurope PMCPMC
  5. Successful extravascular implantable cardioverter defibrillator implantation in a patient with ankylosing spondylitis and severe thoracic deformity: a case report.
    Jia He, Qiming Liu, Zean Zhu +2
    European heart journal. Case reportsPeer-reviewedCC BY-NCFull textCardiovascular medicineEurope PMC

Cite

BibTeXRIS
BibTeX
@article{zhou2026efficacy,
  title = {{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}},
  author = {Ling Zhou and Ran Yan and Songying Ye and Juan Zhao and Xiaofei Shi and Guixiu Shi and Shujie Li and Yanfei Chen and Hui Luo and Yongtao Chen and Rui Wu and Jinying Lin and Zhenyu Jiang and Lingyun Sun and Jiankang Hu and Xiaomei Li and Zhenchun Zhang and Yi Zhao and Jian Xu and Xiaoping Hong and Lei Zhou and Lingli Dong and Guohua Yuan and Huaxiang Wu and Qian Xing and Yongjun Mei and Xiaoxia Wang and Yang Li and Rong Mu and Wei Wei and Zunfang Xu and Shudian Lin and Min Yang and Qingchun Huang and Qiong Fu and Wei Gou and Hongbin Li and Lijun Wu and Xiaodan Kong and Jian Wu and Jianguo You and Ke Ren and Li Guo and Chen Dong and Huji Xu},
  journal = {hLife},
  year = {2026},
  month = oct,
  doi = {10.1016/j.hlife.2026.07.005},
  url = {https://doi.org/10.1016/j.hlife.2026.07.005},
  note = {CC BY-NC-ND},
}
RIS
TY  - JOUR
TI  - 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
AU  - Ling Zhou
AU  - Ran Yan
AU  - Songying Ye
AU  - Juan Zhao
AU  - Xiaofei Shi
AU  - Guixiu Shi
AU  - Shujie Li
AU  - Yanfei Chen
AU  - Hui Luo
AU  - Yongtao Chen
AU  - Rui Wu
AU  - Jinying Lin
AU  - Zhenyu Jiang
AU  - Lingyun Sun
AU  - Jiankang Hu
AU  - Xiaomei Li
AU  - Zhenchun Zhang
AU  - Yi Zhao
AU  - Jian Xu
AU  - Xiaoping Hong
AU  - Lei Zhou
AU  - Lingli Dong
AU  - Guohua Yuan
AU  - Huaxiang Wu
AU  - Qian Xing
AU  - Yongjun Mei
AU  - Xiaoxia Wang
AU  - Yang Li
AU  - Rong Mu
AU  - Wei Wei
AU  - Zunfang Xu
AU  - Shudian Lin
AU  - Min Yang
AU  - Qingchun Huang
AU  - Qiong Fu
AU  - Wei Gou
AU  - Hongbin Li
AU  - Lijun Wu
AU  - Xiaodan Kong
AU  - Jian Wu
AU  - Jianguo You
AU  - Ke Ren
AU  - Li Guo
AU  - Chen Dong
AU  - Huji Xu
PY  - 2026
DA  - 2026/10/24
JO  - hLife
DO  - 10.1016/j.hlife.2026.07.005
UR  - https://doi.org/10.1016/j.hlife.2026.07.005
AB  - 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 the proportion of patients achieving an Assessment of SpondyloArthritis international Society ≥ 40% improvement (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.
SN  - 2949-9283
ER  -