Strategies for designing clinical trials for oligonucleotide therapeutics.

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.