title: Amyloid PET Screening for Enrichment of Early-Stage Alzheimer Disease Clinical Trials: Experience in a Phase 1b Clinical Trial.
abstract: Amyloid positron emission tomography (PET) imaging is being investigated as a screening tool to identify amyloid-positive patients as an enrichment strategy for Alzheimer disease (AD) clinical trial enrollment. In a multicenter, phase 1b trial, patients meeting clinical criteria for prodromal or mild AD underwent florbetapir PET scanning at screening. PET, magnetic resonance imaging, and coregistered PET/magnetic resonance imaging scans were reviewed by 2 independent readers and binary visual readings tabulated. Semiquantitative values of cortical to whole cerebellar standard uptake value ratios were computed (threshold 1.10). Of 278 patients with an evaluable PET scan, 170 (61%) and 185 (67%) were amyloid-positive by visual reading and quantitative analysis, respectively; 39% were excluded from the study due to an amyloid-negative scan based on visual readings. More ApoE ε4 carriers than noncarriers were amyloid-positive (80% vs. 43%). Comparison of visual readings with quantitative results identified 21 discordant cases (92% agreement). Interreader and intrareader agreements from visual readings were 98% and 100%, respectively. Amyloid PET imaging is an effective and feasible screening tool for enrollment of amyloid-positive patients with early stages of AD into clinical trials.
authors.affiliation: *Biogen, Cambridge, MA †Bioclinica Inc., Newark ‡California Pacific Medical Center §Department of Radiology, University of California San Francisco, San Francisco, CA.
authors.forename: Jeff
authors.initials: J
authors.lastname: Sevigny
authors.forename: Joyce
authors.initials: J
authors.lastname: Suhy
authors.forename: Ping
authors.initials: P
authors.lastname: Chiao
authors.forename: Tianle
authors.initials: T
authors.lastname: Chen
authors.forename: Gregory
authors.initials: G
authors.lastname: Klein
authors.forename: Derk
authors.initials: D
authors.lastname: Purcell
authors.forename: Joonmi
authors.initials: J
authors.lastname: Oh
authors.forename: Ajay
authors.initials: A
authors.lastname: Verma
authors.forename: Mehul
authors.initials: M
authors.lastname: Sampat
authors.forename: Jerome
authors.initials: J
authors.lastname: Barakos
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000473:pathology*; D000814:Aniline Compounds; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use; D053327:Apolipoprotein E4 / Q000235:genetics; D001057:Apolipoproteins E / Q000235:genetics; D001921:Brain / Q000473:pathology; D002540:Cerebral Cortex / Q000000981:diagnostic imaging / Q000473:pathology; D060825:Cognitive Dysfunction / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000473:pathology*; D004311:Double-Blind Method; D005026:Ethylene Glycols; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D058225:Plaque, Amyloid / Q000000981:diagnostic imaging*; D049268:Positron-Emission Tomography / Q000379:methods*
chemical_list: D000814:Aniline Compounds; D061067:Antibodies, Monoclonal, Humanized; D053327:Apolipoprotein E4; D001057:Apolipoproteins E; D005026:Ethylene Glycols; C000600266:aducanumab; C545186:florbetapir