Expert opinion on investigational drugs · 2025
Pharmacokinetics, pharmacodynamics, and safety of HE009, a novel selective S1P1 receptor modulator, in healthy Chinese subjects.
СтатьяРандомизированное исследованиеКлиническое исследование I фазыНазвание и аннотация: Перевод в очереди
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Ding Jie, Zhang Qian, Yang Qin, Zhang Qin, Tu Sihui, Zuo Yangyang, Yao Zhiwei, Deng Peng, Tao Lin, Zheng Liang, Hu Wei
Аннотация
OBJECTIVE: HE009, a novel selective sphingosine-1-phosphate receptor-1 (S1P1) modulator, was evaluated in healthy Chinese subjects to assess its pharmacokinetics, pharmacodynamics, and safety profile.
RESEARCH DESIGN AND METHODS: This randomized, placebo-controlled phase I study comprised single ascending dose (SAD, 0.05-4.0 mg), multiple ascending dose (MAD, 0.5-3.0 mg), dose titration, and food effect components.
RESULTS: HE009 exhibited dose-proportional exposure, with Tmaxof 4-6 h and t1/2 of 16-24 h, supporting once-daily dosing. Steady-state was achieved by day 7 with minimal accumulation (1.7-2.0 fold). A clear concentration-effect relationship was observed, with maximum lymphocyte count reductions of 58% (SAD) and 70-80% (MAD). Notably, HE009 demonstrated a favorable cardiac safety profile, with transient, asymptomatic bradycardia mitigated by dose titration. No events related to hypertension were observed during the study period.
CONCLUSION: These findings suggest HE009 offers potential advantages in efficacy, safety, and dosing flexibility compared to existing S1P receptor modulators for treating autoimmune disorders like systemic lupus erythematosus.
TRIAL REGISTRATION: The trial was registered on the Chinese Clinical Trial Registry, (Identifier No. ChiCTR2200066345), Registered December 1, 2022.
RESEARCH DESIGN AND METHODS: This randomized, placebo-controlled phase I study comprised single ascending dose (SAD, 0.05-4.0 mg), multiple ascending dose (MAD, 0.5-3.0 mg), dose titration, and food effect components.
RESULTS: HE009 exhibited dose-proportional exposure, with Tmaxof 4-6 h and t1/2 of 16-24 h, supporting once-daily dosing. Steady-state was achieved by day 7 with minimal accumulation (1.7-2.0 fold). A clear concentration-effect relationship was observed, with maximum lymphocyte count reductions of 58% (SAD) and 70-80% (MAD). Notably, HE009 demonstrated a favorable cardiac safety profile, with transient, asymptomatic bradycardia mitigated by dose titration. No events related to hypertension were observed during the study period.
CONCLUSION: These findings suggest HE009 offers potential advantages in efficacy, safety, and dosing flexibility compared to existing S1P receptor modulators for treating autoimmune disorders like systemic lupus erythematosus.
TRIAL REGISTRATION: The trial was registered on the Chinese Clinical Trial Registry, (Identifier No. ChiCTR2200066345), Registered December 1, 2022.