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.
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.
| 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. 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.
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
Parkinson's disease affects approximately 10 million people worldwide, making it the second most common neurodegenerative disorder after Alzheimer's disease. 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 community
¶ Primary and Secondary 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.
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
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
- 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 consent
- 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 trial
The EJS ACT-PD platform trial is conducted at multiple centers across the United Kingdom, with expansion to additional international sites anticipated:
- 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.
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:
-
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
- Microgliatargeted 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.
A key innovation of the EJS ACT-PD platform is its integration of biomarker assessments throughout the trial. Biomarkers serve multiple purposes:
- Confirm PD diagnosis and exclude atypical parkinsonism
- Identify disease subtype for patient stratification
- Identify patients at higher risk of progression
- Predict response to specific therapies
- Demonstrate target engagement of experimental therapies
- Provide early signals of biological activity
- Track disease progression
- Detect adverse effects early
- 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
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
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 adjusted
The shared placebo control group provides several advantages:
- Reduced total number of participants needed
- More precise effect estimates
- Ethical advantages of fewer placebo exposures
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 therapies
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
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.
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 communication
¶ Data 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
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
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
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
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
As of the latest update:
- Status: RECRUITING
- Enrollment: 1,200 participants (estimated)
- Start date: September 12, 2025
- Expected completion: July 31, 2031
| 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 |
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 approaches
The 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
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
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 |
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
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
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
¶ 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
The platform strengthens collaborative networks:
- Academic consortium across UK universities
- Industry partnerships for compound provision
- Patient organization engagement
- International research connections
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.