The qualification of an enrichment biomarker for clinical trials targeting early stages of Parkinson’s disease

Stephenson, D. et al. (2019) The qualification of an enrichment biomarker for clinical trials targeting early stages of Parkinson’s disease. Journal of Parkinson's Disease, 9(3), pp. 553-563. (doi: 10.3233/jpd-191648) (PMID:31306141)

Abstract

As therapeutic trials target early stages of Parkinson’s disease (PD), appropriate patient selection based purely on clinical criteria poses significant challenges. Members of the Critical Path for Parkinson’s Consortium formally submitted documentation to the European Medicines Agency (EMA) supporting the use of Dopamine Transporter (DAT) neuroimaging in early PD. Regulatory documents included a comprehensive literature review, a proposed analysis plan of both observational and clinical trial data, and an assessment of biomarker reproducibility and reliability. The research plan included longitudinal analysis of the Parkinson Research Examination of CEP-1347 Trial (PRECEPT) and the Parkinson’s Progression Markers Initiative (PPMI) study to estimate the degree of enrichment achieved and impact on future trials in subjects with early motor PD. The presence of reduced striatal DAT binding based on visual reads of single photon emission tomography (SPECT) scans in early motor PD subjects was an independent predictor of faster decline in UPDRS Parts II and III as compared to subjects with scans without evidence of dopaminergic deficit (SWEDD) over 24 months. The EMA issued in 2018 a full Qualification Opinion for the use of DAT as an enrichment biomarker in PD trials targeting subjects with early motor symptoms. Exclusion of SWEDD subjects in future clinical trials targeting early motor PD subjects aims to enrich clinical trial populations with idiopathic PD patients, improve statistical power, and exclude subjects who are unlikely to progress clinically from being exposed to novel test therapeutics.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Grosset, Professor Donald
• Authors: Stephenson, D., Hill, D., Cedarbaum, J. M., Tome, M., Vamvakas, S., Romero, K., Conrado, D. J., Dexter, D. T., Seibyl, J., Jennings, D., Nicholas, T., Matthews, D., Xie, Z., Imam, S., Maguire, P., Russell, D., Gordon, M. F., Stebbins, G. T., Somer, E., Gallagher, J., Roach, A., Basseches, P., Grosset, D., and Marek, K.
• College/School: College of Medical Veterinary and Life Sciences > School of Psychology & Neuroscience
• Journal Name: Journal of Parkinson's Disease
• Publisher: IOS Press
• ISSN: 1877-7171
• ISSN (Online): 1877-718X
• Published Online: 30 July 2019
• Copyright Holders: Copyright © 2019 IOS Press and the authors
• First Published: First published in Journal of Parkinson's Disease 9:553-563
• Publisher Policy: Reproduced under a Creative Commons license