Expert opinion on investigational drugs · 2023
Safety and pharmacokinetics of IBI112, an IL-23 monoclonal antibody, in Chinese healthy volunteers: a first-in-human phase 1 study.
Рандомизированное исследованиеКлиническое исследование I фазыСтатьяНазвание и аннотация: Перевод пока не подготовлен
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He Jinjie, Du Weijuan, Yang Haijing, Wang Jingjing, Cai Chenghang, Ma Qingyang, Li Nanyang, Yu Jicheng, Wu Xiaojie, Wu Jufang, Chen Yuancheng, Cao Guoying, Zhang Jing
Аннотация
BACKGROUND: Interleukin (IL) 23p19 monoclonal antibodies were efficacious and safe in the treatment of psoriasis. A first-in-human (FIH) study was conducted to evaluate the safety, tolerability, pharmacokinetics (PK) and immunogenicity of IBI112, a novel IL-23p19 monoclonal antibody.
METHODS: In this FIH, randomized, double-blind, placebo-controlled, single-ascending-dose study, a subcutaneous (SC, 5-600 mg) or intravenous (IV, 100 and 600 mg) or placebo was administered to eligible healthy subjects. Safety was assessed by physical examinations, vital signs, laboratory tests, and electrocardiograms. Furthermore, non-compartment analysis and population PK modeling were conducted to characterize PK, and model-based simulation was applied to justify dose selection for psoriasis patients.
RESULTS: A total of 46 subjects were enrolled, with 35 receiving IBI112 and 11 receiving placebo. No serious adverse events (SAEs) and no clinically significant adverse events were identified. After a single SC of IBI112, the median Tmax was 4-10.5 days, and the half-life (t1/2) ranged from 21.8 to 35.8 days. IBI112 exposures (Cmax and AUCinf) approached dose proportionality across 5-300 mg range.
CONCLUSION: IBI112 was well tolerated and safe at SC or IV dose up to 600 mg and showed a linear PK characteristics at SC dose from 5 to 300 mg.
CLINICAL TRIAL REGISTRATION: ClinicalTrial.gov NCT04511624.
METHODS: In this FIH, randomized, double-blind, placebo-controlled, single-ascending-dose study, a subcutaneous (SC, 5-600 mg) or intravenous (IV, 100 and 600 mg) or placebo was administered to eligible healthy subjects. Safety was assessed by physical examinations, vital signs, laboratory tests, and electrocardiograms. Furthermore, non-compartment analysis and population PK modeling were conducted to characterize PK, and model-based simulation was applied to justify dose selection for psoriasis patients.
RESULTS: A total of 46 subjects were enrolled, with 35 receiving IBI112 and 11 receiving placebo. No serious adverse events (SAEs) and no clinically significant adverse events were identified. After a single SC of IBI112, the median Tmax was 4-10.5 days, and the half-life (t1/2) ranged from 21.8 to 35.8 days. IBI112 exposures (Cmax and AUCinf) approached dose proportionality across 5-300 mg range.
CONCLUSION: IBI112 was well tolerated and safe at SC or IV dose up to 600 mg and showed a linear PK characteristics at SC dose from 5 to 300 mg.
CLINICAL TRIAL REGISTRATION: ClinicalTrial.gov NCT04511624.