Design and implementation of an adaptive confirmatory trial in Japanese patients with palmoplantar pustulosis.

Background/Aims: More and more literature describes how to overcome challenges in the implementation of adaptive designs for trials for drug approval process. Most adaptive trials were conducted in Western Europe or USA for Phase II or Phase II/III settings; however, examples of non-oncology pivotal adaptive trials used for regulatory approval in Japan are rare. This article elaborates on our experience with designing and implementing a Phase III adaptive confirmatory trial permitting unblinded sample size re-estimation and futility analysis after a single interim analysis in Japanese patients with palmoplantar pustulosis (PPP) receiving guselkumab. Methods: We provide insights into consideration at the design stage of an adaptive study, including design options, development duration, operational risks, and statistical methods. We also share our experience from two aspects of implementation: conducting an adaptive clinical trial in Japan and setting up a Japanese domestic independent data monitoring committee. Results: Final analysis results of this study successfully demonstrated the effectiveness of guselkumab for the treatment of PPP. Based on the interim analysis results, it was recommended to continue the study without sample size adjustment. Conclusion: We discuss results versus design assumptions and advantages to the conduct of the study with the adaptive design approach. Significant cost savings were gained and development time was reduced compared to the alternative option of a fixed conservative design. Several limitations of our study are also discussed.