Evolution of Clinical Trial Design in ADPKD

Area of Science:

• Nephrology
• Clinical Trial Design
• Biomarker Development

Background:

• Autosomal Dominant Polycystic Kidney Disease (ADPKD) involves slow cyst growth over decades.
• Traditional clinical trials for ADPKD rely on functional outcomes (e.g., eGFR), requiring extensive time and resources.
• This necessitates innovative approaches for efficient therapeutic development.

Purpose of the Study:

• To review the evolution of clinical trial designs for ADPKD.
• To highlight the shift towards using Total Kidney Volume (TKV) as a surrogate endpoint.
• To explore advanced methodologies for improving trial efficiency and accelerating ADPKD treatments.

Main Methods:

• Review of foundational studies (e.g., CRISP) validating TKV as a prognostic biomarker.
• Analysis of interventional trials (e.g., HALT-PKD, TEMPO 3:4) assessing TKV utility.
• Examination of innovative trial designs like adaptive methods and master protocols.

Main Results:

• Total Kidney Volume (TKV) has been validated as a prognostic biomarker in ADPKD.
• TKV enables a move away from lengthy functional endpoints in clinical trials.
• Subsequent trials confirmed TKV's utility but also revealed nuances in its relationship with kidney function.

Conclusions:

• The use of TKV as a surrogate endpoint has significantly advanced ADPKD clinical trial design.
• Innovative approaches like adaptive trials and master protocols can further enhance efficiency and reduce study size.
• These advancements are crucial for accelerating the development of effective therapies for ADPKD.