Path to Prevention Platform Trial in Early-Stage Neuronal Alpha-Synuclein Disease: Study Design

Path to Prevention (P2P) will test biologically targeted therapies in early-stage neuronal alpha-synuclein disease (NSD) Stage 2B, using a platform design with 125 active and shared placebo participants per regimen.

• Why it matters: Biologically targeted therapeutics for Parkinson’s disease have been slowed by reliance on clinically defined populations with already advanced pathobiology. P2P addresses the need to intervene earlier using a biological definition of NSD.
• What they did: P2P is a phase 2A randomized, double-blind, placebo-controlled platform trial embedded in PPMI, enrolling participants at least 60 years old with NSD Stage 2B. It uses Bayesian modeling with PPMI data and tests multiple interventions under a Master Protocol across ~35 sites in North America and Europe.
• The result: Primary endpoints are the rate of change in mean putamen specific binding ratio and the rate of change in MDS-UPDRS Part III motor examination, assessed through follow-up or dopaminergic treatment initiation. Scheduled to begin enrollment in December 2026, it aims to provide tools for earlier intervention in neurodegeneration.

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