A Study to Evaluate the Safety and Efficacy of CT1812 in Early Alzheimer's Disease

Synaptic Therapy Alzheimer's Research Trial (START): A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Trial to Evaluate the Safety and Efficacy of CT1812 in Early Alzheimer's Disease Over 18 Months.

This is a multicenter randomized, double-blind, placebo-controlled Phase 2 study designed to evaluate the efficacy, safety, and tolerability of two doses of CT1812 compared to placebo in participants diagnosed with early Alzheimer's disease.

Study Overview

• Status: Active, not recruiting
• Conditions: Early Alzheimer's Disease
• Intervention / Treatment: Drug: Placebo; Drug: CT1812

Detailed Description

This is a multicenter randomized, double-blind, placebo-controlled Phase 2 study designed to evaluate the efficacy, safety, and tolerability of two doses of CT1812 compared to placebo for approximately 18 months (72 weeks) in approximately 540 participants diagnosed with early Alzheimer's disease

Participants will be randomized 1:1:1 to receive either 100mg or 200mg of CT1812 or placebo. CT1812 or placebo will be administered as 2 capsules to be taken orally once daily.

• Study Type: Interventional
• Enrollment (Estimated): 540
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • University of Alabama at Birmingham
  • Arizona
    • Phoenix, Arizona, United States, 85006
      • Banner Alzheimer's Institute
    • Sun City, Arizona, United States, 85351
      • Banner Sun Health Research Institute
  • California
    • Irvine, California, United States, 92697
      • University of California
    • Palo Alto, California, United States, 94304
      • Stanford University
    • Sacramento, California, United States, 95816
      • Sutter Institute for Medical Research
  • Connecticut
    • New Haven, Connecticut, United States, 06510
      • Yale University
  • District of Columbia
    • Washington D.C., District of Columbia, United States, 20057
      • Georgetown University
    • Washington D.C., District of Columbia, United States, 20060
      • Howard University
  • Florida
    • Delray Beach, Florida, United States, 33445
      • Brain Matters Research
    • Fort Myers, Florida, United States, 33912
      • Neuropsychiatric Research Center of Southwest Florida
    • Jacksonville, Florida, United States, 32216
      • Mayo Clinic,Jacksonville
    • Lake Worth, Florida, United States, 33462
      • JEM Research Institute
    • Maitland, Florida, United States, 32751
      • K2 Medical Research, LLC
    • Miami, Florida, United States, 33135
      • Advanced Clinical Research Network, Corp
    • Orlando, Florida, United States, 32819
      • Headlands Research Orlando
    • Orlando, Florida, United States, 32803
      • Charter Research
    • Stuart, Florida, United States, 34997
      • Brain Matters Research Stuart
    • Tampa, Florida, United States, 33613
      • University of South Florida
    • Winter Park, Florida, United States, 32789
      • Conquest Research, LLC
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Rush University Medical Center
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University
  • Kentucky
    • Lexington, Kentucky, United States, 40504
      • Sanders-Brown Center on Aging
  • Maryland
    • Baltimore, Maryland, United States, 21224
      • John Hopkins University
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Brigham and Women's Hospital
    • Plymouth, Massachusetts, United States, 02360
      • Highlands Research Eastern MA
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan, Ann Arbor
  • Minnesota
    • Rochester, Minnesota, United States, 55901
      • Mayo Clinic, Rochester
  • Missouri
    • St Louis, Missouri, United States, 63110
      • Washington University School of Medicine
  • Nevada
    • Las Vegas, Nevada, United States, 89106
      • Cleveland Clinic Lou Ruvo Center for Brain Health
  • New York
    • New York, New York, United States, 10032
      • Columbia University Medical Center
    • New York, New York, United States, 10029
      • Mount Sinai School of Medicine
    • Rochester, New York, United States, 14620
      • University of Rochester Medical Center
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest University Health Sciences
  • Ohio
    • Beachwood, Ohio, United States, 44122
      • Case Western Reserve University / University Hospitals
    • Columbus, Ohio, United States, 43210
      • Ohio State University
  • Oklahoma
    • Tulsa, Oklahoma, United States, 74136
      • Central States Research, LLC
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health & Science University
    • Portland, Oregon, United States, 97210
      • Summit Headlands LLC
  • Pennsylvania
    • Abington, Pennsylvania, United States, 19001
      • Abington Neurological Associates
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania
  • Rhode Island
    • Providence, Rhode Island, United States, 02906
      • Butler Hospital
  • South Carolina
    • Charleston, South Carolina, United States, 29401
      • Ralph H. Johnson VA MC
  • Tennessee
    • Nashville, Tennessee, United States, 37212
      • Vanderbilt University Medical Center Center for Cognitive Medicine
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University Medical Center Center for Cognitive Medicine
  • Texas
    • Dallas, Texas, United States, 75390
      • University of Texas Southwestern Medical Center
    • Houston, Texas, United States, 77030
      • Baylor College of Medicine
    • Houston, Texas, United States, 77030
      • Houston Methodist Neurological Institute
    • San Antonio, Texas, United States, 78229
      • University of Texas Health Science Center
  • Wisconsin
    • Madison, Wisconsin, United States, 53726
      • University of Wisconsin

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Ages 50-85 years.
2. Diagnosis of either MCI due to AD or mild AD dementia.
3. MMSE 20-30 (inclusive).
4. Amyloid PET scan of the brain or CSF biomarkers consistent with AD.
5. Neuroimaging (MRI) obtained during screening consistent with the clinical diagnosis of Alzheimer's disease, as based on central read.

Exclusion Criteria:

1. Screening MRI of the brain indicative of significant abnormality.
2. Clinically significant abnormalities in screening laboratory tests.

3. Clinical or laboratory findings consistent with:

   1. Other primary degenerative dementia, (dementia with Lewy bodies, fronto-temporal dementia, Huntington's disease, Creutzfeldt-Jakob Disease, Down syndrome, etc.).
   2. Other neurodegenerative condition (Parkinson's disease, amyotrophic lateral sclerosis, etc.).
   3. Other infectious, metabolic or systemic diseases affecting the central nervous system (syphilis, present hypothyroidism, present vitamin B12, other laboratory values etc.)
4. A participant known to be actively infected with hepatitis B or hepatitis C at screening. History of acute/chronic hepatitis B or C and/or carriers of hepatitis B (seropositive for hepatitis B surface antigen [HbsAg] or anti-hepatitis C [HCV] antibody). Participants who have evidence of resolved hepatitis infection (e.g., HCV RNA negative) may be considered following discussion with the Medical Monitor.
5. A current DSM-V diagnosis of active major depression or GDS > 6, schizophrenia, or bipolar disorder.

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
Active Comparator: CT1812 100 mg; CT1812 at a dose of 100 n=180 group	Drug: CT1812; Study Drug; Other Names: Study Drug Active
Active Comparator: CT1812 200 mg; CT1812 at a dose of 300mg, n=180 group	Drug: CT1812; Study Drug; Other Names: Study Drug Active
Placebo Comparator: Placebo; Placebo, n=180 group	Drug: Placebo; Non-active study drug; Other Names: Matching Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in the Clinical Dementia Rating Scale Sum of Boxes (CDR-SB) scale.	The Clinical Dementia Rating (CDR) is a clinical scale that describes 5 levels of impairment in performance on each of 6 categories of function including memory, orientation, judgment and problem solving, community affairs, home and hobbies, and personal care. The ratings of degree of impairment obtained on each of the 6 categories of function are synthesized into 1 global rating of dementia as absent, questionable, mild, moderate, or severe (global CDR scores of 0, 0.5, 1, 2, or 3, respectively). The score is based on interviews with the participant and study partner, using a structured interview. A sum of boxes score (CDR-SB) provides an additional measure of change where each category has a maximum possible score of 3 points and the total score is a sum of the category scores giving a total possible score of 0 to 18 with higher scores indicating more impairment.	18 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Alzheimer's Disease Assessment Scale-Cognition (ADAS-Cog 13)	Change from baseline in the Alzheimer's Disease Assessment Scale-Cognition (ADAS-Cog 13) at 18 months.	18 months
Alzheimer's Disease Cooperative Study - Activities of Daily Living Scale (ADCS - ADL) in people with Mild Cognitive Impairment (MCI) - ADCS-ADL-MCI.	Change from baseline in the Alzheimer's Disease Cooperative Study - Activities of Daily Living Scale (ADCS - ADL) in people with Mild Cognitive Impairment (MCI) - ADCS-ADL-MCI at 18 months.	18 months
Plasma measures of Aβ fragments, ptau, and Neurofilament light (NfL)	Change from baseline at 18 months.	18 months
Volumetric Magnetic Resonance Imaging (MRI) including hippocampal and whole brain volume change	Change from baseline at 18 months.	18 months
Cerebrospinal fluid (CSF) concentrations of beta-amyloid (Aβ) 40 and 42, tau, phospho-tau (ptau), neurofilament light (NfL), neurogranin, and synaptotagmin.	Change from baseline at 18 months.	18 months

Collaborators and Investigators

• Sponsor: Cognition Therapeutics
• Collaborators: National Institute on Aging (NIA); Alzheimer's Clinical Trials Consortium
• Investigators: Study Director: Anthony Caggiano, MD, Cognition Therapeutics

Study record dates

Study Major Dates

• Study Start (Actual): June 28, 2023
• Primary Completion (Estimated): April 1, 2027
• Study Completion (Estimated): April 1, 2027

Study Registration Dates

• First Submitted: August 8, 2022
• First Submitted That Met QC Criteria: September 2, 2022
• First Posted (Actual): September 8, 2022

Study Record Updates

• Last Update Posted (Actual): September 22, 2025
• Last Update Submitted That Met QC Criteria: September 16, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Keywords: Alzheimer's Disease
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Mental Disorders; Neurocognitive Disorders; Dementia; Tauopathies; Neurodegenerative Diseases; Alzheimer Disease
• Other Study ID Numbers: COG0203; R01AG065248 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

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