Safety and tolerability of a single dose T0001 in Chinese healthy adult volunteers: a first-in-human ascending dose study

T0001 is the first mutant of etanercept with a higher affinity to tumor necrosis factor α (TNF-α) than etanercept. In order to investigate the safety and tolerability of T0001, a study was carried out in healthy Chinese subjects. A first-in-human, dose escalation study was conducted in healthy Chinese subjects. Fifty-six subjects were divided into six dose cohorts (10 mg, 20 mg, 35 mg, 50 mg, 65 mg and 75 mg) to receive a single subcutaneous injection of T0001. Safety and tolerability assessment were based on the records of vital signs, physical examinations, clinical laboratory tests, 12-lead electrocardiograms and adverse events (AEs). All subjects were in good compliance and none withdraw due to AEs. No serious AEs occurred. A total of twenty-three AEs in sixteen subjects were recorded, and eighteen of these AEs were believed to be related to T0001. The most frequently reported AEs were injection site reactions and white blood cell count increase. All these AEs were of mild to moderate intensity and most of them recovered spontaneously within 14 days. In this study, no dose-limiting toxicity was observed, and the maximum tolerated dose was identified as 75 mg. T0001 was considered safe and generally well tolerated at doses up to 75 mg in healthy Chinese volunteers.

T0001是依那西普（etanercept）的首个突变体，对肿瘤坏死因子α（tumor necrosis factor α，TNF-α）的亲和力高于依那西普。为考察T0001的安全性与耐受性，研究团队在健康中国受试者中开展了一项首次人体剂量递增临床试验：将56名受试者分为6个剂量组（10 mg、20 mg、35 mg、50 mg、65 mg及75 mg），给予单次皮下注射T0001。安全性与耐受性评估基于生命体征、体格检查、临床实验室检测、12导联心电图（12-lead electrocardiograms）以及不良事件（adverse events，AEs）的记录。所有受试者依从性良好，无1例因不良事件退出研究，未发生严重不良事件。共记录16名受试者的23例不良事件，其中18例被认为与T0001相关。最常见的不良事件为注射部位反应与白细胞计数升高，所有不良事件均为轻至中度，多数可在14天内自行缓解。本研究未观察到剂量限制性毒性，确定最大耐受剂量为75 mg。在健康中国志愿者中，T0001在最高75 mg的给药剂量下安全性良好，总体耐受性佳。