Abstract
Background:
Previous clinical trials assessing potential disease-modifying therapies (DMTs) for Parkinson’s disease (PD) have been hugely inefficient in terms of time and resources, resulting in >10 years for a single therapy to complete phase 3 assessment. Additionally, un-representative trial populations limit the generalisability of findings. Increased efficiency of clinical trial conduct has been successfully demonstrated in multi-arm, multi-stage (MAMS) trials, which assess multiple therapies in parallel and identify ineffective therapies at early-stage analyses. New arms can be added within existing trial infrastructure, providing opportunities to build on delivery frameworks and expertise. The Edmond J Safra Accelerating Clinical Trials in PD (EJS ACT-PD) initiative was set-up to address trial design inefficiencies and produce an inclusive protocol for a neuroprotective MAMS PD trial.
Methods:
Over 90 key stakeholders from across the UK, including people with PD and care partners form the EJS ACT-PD consortium. Six working groups have addressed trial design, outcome measures, therapy selection, infrastructure, funding and sustainability, and patient and public inclusion. Design decisions have been further informed by: a community advisory panel; an international advisory group; the MHRA; results of a UK-wide Site Capability Survey; a robust treatment selection process; statistical modelling; and literature reviews.
Results:
We have designed a phase 3 multi-centre, MAMS, randomised, double-blind, placebo-controlled trial to assess the clinical and cost effectiveness of potential DMTs in a representative PD population. The trial aims to recruit across 40 UK sites from December 2024. Wide-spread site inclusion and diverse recruitment will be supported by remote visit options; broad inclusion criteria; core-funded staff; and a tiered delivery approach based on site capabilities. The primary outcome of a patient-reported measure of PD impact will ensure meaningful results.
Conclusion:
MAMS trials offer exciting opportunities to accelerate the assessment of potential therapies whilst building on national infrastructure and encouraging diverse participant recruitment.