Abstract: TH-PO1217
Multicenter, Randomized Phase 2 Study Evaluating the Efficacy and Safety of HRS-5965 in Patients with Primary IgAN
Session Information
- Late-Breaking Research Posters
November 06, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1402 Glomerular Diseases: Clinical, Outcomes, and Therapeutics
Authors
- Lv, Jicheng, Peking University First Hospital, Beijing, China
- Zha, Yan, Guizhou Provincial People's Hospital, Guiyang, Guizhou, China
- Liu, Shuxin, Central Hospital of Dalian University of Technology (Dalian Municipal Central Hospital), Dalian, China
- Zheng, Dongwen, The Tenth Affiliated Hospital of Southern Medical University (Dongguan People's Hospital), Dongguan, China
- Yan, Rui, The Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, China
- Li, Zengyan, The First Affiliated Hospital of Baotou Medical College, Inner Mongolia University of Science and Technology, Baotou, China
- Li, Yinan, The First Affiliated Hospital of Xiamen University, Xiamen, Fujian, China
- Qi, Sheng, Jiangsu Hengrui Medicine Co. Ltd, Shanghai, China
- Zou, Yanfang, Jiangsu Hengrui Medicine Co. Ltd, Shanghai, China
- Zhang, Kaiyun, Jiangsu Hengrui Medicine Co. Ltd, Shanghai, China
- Shu, Chang, Jiangsu Hengrui Medicine Co. Ltd, Shanghai, China
- Huang, Rong, Jiangsu Hengrui Medicine Co. Ltd, Shanghai, China
- Zhang, Liuchao, Jiangsu Hengrui Medicine Co. Ltd, Shanghai, China
- Zhang, Hong, Peking University First Hospital, Beijing, China
Background
Complement system activation plays a significant role in the glomerular inflammation of IgAN. HRS-5965 is a novel, selective small molecule inhibitor of complement factor B by inhibiting complement alternative pathway activation. This study aimed to evaluate the efficacy and safety of HRS-5965 in patients with primary IgAN.
Methods
This phase 2 study enrolled patients (pts) with primary IgAN who had received optimal RAS blockade at least 12 weeks. Eligible pts were randomized in a 1:2:2:2 ratio to receive 25, 50, 75 mg of HRS-5965 or placebo twice daily for 24 wks. The primary endpoint was the ratio of 24-hour urine protein-to-creatinine ratio (24-UPCR) from baseline at wk 12. Secondary endpoints included 24-UPCR from baseline at wk 24, ratio of 24-hour urinary protein excretion (24-UPE), ratio of UACR, change from baseline in eGFR at each visit and safety profiles.
Results
111 pts were randomized and all received at least one dose of study drugs. At wk 12, percentage changes from baseline in 24-UPCR were -27.8%, -30.8% and –39.7% in HRS-5965 25, 50 and 75 mg groups, compared with -3.0% in the placebo (p=0.0492, 0.0052 and 0.0001). At wk 24, percentage changes from baseline in 24-UPCR and 24-UPE in HRS-5965 75 mg group were up to -43.0% and -41.1%, compared with -2.0% and 2.6% in the placebo. Change from baseline in eGFR in HRS-5965 75 mg group was up to 5.5 ml/min/1.73m2 (vs 2.0 in the placebo). The reduction in urinary protein was numerically dose-dependent. In safety, most TEAEs were mild or moderate. The incidence of TEAEs were comparable between HRS-5965 groups and placebo (83.3% vs 87.9%). Most common TEAEs (＞ 10%) in HRS-5965 groups were upper respiratory tract infection and hyperuricemia.
Conclusion
HRS-5965 showed proteinuria reduction in IgAN patients with acceptable safety and tolerability, which will further support the evaluation of HRS-5965 in phase 3 clinical trials.
Funding
- Commercial Support – Jiangsu Hengrui Pharmaceuticals Co., Ltd.