A Randomized, Double‐blind, Sham‐controlled, Adaptive‐Design Pivotal Trial of Sensory Stimulation in Subjects with Alzheimer’s Disease

Abstract

AbstractBackgroundIn three prospective clinical trials (Overture: NCT03556280, Etude: NCT03661034, Flicker: NCT03543878) non‐invasive, visual and auditory gamma (40 Hz) sensory stimulation diminished Alzheimer’s disease (AD) symptoms, including a reduction in decline in cognitive and functional symptoms. These trials initiated the design of the Cognito Therapeutics sponsored Hope pivotal trial which examines the safety and efficacy of Cognito Therapeutics’ Sensory Stimulation System.MethodThe US‐based multicenter Hope trial will randomize (1:1) approximately 500 subjects aged 50 and older diagnosed with mild to moderate AD (MMSE 15‐26) and will stratify them to active and sham in a blinded manner across MMSE score ranges: 15‐20 and 21‐26. Subjects in both study arms will self‐administer therapy via the Sensory Stimulation System for 60 minutes daily for 12 months. An interim analysis will employ the promising zone methodology, allowing the sample size to be adjusted if the effect is trending toward success, but additional subjects are needed to maintain greater than 80% power.ResultThe primary outcome measure will be the Alzheimer’s Disease Cooperative Study – Activities of Daily Living (ADCS‐ADL) test. Changes in function and cognition will be evaluated using a combined statistical test for ADCS‐ADL and the Mini Mental State Exam (MMSE). The key secondary outcome is change in cognition using the MMSE. Other clinical efficacy assessments include instrumental activities of daily living (IADL), Zarit Burden Index (ZBI), the Clinical Dementia Rating Scale (CDR) and The Neuropsychiatric Inventory anxiety subscale (NPI – Anxiety). Key biomarker assessments include whole brain, white matter, and hippocampal volume and occipital cortical thickness. Sleep fragmentation will be assessed in a subgroup of subjects using actigraphy. Exploratory measures will include additional brain structural change, plasma biomarkers, EEG assessed coherence, and at‐home tablet‐based tasks. Safety will be evaluated via routine clinical laboratory assessments, review of adverse events, concurrent medication use, physical and neurological exams, vital signs, MRI, and a suicidality scale.ConclusionThe Hope pivotal trial is designed to demonstrate the efficacy and safety of daily in‐home gamma sensory stimulation in AD patients to support a regulatory filing with the FDA.