Phase I Clinical Research Center, Huashan Hospital of Fudan University, Shanghai, China.
The Clinical Pharmacology Department, Innovent Biologics (Suzhou), Suzhou, China.
Expert Opin Investig Drugs. 2023 Jul-Dec;32(7):669-675. doi: 10.1080/13543784.2023.2230122. Epub 2023 Jun 29.
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.
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.
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 was 4-10.5 days, and the half-life (t) ranged from 21.8 to 35.8 days. IBI112 exposures (C and AUC) approached dose proportionality across 5-300 mg range.
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.
ClinicalTrial.gov NCT04511624.
白细胞介素（IL）23p19 单克隆抗体在治疗银屑病方面是有效且安全的。进行了一项首次人体（FIH）研究，以评估新型 IL-23p19 单克隆抗体 IBI112 的安全性、耐受性、药代动力学（PK）和免疫原性。
在这项 FIH、随机、双盲、安慰剂对照、单递增剂量研究中，合格的健康受试者接受了皮下（SC，5-600mg）或静脉内（IV，100 和 600mg）或安慰剂给药。安全性通过体格检查、生命体征、实验室检查和心电图评估。此外，进行了非房室分析和群体 PK 建模以描述 PK，并应用基于模型的模拟来证明银屑病患者的剂量选择。
共纳入 46 名受试者，其中 35 名接受了 IBI112，11 名接受了安慰剂。未确定严重不良事件（SAE）和无临床意义的不良事件。单次 SC 给予 IBI112 后，中位 为 4-10.5 天，半衰期（t）范围为 21.8-35.8 天。在 5-300mg 范围内，IBI112 的暴露（C 和 AUC）接近剂量比例关系。
IBI112 在 SC 或 IV 剂量高达 600mg 时具有良好的耐受性和安全性，并且在 SC 剂量为 5-300mg 时表现出线性 PK 特征。
ClinicalTrials.gov NCT04511624。
