Amyloid PET Screening for Enrichment of Early-Stage Alzheimer Disease Clinical Trials: Experience in a Phase 1b Clinical Trial

Alzheimer Dis Assoc Disord. 2016 Jan-Mar;30(1):1-7. doi: 10.1097/WAD.0000000000000144.

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.

Publication types

  • Clinical Trial, Phase I
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / diagnostic imaging
  • Alzheimer Disease / drug therapy
  • Alzheimer Disease / pathology*
  • Aniline Compounds
  • Antibodies, Monoclonal, Humanized / therapeutic use
  • Apolipoprotein E4 / genetics
  • Apolipoproteins E / genetics
  • Brain / pathology
  • Cerebral Cortex / diagnostic imaging
  • Cerebral Cortex / pathology
  • Cognitive Dysfunction / diagnostic imaging
  • Cognitive Dysfunction / drug therapy
  • Cognitive Dysfunction / pathology*
  • Double-Blind Method
  • Ethylene Glycols
  • Female
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Plaque, Amyloid / diagnostic imaging*
  • Positron-Emission Tomography / methods*

Substances

  • Aniline Compounds
  • Antibodies, Monoclonal, Humanized
  • Apolipoprotein E4
  • Apolipoproteins E
  • Ethylene Glycols
  • aducanumab
  • florbetapir