Practical use of platform in clinical trials for Alzheimer disease

Abstract

Current treatments for Alzheimer disease (AD) approved in Japan consist of three cholinesterase inhibitors and one NMDA receptor antagonist. These agents do not suppress neurodegeneration itself and remain symptomatic therapies that provide only temporary relief. Disease–modifying therapies (DMTs), which target the underlying disease process and slow disease progression, have therefore been expected as a major breakthrough. Drug development based on the amyloid hypothesis initially shifted from unsuccessful vaccine approaches to antibody therapies ; however, solanezumab and aducanumab failed to demonstrate sufficient clinical efficacy. Lecanemab represented a turning point by reducing clinical deterioration by approximately 27% over 18 months in patients with mild cognitive impairment and mild AD, leading to its approval in Japan in 2023. Subsequently, donanemab was also approved, demonstrating an association between amyloid clearance and clinical efficacy. Nevertheless, neither agent halts disease progression or induces clinical improvement, and careful safety management for adverse events such as amyloid–related imaging abnormalities (ARIA) remains essential to ensure optimal use. In addition, AD clinical trials are inherently challenging because of the disease's unknown etiology, slow progression, and difficulties in participant recruitment. To address these issues, the CLIC–D platform was established to accelerate subject recruitment. This platform manages participant contact information and provides end–to–end support for trial participation, thereby facilitating more efficient drug development, including at the preclinical stage.