Wacheck Volker
Department of Clinical Pharmacology, Section of Experimental Oncology and Molecular Pharmacology, Medical University Vienna, Währinger Gürtel 18-20, A-1090 Vienna, Austria.
Drug Discov Today. 2004 Nov 1;9(21):918-23. doi: 10.1016/S1359-6446(04)03263-5.
Recent Phase III clinical trials for oligonucleotide therapeutics have yielded disappointing results. There is growing evidence that trial designs that consider the specific mode of action of these compounds are of crucial importance for their clinical testing. Early trials for oligonucleotide therapeutics should consider additional endpoints for the definition of a biologically active dose rather than focusing on the traditional concept of maximal tolerated dose. In later phases, alternative clinical endpoints and enriching sensitive study populations through innovative trial designs could improve the efficiency of clinical trials for oligonucleotide therapeutics.
近期针对寡核苷酸疗法的III期临床试验结果令人失望。越来越多的证据表明，考虑这些化合物特定作用方式的试验设计对其临床试验至关重要。寡核苷酸疗法的早期试验应考虑用于定义生物活性剂量的额外终点指标，而不是专注于传统的最大耐受剂量概念。在后期阶段，通过创新试验设计采用替代临床终点指标并富集敏感研究人群，可能会提高寡核苷酸疗法临床试验的效率。
