DOP058Efficacy and safety of picankibart in patients with moderately to severely active ulcerative colitis: a randomised, double-blind, placebo-controlled phase 2 trial

Background Interleukin-23 inhibition is effective in treating ulcerative colitis. Picankibart is a monoclonal antibody that selectively targets the IL-23p19 subunit and has a longer half-life than guselkumab. We aimed to evaluate the efficacy and safety of picankibart as induction and maintenance therapy in patients with ulcerative colitis. Methods This phase 2, randomised, double-blind, placebo-controlled trial enrolled patients (18-75 years) with moderately to severely active ulcerative colitis. In the induction period, patients were randomly assigned (1:1:1) to receive picankibart 200 mg, picankiabrt 600 mg or placebo, administrated intravenously, at weeks 0, 4, and 8. At week 12, patients with picankibart achieving clinical response entered the maintenance period and were randomly assigned in a 1:1 ratio to receive picankibart 200 mg every 4 weeks or every 8 weeks, administrated subcutaneously. Patients with clinical response receiving placebo in the induction period continued the administration of placebo (every 4 weeks, subcutaneously) during the maintenance period. The primary endpoint was clinical remission at week 12. Secondary efficacy endpoints included clinical response, symptomatic remission, endoscopic remission, histologic-endoscopic mucosal remission, inflammatory bowel disease questionnaire, and 36-item short form healthy survey at week 12 and 52. Results A total of 150 patients were enrolled in the induction period. At week 12, a significantly greater proportion of patients receiving picankibart 200 mg or 600 mg intravenously achieved a clinical remission than in the placebo group (200 mg vs placebo: 20% vs. 2%, p = 0.0044; 600 mg vs. placebo: 14% vs. 2%, p = 0.0283). For all secondary endpoints excluding histologic-endoscopic mucosal remission, patients with picancibart 200 mg or 600 mg intravenously had a significantly greater proportion than with placebo. During the maintenance period, at week 52, proportions of patients achieving clinical remission were 46.9% in patients with picankibart 200 mg every 4 weeks, 48.5% in patients with picankibart 200 mg every 8 weeks, and 18.2% in patients with placebo, respectively. Most common adverse event in both induction and maintenance period was upper respiratory tract infection, and its incidence was higher in patients receiving picankibart than receiving placebo. No new safety signals were observed. Conclusion Picankibart was effective and safe as induction and maintenance therapy in patients with moderately to severely active ulcerative colitis. These findings support advancing to phase 3 clinical trials in this patient population. Conflict of interest: Chen, Baili: I have received research funding from Takeda (China). Zhuang, Kun: No conflict of interest Gao, Xiang: No conflict of interest Huang, Caibin: No conflict of interest Zheng, Changqing: no conflict o Liu, Wenjia: No conflict of interest Jiang, Qi: I have received research funding from Takeda (China). Yuan, Haipeng: No conflict of interest Qu, Bo: No conflict of interest Liu, Bingrong: No conflict of interest Lv, Xiaoping: No conflict of interest An, Ping: No conflict of interest Zhong, Lan: No conflict of interest Zhang, Yingjian: No conflict of interest Gao, Chunxian: No conflict of interest Tuo, Biguang: No conflict of interest Wang, Junping: No conflict of interest Pei, Zejun: No conflict of interest Gong, Lei: No conflict of interest Chen, Yan: No conflict of interest Zhang, Hongjie: No conflict of interest Li, Yanqing: No conflict of interest Huo, Xiaohui: No conflict of interest Deng, Tianwei: No conflict of interest Zhu, Haichao: No conflict of interest Du, Yiqi: No conflict of interest Tang, Wen: No conflict of interest Zhang, Xiaomei: No conflict of interest Li, Fangfang: No conflict of interest Tang, Tongyu: No conflict of interest Han, Yu: No conflict of interest Wang, Bangmao: No conflict of interest Wang, Xiaozhong: No conflict of interest Han, Wei: No conflict of interest Liu, Yulan: No conflict of interest Cai, Chenghang: The employee of Innovent Biologics Ye, Rouxuan: The employee of Innovent Biologics Chen, Mingxia: The employee of Innovent Biologics Qian, Lei: The employee of Innovent Biologics Chen, Minhu: I have received speaker honoraria from Takeda China, Xian Janssen, and AbbVie China, as well as research funding from Takeda (China).