Addressing the Need for Clinical Trial End Points in Autosomal Dominant Polycystic Kidney Disease: A Report From the Polycystic Kidney Disease Outcomes Consortium (PKDOC)

Abstract

Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary kidney disease. Expansion of multiple cysts throughout both kidneys is thought to lead to progressive loss of kidney function and kidney failure in some patients. In recent years, much has been learned about the pathophysiology of ADPKD. However, to date, only one therapy has been approved in the United States and in other regions for the treatment of ADPKD. Feasible end points and a clear regulatory pathway may stimulate further development in this area and ultimately lead to more treatments for ADPKD successfully reaching the market. In July 2016, the PKD Outcomes Consortium under the auspices of the Critical Path Institute and the PKD Foundation convened a PKD Summit to facilitate a discussion among patients, regulators, pharmaceutical sponsors, and academic clinical trialists regarding trial end points and the regulatory path to approval of new drugs for ADPKD. Following the summit, participants continued the dialogue using regularly scheduled teleconferences. This article addresses key considerations related to the design of clinical trials in ADPKD based on these discussions.

Keywords: PKD Outcomes Consortium (PKDOC); Polycystic kidney; autosomal dominant polycystic kidney disease (ADPKD); biomarker; clinical trials; drug approval; drug development; progression; surrogate endpoint; total kidney volume (TKV); trial design.