The Phase 2, Randomized, Placebo-controlled PRECEDENT Trial of SAGE-718 in Patients With Parkinson's Disease Cognitive Impairment: Clinical Trial in Progress
Amy Bullock1, Aaron Koenig1, Katrina Paumier1, Emily Freitag1, Jeffrey Wald1, Sola Park1, Michael Quirk1, Jennifer Petrillo Billet1, James Doherty1
1Sage Therapeutics, Inc.
Objective:
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).
Background:
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.
Design/Methods:
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.
Results:
PRECEDENT is currently enrolling at sites in the United States.
Conclusions:
PRECEDENT is designed to evaluate the efficacy, safety, and tolerability of SAGE-718 in patients with cognitive impairment due to PD.