Quest for Alzheimer Disease Treatments Continues
The quest for effective treatment of Alzheimer disease (AD) continues as phase 2B and 3 clinical trials meet major milestones.
Enrollment is complete for a trial of once-daily low dose of the antiseizure medication levetiracetam (AGB101; AgeneBio, Baltimore, MD) for treatment of amnestic mild cognitive impairment (MCI) due to AD. The clinical trial HOPE4MCI (NCT03486938), is a 78-week study randomized double-blind placebo-controlled study that has enrolled 164 participants. The HOPE4MCI study builds on an earlier trial that demonstrated the efficacy of levetiracetam to reduce hippocampal overactivity and improve episodic memory.
The HOPE4MCI trial also includes a sub-study of brain PET imaging to track measures of neurodegeneration (structural MRI, Tau PET). The use of [18F]MK-6240 scanning for tau, developed by Cerveau Technologies, together with a structural brain analysis developed in collaboration with the Johns Hopkins Center for Imaging Science and Bioclinica, will trace the spread of pathology over the length of the clinical protocol and its potential modification by therapeutic treatment.
A phase 3 trial (NCT03887455) of lecanemab, a monoclonal antibody to soluble amyloid ß (Aß) fibrils, for treatment of early symptomatic AD also reached full enrollment with 1,795 participants. The study is a placebo-controlled double-blind parallel-group 18-month study with an open-label extension phase designed to confirm safety and efficacy of lecanemab in subjects with early AD. Earlier studies have shown that lecanamab reduced brain Aß and clinical decline in early AD at the highest doses.
A study (NCT03446001) of hydromethyl methionine (LMTM)(TRx0237; IPS Research Company, Oklahoma City, OK), also known as methylene blue, has completed the random assignment phase. This trial is the only late-stage clinical trial specifically targeting the tau pathology seen in AD. LMTM has been tested in over 2000 participants in a total of 3 previous phase 3 trials in mild and moderate AD, and behavioral variant frontotemporal dementia.