Recruitment begins in Elayta Phase 2 trial for early Alzheimer’s
Study expects to enroll about 540 adults across North America
START (NCT05531656) expects to enroll about 540 adults, ages 50-85. The University of Kentucky Sanders-Brown Center on Aging (SBCoA) is the first to launch from about 50 planned sites across North America. Elayta is also known as CT1812.
“Our START study represents a unique and important opportunity for Cognition to study CT1812 in people with early Alzheimer’s disease,” Lisa Ricciardi, president and CEO of Cognition, said in a company press release. “It is incredibly exciting and humbling to have reached the stage where patient recruitment can finally begin.”
Paul Aisen, MD, professor of neurology at the University of Southern California and the director of the Alzheimer’s Therapeutic Research Institute, said: “We’re looking forward to partnering with the team at SBCoA and other investigators who are working to bring their sites online so we can begin screening people with early Alzheimer’s disease who are interested in becoming participants in the START study.”
Hallmark symptoms of Alzheimer’s patients, such as memory loss, are caused by the toxic buildup of beta-amyloid protein in the brain.
Elayta is an orally available small molecule that can reach the brain and bind to the sigma-2 receptor, a protein thought to mediate beta-amyloid attachment to nerve cells in the brain. It’s intended to prevent or disrupt the binding between beta-amyloid and the sigma-2 receptor to slow nerve cell loss and cognitive decline.
SEQUEL’s top-line results with Elayta
START’s launch comes on the heels of an announcement of positive top-line data from the completed Phase 2 pilot trial, dubbed SEQUEL (NCT04735536), that tested Elayta against a placebo in 16 adults with mild to moderate Alzheimer’s. The study was conducted at a single site in the Netherlands.
Using a crossover design, the participants were randomly assigned to receive 300 mg of Elayta or a placebo, once daily for four weeks, before being switched to the opposing regimen for another four weeks.
The results, detailed in a company webcast, showed Elayta was generally safe and tolerated well, with no reports of severe or serious side effects and none that led to the treatment being discontinued or to death.
It was also associated with positive effects on brain wave activity, as assessed with an electroencephalogram (EEG). During the treatment phase, participants showed a reduction in theta waves dominance over others — a hallmark of Alzheimer’s — while the placebo phase was linked to an increase in theta wave dominance.
Dominance of alpha waves, which is usually seen in healthy brains, showed opposing trends, increasing with Elayta and reducing with a placebo.
Theta and alpha wave differences between Elayta and placebo phases failed to reach statistical significance, however.
Reductions in theta wave dominance were seen in all evaluated brain regions, with a statistically significant change in the central region.
Also, a detailed EEG data analysis showed Elayta significantly improved connectivity between brain regions, which is critical to cognition. This suggested “the brain’s ability to communicate and exchange information between regions can be rescued by CT1812,” according to the webcast.
“These data really demonstrated that CT1812 has an impact on brain activity in these individuals with mild to moderate Alzheimer’s disease,” Anthony Caggiano, MD, PhD, chief medical officer and head of R&D at Cognition, said in the webcast.
Goals of Phase 2 START study
The Phase 2 START Study will enroll adults with mild cognitive impairment due to Alzheimer’s or mild Alzheimer’s dementia who have elevated beta-amyloid. They will be randomly assigned to one of two Elayta doses (100, 200 mg) or a placebo for 18 months, or about 1.5 years.
Its main goal is to evaluate changes in the Clinical Dementia Rating Scale Sum of Boxes scale, which assesses memory, orientation, judgment and problem-solving, community affairs, home and hobbies, and personal care.
Secondary goals include changes in the Alzheimer’s Disease Assessment Scale-Cognition and the Alzheimer’s Disease Cooperative Study-Activities of Daily Living Scale. Beta-amyloid levels in the cerebrospinal fluid, the liquid surrounding the brain and spinal cord, will be measured, along with brain structure changes through MRI scans.
START is being conducted with the Alzheimer’s Clinical Trials Consortium (ACTC) and the support of a $81 million grant from the National Institutes of Health’s National Institute on Aging (NIA), which also funds the ACTC.
“While trials in this patient population are crucial, the long treatment period required to show a change in cognition can be overly burdensome for small biotechnology companies,” Ricciardi said. “Without the support of the ACTC and the NIA’s $81 million grant, we would likely not be in a position to offer these research participants the opportunity to test an oral once daily medication that may slow the progression of Alzheimer’s disease.”
Elayta is also being tested in people with mild to moderate Alzheimer’s disease in the proof-of-concept Phase 2 SHINE trial (NCT03507790). The study is evaluating its safety, tolerability, and impact on clinical biomarkers against a placebo for about six months in up to 144 patients. Recruitment is ongoing in the U.S. and Europe.
According to Cognition, more than 200 healthy volunteers and adults with Alzheimer’s or dementia with Lewy bodies have received oral Elayta in early studies so far, with a consistent tolerability profile. A mild, temporary rise in liver enzymes was observed with Elayta, the only sign of mild liver injury among all the liver tests.