Study Rationale: Assess the impact of putative NSD therapies in participants with Early Stage NSD on Dopamine Transporter Single-photon emission computed Tomography (DAT SPECT) imaging, clinical measures of symptom worsening, feasibility, safety, and tolerability. Additional analyses will examine many other exploratory clinical outcome measures and biomarkers.
Hypothesis: Enrollment of NSD participants into interventional studies offers a unique opportunity to test potential disease modifying interventions at earlier stages of neurodegenerative process. If successful, this approach will create a scientific and regulatory path for future disease prevention studies.
Study Design: The P2P Trial is a perpetual multi-center, multi-regimen clinical trial evaluating the safety and early efficacy of investigational products for the treatment of participants with stage 2B NSD. Participants will be recruited based on presence of n-asyn pathology as determined by n-asyn SAA or other validated biomarkers (as such become available) and dopaminergic dysfunction as determined by DAT SPECT imaging and clinical features as defined by inclusion criteria.
There is a single Master Protocol dictating the conduct of the trial. The Master Protocol describes the overall framework of the platform trial, including the target population, inclusion and exclusion criteria, regimen assignment and randomization schemes, Master Protocol endpoints, schedule of assessments, trial design, the mechanism for adding and removing interventions, and the statistical methodology and recommended statistical methods for evaluating interventions.
Interventions (i.e., investigational products) are tested in trial regimens, in which a regimen denotes both the active intervention and placebo control corresponding to an intervention. Each trial regimen is described in its own Regimen-Specific Sub Protocol (RSSP) appended to the Master Protocol.
Impact on Diagnosis/Treatment of Parkinson’s disease: The prevalence of PD, based on the current diagnostic criteria, the second most common neurodegenerative disease, is 10 million worldwide and is expected to double by 2040. DLB is the second most common degenerative dementia also caused by neuronal accumulation of aggregated n-asyn but associated with early cognitive manifestations. While there is a wide armamentarium of therapeutics to manage motor manifestations of PD, the disease continues to progress relentlessly leading to significant disability in advanced stages. As such, development of effective options to slow / halt disease progression remains an area of urgent need.
Next Steps for Development: With the testing of multiple investigational products using a common protocol and uniform data and sample acquisition processes, the platform is designed to answer multiple scientific questions and to serve as a source of data that can be used to enhance the design of other research projects. Further, accumulated learnings about endpoint behavior can be leveraged to adapt the Master Protocol so that future investigational products will be studied using more efficient biomarkers, outcome measures and analyses.