The Michael J. Fox Foundation (MJFF) is advancing early-intervention Parkinson’s research through the multicenter Path to Prevention (P2P) Platform Trial.
Path to Prevention (P2P) is a Phase 2A platform trial that leverages Parkinson’s Precision Medicine Initiative (PPMI) infrastructure to evaluate investigational products in participants with neuronal alpha-synuclein disease (NSD) Stage 2B. The study is designed to generate insights into therapeutic development, biomarker validation, endpoint performance and clinical trial conduct in biologically defined early-stage NSD.
P2P is sponsored by MJFF and led by lead principal investigator Tanya Simuni, MD, FAAN. The P2P trial will operate across select PPMI sites.
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Building Collaborative Pathway Toward Preventive Research
Findings from more than 15 years of natural history data from PPMI and other studies supported development of the neuronal alpha-synuclein disease integrated staging system (NSD-ISS). NSD Stage 2B identifies individuals with evidence of alpha-synuclein pathology and dopaminergic neurodegeneration who have not yet developed clinically manifest Parkinson’s disease or dementia with Lewy bodies.
Defining the population biologically rather than solely by clinical symptoms enables intervention at an earlier stage of disease, when disease modifying therapies may have the greatest opportunity to alter disease progression, and creates a more homogeneous study population for evaluating therapeutic effects and disease biomarkers.
P2P will first enroll NSD Stage 2B eligible individuals from the PPMI cohort. P2P benefits from data already collected from current Stage 2B participants in PPMI, and co-enrollment is designed to reduce participant burden while maximizing the impact of their research contributions.
Innovative Platform Trial Design
P2P is the first-of-its-kind platform trial designed to evaluate investigational products in individuals with biological evidence of NSD before the development of functional impairment. Platform trials increase efficiency by using a shared infrastructure to simultaneously or sequentially test multiple investigational products. Additionally, platform trials reduce placebo need by utilizing a shared control arm, and interventions can be added over time as promising new investigational products are identified.
Master Protocol and Regimens
The P2P Master Protocol describes the overall framework of the platform trial. Each investigational product is tested in a distinct trial regimen described in its own Regimen Specific Sub Protocol (RSSP). P2P is designed to be a perpetual platform trial, so there is no limit to the number of regimens that can be added to the Master Protocol. The active-to-placebo ratio may vary depending on the number of concurrently enrolling regimens.
Read a release from ABLi on their selected therapeutic.
Randomization Scheme
After consenting and confirmation of eligibility, P2P study participants are randomized using a two-step process.
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Participants are first randomized in an equal manner to one of the actively enrolling regimens for which they qualify.
This step of randomization is not blinded, so participants and investigators are aware of the regimen assignment.
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Participants are then randomized to the active study drug or placebo control within their assigned regimen.
This step of randomization is double blind, so neither participants nor investigators are aware of the assignment. Placebo control data may be shared across regimens.
Key Outcome Measures and Endpoints
The objective of the P2P Platform Trial is to evaluate the safety and early efficacy of investigational products for the treatment of participants with early-stage NSD. P2P will assess the impact of putative NSD therapies using two primary endpoints.
- Primary biomarker endpoint: Rate of change in the mean putamen Specific Binding Ratio (SBR) from baseline through follow-up, measured by Dopamine Transporter Single-photon emission computed Tomography (DAT SPECT) imaging.
- Primary clinical endpoint: Rate of change in Movement Disorder Society-Sponsored Revision of the Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) Part III score from baseline through end of follow-up or dopaminergic treatment initiation.
Beyond assessing overall feasibility, safety and tolerability, additional pre-specified analyses are being conducted to examine multiple exploratory clinical outcome measures and biomarkers.
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P2P functions as both an interventional platform trial and a learning study designed to accelerate therapeutic development in early-stage NSD.
In addition to evaluating investigational products, data generated through P2P will contribute to:
- Biomarker validation
- Clinical endpoint development
- Future secondary prevention trial design
- Improved understanding of disease progression in biologically defined NSD populations
Principal Investigators
P2P is overseen by a lead principal investigator, and each RSSP has a dedicated principal investigator who oversees that regimen.
Tanya Simuni, MD, FAAN
Master Protocol PI
Ruth Schneider, MD
RSSP_1 PI
Andrew Siderowf, MD, MSCE
RSSP_2 PI
Nicola Pavese, MD, PhD, FRCP, FEAN
RSSP_3 PI
Steering Committee
The P2P Steering Committee is responsible for the scientific rationale, study design, site selection, logistics, data management and analysis planning for the study.
| Sohini Chowdhury | Christopher Coffey | Dixie Ecklund | Kimberly Fabrizio |
| Tatiana Foroud | Fred Goldstein | Cornelia Kamp | Karl Kieburtz |
| Catherine Kopil | Maggie Kuhl | Ken Marek | Nicola Pavese |
| Ruth Schneider | Andrew Siderowf | Tanya Simuni | Craig Stanley |
| Caroline Tanner | Thomas Tropea | Tawny Willson |
Therapy Evaluation Committee
The P2P Therapy Evaluation Committee (TEC) includes experts in PD research, drug development, biomarkers and clinical trials. Key evaluation criteria include target relevance, pre-clinical and biomarker data, safety profile and clinical trial readiness of the asset.
The TEC reviews Letter of Intent (LOI) for potential partners on a rolling basis. Organizations interested in exploring partnership opportunities may submit an LOI form or email [email protected]. Selected companies will work collaboratively with P2P and the study sponsor, MJFF, toward formal partnership around the platform trial.
Publications
How PPMI Enabled the First Interventional Platform Trial to Test Therapies in Participants with Early-Stage Neuronal Alpha-Synuclein Disease | Annals of Neurology | May 2026
Contact Us
MJFF is actively collaborating with industry and academic partners to evaluate promising investigational products through the P2P Platform Trial. Do you represent a company that is working on therapeutics relevant to neurodegenerative disorders and want to know more about partnering opportunities in P2P? Please contact [email protected].