Participants will be enrolled for 18 months, with baseline data provided and compared to the lecanemab phase 2 study cohort.
Clinical efficacy and safety of lecanemab (formerly known as BAN2401; Eisai and Biogen), an investigational antiamyloid beta (Aß) protofibril antibody, will be evaluated in a phase 3 placebo-controlled, double-blind, parallel-group study of adults with early Alzheimer disease (AD). Details of the study, entitled Clarity AD (NCT03887455), were presented by Michelle Gee, PhD, director, neuroscience product creation unit, Eisai, at the 2021 Alzheimer’s Association International Conference, where design, endpoints, and comparison to the phase 2 study population were explored.
According to investigators, the lecanemab phase 2 study had encouraging results, making use of a Bayesian design with response adaptive randomization as a multinational, double-blind, placebo-controlled study. As early findings showed 10 mg/kg of lecanemab on a biweekly basis reduced brain Aβ levels, while also helping to slow the decline of cognition and function for patients with both AD and mild cognitive impairment, phase 3 was designed to confirm the safety and efficacy of treatment with lecanemab.
Following the cutoff date of January 6, 2021, Clarity AD enrolled 1536 participants; the median age was 72 years, with patients ranging in age from 50 to 90 years, 81% of whom were over 65 years. Results showed mean baseline values for clinical end points of 3.2 points (Standard deviation [SD], 1.3) on Clinical Dementia Rating-Sum of Boxes (CDR-SB), 0.4 points (SD, 0.1) on Alzheimer’s Disease Composite Score (ADCOMS), 25.4 points (SD, 7.3) on Alzheimer’s Disease Assessment Scale-Cognitive Subscale (ADAS-Cog), 25.6 points (SD, 2.2) on Mini-Mental State Exam (MMSE), and 0.6 points (SD, 0.2) on Global CDR.
When compared to the phase 2 study, investigators found similar aggregate baseline characteristics, with a median patient age of 72 years and an age range of 50 to 90 years, and clinical end points identified mean scores of 3.0 points (SD, 1.4) on CDR-SB, 0.4 points (SD, 0.2) on ADCOMS, 22.2 points (SD, 7.4) on ADAS-Cog, 25.6 points (SD, 2.4) on MMSE, and 0.6 points (SD, 0.2) on Global CDR. Investigators compared additional study demographics, as 52% of participants in phase 3 were women, compared to 50% in phase 3, and 75% of participants in phase 3 were Caucasian, compared to 90% in phase 2.
“Age, sex, and race in Clarity AD very similar to that of the phase 2 study, with a slightly more diverse population in Clarity AD, albeit being predominantly Caucasian,” Gee said in the presentation. “In summary, baseline characteristics in the Clarity AD study, which was designed to confirm clinical efficacy and safety of lecanemab, are consistent with those seen in the phase 2 study and consistent with an early AD patient population.”
The 18-month study will enroll approximately 1766 patients, with enrollment ongoing in China; enrollment has been completed in all other regions (North America, Europe, Asia, and Australia). The primary measure of the study is the change in CDR-SB from baseline at a follow-up at 18 months, and secondary end points include change from baseline in amyloid PET standardized uptake value ratio, ADCOMS scores, and ADAS-Cog14 scores. The open-label extension study will evaluate long-term safety effects, namely treatment-emergent adverse events and change from core study baseline in CDR-SB scores. During the extension phase, long-term effects will be further assessed, according to clinical outcome measures and biomarkers, and whether they are maintained over time.
Lecanemab was granted breakthrough designation by the FDA in June; phase 2 findings were published in Alzheimer’s Research and Therapy earlier this year, led by Jeffrey L. Cummings, MD, ScD, director emeritus, Lou Ruvo Center for Brain Health, Cleveland Clinic, and vice chair, Department of Brain Health, University of Nevada-Las Vegas, that randomized patients to lecanemab across a number of doses (2.5 mg/kg biweekly, 5 mg/kg monthly, 5 mg/kg biweekly, 10 mg/kg monthly, 10 mg/kg biweekly) or placebo.
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