Safety and Tolerability of a Single Dose T0001 in Chinese Healthy Adult Volunteers: A First-in-Human Ascending Dose Study

【摘要】：Objective T0001 is the first mutant of etanercept known to exhibit a higher affinity to tumor necrosis factor α(TNF-α) than etanercept. In order to investigate the safety and tolerability of T0001 in the human body, a study was carried out in healthy Chinese volunteers. Methods A first-in-human, dose escalation design study was conducted to assess safety and tolerability of T0001 using six dose cohorts(10 mg to 75 mg). The subjects(n = 56; male: female ratio of 1:1) were assigned to receive a single subcutaneous injection of T0001. All subjects were then closely monitored by taking recordings of their vital signs, physical examinations, clinical laboratory tests, 12-lead electrocardiograms and adverse events(AEs). Based on these results, the safety and tolerability of T0001 was assessed. Results All subjects were in good compliance and did not withdraw due to AEs. No serious adverse events occurred. A total of 23 AEs in 16 subjects were recorded, and 18 of these AEs were believed to be related to T0001. The most frequently reported AEs were injection site reactions and an increase in white blood cell count. All AEs were of mild to moderate intensity and most recovered spontaneously within 14 days. In this study, no dose-limiting toxicities were observed and the maximum tolerated dose was identified as 75 mg. Conclusion T0001 was considered safe and generally well tolerated at doses up to 75 mg in healthy Chinese volunteers.