Study to Evaluate the Safety, Tolerability and Efficacy of CT1812 in Subjects With Mild to Moderate Dementia With Lewy Bodies (COG1201)

A Randomized, Double-blind, Placebo-controlled, Phase 2, 6-month Study to Evaluate the Safety, Tolerability and Exploratory Efficacy of CT1812 in Subjects With Mild to Moderate Dementia With Lewy Bodies

Multi-center, randomized, double-blind, placebo-controlled, 6- month study in subjects with mild to moderate Dementia with Lewy Bodies.

Study Overview

• Status: Completed
• Conditions: Dementia With Lewy Bodies
• Intervention / Treatment: Drug: CT1812

Detailed Description

The safety and efficacy of CT1812 at doses of 300 and 100mg will be evaluated over a 24 week double-blind treatment period in patient diagnosed with dementia with Lewy bodies.

Patients will be randomized 1:1:1 to placebo, 100mg CT1812 or 300mg CT1812. Oral CT1812 will be taken daily. Subjects meeting eligibility requirement and signing informed consent will be assessed by repeated psychometric/neurologic testing, safety procedures and PK and PD sample collection at defined intervals throughout the study. Plasma and CSF biomarkers will also be followed.

• Study Type: Interventional
• Enrollment (Actual): 130
• Phase: Phase 2

Expanded Access

No longer available outside the clinical trial. See expanded access record.

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85013
      • Barrow Neurological Institute
    • Sun City, Arizona, United States, 85351
      • Banner Sun Health Research Institute
    • Tucson, Arizona, United States, 85724
      • University of Arizona - Health Sciences Center
  • California
    • Palo Alto, California, United States, 94304
      • Stanford University
    • Santa Monica, California, United States, 90404
      • Pacific Neuroscience Institute
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado
    • Englewood, Colorado, United States, 80113
      • CenExel Rocky Mountain Clinical Research, LLC
  • Connecticut
    • Stamford, Connecticut, United States, 06905
      • New England Institute for Neurology and Headache (NEINH)
  • Florida
    • Atlantis, Florida, United States, 33462
      • JEM Research Institute
    • Boca Raton, Florida, United States, 33486
      • Parkinson's Disease and Movement Disorders Center of Boca Raton
    • Boca Raton, Florida, United States, 33433
      • University of Miami Miller School of Medicine Comprehensive Center for Brain Health
    • Lady Lake, Florida, United States, 32156
      • Charter Research
    • Ocala, Florida, United States, 34770
      • Renstar Medical Research
    • Winter Park, Florida, United States, 32792
      • Charter Research
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Rush University Medical Center Section of Parkinson Disease and Movement Disorder
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • IU Health Neuroscience Center, Goodman Hall
    • Indianapolis, Indiana, United States, 46256
      • Josephson Wallack Munshower Neurology, P.C
  • Kansas
    • Fairway, Kansas, United States, 66205
      • The University of Kansas Alzheimer's Disease Research Center
  • Kentucky
    • Lexington, Kentucky, United States, 40504
      • University Of Kentucky
  • Massachusetts
    • Plymouth, Massachusetts, United States, 02360
      • Headlands Research Eastern Massachusetts, LLC
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
  • New York
    • New York, New York, United States, 10032
      • Columbia University
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • UNC Department of Neurology
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Main Campus
    • Columbus, Ohio, United States, 43210
      • Ohio State University
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health and Science University
    • Portland, Oregon, United States, 97210
      • Summit Headlands, LLC
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • University of Pennsylvania
  • Texas
    • Dallas, Texas, United States, 75390
      • University of Texas Southwestern
    • Houston, Texas, United States, 77074
      • Clinical Trial Network
  • Virginia
    • Charlottesville, Virginia, United States, 22903
      • University of Virginia Adult Neurology
    • Richmond, Virginia, United States, 23298
      • Virginia Commonwealth University
  • Washington
    • Kirkland, Washington, United States, 98034
      • Evergreen Health Research
    • Seattle, Washington, United States, 98104
      • Universtiy of Washington Department of Neurology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Men or women 50-85 years of age (inclusive), meeting criteria for probable Dementia with Lewy Bodies (DLB).
• MRI, or CT scan due to contraindication of MRI if approved by medical monitor) obtained during screening consistent with the clinical diagnosis of DLB and without findings of significant exclusionary abnormalities. An historical MRI (or CT scan), up to 1 year prior to screening, may be used if there is no history of intervening neurologic disease or clinical events (such as a stroke, head trauma etc.) and the subject is without clinical symptoms or signs suggestive of such intervening events.
• MMSE 18-27 inclusive

Exclusion Criteria:

• Any neurological condition that may be contributing to cognitive impairment above and beyond those caused by the subject's DLB, including any co-morbidities detected by clinical assessment or MRI (or CT scan due to contraindication of MRI, if approved by medical monitor)
• Screening MRI (or historical MRI or CT scan due to contraindication of MRI if approved by medical monitor) or historical MRI/CT scan, if applicable. of the brain indicative of significant abnormality, including, but not limited to, prior hemorrhage or infarct > 1 cm3, >3 lacunar infarcts, cerebral contusion, encephalomalacia, aneurysm, vascular malformation, subdural hematoma, hydrocephalus, space-occupying lesion (e.g. abscess or brain tumor such as meningioma). If a small incidental meningioma is observed, the medical monitor may be contacted to discuss eligibility.

• Clinical, laboratory findings or medical history consistent with:

  1. Other primary degenerative dementia (fronto-temporal dementia, Huntington's disease, Creutzfeldt-Jakob Disease, Down syndrome, etc.).
  2. Other neurodegenerative condition (amyotrophic lateral sclerosis, etc.).
  3. Seizure disorder.
  4. Other infectious, metabolic or systemic diseases affecting the central nervous system (syphilis, present hypothyroidism, present vitamin B12 or folate deficiency, other laboratory values etc.).
• Any major psychiatric diagnosis, including schizophrenia, bipolar disorder, and current major depressive disorder as per Diagnostic and Statistical Manual of Mental Disorders Fifth Edition
• Clinically significant, advanced or unstable disease that may interfere with outcome evaluations.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: CT1812; Orally administered CT1812
Active Comparator: CT1812 300 mg	Drug: CT1812; Orally administered CT1812
Active Comparator: CT1812 100 mg	Drug: CT1812; Orally administered CT1812

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Study Participants With at Least One Mild, Moderate, or Severe Treatment Emergent Adverse Events (TEAEs)	All adverse events (AE) summaries were restricted to TEAEs, which were defined as those AEs that occurred on or after the date of first dose and those existing AEs that worsened during the study. If it could not be determined whether the AE was treatment-emergent due to a partial onset date, then it was counted as such. Verbatim terms were mapped to System Organ Class (SOC) and preferred terms using MedDRA version 24.1.	Up to 210 Days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Montreal Cognitive Assessment Scale (MoCA)	MOCA is a dementia screening assessment with a 0-30 range with lower scores meaning more impairment	Baseline, Day 28, Day 98, and Day 182
Epworth Sleepiness Scale (ESS)	The ESS is an assessment of subjective sleepiness over the prior two weeks. The scale is on 4 point scale (0 = no chance of dozing; 1 = slight chance of dozing; 2 = moderate chance of dozing; 3 = high chance of dozing) Total score sums up all sub-scores and can range from 0 to 24. A higher score is associated with increased sleepiness. An ESS score ≥10 is considered abnormal and consistent with excessive daytime sleepiness An ESS score > 10 is considered consistent with excessive daytime sleepiness	Baseline, Day 28, Day 98, and Day 182
Clinician Assessment of Fluctuation (CAF)	Assessment of cognitive fluctuations, with range of 1-16, with higher scores representing more severe fluctuations	Baseline, Day 28, Day 98, and Day 182
Alzheimer's Disease Cooperative Study - Clinical Global Impression of Change (ADCS-CGIC)	The ADCS-CGIC is a 7-point scale similar to other global change scales, where a higher score indicates marked improvement. The 7 responses and corresponding numeric scores for each response of the ADCS-CGIC are: Marked improvement (1), Moderate improvement (2), Minimal improvement (3), No change (4), Minimal worsening (5), Moderate worsening (6), Marked worsening (7). The observed scores at each visit were summarized. A responder was defined as a participant who responded as "Marked improvement, Moderate improvement, Minimal improvement, No change" and non-responder was defined as a participant who responded as "Minimal worsening, Moderate worsening, Marked worsening."	Day 28, Day 98, and Day 182
ADCS - Activities of Daily Living (ADCS-ADL)	Assessment of functional impairment in activities of daily living. The total score range is from 0-78 with lower scores indicating greater functional impairment.	Baseline, Day 28, Day 98, and Day 182
Movement Disorder Society - United Parkinson's Disease Rating Scale Part III (MDS-UPDRS Part III)	This exam covers 18 motor signs associated with parkinsonism covering bradykinesia, rigidity, tremor, and gait with a range of scores from 0-136, with higher scores supporting more severe symptoms. A score of 6 or greater suggest the presence of parkinsonism	Baseline, Day 28, Day 98, and Day 182
Change From Baseline in the Power of Attention Composite Score of the Cognitive Drug Research (CDR) System Battery	The CDR tests are designed to evaluate the effects of novel compounds on the quality of cognitive functioning which includes tests of attention (simple and choice reaction time, digit vigilance), working memory (spatial and numeric) and episodic memory (word recognition, picture recognition).Power of Attention is a composite score derived from the CDR that measures the intensity of concentration (i.e., the ability to focus attention). Faster responses indicate that greater cognitive processing resources are being applied to the task. Power of Attention is calculated as the sum of three cognitive function speed tests: simple reaction time, choice reaction time, and digit vigilance. Scores range from 450 milliseconds (msec) to 61,500 msec. Lower scores reflect faster reaction times and greater intensity of concentration. An increase from baseline, resulting in higher values, indicates worsening compared to the baseline assessment.	Baseline and Day 182
Neuropsychiatric Inventory (NPI-12) - Domain: Total Score A-L (Frequency x Severity)	The Neuropsychiatric Inventory (NPI) was used to assess common neuropsychiatric symptoms associated with dementia. A structured caregiver interview was conducted to evaluate 12 behavioral domains, including delusions, hallucinations, dysphoria, euphoria, anxiety, agitation/aggression, apathy, irritability/lability, disinhibition, aberrant motor behavior, sleep disturbances, and appetite/eating disorders. Symptom frequency was rated on a 4-point scale (1 = occasionally, 2 = often, 3 = frequently, 4 = very frequently), and symptom severity was rated on a 3-point scale (1 = mild, 2 = moderate, 3 = marked). Domain scores were calculated as the product of frequency and severity ratings. The total NPI score was calculated as the sum of all domain scores and ranges from 0 to 144 (12 domains, each with a maximum score of 12). Increases from baseline (higher scores) indicate worsening of symptoms.	Baseline, Day 28, Day 98, Day 182

Collaborators and Investigators

• Sponsor: Cognition Therapeutics
• Collaborators: National Institute on Aging (NIA)
• Investigators: Study Director: Anthony Caggiano, MD, Cognition Therapeutics Inc.

Publications and helpful links

General Publications

• Galvin JE, Tolea MI, Scharre DW, Hamby ME, Iaci JF, Grundman M, Caggiano AO. Phase 2 study of zervimesine (CT1812) in participants with mild-to-moderate dementia with Lewy bodies (DLB). Alzheimers Dement. 2025 Dec;21(12):e71004. doi: 10.1002/alz.71004.

Helpful Links

• Title: "Together we can light the way for Dementia with Lewy Bodies research."

Study record dates

Study Major Dates

• Study Start (Actual): May 19, 2022
• Primary Completion (Actual): November 25, 2024
• Study Completion (Actual): November 25, 2024

Study Registration Dates

• First Submitted: January 11, 2022
• First Submitted That Met QC Criteria: January 26, 2022
• First Posted (Actual): February 4, 2022

Study Record Updates

• Last Update Posted (Actual): March 12, 2026
• Last Update Submitted That Met QC Criteria: February 20, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: Dementia
• Additional Relevant MeSH Terms: Synucleinopathies; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Mental Disorders; Neurocognitive Disorders; Neurodegenerative Diseases; Movement Disorders; Parkinsonian Disorders; Basal Ganglia Diseases; Dementia; Lewy Body Disease
• Other Study ID Numbers: COG1201; R01AG071643 (U.S. NIH Grant/Contract)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No