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

IF 7.6 1区医学 Q1 CLINICAL NEUROLOGY Movement Disorders Pub Date : 2025-04-18 DOI:10.1002/mds.30190

Cristina Gonzalez-Robles MD, Dilan Athauda PhD, Thomas R. Barber DPhil, MRCP, Roger A. Barker MRCP, PhD, David T. Dexter PhD, FBPhS, Susan Duty PhD, FBPhS, Romy Ellis-Doyle BSc, Sonia Gandhi PhD, Joel Handley MSc, MRCP, Edwin Jabbari PhD, MRCP, Keith Martin PhD, MRPharmS, Kevin McFarthing PhD, Georgia Mills MRes, Heather Mortiboys PhD, Stephen Mullin PhD, Rebecca Petty MClinRes, Esther Sammler PhD, Paula Scurfield MA, Simon R.W. Stott PhD, George K. Tofaris FRCP, PhD, Li Wei PhD, Caroline H. Williams-Gray FRCP, PhD, Alan Wong MSc, Marie-Louise Zeissler PhD, Richard K. Wyse PhD, Camille B. Carroll MRCP, PhD, Thomas Foltynie FRCP, PhD, Oliver Bandmann MD, PhD, Anthony H.V. Schapira MD, DSc, FRCP, FMedSci, the EJS ACT-PD Consortium

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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.

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EJS ACT-PD MAMS试验平台的治疗选择和优先级。

背景：目前还没有针对帕金森病（PD）的疾病修饰疗法（dmt）。Edmond J. Safra加速帕金森病临床试验（EJS ACT-PD）计划将通过多组多阶段（MAMS）试验加快对假定的dmt的临床评估，测试几种治疗方法与常见安慰剂组的对照，并早期替代不成功的治疗方法。目的本研究的目的是描述EJS ACT-PD临床试验平台的治疗选择过程。方法治疗选择工作组（TSWG）采用文献检索、相关倡议（治愈帕金森病国际关联临床试验[iLCT]倡议）和专家建议等互补策略确定化合物。化合物被分为5个机制亚群（线粒体、溶酶体、蛋白质、炎症和“其他”）。“去/不去”标准和评分系统涵盖临床前，药理学和临床证据设计。专家们对候选人进行了定量排名。根据iLCT文件改编的档案是为排名靠前的化合物制作的，然后由TSWG优先排序。指导委员会的实际和后勤考虑指导了最后的决定。患者和公众参与和参与代表在整个过程中提供了反馈。结果共发现293项干预措施，其中52项通过“Go/No-Go”标准并进行评分。将排名前14位的化合物提交给SC。选择替米沙坦、特拉唑嗪和熊去氧胆酸作为初始干预措施。结论DMT - PD - MAMS试验的药物选择需要考虑科学和实际问题。我们提出了一个强大的系统，可以通知类似的倡议。©2025作者。Wiley期刊有限责任公司代表国际帕金森和运动障碍学会出版的《运动障碍》。

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来源期刊

Movement Disorders 医学-临床神经学

CiteScore

13.30

自引率

8.10%

发文量

371

审稿时长

12 months

期刊介绍： Movement Disorders publishes a variety of content types including Reviews, Viewpoints, Full Length Articles, Historical Reports, Brief Reports, and Letters. The journal considers original manuscripts on topics related to the diagnosis, therapeutics, pharmacology, biochemistry, physiology, etiology, genetics, and epidemiology of movement disorders. Appropriate topics include Parkinsonism, Chorea, Tremors, Dystonia, Myoclonus, Tics, Tardive Dyskinesia, Spasticity, and Ataxia.

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