Global Alzheimer's Platform Trial-Ready Cohort for Preclinical/Prodromal Alzheimer's Disease (GAP TRC-PAD) Academic PIs: Paul Aisen, Reisa Sperling, Jeff Cummings SUMMARY Based on growing recognition that the long pre-dementia stages of Alzheimer's disease (AD) represent the optimal time for interventions aimed at modifying the neurobiology of the disease, most recent drug development programs enroll participants at the preclinical/asymptomatic and prodromal/mild cognitive impairment stages. However, the timeframe, complexity and expense of the recruitment process and site activation for these secondary prevention trials are extremely challenging, and indeed site start-up and trial enrollment, in general, represent the greatest bottleneck for drug development for AD. Thus, there is growing consensus in our field that we must fundamentally overhaul the current clinical trial recruitment and assessment process for these early intervention trials. The overarching goal of this proposal is to accelerate current and future secondary prevention trial enrollment through an innovative, highly efficient approach to identify, evaluate, and enroll appropriate preclinical and prodromal trial candidates, supported by a new site network with enhanced capacities for more efficient and effective conduct of AD clinical trials. It is our view that this can be accomplished only through a public-private partnership, the GAP Partnership, between this project and the GAP Foundation. Beginning in early 2014, the Global Alzheimer Platform (GAP) brought together academic, industry, advocacy and other Alzheimer's leaders to identify the necessary components to build large ?trial-ready cohorts? (TRC) for preclinical/prodromal AD (PAD) trials (TRC-PAD) and to support a network (GAP-Net) of pre-qualified ?trial-ready sites? with specific expertise in and uniform processes for the clinical and biomarker assessments required for prevention trials. The specific goal of the current project is to build a large TRC-PAD (n=2000; 1000 preclinical/1000 prodromal AD), to facilitate enrollment into ongoing PAD trials using the GAP-Net framework. This application describes a process of connecting existing ?feeder? registries and studies to a GAP Registry to capture demographic, genetic and longitudinal clinical and cognitive information on older, non-demented individuals interested in trials. The Registry data generates risk scores for AD pathology (initially elevated amyloid in brain, but with methods adaptable to tau pathology and other biomarkers), that allows efficient selection of candidates for in-person biomarker (initially amyloid PET scans) and clinical assessment. The results of these assessments, in turn, allow an adaptive statistical algorithm to improve the selection process moving forward. Individuals with PET scans showing amyloid accumulation in brain (or alternative biomarker confirmation) are invited to join the GAP Cohort, with semi-annual in-person follow-up within the GAP-Net network of pre-qualified clinical sites, from which they can be invited to enroll in early stage trials. Overall, the process will dramatically shorten the timeline for preclinical/prodromal trials, and will address a series of scientific hypotheses to guide further development in the field.
Alzheimer?s disease (AD) remains one of greatest unmet medical needs in our country with estimates of over 5 million Americans suffering from the disease in 2015. No new symptomatic therapies have been approved over the past 12 years, and there are currently no approved disease-modifying agents. A number of trials in are underway or currently being planned. However, the timeframe, complexity and expense of the recruitment process and site activation for these secondary prevention trials are extremely challenging, and indeed trial enrollment and site network construction, in general, represent the greatest bottleneck for drug development for AD. There is growing consensus in the AD field that we must fundamentally overhaul the current clinical trial recruitment and assessment process for early intervention trials to succeed. This proposal aims to address this need.
| Aisen, P; Touchon, J; Amariglio, R et al. (2017) EU/US/CTAD Task Force: Lessons Learned from Recent and Current Alzheimer's Prevention Trials. J Prev Alzheimers Dis 4:116-124 |
