First Patient Joins Tau NexGen Study in Early-onset Alzheimer’s
A first patient has joined the Tau NexGen study that will test two antibodies in combination — targeting both amyloid and tau proteins — as a potential treatment for early-onset Alzheimer’s disease caused by genetic mutations, according to a press release.
Tau NexGen is a newly added arm of a Phase 2/3 platform trial, called DIAN-TU001 (NCT01760005), which is led by the Dominantly Inherited Alzheimer Network Trials Unit (DIAN-TU), a network of researchers working around dominantly inherited Alzheimer’s disease (DIAD), a rare disease form that causes memory loss and dementia, typically in people between the ages of 30 and 60.
Platform trials allow for the “simultaneous testing of multiple treatments in parallel from industry partners to enable trial efficiencies, such as pooled placebo groups,” DIAN-TU said on a Washington University School of Medicine webpage. The St. Louis, Missouri, university launched the network in 2021 and the trial arm’s first patient was enrolled there.
Tau NexGen is enrolling DIAD patients and people at known risk for dominantly inherited Alzheimer’s to test the antibodies, lecanemab and E2814, which are both part of Eisai.
An update about the trial arm is not yet posted on DIAN-TU001’s clinical trials website, Eisai wrote in an email to Alzheimer’s News Today, but one is expected. Contact information can be found here. Trial sites and information on patient eligibility will be released with the update.
DIAN-TU001 opened in late 2012 to test gantenerumab and solanezumab in people with Alzheimer’s due to inherited mutations in what is now its initial trial arm, with listed sites in the U.S., Australia, Canada, Europe, South America, and the U.K.
E2814, an antibody developed by Eisai in collaboration with University College London, is designed to bind to and prevent tau “seeds” from traveling from one brain region to another, a process that helps the protein accumulate to toxic levels as tangles in Alzheimer’s.
DIAN-TU added the antibody lecanemab to the trial amid growing clinical evidence that targeting amyloid — another protein that accumulates as plaques in the brain of people with Alzheimer’s — can ease disease biomarkers. Lecanemab is designed to bind to amyloid so it can be cleared by the immune system before it forms clumps.
The goal of the Tau NexGen study is to evaluate the safety, tolerability, and efficacy of the investigational therapies, based on biomarkers and cognitive measures, in people who know they have an Alzheimer’s disease-causing mutation, and are with or without symptoms.
Lecanemab, developed by Eisai in collaboration with Biogen, will serve as the background therapy. This means that patients with symptoms will be given lecanemab for six months before being randomly assigned to receive E2814 or a placebo.
Since accumulation of amyloid plaques precedes tau tangles in Alzheimer’s, this type of study design allows the researchers to assess whether targeting amyloid provides an opportunity for E2814 to work best, Eisai said in its release.
In turn, patients who do not yet have symptoms will be randomly assigned to either E2814 or a placebo for one year before starting on lecanemab. This approach allows the researchers to also study the effects of E2814 alone.
The trial’s primary endpoint, or goal, is to slow tau accumulation in the brains of symptomatic patients. The secondary endpoint will be to evaluate the therapies’ effect on the levels of a type of tau (phosphorylated tau 217) in the cerebrospinal fluid — the liquid that surrounds the brain and spinal cord — of presymptomatic patients.
If the results of the trial’s primary and secondary endpoints are positive in analyses after two years of treatment, the study will be extended for two more years. This extension will let researchers test how well E2814 works in slowing cognitive decline, and its other effects on tau.
Lecanemab was granted fast track status by the U.S. Food and Drug Administration earlier this year as a potential Alzheimer’s treatment.