EJS ACT-PD Platform Trial to Test Multiple Potential Disease-Modifying Treatments for Parkinson Disease

A new phase 3, multicenter, platform study dubbed EJS ACT-PD (NCT07207057), will test the clinical and cost-effectiveness of several investigational agents as potential disease-modifying treatments for Parkinson disease (PD) against a shared placebo. Through this large-scale, double-blind trial, investigators are hoping to strengthen UK PD research infrastructure and promote research inclusivity.¹

Otherwise known as the Edmond J Safra Accelerating Clinical Trials in PD Initiative, this placebo-controlled study will aim to recruit 1600 participants from over 40 UK sites over a 4-year period. Presented as a poster at the 2026 Alzheimer’s & Parkinson’s Disease Conference (AD/PD), the study will test several different agents and their effectiveness using change in Movement Disorders Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) Parts I and II combined as the primary end point.

Led by Camille Carroll, MD, Professor of Clinical Neuroscience at Newcastle University, the trial will start with two treatment arms–telmisartan and terazosin–and one placebo arm, with a third treatment arm added after 1 year. If the treatments do not show positive results, they will be discontinued and replaced with new candidates. Throughout the study, patients will be given the option to attend their study visits virtually instead of in-clinic, with medications delivered directly to participants’ homes, further reducing the travel burden.

Outside of the MDS-UPDRS, other key secondary outcomes include change in Hoehn and Yahr scale, Montreal Cognitive Assessment, levodopa-equivalent daily dose, and MDS-UPDRS Parts III and IV. In addition, investigators will track severity of depression, quality of life, caretaker quality of life, use of health and social care resources, and safety, through adverse events and tolerability.²

The first two therapies to be tested in EJS ACT-PD are telmisartan, an angiotensin II receptor blocker, and terazosin, an alpha-1 adrenergic receptor antagonist. Both therapies have been traditionally used for hypertension, although terazosin is also indicated for benign prostatic hyperplasia.

For telmisartan, there is belief that this drug could modify disease progression by targeting vascular inflammatory, and metabolic pathways implicated in neurodegeneration, rather than just treating the symptoms. Preclinical data has suggested it may reduce neuroinflammation, protect dopaminergic neurons, and improve mitochondrial function.

For terazosin, this medication has been known to enhance phosphoglycerate kinase 1 activity, which leads to increased glycolysis and cellular ATP production. The belief is that through this agent, patients may experience improved cellular bioenergetics, potentially slowing neurodegeneration.

A 2021 pilot study published in Parkinsonism Related Disorders assessed the target engagement and safety of terazosin in patents in PD over a 12-week period. In the study, 13 participants were randomized to receive 5 mg of the investigational agent or placebo, with both groups blinded to treatment. Compared with the placebo group, the terazosin group had a significant increase in the ratio of ßATP to inorganic phosphate in the brain, as well as a significantly higher increase in blood ATP levels (P <.01).³

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The study authors of that analysis concluded that these data, combined with other mechanistic data from multiple animal models, retrospective analyses of the Parkinson’s Progression Markers Initiative database, and independent retrospective pharmacoepidemiologic analyses, revealed that terazosin is associated with a decreased risk of PD. They added that prospective, randomized, placebo-controlled trials, like EJS ACT-PD, would be needed to determine if this therapy is effective in slowing or preventing neurodegeneration in PD.

For EJS ACT-PD, there are several notable inclusion and exclusion criteria for this platform trial. In the study, participants were required to be on stable dopaminergic therapy, including levodopa or dopamine agonists, for at least 2 months prior to screening. Standard safety measures are also applied, including pregnancy testing and use of effective contraception where appropriate.²

Key exclusions focus on ensuring a well-defined PD population and minimizing confounding conditions. Patients with alternative causes of parkinsonism, significant cognitive impairment or dementia, or major psychiatric illness such as severe depression or recent suicidal ideation were excluded. Individuals with prior advanced therapies such as deep brain stimulation, recent participation in other interventional trials, or significant uncontrolled systemic disease were also not eligible. Additional exclusions included unstable cardiovascular status, significant liver abnormalities, active malignancy requiring treatment, and conditions that could compromise safety or long-term participation.

REFERENCES
1. Mills G, Zeissler M, Gonzalez-Robles C, et al. EJS ACT-PD: AN ITERATIVE MULTI-ARM, MULTI-STAGE PLATFORM TRIAL FOR ONGOING ASSESSMENT OF POTENTIAL DISEASE-MODIFYING THERAPIES FOR PARKINSON’S DISEASE. Presented at: 2026 AD/PD Conference; March 17-21; Copenhagen, Denmark. ABSTRACT 971.
2. Edmond J. Safra Accelerating Clinical Trials in Parkinson's Disease: A Multiarm Multi-stage Platform Trial (EJS ACT-PD). Clinicaltrials.gov. Updated March 3, 2025. Accessed March 17, 2026. https://clinicaltrials.gov/study/NCT07207057
3. Schultz JL, Brinker AN, Xu J, et al. A Pilot to Assess Target Engagement of Terazosin in Parkinson’s Disease. Parkinsonism Relat Disord. 2021;94:79-83. doi:10.1016/j.parkreldis.2021.11.022