The Phase 2, Randomized, Placebo-controlled PRECEDENT Trial of SAGE-718 in Patients With Parkinson's Disease Cognitive Impairment: Clinical Trial in Progress (P2-11.005)

Abstract

<h3>Objective:</h3> The randomized, placebo-controlled PRECEDENT Study is designed to evaluate the efficacy, safety, and tolerability of SAGE-718 as a potential treatment for cognitive impairment due to Parkinson’s disease (PD). <h3>Background:</h3> PD is a multisystem disorder with diverse clinical features, including neuropsychiatric symptoms and non-motor manifestations alongside motor symptomatology. Cognitive impairment, a common non-motor symptom of PD, contributes to poor functional outcomes, loss of independence, and increased risk of dementia. A significant unmet need exists for effective and well-tolerated pharmacotherapies that address cognitive impairment due to PD. Positive modulation of NMDA receptors may improve cognitive deficits. SAGE-718, an investigational NMDA receptor positive allosteric modulator, has been associated with improved cognitive performance in patients with PD and other neurodegenerative diseases. <h3>Design/Methods:</h3> PRECEDENT (NCT05318937) is a Phase 2, randomized, double-blind, placebo-controlled trial that includes a 3-week screening period, a 1-week baseline period, a 6-week treatment period, and a 4-week follow-up period. Approximately 76 patients aged 50–75 years meeting Movement Disorder Society Task Force Criteria for PD Mild Cognitive Impairment with mild-to-moderate motor involvement will be randomized 1:1 to receive either SAGE-718 or placebo once daily for 42 days. The primary endpoint is change from baseline in the Wechsler Adult Intelligence Scale-IV Coding score (a measure of executive functioning) at Day 42. Secondary endpoints include the proportion of patients with treatment-emergent adverse events (TEAEs), severity of TEAEs, and number of patients who withdraw from the study due to TEAEs. Other endpoints include additional assessments of cognitive performance, safety/tolerability, motor symptoms, functioning, and pharmacokinetics. <h3>Results:</h3> PRECEDENT is currently enrolling at sites in the United States. <h3>Conclusions:</h3> PRECEDENT is designed to evaluate the efficacy, safety, and tolerability of SAGE-718 in patients with cognitive impairment due to PD. <b>Disclosure:</b> Dr. Bullock has received personal compensation for serving as an employee of Sage Therapeutics, Inc. . Dr. Bullock has stock in Sage Therapeutics, Inc. Aaron Koenig has received personal compensation for serving as an employee of Sage Therapeutics. Dr. Paumier has nothing to disclose. Ms. Freitag has nothing to disclose. Jeffrey Wald has received personal compensation for serving as an employee of Sage Therapeutics. Jeffrey Wald has received stock or an ownership interest from Sage Thereapeutics. Dr. Park has nothing to disclose. Michael Quirk has received personal compensation for serving as an employee of Sage Therapeutics. Michael Quirk has received stock or an ownership interest from Sage Therapeutics. Jennifer Petrillo, 14951 has received personal compensation for serving as an employee of Sage Therapeutics. Jennifer Petrillo, 14951 has received stock or an ownership interest from Sage Therapeutics. Dr. Doherty has received personal compensation for serving as an employee of Sage Therapeutics. Dr. Doherty has received stock or an ownership interest from Sage Therapeutics.