A Randomized, Double-blind, Placebo-Controlled, Parallel-Group, Phase II Study to Evaluate the Safety and Efficacy of CT1812 in Subjects with Mild to Moderate Alzheimerʼs Disease

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ABSTRACT. Soluble oligomers of beta amyloid (Aβ) protein are the most potent neuroactive structural form of this protein and evidence suggests they cause the synaptotoxic changes resulting in cognitive decline in Alzheimer's disease (AD) (Selkoe and Hardy 2016, Viola and Klein 2015). Cognition Therapeutics, Inc. (CogRx) is developing CT1812, the first brain penetrant small molecule that selectively clears toxic oligomers from the brain into the cerebrospinal fluid (CSF). This drug candidate displaces AβOs bound to neuronal receptors at synapses and protects synapses from toxic oligomer effects. When administered once daily for 28 days to mild to moderate AD patients, CT1812 significantly reduces concentrations of synaptic degeneration markers in AD patient CSF, and phospho-tau. CT1812's mechanism of action can potentially halt or slow cognitive decline, significantly alleviating the suffering of AD patients. An ongoing study COG0201 (SHINE) funded by the NIA under the award AG058660 is evaluating the safety and efficacy of two doses of CT1812 on cognitive function in a Phase 2 randomized, double-blind, placebo-controlled parallel group clinical trial in mild to moderate AD patients. This important proof of concept trial will be critical for CT1812's continued development. Excellent progress has been made on this study and award. Study COG0201 is proceeding well at nine clinical research sites across the US and Australia. Regulatory interactions have resulted in changes to the study design which have increased per patient costs; this competing revision application requests additional funds to enroll sufficient patients and reach the appropriate number of patients per group and adequately measure changes in cognitive function (N=48/group) and complete a fully powered trial (revised AIM 1). Adequately powered assessment of clinical outcomes is vital to CT1812's further development. Completion of this study in AD patients will inform the design and methods of the subsequent disease modification Phase III trials with CT1812. Advancement of CT1812 clinical development would substantially improve the lives of the 50 million people worldwide suffering from AD, for whom no disease-modifying pharmacological treatments exist.