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. 2025 Jul;40(7):1307-1317.
doi: 10.1002/mds.30190. Epub 2025 Apr 18.

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

Cristina Gonzalez-Robles  1 , Dilan Athauda  1 , Thomas R Barber  1 , Roger A Barker  2 , David T Dexter  3 , Susan Duty  4 , Romy Ellis-Doyle  1 , Sonia Gandhi  1 , Joel Handley  5 , Edwin Jabbari  1 , Keith Martin  6 , Kevin McFarthing  6 , Georgia Mills  1 , Heather Mortiboys  7 , Stephen Mullin  8 , Rebecca Petty  8 , Esther Sammler  9   10 , Paula Scurfield  1   6 , Simon R W Stott  11 , George K Tofaris  12 , Li Wei  13 , Caroline H Williams-Gray  2 , Alan Wong  14 , Marie-Louise Zeissler  8 , Richard K Wyse  11 , Camille B Carroll  8   15 , Thomas Foltynie  1 , Oliver Bandmann  7 , Anthony H V Schapira  1 ; EJS ACT‐PD Consortium
Collaborators, Affiliations

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

Cristina Gonzalez-Robles et al. Mov Disord. 2025 Jul.

Abstract

Background: There are currently no disease-modifying therapies (DMTs) registered for Parkinson's disease (PD). The Edmond J. Safra Accelerating Clinical Trials in Parkinson Disease (EJS ACT-PD) initiative will expedite clinical assessment of putative DMTs through a multi-arm multistage (MAMS) trial, testing several treatments against a common placebo arm and replacing unsuccessful therapies early.

Objective: The objective of this study was to describe the treatment selection process for the EJS ACT-PD clinical trial platform.

Methods: A Treatment Selection Working Group (TSWG) identified compounds using complementary strategies, such as literature search, related initiatives (Cure Parkinson's International Linked Clinical Trials [iLCT] initiative), and expert suggestions. Compounds were classified into five mechanistic subgroups (mitochondrial, lysosomal, protein, inflammation, "other"). "Go/No-Go" criteria and a scoring system covering preclinical, pharmacological, and clinical evidence were devised. Experts scored the candidates for quantitative rankings. Dossiers adapted from iLCT documents were produced for the top-ranked compounds and in turn prioritized by the TSWG. Practical and logistical considerations from the Steering Committee (SC) guided the final decision. Patient and Public Involvement and Engagement representatives provided feedback throughout the process.

Results: A total of 293 interventions were identified, 52 of which passed the "Go/No-Go" criteria and were scored. Dossiers of the 14 top-ranked compounds were submitted to the SC. Telmisartan, terazosin, and ursodeoxycholic acid were selected as the initial interventions.

Conclusions: Drug selection in DMT PD MAMS trials requires consideration of scientific and practical issues. We present a robust system that can inform similar initiatives. © 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Keywords: Parkinson's disease; adaptive clinical trial; methodology; neuroprotection; neuroprotective agents.

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Figures

FIG 1
FIG 1
Simplified flowchart of the Edmond J. Safra Accelerating Clinical Trials in Parkinson Disease (EJS ACT‐PD) treatment selection process. LRRK2, leucine‐rich repeat kinase‐2; PD, Parkinson's disease; PPIE, Patient and Public Involvement and Engagement; TSWG, Treatment Selection Working Group. [Color figure can be viewed at wileyonlinelibrary.com]
See this image and copyright information in PMC

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