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NCT05619692

A Study to Evaluate the Effects of SAGE-718 in Participants With Mild Cognitive Impairment or Mild Dementia Due to Alzheimer's Disease (AD)

Completed Phase 2 Results posted Last updated 15 September 2025
What this trial tests

Phase 2 trial testing SAGE-718 in Mild Cognitive Impairment in 174 participants. Completed in 9 July 2024.

Timeline
29 November 2022
Primary endpoint
5 June 2024
9 July 2024

Quick facts

Lead sponsorSupernus Pharmaceuticals, Inc.
PhasePhase 2
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingquadruple
Primary purposetreatment
Enrollment174
Start date29 November 2022
Primary completion5 June 2024
Estimated completion9 July 2024
Sites39 locations across Puerto Rico, United States

Drugs / interventions tested

Conditions studied

Sponsor

Supernus Pharmaceuticals, Inc. — full company profile →

Who can join

Adults 50 to 80, any sex, with Mild Cognitive Impairment or Mild Dementia. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Change From Baseline in the Wechsler Adult Intelligence Scale-IV (WAIS-IV) Coding Test Score Primary · Baseline, Day 84

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 baselin

GroupValue95% CI
Placebo3.8± 0.77
SAGE-7185.3± 0.79
Number of Participants With at Least One Treatment-Emergent Adverse Event (TEAE) Secondary · Up to Day 112

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

GroupValue95% CI
Placebo50
SAGE-71842
Number of Participants With at Least One TEAE by Severity Secondary · Up to Day 112

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 ma

Mild
GroupValue95% CI
Placebo29
SAGE-71820
Moderate
GroupValue95% CI
Placebo19
SAGE-71820
Severe
GroupValue95% CI
Placebo2
SAGE-7182
Number of Participants Who Withdrew From Study Due to TEAEs Secondary · Up to Day 112

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 conditi

GroupValue95% CI
Placebo2
SAGE-7182

Adverse events — posted to ClinicalTrials.gov

Time frame: Up to Day 112. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Placebo
Serious: 5/86 (6%)
Deaths: 1/86
SAGE-718
Serious: 4/84 (5%)
Deaths: 0/84

Serious adverse events (11 terms)

ReactionSystemPlaceboSAGE-718
Prostate cancer recurrentNeoplasms benign, malignant and unspecified (incl cysts and polyps)
Squamous cell carcinomaNeoplasms benign, malignant and unspecified (incl cysts and polyps)
Squamous cell carcinoma of the tongueNeoplasms benign, malignant and unspecified (incl cysts and polyps)
FallInjury, poisoning and procedural complications
Femoral neck fractureInjury, poisoning and procedural complications
Hip fractureInjury, poisoning and procedural complications
Upper limb fractureInjury, poisoning and procedural complications
Atrial fibrillationCardiac disorders
CellulitisInfections and infestations
Carotid artery stenosisNervous system disorders
Completed suicidePsychiatric disorders
Other adverse events (3 terms — click to expand)

ReactionSystemPlaceboSAGE-718
HeadacheNervous system disorders
Upper respiratory tract infectionRespiratory, thoracic and mediastinal disorders
DizzinessNervous system disorders

Most-reported serious reactions: Prostate cancer recurrent, Squamous cell carcinoma, Squamous cell carcinoma of the tongue, Fall, Femoral neck fracture, Hip fracture, Upper limb fracture, Atrial fibrillation.

Data from ClinicalTrials.gov NCT05619692 adverse events section.

Sponsor's own description

The primary purpose of this study is to evaluate the effect of SAGE-718 on cognitive performance in participants with Alzheimer's Disease.

Publications & conference data

6 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Alzheimer's disease drug development pipeline: 2023.
    Cummings J, Zhou Y, Lee G, Zhong K, et al · · 2023 · cited 326× · PMID 37251912 · DOI 10.1002/trc2.12385
  2. Alzheimer's disease drug development pipeline: 2024.
    Cummings J, Zhou Y, Lee G, Zhong K, et al · · 2024 · cited 209× · PMID 38659717 · DOI 10.1002/trc2.12465
  3. Alzheimer's Disease: Novel Targets and Investigational Drugs for Disease Modification.
    Cummings JL, Osse AML, Kinney JW. · · 2023 · cited 75× · PMID 37728864 · DOI 10.1007/s40265-023-01938-w
  4. GluN2B-containing NMDARs in the mammalian brain: pharmacology, physiology, and pathology.
    Ge Y, Wang YT. · · 2023 · cited 29× · PMID 37324591 · DOI 10.3389/fnmol.2023.1190324
  5. Recent advancements in the therapeutic approaches for Alzheimer's disease treatment: current and future perspective.
    Sharma A, Rudrawar S, Bharate SB, Jadhav HR. · · 2025 · cited 14× · PMID 39790124 · DOI 10.1039/d4md00630e
  6. Mechanisms of Transsynaptic Degeneration in the Aging Brain.
    Wall RV, Basavarajappa D, Klistoner A, Graham S, et al · · 2024 · cited 7× · PMID 39191395 · DOI 10.14336/ad.2024.03019

Verify or expand the search:

Other trials of SAGE-718

Trials testing the same drug.

Other recruiting trials for Mild Cognitive Impairment

Currently open trials in the same condition.

Other Supernus Pharmaceuticals, Inc. trials

Trials by the same sponsor.

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Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing