AHEAD 3‐45 study: Preliminary screening and baseline characteristics from a placebo‐controlled, double‐blind study evaluating lecanemab in participants with preclinical Alzheimer's disease and elevated (A45 trial) and intermediate (A3 trial) amyloid. (31st December 2021) - Zhou, Jin
Abstract: Background: Amyloid beta (Aβ) accumulation begins 10‐20 years before the onset of cortical tauopathy, neurodegeneration, and clinical symptoms in Alzheimer's disease. Lecanemab (BAN2401), a humanized IgG1 monoclonal antibody that preferentially targets soluble aggregated Aβ (ie, oligomers, protofibrils), reduced amyloid on PET and slowed cognitive decline in a phase 2 study in early Alzheimer's disease. AHEAD 3‐45 is evaluating lecanemab treatment in cognitively normal (CN) individuals to determine if very early intervention can prevent pathological progression and cognitive decline prior to significant irreversible neurodegeneration. This study is conducted as a Public‐Private Partnership of the Alzheimer's Clinical Trial Consortium (ACTC), National Institutes of Health (NIH), and Eisai Inc. Method: AHEAD 3‐45 consists of two trials (A3 and A45) with distinct dosing regimens tailored to baseline brain amyloid levels. Both individual trials are conducted under a single protocol, screening process, and common schedule of assessments. In the A3 Trial, approximately 400 CN participants with intermediate amyloid (approximately 20‐40 centiloids) who are at risk for further amyloid accumulation will be randomized 1:1 to placebo or lecanemab, with infusion every 4‐weeks . In the A45 Trial, approximately 1000 CN participants with elevated amyloid (>40 centiloids) who are at risk for cognitive decline will be randomized 1:1 to placebo or lecanemab, with infusions initially biweekly then every 4‐weeks. The primary outcome measures are brain amyloid accumulation by amyloid PET (A3) and the Preclinical Alzheimer's Disease Cognitive Composite 5 (PACC5) scale (A45), both at 216 weeks. Result: As of January 19, 2021, 194 participants were screened, and 20 participants were randomized into A3 (2) and A45 (18). Overall, 37% of participants (n=109) who completed amyloid PET are eligible for A3 (n=10) and A45 (n=30) based on amyloid level. Initial screening and baseline characteristics data will be presented. Preliminary results of PET eligibility across the two trials appear consistent with projections based on existing observational data (ADNI and HABS). Conclusion: The initial experience with screening and randomization from the AHEAD 3‐45 Study suggests it is feasible to identify participants across the continuum of preclinical Alzheimer's disease, who are at‐risk for amyloid accumulation and cognitive decline, for disease modifying treatment trials.