Conventional trials in exploring effectiveness and safety of drugs are costly and time consuming. Attempts to increase efficiency and decrease participant burden have led to novel trial designs different than those historically conducted. Adaptive strategies are one such approach, allowing for prospectively planned modifications to aspects of the study based on accumulated data from subjects within the trial as it is ongoing. Planned adaptations are specified beforecomparative analyses of trial data are conducted, allowing modifications to the trial itself.

Our first phase 1/2 trial will be a randomized, placebo-controlled multiple ascending dose (MAD) study in healthy volunteers and TED patients to explore safety, tolerability, and dose response effects on multiple metrics of efficacy. If appropriate and warranted, extension cohorts characterized after results of the MAD segment allow for further exploration of regimens and dosages. 

Dependent upon data observed from this phase 1/2 study, further exploration of VRDN-001 in a potential phase 2/3 trial design would include elements of adaptive design with a placebo and multiple drug dosage arms. Such a study would include a masked interim analysis in which the least promising dose cohort(s) would be stopped with no further recruitment into those dropped cohorts; the trial would continue with the placebo arm and the surviving selected dose cohorts, thus protecting statistical validity.