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DT‐01‐07: TREATMENT OF EARLY AD SUBJECTS WITH BAN2401, AN ANTI‐Aβ PROTOFIBRIL MONOCLONAL ANTIBODY, SIGNIFICANTLY CLEARS AMYLOID PLAQUE AND REDUCES CLINICAL DECLINE
Author(s) -
Swanson Chad J.,
Zhang Yong,
Dhadda Shobha,
Wang Jinping,
Kaplow June,
Lai Robert YK.,
Lannfelt Lars,
Kramer Lynn Darden,
Luthman Johan
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.2018.07.009
Subject(s) - placebo , repeated measures design , medicine , analysis of variance , randomization , clinical endpoint , amyloid (mycology) , monoclonal antibody , clinical trial , gastroenterology , nuclear medicine , urology , antibody , pathology , immunology , mathematics , statistics , alternative medicine
estimated the effect of Ab pathology on decline over a spectrum of cognitive domains. Results:Despite considerable study differences in terms of demographics, recruitment, follow-up schedule, and neuropsychological test battery, the magnitude of the differences in decline between Ab groups was consistent for the cognitive composite (PACC, the Preclinical Alzheimer Cognitive Composite) (Figure 1). To achieve 80% power with 800 subjects per arm in a simulated 4-year treatment trial in preclinical AD, estimates of the required drug effect ranged from 34% to 50%. Ab+ groups declined significantly faster on all cognitive domains in all cohorts compared to the Abgroups (Figure 2, the only exception was Trails B in BioFINDER). Several baseline factors interacted significantly with Ab to predict cognitive decline including APOE e4-positivity, baseline cognition, and education in AIBL; age in BioFINDER; and sex in ADNI, however these interactions were cohort specific. On average, Ab+ subjects performed similarly to early MCI patients on cognitive tests 6 years after baseline. Conclusions: We provide robust estimates of expected cognitive decline in preclinical AD. Comparing cohorts side by side demonstrates that large sample sizes with sufficient follow-up times result in consistent estimates of cognitive decline in preclinical AD across measures spanning multiple cognitive domains. Despite design differences, cognitive composites can provide precise information with which to inform study design decisions. These results support the potential for internationally-conducted clinical trials in preclinical AD.