A new phase 3 clinical study, AHEAD 3-45 (NCT04468659), of an antiamyloid-beta (Aβ) protofibril antibody (BAN2401; Alzforum, Cambridge, MA), has been initiated for individuals with preclinical Alzheimer disease (AD). Currently, the antiamyloid beta is being studied in a pivotal phase 3 clinical study in symptomatic early AD (Clarity AD), following the outcome of the phase 2 clinical study (Study 201).
The AHEAD 3-45 is a phase 3 clinical study, conducted as a public-private partnership between the Alzheimer's Clinical Trials Consortium (ACTC), funded by the National Institute on Aging, part of the National Institutes of Health, and Eisai. After a common screening period in AHEAD 3-45, participants will be enrolled into one of two randomized, double-blind, placebo-controlled trials based on the level of amyloid in the brain: the A45 trial and the A3 trial. A total of 1400 participants will be enrolled and treated with antiamyloid beta for 216 weeks.
The A45 trial will enroll cognitively unimpaired participants who have elevated levels of amyloid in the brain and aims to prevent cognitive decline and suppress the progression of brain AD pathology with antiamyloid beta administration. The primary endpoint for A45 is the change from baseline in the Preclinical Alzheimer Cognitive Composite 5 (PACC5) at 216 weeks of treatment. Secondary endpoints are changes from baseline in brain amyloid levels as measured by amyloid positron emission tomography (PET) and in brain tau levels as measured by tau PET and Cognitive Function Index, a participant and study partner reported outcome.
The A3 trial will enroll cognitively unimpaired participants who have an intermediate amount of amyloid in the brain, and who are at high risk for further Aβ accumulation. The primary endpoint for A3 is change from baseline in brain amyloid levels as measured by amyloid PET. The secondary endpoint is change from baseline in brain tau levels as measured by tau PET. Both trials include additional clinical assessment scales, imaging, blood biomarkers and cerebrospinal fluid (CSF) in a subset, as exploratory endpoints.
"It is hoped that initiating treatment much earlier in the disease process may be advantageous in preventing future cognitive decline. The AHEAD 3-45 should provide critically important answers about the optimal time to intervene with antiamyloid therapy," said Dr. Reisa Sperling, director, Center for Alzheimer Research and Treatment at Brigham and Women's Hospital and coprincipal investigator, ACTC.
James Geyer, MD, and Paul Cox
F. Stephen Benesh, MD, and Shruti P. Agnihotri, MD
Jakai D. Nolan, DO, MPH, and Jacqueline A. Nicholas, MD, MPH