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P4‐014: ESTIMAND IN EARLY ALZHEIMER'S DISEASE: PROGRESS UPDATE FROM THE INTERNATIONAL ALZHEIMER'S DISEASE SCIENTIFIC WORKING GROUP (AD SWG) SUBSTREAM
Author(s) -
Delmar Paul,
Voyle Nicola,
Caputo Angelika,
Donohue Michael C.,
Li David Jianjun,
Mackey Howard,
Quarg Peter,
Zhu Ying,
Bell James,
Model Fabian,
Liu-Seifert Hong
Publication year - 2018
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2018.06.2416
Subject(s) - context (archaeology) , disease , clinical trial , psychology , working group , medicine , political science , pathology , law , paleontology , biology
(CSF) and brain of rodents and primates, as well as in the CSF of patients with AD. In a previous Phase-3 trial (EPOCH) verubecestat was not effective for slowing clinical progression in participants with mild-to-moderate AD despite near maximal reduction of CSF Ab. Since Ab deposition takes place many years before clinical symptoms become apparent, implementing treatments targeting Ab earlier in the disease process may be effective. Here we report on the design of the APECS trial in prodromal AD.Methods: APECS (clinicaltrials.gov NCT01953601) is an ongoing Phase-3 randomized, double-blind, 24-month, placebo-controlled trial of verubecestat (12mg and 40mg) in participants with prodromal AD/amnestic mild cognitive impairment due to AD. Key entry criteria included: subjective memory decline with gradual onset and slow progression for at least 1 year, corroborated by an informant; objective impairment in episodic memory 1 SD below the appropriate population mean on the delayed memory index score of the Repeatable Battery for the Assessment of Neuropsychological Status; positive Ab imaging PET scan; Mini Mental State Examination score 24. Key exclusion criteria included diagnosis of dementia or other relevant neurological or psychiatric disorder. The primary efficacy endpoint is change-from-baseline in the Clinical Dementia Rating – Sum of Boxes score at Month 24. Secondary endpoints include changes in cognitive test scores, changes in biomarkers, and time to progression to AD. Results: 4483 people were screened and 1454 were randomized between 2013 and 2017 (screening failure rate of 68%). Preliminary baseline data showed a trial population with the following demographic characteristics: 53%male, mean (SD) age of 71.4 (7.2) years, 81%white (17%Asian, 1%other), 51%with an undergraduate degree or higher, 46%usingAD treatment, 69%APOE4 carriers, andmean (SD)Mini Mental State Examination score of 26.3 (1.8). The trial is expected to complete in 2019. Conclusions: Results from the APECS trial will help inform whether blocking Ab production is effective in slowing clinical progression in participants with prodromal AD.