A new study will combine an Alzheimer's medication that slows disease progression in some patients with two other drugs to see if their effects can be amplified. The trial will be the first to test drugs acting on two disease-driving proteins, amyloid and tau, for patients with late-onset Alzheimer's, the most common type of dementia.
The trial will recruit 900 participants with early Alzheimer's at UC San Francisco and other sites nationwide. It is funded by a grant from the National Institute on Aging, part of the National Institutes of Health. It is awarded to Adam Boxer, MD, PhD, principal investigator and project leader of the trial, and endowed professor in memory and aging in the Department of Neurology at UC San Francisco. It is co-led by Keith Johnson, MD, professor of radiology and neurology at the Harvard Medical school.
In the trial, known as the Alzheimer's Tau Platform (ATP), researchers will evaluate the effects of two anti-tau therapies and an anti-amyloid therapy like lecanemab (Leqembi), which was approved in January 2023 after demonstrating a 27% reduction in global impairment compared with placebo.
Lecanemab and related drugs clear amyloid and have also been shown to reduce tau. But drugs that specifically target tau may be more effective since their levels and locations correlate more closely with symptoms.
Multiple meds may create synergistic effect
The ATP trial represents the next era in Alzheimer's treatment developments, since it will use a combination of therapies that may have additive or synergistic effects. In addition to potentially better clinical results, this treatment approach is constructed on a novel, more efficient clinical trial design."
Adam Boxer, MD, PhD, director of the UCSF Alzheimer's Disease and Frontotemporal Dementia Clinical Trials Program and director of the Neurosciences Clinical Research Unit
Final details of the trial are pending, but researchers will likely recruit participants aged 60 or older with asymptomatic Alzheimer's or mild cognitive impairment, confirmed by tau blood tests, PET scans and cognitive testing.
Trial may exclude placebo, due to ethical considerations
Participants will be divided into multiple parallel groups and randomized to receive a combination of the anti-amyloid medication with or without one or two of the tau medications for a duration of 24 months. It is not yet known whether a small subgroup will receive placebo, with some researchers questioning if its use is ethical in this population.
The study concludes with cognitive testing, brain imaging and blood levels of tau and related proteins.
The trial is expected to save up to 50% in costs because it replaces multiple trials testing each tau therapy alone followed by combination trials, and it requires substantially fewer participants, said Boxer, who is also affiliated with the UCSF Weill Institute for Neurosciences.
Eventually other drugs may be added to the "rolling platform" format of the trial, said Boxer. These include those that target other disease drivers, such as metabolic dysfunction or inflammation. It is believed that trials such as this one will lead to "clinically meaningful advances at a much faster rate than in the past," he said.
The ATP trial follows a smaller study using lecanemab and a tau drug for a genetic variant of early-onset Alzheimer's.
For more information about participating in the study, contact the Alzheimer's Clinical Trials Consortium in early-to-mid 2024.
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