Attarwala H
Department of Pharmaceutical Sciences, School of Pharmacy, Northeastern University, Boston, MA, USA.
J Young Pharm. 2010 Jul;2(3):332-6. doi: 10.4103/0975-1483.66810.
After a drug is confirmed as safe and efficacious in preclinical studies, it is tested in healthy human volunteers for first in man trials. In 2006, a phase I clinical study was conducted for a CD28 superagonist antibody TGN1412 in six human volunteers. After very first infusion of a dose 500 times smaller than that found safe in animal studies, all six human volunteers faced life-threatening conditions involving multiorgan failure for which they were moved to intensive care unit. After this particular incident, a lot was changed over how first in man trials are approved by regulatory authorities and the way clinical trials are conducted. This review primarily deals with preclinical studies conducted by TeGenero, results of which encouraged them to test the antibody on human subjects, reasons why this drug failed in human trial and aftermath of this drug trial. In addition, another drug-Fialuridine which failed in phase 2 clinical trial leading to death of five human subjects is briefly reviewed.
在一种药物在临床前研究中被确认为安全有效后，它会在健康人类志愿者身上进行首次人体试验。2006年，针对一种CD28超级激动剂抗体TGN1412，在六名人类志愿者身上进行了一项I期临床研究。在首次输注的剂量比在动物研究中发现的安全剂量小500倍之后，所有六名人类志愿者都面临危及生命的状况，包括多器官衰竭，为此他们被转移到重症监护病房。在这一特殊事件之后，监管机构批准首次人体试验的方式以及进行临床试验的方式发生了很大变化。本综述主要涉及TeGenero公司进行的临床前研究，其结果促使他们在人体受试者身上测试该抗体，该药物在人体试验中失败的原因以及该药物试验的后果。此外，还简要回顾了另一种在II期临床试验中失败并导致五名人类受试者死亡的药物——氟阿糖胞苷。
