Global Phase 3 Trial Will Test BAN2401 in Early-stage Asymptomatic Alzheimer’s

BAN2401, an experimental treatment for Alzheimer’s disease (AD), will be tested in the new global AHEAD 3-45 clinical trial, its developers have announced.

The Phase 3 study — to be conducted in the U.S., Canada, Japan, Australia, Singapore, and Europe — will test the therapy in people who are in the early stage of the neurological disorder and do not yet show symptoms.

The trial was initiated by Eisai in collaboration with Biogen and the Alzheimer’s Clinical Trials Consortium (ACTC). The ACTC is a network of clinical sites across the U.S., established by the National Institute on Aging to accelerate testing of potential treatments for Alzheimer’s.

AHEAD 3-45 (NCT04468659) will evaluate the therapeutic effect of BAN2401 on the progression of Alzheimer’s in patients who are clinically normal (asymptomatic) but have intermediate or elevated levels of beta-amyloid protein fiber aggregates, or clumps — a hallmark of the disease — in their brains. 

The therapy, which is jointly being developed by Eisai and Biogen, is an antibody-based treatment designed to bind, neutralize, and eliminate these beta-amyloid clumps selectively. 

Currently, BAN2401 is being studied in the pivotal Clarity AD Phase 3 clinical study (NCT03887455). Participants in that trial also have early-stage Alzheimer’s, but do show disease symptoms.

“We welcome the initiative to perform this new and extensive Phase 3 program with BAN2401,” Gunilla Osswald, PhD, CEO at BioArctic AB, Esai’s business partner, said in a press release.

“In contrast to the Clarity AD study, AHEAD 3-45 will investigate BAN2401 as a potential preventive treatment in the pre-symptomatic stages of the disease continuum,” Osswald said. “A successful outcome would provide opportunities to treat patients at a very early stage, or even preventing the disease, thereby substantially reducing patients’ suffering and providing substantial cost savings for society at large.”  

BAN2401 also is being evaluated in a large, ongoing, Phase 2 clinical trial (NCT01767311) called Study 201, which began in 2012. That trial is assessing the experimental therapy in Alzheimer’s patients with mild cognitive impairment or dementia. 

The results from the first 18 months of the trial, involving 856 participants, showed a statistically significant decrease in cognitive decline as well as reduced accumulation of beta-amyloid in the brains of treated patients, compared with those given a placebo. The study is now in its extension phase.

After a standard screening process, AHEAD 3-45 will enroll an estimated 1,400 participants. It will test BAN2401 against a placebo in two separate trials — named A3 and A45 — based on the level of beta-amyloid in the brain, for approximately four years.

The A3 trial will enroll people without any signs of cognitive impairment who have a moderate amount of beta-amyloid in their brains. These patients have a high risk of further accumulation. The primary goal will be to stop or reduce beta-amyloid buildup, as measured by PET scans, in the brain before the appearance of symptoms. 

People with little-to-no cognitive impairment, but who have elevated levels of beta-amyloid in the brain, will be enrolled in the A45 trial. The primary aim of this trial is to test BAN2401’s effects on preventing cognitive decline as measured by the Preclinical Alzheimer Cognitive Composite 5, known as PACC5. This assessment combines tests for memory, overall cognition, and executive function. Beta-amyloid levels also will be measured as a secondary endpoint.

Both trials will include scans to measure the impact of BAN2401 on levels of another protein, called tau, that is known to accumulate in the brains of Alzheimer’s patients.

“It is hoped that initiating treatment much earlier in the disease process may be advantageous in preventing future cognitive decline,” Reisa Sperling, director of the center for Alzheimer’s research and treatment at Brigham and Women’s Hospital, in Boston, and co-principal investigator at ACTC, said in another press release.

“The AHEAD 3-45 should provide critically important answers about the optimal time to intervene with anti-amyloid therapy,” Sperling said.