Treatment Selection and Prioritization for the EJS ACT-PD MAMS Trial Platform

Area of Science:

• Neuroscience
• Clinical Pharmacology
• Drug Development

Background:

• Parkinson's disease (PD) currently lacks approved disease-modifying therapies (DMTs).
• The Edmond J. Safra Accelerating Clinical Trials in Parkinson Disease (EJS ACT-PD) initiative aims to accelerate the evaluation of potential DMTs.
• This initiative employs a multi-arm multistage (MAMS) trial design to efficiently test multiple treatments against a common placebo.

Purpose of the Study:

• To detail the systematic process used for selecting treatments for the EJS ACT-PD clinical trial platform.
• To outline a robust methodology for identifying and prioritizing drug candidates for Parkinson's disease.

Main Methods:

• A Treatment Selection Working Group (TSWG) utilized literature reviews, related initiatives, and expert input to identify potential compounds.
• Compounds were categorized by mechanism (mitochondrial, lysosomal, protein, inflammation, other) and evaluated using "Go/No-Go" criteria and a scoring system.
• A multi-stage prioritization process involved expert scoring, dossier preparation, and consideration of practical/logistical factors by the Steering Committee (SC).

Main Results:

• Out of 293 identified interventions, 52 met the "Go/No-Go" criteria and were scored.
• Dossiers for the 14 highest-ranked compounds were reviewed by the SC.
• Telmisartan, terazosin, and ursodeoxycholic acid were chosen as the initial interventions for the trial.

Conclusions:

• Selecting disease-modifying therapies for Parkinson's disease MAMS trials necessitates balancing scientific evidence with practical considerations.
• The presented drug selection system provides a robust framework applicable to similar clinical trial initiatives.
• This systematic approach aids in advancing the development of novel Parkinson's disease treatments.