Edmond J. Safra Accelerating Clinical Trials in Parkinson's Disease: A Multiarm Multi-stage Platform Trial

NCT07207057 | Recruiting Phase 3 DMC

• 2 other identifiers: ND002ISRCTN17799294
• Study Type: interventional
• Target: 1,200
• Locations: 1 country
• Sites: 2

Brief Summary

Parkinson's disease (PD) is currently the fastest-growing neurological condition globally. It is projected to affect 172,000 people in the UK by 2030,with the current annual cost to the country being \~£3.6 billion. The disease progressively impairs physical abilities, leading to increased disability, falls, and difficulties with speech, swallowing, mood, thinking, and memory. While existing treatments can alleviate some symptoms, their effectiveness diminishes over time, and they can cause severe side effects. This trial uses a Multi-Arm,Multi-Stage (MAMS) design where multiple treatments are tested simultaneously in separate groups, called "arms." Each treatment is compared against a placebo, a dummy treatment with no active ingredients, to evaluate its effectiveness and safety. Throughout the trial, each treatment undergoes periodic reviews, known as interim analyses, to assess its safety and potential benefits. If a treatment shows promise, it continues in the trial until a final assessment determines its overall effectiveness. Treatments that do not show positive results are discontinued and replaced with new candidates. This approach reduces the number of participants needed to obtain reliable results and is more cost-effective and faster than conducting separate trials for each treatment. The treatments selected for this trial were chosen based on careful consideration of existing evidence regarding their safety and effectiveness. To choose the treatments we want to test, we carefully considered evidence for safety and effectiveness. The trial will start with two treatment arms (telmisartan and terazosin) and one placebo arm, with a third treatment arm added after one year. We can identify new treatments to add to the trial each year. Participants will be followed up for up to 36 months. After an in-person screening visit, all remaining visits at 3 months,6 months and then every 6 months after, for a total of up to 36 months can be completed remotely. The visits will include questionnaires, assessment of Parkinson's symptoms and discussions about any side effects. Participants will informed of trial progress. Results will be shared via the trial website and published in a medical journal.

Conditions

Parkinsons Disease (PD)

Outcome Measures

Primary Outcomes (1)

• Movement Disorder Society-Sponsored Revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Parts I and II combined

  The rate of Parkinson's disease progression between the active treatment and placebo arms is measured by the MDS-UPDRS Parts I and II combined with equal weighting

  baseline, week 13, week 26, week 52, week 78, week 104, week 130, week 156 (end of study visit) or early termination and week 165

Secondary Outcomes (15)

• Hoehn and Yahr Scale (H&Y)

  screening, week 0, week 13, week 26, week 52, week 78, week 104, week 130, week 156 (end of study visit) or early termination and week 165

• Montreal Cognitive Assessment (MoCA)

  screening, week 0, week 26, week 52, week 104, week 156 or early termination.

• levodopa-equivalent daily dose (LEDD)

  all study visits

• Movement Disorder Society-Sponsored Revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III (Remote)

  screening, week 0, week 13, week 26, week 52, week 78, week 104, week 130, week 156 (end of study visit) or early termination and week 165.

• Movement Disorder Society-Sponsored Revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part IV

  screening, week 0, week 13, week 26, week 52, week 78, week 104, week 130, week 156 (end of study visit) or early termination and week 165

Study Arms (3)

Placebo (Arm A)

PLACEBO COMPARATOR

Standard of Care (SoC) plus placebo.

Drug: Placebo

Telmisartan (Arm B)

EXPERIMENTAL

Standard of Care (SoC) plus telmisartan

Drug: Telmisartan

Terazosin (Arm C)

EXPERIMENTAL

Standard of Care (SoC) plus terazosin

Drug: Terazosin (Hytrin)

Interventions

Placebo DRUG

An over-encapsulated placebo capsule taken once daily to match the treatment arms following a 5-week titration phase.

Placebo (Arm A)

Telmisartan DRUG

Over-encapsulated telmisartan 40mg per day for 36 months (plus their usual SoC) following a 5-week titration phase. Titration phase for telmisartan: Week 1-3: one 20 mg capsule per day; Week 4-5: one 40 mg capsule per day

Telmisartan (Arm B)

Terazosin (Hytrin) DRUG

Over-encapsulated terazosin 5mg per day for 36 months (plus their usual SoC) following a 5-week titration phase. Titration phase for terazosin: Week 1: one 1 mg capsule per day; Week 2: one 2 mg capsule per day; Week 3: one 3 mg capsule per day; Week 4: one 4 mg capsule per day; Week 5: one 5 mg capsule per day

Terazosin (Arm C)

Eligibility Criteria

• Age: 30 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis by neurologist, movement disorders specialist or appropriately experienced clinician of clinically established or clinically probable PD in the clinician's opinion. In the presence of any diagnostic doubt, the Movement Disorder Society diagnostic criteria will be applied.
• Diagnosed with Parkinson's disease at age 30 years or older, no upper age limit.
• Currently on Parkinson's medication (levodopa-containing preparations or dopamine agonists, used either as single agents or in combination) for at least 2 months prior to screening visit.
• Female participants who are women of child-bearing potential (WOCP) must have confirmation of a negative pregnancy test at screening visit.
• Female participants who are WOCP and male participants and their partners who are WOCP must be taking highly effective contraceptive treatment(s).
• Documented informed consent.
• Randomisation should ideally take place within 3 weeks of the screening visit but no later than 4 weeks after the screening visit.
• If a participant is being re-randomised into the trial, additional timing of entry requirements must also be met:
• For participants being re-randomised after completing 36 months' follow-up and the arm was not closed due to lack of activity, a 26-week washout period from last dose of IMP must be completed before their screening visit. If the primary analysis indicates that the IMP was ineffective then this washout period can be reduced to 6 weeks.
• For participants being re-randomised following treatment arm termination due to lack of activity, a 6-week washout period from their last dose of IMP must be completed prior to screening assessment.

You may not qualify if:

• Diagnosis or suspicion of other cause for parkinsonism such as atypical parkinsonism, dystonic tremor, essential tremor, drug-induced parkinsonism.
• Known carriers of recessive PD gene mutations PRKN, PINK1 or DJ1 (based on previous medical tests / notes).
• Clinical diagnosis of dementia or MoCA \<21 at screening visit.
• Currently in another ongoing interventional trial or exposure to any IMP within an experimental interventional trial within 6 months prior to screening visit (exception for EJS ACT-PD participants that are being re-randomised due to treatment arm termination following lack of activity as only a 6-week wash out period is required).
• Unable or unwilling to comply with study requirements.
• Diagnosis of clinically significant depression or \>14 on PHQ-9 at screening visit.
• Current suicidal ideation within one year prior to the screening visit as evidenced by answering "yes" to Questions 4 or 5 on the suicidal ideation portion of the Columbia-Suicide Severity Rating Scale (C-SSRS).
• Previous brain surgery or on a waiting list for brain surgery including deep brain stimulation and / or currently taking or on a waiting list for advanced therapies for Parkinson's disease (such as any infusion therapy).
• Monotherapy with monoamine oxidase-B inhibitor (MAO-BI).
• Previous exposure to any of the currently recruiting IMPs within 6 months prior to screening visit or previous intolerance of any of the IMPs.
• Participant has any concurrent medical condition, abnormal laboratory tests, progressive neurological disorder or uncontrolled, clinically significant systemic disease that, in the opinion of the Investigator, could cause study participation to be detrimental to the participant (e.g., end stage renal failure, severe heart failure, unstable angina, uncontrolled hypertension or uncontrolled orthostatic hypotension, severe liver disease, uncontrolled diabetes, or severe anaemia).
• Pregnant or breastfeeding or intending to become pregnant during the study or within 70 days after the final dose of study drug.
• Confirmed diagnosis of cancer and is requiring active management of that cancer and/or in the view of the local team, the diagnosis and/ or its treatment may compromise their ability to remain participating in the trial for 36 months or tolerate any of the active treatments.
• Participants with hepatobiliary disorders or abnormal liver function tests at the screening visit consisting of one of the following:
• ALT or AST \>2x the upper limit of normal

Sponsors & Collaborators

• University College, London: lead
• Cure Parkinson's: collaborator
• Parkinson's UK: collaborator
• National Institute for Health Research, United Kingdom: collaborator
• John Black Charitable Foundation: collaborator
• Medical Research Council: collaborator
• Newcastle University: collaborator
• Van Andel Research Institute: collaborator
• Michael J. Fox Foundation for Parkinson's Research: collaborator
• Gatsby Foundation: collaborator

Study Sites (2)

UCLH

London, NW1 2PG, United Kingdom

RECRUITING

Clinical Ageing Research Unit

Newcastle, NE4 5PL, United Kingdom

RECRUITING

Related Links

• EJS ACT-PD Website

MeSH Terms

Conditions

Parkinson Disease

Interventions

Telmisartan; Terazosin

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases

Intervention Hierarchy (Ancestors)

Biphenyl Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Prof Thomas Foltynie

  University College, London

  PRINCIPAL INVESTIGATOR

• Prof Camille Carroll

  Newcastle University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

MRC CTU at UCL Trial Team

CONTACT

+44 (0) 20 7670 4700; mrcctu.ejsactpd@ucl.ac.uk

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: As the trial is double-blinded, neither participants nor delivery staff will be aware of which treatment a participant has been randomised to. Participants' treatment allocations will be stored only in the randomisation server, separate to the EJS ACT-PD Trial database There will be a Trial Statistician at the MRC CTU at UCL who will be unblinded.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Multi-arm multi-stage (MAMS) trial

Study Record Dates

• First Submitted: May 9, 2025
• First Posted: October 3, 2025
• Study Start: September 12, 2025
• Primary Completion (Estimated): May 1, 2031
• Study Completion (Estimated): July 31, 2031
• Last Updated: October 3, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will share

Locations

GB (2)