A Study to Evaluate the Effects of SAGE-718 in Participants With Parkinson's Disease Cognitive Impairment

Phase 2

Completed

• Conditions: Parkinson Disease; Cognitive Dysfunction
• Interventions: Drug: SAGE-718-matching placebo; Drug: SAGE-718

• Registration Number: NCT05318937
• Lead Sponsor: Sage Therapeutics

Brief Summary

The primary purpose of this study is to evaluate the effect of SAGE-718 on cognitive performance in participants with Parkinson's disease mild cognitive impairment (PD-MCI).

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2022-04-01
• Study First Submitted QC: 2022-04-01
• Study First Posted: 2022-04-08
• Study Start: 2022-06-06
• Primary Completion: 2024-01-17
• Study Completion: 2024-02-23
• Status Verified: 2025-01
• Results First Submitted: 2025-01-15
• Results First Submitted QC: 2025-01-15
• Last Update Submitted: 2025-01-15
• Results First Posted: 2025-02-06
• Last Update Posted: 2025-02-06

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 86

Inclusion Criteria

1. Meet the following criteria for PD-MCI: Have a confirmed diagnosis of idiopathic Parkinson's disease (PD) according to 2015 Movement Disorder Society (MDS) clinical diagnostic criteria and meet MDS Task Force criteria for MCI in PD (excluding requirement for United Kingdom PD Brain Bank diagnostic criteria).
2. Meet the following criteria for Montreal Cognitive Assessment (MoCA): For participants meeting Level 1 PD-MCI criteria, have a MoCA score of 20 to 25 (inclusive) at Screening; For participants meeting Level 2 PD-MCI criteria (within the past year), have a MoCA score of 18 to 25 (inclusive) at Screening.
3. Meet criteria for modified Hoehn & Yahr Stage I to III (mild to moderate motor severity) at Screening.
4. Have stable motor symptoms for at least 4 weeks prior to Screening, in the opinion of the investigator.
5. Must be able to complete the Color Trails Test 1 (including the ability to follow rater redirection and correct errors), and, based on participant's performance and investigator's opinion, participant is expected to be capable of engaging in prolonged cognitive testing for the duration of the study.

Exclusion Criteria

1. Have a diagnosis of dementia of any etiology, including but not limited to: Dementia with Lewy bodies, Alzheimer's dementia, and vascular dementia.
2. Have any parkinsonism other than PD, including secondary parkinsonism or atypical parkinsonism.
3. In the opinion of the investigator, be experiencing fluctuations in motor symptoms associated with PD that will interfere with completing study procedures.
4. Have an ongoing central nervous system condition other than PD that in the opinion of the investigator could influence the outcome of the study.
5. Have experienced significant psychotic symptoms, including hallucinations or delusions, within the past 3 months, in the opinion of the investigator.
6. Have a history of brain surgery, deep brain stimulation, or any history of hospitalization due to a brain injury.
7. Have a history, presence, and/or current evidence clinically relevant intracranial abnormality (e.g., stroke, hemorrhage, space-occupying lesion).

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	SAGE-718-matching placebo	Participants received SAGE-718-matching placebo, oral capsules, once daily (QD), in the morning for 42 days.
SAGE-718	SAGE-718	Participants received SAGE-718, 1.2 milligrams (mg), oral capsules, QD in the morning for 42 days.

Primary Outcome Measures

Name	Time	Method
Change From Baseline in the Wechsler Adult Intelligence Scale-IV (WAIS-IV) Coding Test Score	Baseline, Day 42	The WAIS-IV coding test is a valid and sensitive measure of cognitive dysfunction that correlates with real-world functional outcomes (e.g., the ability to accomplish everyday tasks) and recovery from functional disability used to assess processing speed. The participant is required to identify the symbols matched to numbers using a key and write in the symbol beneath the associated number. The total score ranges from 0 to 135 and is based on the total number of codes correctly completed over a 120-second time limit. Higher scores indicate better processing speed. Positive change from baseline indicates better processing speed. Least Squares (LS) Means were calculated using a mixed-effects model for repeated measures (MMRM) approach.

Secondary Outcome Measures

Name	Time	Method
Number of Participants With at Least One Treatment-emergent Adverse Event (TEAE)	Up to Day 70	An adverse event (AE) was defined as any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom or disease temporally associated with the use of a medicinal (investigational) product whether or not related to the medicinal (investigational) product. A TEAE is defined as any AE on or after the first dose of IP or any worsening of a pre-existing medical condition/AE with onset after the start of IP and throughout the study.
Number of Participants With at Least One TEAE by Severity	Up to Day 70	A TEAE is defined as any AE on or after the first dose of IP or any worsening of a pre-existing medical condition/AE with onset after the start of IP and throughout the study. Severity was assessed as: * Mild: symptoms barely noticeable to participant or does not make participant uncomfortable; does not influence performance or functioning; prescription drug not ordinarily needed for relief of symptoms; * Moderate: symptoms of a sufficient severity to make participant uncomfortable; performance of daily activity is influenced; participant is able to continue in study; treatment for symptoms may be needed; * Severe: symptoms cause severe discomfort; symptoms cause incapacitation or significant impact on participant's daily life; severity may cause cessation of treatment with IP; treatment for symptoms may be given and/or participant hospitalized.; Participant with multiple instances of events is counted only once using maximum intensity.
Number of Participants Who Withdrew From Study Due to TEAEs	Up to Day 70	An AE was defined as any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom or disease temporally associated with the use of a medicinal (investigational) product whether or not related to the medicinal (investigational) product. A TEAE is defined as any AE on or after the first dose of IP or any worsening of a pre-existing medical condition/AE with onset after the start of IP and throughout the study.

Trial Locations

Locations (1)

Sage Investigational Site; 🇺🇸 Madison, Wisconsin, United States