PRECLINICAL ALZHEIMER'S CLINICAL TRIALS: TRC-PAD AND A4 IN JAPAN
- Takeshi Iwatsubo, Japan
Abstract
Aims
There is a compelling need for the very early treatment of Alzheimer’s disease (AD) at the asymptomatic stage. The Anti-Amyloid Treatment in Asymptomatic AD (A4) Study is a secondary prevention trial of solanezumab in amyloid-PET positive, clinically normal older individuals being conducted at 67 sites in the North America, Australia and Japan. Furthermore, trial ready cohorts for preclinical and prodromal AD are being established to maximize the efficiency of recruitment for the emerging preclinical AD trials.
Abstract Body
A number of disease-modifying therapies (DMT) against Alzheimer’s disease (AD) are currently being tested in clinical trials, some of which met the clinical endpoints in early-phase trials whereas others, especially those conducted in dementia stages, have failed, underscoring the needs for early intervention and biomarkers. To establish imaging and fluid biomarkers that surrogate the clinical and pathophysiological progression of AD, longitudinal observational studies as represented by AD Neuroimaging Initiative (ADNI) in US, as well as the Japanese ADNI, has been conducted, which contributed greatly towards the goal of very early treatment at the prodromal and preclinical AD stages by delineating the early natural course of AD. It has been demonstrated that the clinical and biomarker profiles of prodromal AD in J-ADNI were remarkably similar to those in North American ADNI, supporting the harmonization of global clinical trials. Furthermore, secondary prevention trials in preclinical AD, i.e., anti-Abeta therapies in asymptomatic, amyloid positive elderly individuals (the A4 study), as well as projects to establish trial ready cohorts of preclinical and prodromal AD, are being conducted in US and Japan. J-TRC is comprised of a webstudy and an on-site study, recruiting ~4700 and ~140 participants, respectively. These clinical activities, accelerated by the development and implementation of biomarkers, will pave the way toward the development of very early treatment of AD.Methods
We report the screening data results of the A4 study conducted in Japan, as well as the current status of the Japanese Trial-Ready Cohort for preclinical and prodromal AD (J-TRC).
Results
In Japan, 161 volunteers were screened for A4, 100 underwent florbetapir amyloid PET, and 20 were characterized as Aβ+. The age (mean: 75.5 y in Aβ+) and APOE4 positivity (45% in Aβ+, 18% in Aβ-) were significantly higher in Aβ+. In Aβ+, PACC at screening showed a trend of worsening and CFI-Participant was significantly higher. These results were consistent with those from the whole cohort including North America and Australia. The J-TRC has a similar structure to that of US-TRC-PAD, consisting of the J-TRC webstudy and an in-person, J-TRC on-site study, having recruited ~4500 and ~40 participants, respectively, as of Sep 2020. Machine-learning algorithms based on the A4 screen data were useful in the prediction of Aβ+ individuals in the J-TRC candidates.
Conclusions
Treating AD at the asymptomatic stage would be vital to its prevention, which will be facilitated by the establishment of trial-ready cohorts for preclinical AD.