Dai Yuyang, Wu Feng, Ni Siyang, Hu Xiaojun, Han Ying, Jiao Ying, Lu Huan, Liu Yilin, Wang Lingling, Lin Yunfei, Chen Meixia, Wang Chao, Wu Qinghe, Li Fangqiong, Lu Laichun
National Institute for Drug Clinical Trial, Beijing Tongren Hospital, Capital Medical University, Beijing, China.
Haisco Pharmaceutical Group Co., Ltd., Chengdu, Sichuan Province, China.
Clin Transl Sci. 2025 Jul;18(7):e70281. doi: 10.1111/cts.70281.
HSK39297 is a novel complement factor B inhibitor, and this phase 1 trial was designed to assess its pharmacokinetics (PK), pharmacodynamics (PD), safety, and tolerability in healthy Chinese subjects. This study included 46 subjects in the single ascending dose (SAD) part (50-600 mg) and 50 subjects in the multiple ascending dose (MAD) part (50-125 mg BID and 200-300 mg QD). Among them, a food effect study was conducted in the SAD 200 mg group. Adverse events (AEs) reported after the initial dose of the study drug were considered treatment-emergent AEs (TEAEs). Blood samples were collected to measure plasma concentrations of HSK39297 at predefined time points and analyzed at a centralized laboratory. In addition, PD analysis was conducted by measuring complement alternative pathway (AP) activity and Bb concentrations. According to the results, we found single and multiple doses of HSK39297 were safe and well tolerated in all subjects. Within SAD of 50-600 mg dose range, the C, AUC, and AUC exhibited nonlinear PK characteristics. The high-fat meals did not significantly affect the absorption rate and systemic exposure levels of HSK39297, and GMRs for fed versus fasting states were 108.05% (99.66%, 117.15%), 98.73% (89.34%, 109.09%), and 97.86% (84.66%, 113.11%), respectively. In MAD part, dose-drug exposure showed a linear relationship. PD analysis indicated that oral administration of HSK39297 tablets resulted in dose-dependent inhibition of the AP activity and Bb concentration. These findings support advancing HSK39297 into later-phase trials for complement-mediated glomerular diseases.
HSK39297是一种新型补体因子B抑制剂,该1期试验旨在评估其在中国健康受试者中的药代动力学(PK)、药效动力学(PD)、安全性和耐受性。本研究包括单剂量递增(SAD)部分的46名受试者(50 - 600毫克)和多剂量递增(MAD)部分的50名受试者(50 - 125毫克,每日两次和200 - 300毫克,每日一次)。其中,在SAD 200毫克组进行了食物影响研究。研究药物初始剂量后报告的不良事件(AE)被视为治疗中出现的不良事件(TEAE)。在预定时间点采集血样以测量HSK39297的血浆浓度,并在中心实验室进行分析。此外,通过测量补体替代途径(AP)活性和Bb浓度进行PD分析。根据结果,我们发现单剂量和多剂量的HSK39297在所有受试者中均安全且耐受性良好。在50 - 600毫克剂量范围内的SAD中,Cmax、AUC和AUC呈现非线性PK特征。高脂餐对HSK39297的吸收速率和全身暴露水平无显著影响,进食与空腹状态下的几何平均比值(GMR)分别为108.05%(99.66%,117.15%)、98.73%(89.34%,109.09%)和97.86%(84.66%,113.11%)。在MAD部分,剂量 - 药物暴露呈线性关系。PD分析表明,口服HSK39297片剂可导致AP活性和Bb浓度的剂量依赖性抑制。这些发现支持将HSK39297推进到补体介导的肾小球疾病的后期试验。