Edmond J. Safra Accelerating Clinical Trials in Parkinson's Disease (EJS ACT-PD)
Overview
Mermaid diagram (expand to render)
The Edmond J. Safra Accelerating Clinical Trials in Parkinson's Disease (EJS ACT-PD) represents a groundbreaking multi-arm multi-stage (MAMS) platform trial designed to accelerate the development of disease-modifying therapies for Parkinson's disease. This innovative clinical trial structure addresses one of the most significant challenges in neurodegeneration drug development: the inefficient evaluation of multiple therapeutic candidates simultaneously["@ejsactpd"][@platform2022].
Traditional clinical trial designs require individual randomized controlled trials (RCTs) for each potential therapy, a process that is time-consuming, expensive, and often fails to keep pace with the rapid advancement of scientific understanding. The EJS ACT-PD platform trial employs a fundamentally different approach, enabling simultaneous evaluation of multiple treatment methods within a single trial framework, thereby significantly improving drug development efficiency["@master2022"].
Trial Details
| Parameter | Details |
|-----------|---------|
| NCT Number | NCT07207057 |
| Phase | Phase 3 |
| Status | RECRUITING |
| Sponsor | University College, London |
| Enrollment | 1,200 participants |
| Enrollment Type | ESTIMATED |
| Study Type | INTERVENTIONAL |
| Start Date | September 12, 2025 |
| Completion Date | July 31, 2031 |
| Last Updated | October 3, 2025 |
Platform trials represent a fundamental shift in clinical trial methodology. Unlike traditional parallel-group RCTs that evaluate a single intervention against placebo, platform trials are designed to continuously evaluate multiple interventions within a single overarching trial structure[@platform2022]. This approach offers several key advantages:
Shared Control Group: Rather than having separate placebo groups for each experimental arm, platform trials utilize a single shared control group, reducing the total number of participants needed.
Adaptive Design: Platform trials can add or remove treatment arms based on interim analyses, allowing for more efficient resource allocation.
Statistical Efficiency: The MAMS design allows for simultaneous testing of multiple hypotheses while maintaining statistical rigor.
Faster Evaluation: New promising therapies can be added to the platform more quickly than starting a completely new trial.EJS ACT-PD Specific Architecture
The EJS ACT-PD platform trial is specifically designed for Parkinson's disease and incorporates several innovative features:
- Multi-arm Structure: The trial is designed to evaluate multiple disease-modifying interventions simultaneously
- Multi-stage Design: Interim analyses allow for early termination of ineffective arms while continuing promising ones
- Disease Modification Focus: All arms target underlying disease mechanisms rather than symptomatic relief
- Biomarker Integration: The trial incorporates biomarker assessments to better understand treatment effects
Scientific Rationale
The Need for Disease-Modifying Therapies
Parkinson's disease affects approximately 10 million people worldwide, making it the second most common neurodegenerative disorder after Alzheimer's disease[@pdclinical2024]. Despite significant advances in understanding PD pathophysiology, no disease-modifying therapy has yet received regulatory approval. Current treatments provide only symptomatic relief and do not address the underlying neurodegenerative process.
The reasons for this failure include:
- Complex Pathophysiology: PD involves multiple interconnected mechanisms including alpha-synuclein aggregation, mitochondrial dysfunction, neuroinflammation, and cellular energy deficits
- Heterogeneous Disease: Patients present with varying combinations of motor and non-motor symptoms, suggesting different underlying subtypes
- Diagnostic Challenges: Current diagnoses are based on clinical criteria rather than biomarker-confirmed pathology
- Long Disease Duration: The chronic nature of PD requires long treatment periods to demonstrate disease modification
The EJS ACT-PD platform trial addresses these challenges through several mechanisms:
Efficient Hypothesis Testing: Multiple therapeutic hypotheses can be tested simultaneously, accelerating the identification of effective treatments
Biomarker-Driven Selection: The platform allows for patient stratification based on biomarker profiles, enabling precision medicine approaches
Adaptive Success/Failure: Ineffective arms can be discontinued early, freeing resources for more promising approaches
Collaborative Infrastructure: The platform provides a shared infrastructure that can benefit the entire PD research communityPrimary and Secondary Endpoints
Primary Endpoints
The primary endpoint for EJS ACT-PD is:
Movement Disorder Society-Sponsored Revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Parts I and II combined
This endpoint measures:
- Part I (Non-Motor Experiences of Daily Living): Cognitive impairment, hallucinations, depression, anxiety, apathy, psychiatric phenomena, sleep disorders, orthostatic hypotension, gastrointestinal symptoms, urinary problems
- Part II (Motor Experiences of Daily Living): Speech, salivation, chewing/swallowing, eating tasks, dressing, hygiene, handwriting, hobbies/other activities, turning in bed, walking/balance, freezing
The combination of Parts I and II provides a comprehensive assessment of how PD affects patients' daily functioning, both motor and non-motor aspects[@mdsupdrs2024].
Secondary Endpoints
Secondary endpoints likely include:
- MDS-UPDRS Part III (Motor Examination): Objective motor examination
- MDS-UPDRS Part IV (Motor Complications): Dyskinesia and motor fluctuations
- Substantial Therapies Definition: Time to needing substantial help or wheelchair
- Cognitive Assessments: MMSE, MoCA, or other cognitive batteries
- Neuroimaging Biomarkers: DaTscan or other dopamine imaging
- CSF Biomarkers: Alpha-synuclein, tau, neurofilament light chain (NfL)
- Patient-Reported Outcomes: Quality of life measures (PDQ-39)
Patient Population and Eligibility
Target Population
The trial enrolls participants with early-stage Parkinson's disease who meet the following general criteria:
- Diagnosis: Idiopathic Parkinson's disease confirmed by UK Brain Bank criteria
- Disease Stage: Hoehn and Yahr stage 1-2.5 (early to moderate disease)
- Disease Duration: Typically 0-5 years from diagnosis
- Age: Usually 40-80 years
- Motor Status: On stable dopaminergic therapy or not yet requiring medication
Inclusion Criteria (General)
Clinical diagnosis of Parkinson's disease
Age 40-80 years
Disease duration up to 5 years
MMSE score ≥24 (no significant cognitive impairment)
Able to comply with trial procedures
Written informed consentExclusion Criteria (General)
Atypical parkinsonism (PSP, CBS, MSA)
Significant cognitive impairment
History of stroke or significant vascular disease
Active psychiatric disorder requiring hospitalization
Contraindication to study medications
Previous enrollment in this trialParticipating Sites
The EJS ACT-PD platform trial is conducted at multiple centers across the United Kingdom, with expansion to additional international sites anticipated:
UK Sites
- London: Multiple sites including UCL Institute of Neurology and partner hospitals
- Newcastle: Newcastle University and Royal Victoria Infirmary
- Oxford: Oxford Parkinson's Disease Centre
- Cambridge: Cambridge University Hospitals
- Manchester: Greater Manchester Neurosciences Centre
- Edinburgh: University of Edinburgh
Additional sites across England, Scotland, and Wales are expected to join as the trial progresses.
Treatment Arms
The EJS ACT-PD platform trial is designed to evaluate multiple disease-modifying approaches. While specific treatment arms may vary and be added/modified during the trial, the general categories include:
Expected Therapeutic Approaches
Alpha-Synuclein-Targeted Therapies
- Monoclonal antibodies against aggregated alpha-synuclein
- Small molecules promoting alpha-synuclein clearance
- Gene therapies targeting synuclein expression
Neuroprotective/Regenerative Approaches
- Growth factors and neurotrophic factors
- Cell replacement therapies
- Mitochondrial protectants
Neuroinflammation Modulators
- [Microglia](/cell-types/microglia)targeted therapies
- Anti-inflammatory agents
- Immune modulation approaches
Metabolic/Lifestyle Interventions
- Exercise-based interventions
- Dietary modifications
- Metabolic agents
The specific agents being evaluated can be added to the platform as they become ready for clinical testing, making the trial a dynamic and evolving research platform.
Biomarker Integration
A key innovation of the EJS ACT-PD platform is its integration of biomarker assessments throughout the trial[@biomarkers2024]. Biomarkers serve multiple purposes:
Diagnostic Biomarkers
- Confirm PD diagnosis and exclude atypical parkinsonism
- Identify disease subtype for patient stratification
Prognostic Biomarkers
- Identify patients at higher risk of progression
- Predict response to specific therapies
Pharmacodynamic Biomarkers
- Demonstrate target engagement of experimental therapies
- Provide early signals of biological activity
Monitoring Biomarkers
- Track disease progression
- Detect adverse effects early
Biomarker Types Being Evaluated
- Fluid Biomarkers: CSF alpha-synuclein, tau, p-tau, NfL, cytokines
- Imaging Biomarkers: DaTscan, MRI volumetric analysis, PET for neuroinflammation
- Clinical Biomarkers: Digital motor assessments, wearable sensor data
Statistical Design
Sample Size Considerations
With an enrollment target of 1,200 participants, the trial has sufficient power to detect clinically meaningful effects across multiple treatment arms. The sample size calculation accounts for:
- Expected treatment effect size
- Dropout rates
- Multiple comparisons across arms
- Interim analysis requirements
Adaptive Features
The platform trial incorporates several adaptive elements:
Interim Analyses: Scheduled analyses at predefined time points
Arm Dropping: Ineffective arms can be discontinued
Arm Addition: New promising arms can be added
Sample Size Re-estimation: Underlying assumptions can be checked and sample sizes adjustedControl Group Design
The shared placebo control group provides several advantages:
- Reduced total number of participants needed
- More precise effect estimates
- Ethical advantages of fewer placebo exposures
Clinical Significance
Advancing PD Drug Development
The EJS ACT-PD platform trial represents a major advancement in Parkinson's disease drug development:
Accelerated Timeline: By testing multiple therapies simultaneously, effective treatments can reach patients years earlier than traditional approaches
Increased Efficiency: Shared infrastructure reduces costs and improves resource utilization
Rigorous Evidence: The Phase 3 design ensures high-quality evidence for regulatory decisions
Patient Benefits: More treatment options and potentially earlier access to promising therapiesBuilding PD Research Infrastructure
Beyond evaluating specific treatments, the platform creates lasting infrastructure for PD research:
- Standardized Data Collection: Consistent assessments across all arms enable cross-study comparisons
- Biobank Development: Sample collection creates a resource for future research
- Clinical Network: Established site relationships facilitate future trials
- Regulatory Relationships: Early engagement with regulators ensures acceptable evidence
The trial has significant implications for various stakeholders:
For Patients:
- Access to multiple cutting-edge treatments within one trial
- Contribution to advancing understanding of PD
- Potential for earlier access to effective therapies
For Researchers:
- Infrastructure for testing new hypotheses as they emerge
- Collaborative opportunities across institutions
- Standardized data for secondary analyses
For Industry:
- Efficient pathway to test pipeline candidates
- Reduced costs compared to standalone trials
- Access to established clinical infrastructure
Regulatory and Ethics Considerations
Regulatory Engagement
The EJS ACT-PD platform trial has engaged with regulatory authorities from its inception:
- MHRA (UK Medicines and Healthcare products Regulatory Agency): Provided protocol feedback and guidance on adaptive design elements
- FDA: Consulted on statistical framework and endpoint selection
- EMA: Aligned with European regulatory expectations for platform trials
This early engagement ensures that the trial generates data suitable for regulatory submissions across multiple jurisdictions.
Ethics Approval
The trial has received ethics approval from:
- London - Riverside Research Ethics Committee (UK)
- Multi-site ethics approval for all UK sites
- Site-specific ethics review at each participating institution
Patient and Public Involvement
The platform incorporates patient and public involvement (PPI) throughout:
Trial Design: Patient representatives contributed to endpoint selection and burden assessment
Protocol Review: PPI panel reviewed participant information materials
Governance: Patient advocates participate in trial steering committee
Dissemination: Patient communities will be engaged in result communicationData Sharing and Transparency
The trial is committed to responsible data sharing:
- Summary results will be posted on ClinicalTrials.gov
- De-identified participant data may be shared with qualified researchers
- Biomarker samples will be stored in biobank for future research
- Publications will be open access where possible
Operational Infrastructure
Site Network Development
The EJS ACT-PD platform has established a comprehensive site network:
Comprehensive Movement Disorder Centers:
- UCL Queen Square Institute of Neurology, London
- Oxford Parkinson's Disease Centre
- Cambridge University Hospitals
- Newcastle University
- University of Edinburgh
Regional District General Hospitals with Research Capacity:
- Sites across England, Scotland, Wales, and Northern Ireland
- Hub-and-spoke model with centralized expertise
Data Management Systems
The platform employs state-of-the-art data management:
- Electronic Data Capture (EDC): Centralized database with real-time validation
- Direct Data Capture: Integration with wearable devices and digital assessments
- Imaging Repository: Centralized neuroimaging storage and analysis
- Biobank Database: Sample tracking and biomarker result integration
Monitoring and Quality Assurance
Rigorous quality assurance ensures data integrity:
- Risk-based monitoring strategy
- Central statistical monitoring for data quality
- Regular site training and certification
- Audit program for selected sites
Statistical Framework
Primary Analysis Approach
The statistical framework employs established methods:
Frequentist Framework with Adaptive Elements:
- Pre-specified interim analyses at predefined timepoints
- Alpha spending function to control overall type I error
- Sample size re-estimation capability for promising arms
Multi-arm Comparison:
- Control group shared across all treatment arms
- Closed testing procedure to control family-wise error rate
- Hierarchical testing strategy for primary and key secondary endpoints
Sample Size Considerations
The 1,200 participant sample size provides:
- 80% power to detect 25% slowing on MDS-UPDRS
- Adequate power for multiple arm comparisons
- Sufficient sample for subgroup analyses by biomarker status
Missing Data Handling
The analysis plan addresses missing data:
- Multiple imputation for intermittent missing data
- Sensitivity analyses comparing different assumptions
- Pattern mixture models for informative dropout
Current Status and Timeline
Recruitment Progress
As of the latest update:
- Status: RECRUITING
- Enrollment: 1,200 participants (estimated)
- Start date: September 12, 2025
- Expected completion: July 31, 2031
Milestones
| Milestone | Expected Date |
|-----------|---------------|
| First patient enrolled | Q4 2025 |
| 25% enrollment | Q2 2026 |
| 50% enrollment | Q4 2026 |
| 75% enrollment | Q2 2027 |
| Primary endpoint analysis | Q3 2029 |
| Final analysis | Q2 2031 |
Future Directions
Expansion Opportunities
The platform is designed for expansion:
International Sites: Expansion to US, European, and other sites planned
New Treatment Arms: Mechanism to add new compounds as they become ready
Substudies: Additional biomarker and imaging substudies can be added
Combination Therapies: Platform can evaluate combination approachesThe EJS ACT-PD platform can integrate with:
- DIAN-TU: Alzheimer's disease platform trial
- PSP Clinical Trial Platform: Tauopathy platform
- HEALEY ALS Platform: ALS platform trial
- European Platform for Neurodegenerative Disease Research
Long-term Vision
The platform aims to establish a sustainable infrastructure:
- Transform PD drug development from sequential to parallel
- Create lasting clinical research network
- Generate valuable natural history and biomarker data
- Establish new standards for neurodegenerative disease clinical trials
Similar Initiatives
Several platform trials in Parkinson's disease have preceded EJS ACT-PD:
| Platform | Sponsor | Status | Focus |
|----------|---------|--------|-------|
| EJS ACT-PD | UCL | Recruiting | Disease modification |
| PD-STEPS | Michael J. Fox Foundation | Completed | Symptomatic |
| PROSEEK | Various | Completed | Biomarkers |
| PD-MRI | Various | Ongoing | Neuroimaging |
Unique Contributions
EJS ACT-PD contributes uniquely:
- Scale: Largest active PD platform trial
- Design: Most comprehensive adaptive framework
- Integration: Deepest biomarker integration
- Duration: Longest follow-up period
Economic Considerations
Cost Efficiency
The platform design provides significant cost advantages:
- Shared control group reduces total participants needed
- Standardized operations across arms reduce per-site costs
- Adaptive design reduces failed trial investments
- Biobank and data infrastructure benefit all future research
Resource Utilization
The platform optimizes resource utilization:
- Site network maximizes patient access
- Centralized data management reduces redundancy
- Coordinated sample collection improves efficiency
- Standardized assessments enable cross-study comparisons
Impact on PD Research Ecosystem
Training and Capacity Building
The platform contributes to research capacity:
- Clinical research training for site staff
- Methodology development for platform trials
- Data science expertise development
- Patient engagement best practices
Collaborative Networks
The platform strengthens collaborative networks:
- Academic consortium across UK universities
- Industry partnerships for compound provision
- Patient organization engagement
- International research connections
Conclusion
The Edmond J. Safra Accelerating Clinical Trials in Parkinson's Disease (EJS ACT-PD) platform trial represents a transformative approach to Parkinson's disease drug development. By enabling simultaneous evaluation of multiple disease-modifying therapies within a rigorous adaptive framework, this platform addresses fundamental inefficiencies in traditional clinical trial designs.
The trial's comprehensive biomarker program, patient-centered design, and regulatory engagement position it to generate high-quality evidence suitable for global regulatory submissions. Beyond evaluating specific treatments, the platform creates lasting infrastructure that will accelerate future PD research and potentially transform the lives of the 10 million people worldwide living with Parkinson's disease.
Results from the EJS ACT-PD platform will be eagerly anticipated by the entire Parkinson's disease community and will inform the next generation of neurodegenerative disease clinical trials.
Related Pages
Clinical Trials
- [Clinical Trials Overview](/clinical-trials/overview)
- [Drug Development Pipeline](/clinical-trials/drug-pipeline)
- [Prasinezumab Phase 3 Trial](/clinical-trials/nct07174310)
- [PSP Clinical Trial Platform](/clinical-trials/psp-clinical-trial-platform)
Mechanisms
- [Alpha-Synuclein Aggregation](/mechanisms/alpha-synuclein-aggregation)
- [Parkinson's Disease Pathogenesis](/mechanisms/parkinsons-pathogenesis)
- [Lewy Body Formation](/mechanisms/lewy-body-formation)
- [Dopaminergic Neuron Degeneration](/mechanisms/dopaminergic-neuron-degeneration)
- [Mitochondrial Dysfunction in PD](/mechanisms/mitochondrial-dysfunction-parkinsons)
Diseases
- [Parkinson's Disease](/diseases/parkinsons-disease)
- [Parkinson's Disease Subtypes](/diseases/parkinsons-subtypes)
- [Parkinson's Disease Dementia](/diseases/parkinsons-disease-dementia)
Proteins
- [Alpha-Synuclein](/proteins/alpha-synuclein)
- [LRRK2](/genes/lrrk2)
- [GBA](/genes/gba)
- [Parkin](/proteins/parkin-protein)
- [DJ-1](/proteins/dj-1-protein)
Therapeutics
- [Disease-Modifying Therapies Overview](/therapeutics/disease-modifying-therapies-overview)
- [Alpha-Synuclein-Targeting Therapies](/therapeutics/alpha-synuclein-targeting-therapies)
External Links
- [ClinicalTrials.gov Record - NCT07207057](https://clinicaltrials.gov/study/NCT07207057)
- [UCL Parkinson's Disease Research](https://www.ucl.ac.uk/neurosurgery/parkinsons-research)
- [Parkinson's UK Clinical Trials](https://www.parkinsons.org.uk/research/clinical-trials)
- [The Michael J. Fox Foundation for Parkinson's Research](https://www.michaeljfox.org/)
- [Parkinson's Foundation](https://www.parkinson.org/)
References
[Edmond J. Safra Accelerating Clinical Trials in Parkinson's Disease (EJS ACT-PD), ClinicalTrials.gov NCT07207057](https://clinicaltrials.gov/study/NCT07207057)
[Platform trials in neurodegenerative disease: A new paradigm for efficient drug development, Nature Reviews Neurology (2022)](https://doi.org/10.1038/s41582-022-00687-w)
[Parkinson's disease clinical trials 2024: Current landscape and future directions, Movement Disorders (2024)](https://pubmed.ncbi.nlm.nih.gov/38452187/)
[Biomarkers in Parkinson's disease clinical trials, Journal of Parkinson's Disease (2024)](https://doi.org/10.3233/JPD-240202)
[MDS-UPDRS validation in clinical trials, Movement Disorders (2024)](https://doi.org/10.1002/mds.297)
[A Master Protocol Approach to Parkinson's Disease Drug Development, Journal of Parkinson's Disease (2022)](https://doi.org/10.3233/JPD-223541)
[Parkinson's disease biomarkers: Current status and future perspectives, Nature Reviews Neurology (2023)](https://doi.org/10.1038/s41582-023-00800-5)
[Alpha-synuclein seeding and propagation in Parkinson's disease, Nature Reviews Neuroscience (2023)](https://doi.org/10.1038/s41583-023-00735-2)