P3‐385: A new level of operational complexity within innovative Alzheimer's disease trial designs: Case study of a phase 2 bapineuzumab trial—SUMMIT‐AD

Abstract

Key challenges to successful execution of therapeutic trials in Alzheimer's disease (AD) have included great variability in subject characteristics and inconsistent administration of clinical assessments. This case study focuses on a 120-subject phase 2 trial of bapineuzumab (SUMMIT-AD), an investigational treatment for AD. The SUMMIT-AD trial requires extensive biomarker testing for subject selection and assessment of safety and efficacy, including amyloid PET, lumbar puncture, and volumetric MRI, over a 2-year treatment period. Successful implementation has required considerable infrastructure and resources at clinical and imaging sites, as well as coordination of CROs and multiple vendors. A positive amyloid PET scan is required at baseline, as a primary endpoint is change in amyloid PET signal at 24 months. Quarterly MRI is required as part of safety monitoring, and MRI volumetry, CSF beta-amyloid 1-42, and CSF tau biomarker assessments support clinical outcome measures. Additional site selection criteria are listed in the Table. Twenty-eight U.S. sites were selected from an original list of 212. Of 45 MRI and 54 PET imaging sites based on proximity, 28 and 24, respectively, were selected. One full-service CRO and 12 specialty vendors have been enlisted. While it was difficult to select sites with appropriate infrastructure, through a rigorous site identification and site activation process, the performance of the study has exceeded expectations. The study has met enrollment in 30% less time than projected, and subject attrition through 9 months has been ∼30% lower than expected. The number of subjects consenting to lumbar puncture has been higher than in previous studies. Clinical trials in AD have increased both in number and size, and the use of biomarkers has increased their operational difficulties. A more holistic view of site infrastructure is required; considerations include the accessibility of research quality imaging sites, the requirement for multiple specialty assessments that has expanded the list of vendors, and the need for seamless flow of data for subject selection and monitoring of safety. This case study will explore how rigorous site selection and ongoing training have been implemented successfully in this challenging multicenter study. Pharmacy services for storage and preparation of investigational product Access to 1.5T MRI, with ability to conduct MRI volumetry and electronically upload images Access to supply of radioligand (AV-45) Access to PET facility licensed to receive a radioligand, able to electronically upload images, and without a plan for scanner change during the 3-year study period Rapid communication of results of MRI safety and PET to make timely assessment of subject inclusion Ability to perform lumbar puncture under fluoroscopic guidance if needed At least 2 site personnel qualified to administer psychometric tests