Examining amyloid reduction as a surrogate endpoint through latent class analysis using clinical trial data for dominantly inherited Alzheimer's disease

Alzheimers Dement. 2024 Apr;20(4):2698-2706. doi: 10.1002/alz.13735. Epub 2024 Feb 23.

Abstract

Introduction: Increasing evidence suggests that amyloid reduction could serve as a plausible surrogate endpoint for clinical and cognitive efficacy. The double-blind phase 3 DIAN-TU-001 trial tested clinical and cognitive declines with increasing doses of solanezumab or gantenerumab.

Methods: We used latent class (LC) analysis on data from the Dominantly Inherited Alzheimer Network Trials Unit 001 trial to test amyloid positron emission tomography (PET) reduction as a potential surrogate biomarker.

Results: LC analysis categorized participants into three classes: amyloid no change, amyloid reduction, and amyloid growth, based on longitudinal amyloid Pittsburgh compound B PET standardized uptake value ratio data. The amyloid-no-change class was at an earlier disease stage for amyloid amounts and dementia. Despite similar baseline characteristics, the amyloid-reduction class exhibited reductions in the annual decline rates compared to the amyloid-growth class across multiple biomarker, clinical, and cognitive outcomes.

Discussion: LC analysis indicates that amyloid reduction is associated with improved clinical outcomes and supports its use as a surrogate biomarker in clinical trials.

Highlights: We used latent class (LC) analysis to test amyloid reduction as a surrogate biomarker. Despite similar baseline characteristics, the amyloid-reduction class exhibited remarkably better outcomes compared to the amyloid-growth class across multiple measures. LC analysis proves valuable in testing amyloid reduction as a surrogate biomarker in clinical trials lacking significant treatment effects.

Keywords: Dominantly Inherited Alzheimer Network; autosomal dominant Alzheimer's disease; gantenerumab; latent class analysis; solanezumab; surrogate biomarker.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease* / diagnostic imaging
  • Alzheimer Disease* / drug therapy
  • Alzheimer Disease* / genetics
  • Amyloid
  • Amyloid beta-Peptides
  • Amyloidogenic Proteins
  • Biomarkers
  • Double-Blind Method
  • Humans
  • Latent Class Analysis
  • Positron-Emission Tomography / methods

Substances

  • Amyloid
  • Amyloid beta-Peptides
  • Amyloidogenic Proteins
  • Biomarkers