Abstract: FR-PO0840
XH-S003, a Small Molecule Complement Factor B Inhibitor, Shows Favorable Pharmacokinetics and Complete Suppression of an Alternative Pathway at Well-Tolerated Doses in Healthy Volunteers in China
Session Information
- Glomerular Clinical Trials: From Data to Impact
November 07, 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
- Dong, Ruihua, Capital Medical University Affiliated Beijing Friendship Hospital, Beijing, China
- Li, Xiang, Shanghai Fosun Pharmaceutical Industrial Development Co., Ltd., Shanghai, China
- Wang, Xingli, Shanghai Fosun Pharmaceutical Industrial Development Co., Ltd., Shanghai, China
- Xiao, Yue, Beijing Fosun Pharmaceutical Research and Development Co., Ltd., Beijing, China
- Liu, Zhihua, Beijing Fosun Pharmaceutical Research and Development Co., Ltd., Beijing, China
- Zhou, Chao, Beijing Fosun Pharmaceutical Research and Development Co., Ltd., Beijing, China
- Hu, Lin, Beijing Fosun Pharmaceutical Research and Development Co., Ltd., Beijing, China
- Chen, Cheng, Beijing Fosun Pharmaceutical Research and Development Co., Ltd., Beijing, China
Background
The first-in-human phase I study has evaluated the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of XH-S003 in healthy volunteers in Australia, demonstrating the safety and pharmacologic inhibition of complement alternative pathway (AP) in single ascending dose (SAD) and multiple ascending dose (MAD). We now report a bridging phase I study of XH-S003 conducted in China.
Methods
This study included SAD, MAD and food effect (FE) components to evaluate the safety, tolerability, PK and PD of XH-S003 in healthy volunteers in China. AP activity was measured via the Wieslab assay and fragment Bb levels were determined with a validated commercial ELISA kit.
Results
A total of 36 healthy volunteers were enrolled and received XH-S003. It was well tolerated at all doses, 25 mg, 50 mg and 100 mg in SAD, and 25 mg, 75 mg and 150 mg QD for 14 days in MAD. No deaths, no serious adverse events (AEs) or treatment-related AEs leading to drug withdrawal or study discontinuation were reported. Most AEs were mild in severity, with no apparent trends or dose-dependent effects. Similar to the trial in Australia, XH-S003 exhibited rapid drug absorption, moderate clearance and no evidence of food effect of low-fat meal in Chinese healthy volunteers. The terminal half-life was about 29.3-40.0h. XH-S003 also exhibited rapid-onset and sustained suppression of Bb fragment level (around 50%) and AP activity (>95%) within 1 hour. Both the reduction of Bb fragment and the inhibition of AP were well-correlated with plasma concentration of XH-S003 without time delay.
Conclusion
Overall, XH-S003 is safe and well tolerated when administered orally as a single dose up to 100mg and as multiple doses up to 150 mg for 14 days. In addition, XH-S003 showed a rapid-onset, sustained and dose-dependent AP suppression and had a favorable PK profile. XH-S003 showed similar safety and PK/PD profile in healthy volunteers in China and Australia, indicating no significant ethnic differences. (NCT06272747)
Funding
- Commercial Support – Fosun Pharma and S-INFINITY Pharmaceuticals Co., Ltd