HOPE4MCI trial: First trial targeting reduction of hippocampal overactivity to treat mild cognitive impairment due to Alzheimer's disease with AGB101: Human/Human trials: Other. (7th December 2020) - Rosenzweig‐Lipson, Sharon
Abstract: Background: Evidence from preclinical models and human patients demonstrates that neuronal circuits become hyperactive in prodromal AD contributing to the accumulation of Alzheimer's pathology and subsequent cognitive decline. Such data support the hypothesis that neural overactivity in the medial temporal lobe/hippocampus is a critical driver of AD neuropathology, including the deposition of amyloid and spread of tau along connectional pathways. AGB101 (low dose levetiracetam) demonstrates efficacy on a range of molecular, synaptic, electrophysiological, functional and behavioral endpoints across models and species. In a Phase 2 study measuring hippocampal activity during a pattern separation memory test in patients with aMCI, AGB101 normalized hippocampal activity and improved performance on this specific memory assessment of hippocampal function. The HOPE4MCI trial is investigating the effects of AGB101 (220 mg) vs placebo in patients with MCI due to AD. The objective of the study is to assess the efficacy of AGB101 (low‐dose levetiracetam, 220 mg, extended release tablet) compared to placebo in subjects with mild cognitive impairment (MCI) due to Alzheimer's disease (AD) using Clinical Dementia Rating‐Sum of Boxes (CDR‐SB) scores as the sole primary outcome. A substudy will evaluate levels of tau protein in the brain using tau PET ([18F]MK‐6240) at baseline and end of protocol. Method: This is a multicenter, randomized, double‐blind, placebo‐controlled, 78‐week, fixed‐dose study evaluating AGB101 versus placebo as a treatment for slowing the progression of MCI due to AD. Inclusion criteria: Subjects must meet the following inclusion criteria at screening: 1) Subjects between 55 and 85 years old; 2) Have MCI due to AD consistent with the NIA‐AA criteria: MMSE (24‐30); CDR (0.5); Impaired delayed recall on the ISLT; essentially preserved ADLs' 3) Evidence of an amyloid‐positive PET scan Result: The HOPE4MCI trial is currently underway. Sites are currently enrolling in the US and Canada with plans to expand to Europe. Up to date subject demographics, screen failure information, safety and dropout information will be presented at the meeting. Conclusion: HOPE4MCI represents the first and only Phase 3 clinical trial targeting the reduction of hippocampal overactivity for slowing the progression of MCI due to AD.