A Study of ONO-2020 in Participants With Mild to Moderate Alzheimer's Disease

A Phase II, 26-week, Double-blind, Placebo-controlled Study to Assess the Safety, Tolerability, Pharmacokinetics, and Efficacy of ONO-2020 in Patients With Mild to Moderate Alzheimer's Disease

This is a Phase 2, double-blind, parallel-group, placebo-controlled study to assess safety, tolerability, pharmacokinetics, and efficacy of ONO-2020 in participants with mild to moderate Alzheimer's disease (AD). This study aims to determine whether administering ONO-2020, an epigenetic regulator, may improve cognitive functions like memory and cognition in individuals with Alzheimer's disease dementia.

Study Overview

• Status: Active, not recruiting
• Conditions: Alzheimer Disease
• Intervention / Treatment: Drug: ONO-2020; Drug: Placebo

Detailed Description

In the study, participants will undergo a screening period of up to 6 weeks (42 days). Eligible participants will be assigned to receive one of 2 dose levels of ONO-2020 or placebo control arm. ONO-2020 or placebo will be administered orally QD for 26 weeks. All participants who received study intervention will be followed up for 4 weeks after treatment discontinuation. The target sample size is 240 participants , out of which up to 45 participants will undergo additional special CSF biomarker evaluation. After enrollment, participants will be randomized in a 1:1:1 ratio to one of 3 treatment arms.

• Study Type: Interventional
• Enrollment (Estimated): 240
• Phase: Phase 2

Contacts and Locations

Study Locations

• Japan
  • Aichi, Japan
    • National Center for Geriatrics and Gerontology
  • Chiba, Japan
    • Mabashi Clinic
  • Chiba, Japan
    • Inage Neurology and Memory Clinic
  • Fukushima, Japan
    • Southern TOHOKU Medical Clinic
  • Gunma, Japan
    • Ikuseikai Shinozuka Hospital
  • Hiroshima, Japan
    • Imon Yukari Neurology Clinic
  • Hiroshima, Japan
    • NHO Hiroshima-Nishi Medical Center
  • Hyōgo, Japan
    • Himeji Central Hospital Clinic
  • Hyōgo, Japan
    • Kobe City Medical Center General Hospital
  • Ibaraki, Japan
    • Memory Clinic Toride
  • Kagawa, Japan
    • Kagawa Prefectural Central Hospital
  • Nagasaki, Japan
    • Meiwakai Izaki Clinic
  • Okayama, Japan
    • Katayama Medical Clinic
  • Saitama, Japan
    • Takesato Hospital
  • Tochigi, Japan
    • Jichiidai Station Brain Clinic
  • Tokushima, Japan
    • Ichiekai Itsuki Hospital
  • Tokyo, Japan
    • Tokyo Medical University Hospital
  • Tokyo, Japan
    • Tokyo Metropolitan Institute for Geriatrics and Gerontology
  • Tokyo, Japan
    • Federation of National Public Service Personnel Mutual Aid Associations Tachikawa Hospital
  • Tokyo, Japan
    • Memory Clinic Ochanomizu
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • University of Alabama at Birmingham
  • Arizona
    • Phoenix, Arizona, United States, 85006
      • Banner Alzheimer's Institute (BAI)
    • Scottsdale, Arizona, United States, 85258
      • Clinical Endpoints
    • Sun City, Arizona, United States, 85351
      • Banner Sun Health Research Institute
    • Tucson, Arizona, United States, 85718
      • Center for Neurosciences-Research
  • California
    • Carlsbad, California, United States, 92011
      • Profound Research LLC at The Neurology Center of Southern California
    • Fullerton, California, United States, 92835
      • Neurology Center of North Orange County
    • Palo Alto, California, United States, 94304
      • Stanford University
    • Walnut Creek, California, United States, 94596
      • Sunwise Clinical Research
  • Colorado
    • Englewood, Colorado, United States, 80113
      • Cenexel Rocky Mountain Clinical Research
  • Florida
    • Delray Beach, Florida, United States, 33445
      • Brain Matters Research
    • Hallandale, Florida, United States, 33009
      • Velocity Clinical Research, Hallandale Beach
    • Miami, Florida, United States, 33122
      • Premier Clinical Research Institute; Inc.
    • Miami Beach, Florida, United States, 33140
      • Quantum Clinical Trials
    • New Port Richey, Florida, United States, 34652
      • Suncoast Clinical Research
    • Ocala, Florida, United States, 34470
      • Renstar Medical Research
    • Orlando, Florida, United States, 32803
      • Charter Research - Orlando
    • Port Orange, Florida, United States, 32127
      • Accel Research Sites - Brain and Spine Institute
    • Tampa, Florida, United States, 33613
      • USF Health Byrd Alzheimer's Institute
    • Tampa, Florida, United States, 33647
      • ForCare Clinical Research
    • The Villages, Florida, United States, 32162
      • Charter Research - The Villages
    • Winter Park, Florida, United States, 32789
      • Conquest Research LLC
  • Georgia
    • Decatur, Georgia, United States, 30030
      • Sandhill Research, LLC d/b/a Accel Research Sites - NeuroStudies CRU
    • Savannah, Georgia, United States, 31405
      • CenExel iResearch, LLC
  • Idaho
    • Meridian, Idaho, United States, 83642
      • Velocity Clinical Research, Boise
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Re:Cognition Health-Chicago
    • Chicago, Illinois, United States, 60618
      • Charter Research - Chicago
    • Elk Grove Village, Illinois, United States, 60007
      • Ascension Alexian Brothers Medical Center
  • Kansas
    • Fairway, Kansas, United States, 66205
      • University of Kansas Medical Center
  • Kentucky
    • Lexington, Kentucky, United States, 40504
      • Univ of Kentucky Sanders-Brown Center on Aging
  • Massachusetts
    • Boston, Massachusetts, United States, 02131
      • Boston Clinical Trials
    • Methuen, Massachusetts, United States, 01844
      • ActivMed Research
  • Michigan
    • Farmington Hills, Michigan, United States, 48334
      • Quest Research Institute
  • Nevada
    • Las Vegas, Nevada, United States, 89106
      • Cleveland Clinic Lou Ruvo Center for Brain Health
    • Las Vegas, Nevada, United States, 89128
      • Vector Clinical Trials
  • New Jersey
    • Springfield, New Jersey, United States, 07081
      • The Cognitive and Research Center of New Jersey
    • Toms River, New Jersey, United States, 08755
      • Advanced Memory Research Institute of NJ (CenExel AMRI)
    • West Long Branch, New Jersey, United States, 07764
      • Advanced Clinical Institute Inc.
  • New York
    • Brooklyn, New York, United States, 11229
      • Integrative Clinical Trials
    • Buffalo, New York, United States, 14203
      • University at Buffalo
    • East Syracuse, New York, United States, 13057
      • Velocity Clinical Research; Syracuse
    • Manhasset, New York, United States, 11030
      • The Feinstein Institutes for Medical Research
    • New York, New York, United States, 10016
      • NYU Center for Cognitive Neurology
    • Rochester, New York, United States, 14620
      • AD-CARE; University of Rochester
    • Stony Brook, New York, United States, 11794
      • Stony Brook University Hospital
  • North Carolina
    • Charlotte, North Carolina, United States, 28211
      • New Hope Clinical Research
    • Raleigh, North Carolina, United States, 27607
      • Velocity Clinical Research at Raleigh Neurology
    • Raleigh, North Carolina, United States, 27607
      • Eximia Research-Raleigh
  • Ohio
    • Canton, Ohio, United States, 44718
      • NeuroScience Research Center
    • Cincinnati, Ohio, United States, 45219
      • University of Cincinnati
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic
    • Columbus, Ohio, United States, 43221
      • The Ohio State University
    • Dayton, Ohio, United States, 45459
      • Neurology Diagnostics Research
    • North Canton, Ohio, United States, 44720
      • Neuro Behavioral Clinical Research, Inc.
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health & Science University
    • Portland, Oregon, United States, 97225
      • Neural Net Research / Center for Cognitive Health
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Penn Medicine
  • Rhode Island
    • Providence, Rhode Island, United States, 02903
      • Rhode Island Hospital
  • Tennessee
    • Cordova, Tennessee, United States, 38018
      • Neurology Clinic, P.C.
    • Knoxville, Tennessee, United States, 37920
      • Alliance for Multispecialty Research;LLC-Knoxville
    • Nashville, Tennessee, United States, 37212
      • Vanderbilt UMC-Cognitive Med
  • Texas
    • Austin, Texas, United States, 78731
      • FutureSearch Trials of Neurology
    • Cypress, Texas, United States, 77429
      • Horizon Clinical Research Group
    • Dallas, Texas, United States, 75206
      • Texas Neurology
    • Dallas, Texas, United States, 75251
      • FutureSearch Trials of Dallas LLC
    • Fort Worth, Texas, United States, 76104
      • Re:Cognition Health - Fort Worth
    • Houston, Texas, United States, 77030
      • Re:Cognition Health - Houston
    • Katy, Texas, United States, 77450
      • Olympus Clinical Research - Katy
    • Round Rock, Texas, United States, 78681
      • Central Texas Neurology Consultants
    • Round Rock, Texas, United States, 78681
      • Be Well Clinical Studies
    • Wichita Falls, Texas, United States, 76309
      • Grayline Research Center
  • Utah
    • Salt Lake City, Utah, United States, 84107
      • Wasatch Clinical Research; LLC
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Re:Cognition Health - Fairfax
    • Norfolk, Virginia, United States, 23510
      • Sentara Neurology Specialists
  • Washington
    • Bellevue, Washington, United States, 98007
      • Northwest Clinical Research Center
    • Spokane, Washington, United States, 99201
      • Kingfisher Cooperative; LLC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Have a diagnosis of Alzheimer's disease according to the recommendations from the revised criteria for diagnosis and staging of Alzheimer's disease: Alzheimer's Association Workgroup , along with any positive AD-specific biomarker results (abnormal Core 1 or Core 2 biomarkers) from a previous diagnosis or at screening.
2. Have a previous MRI or CT scan of the brain, which was performed within 1 year prior to enrollment in the study, to confirm that more recent neurological events (e.g., stroke) would not potentially constitute a confounder in the assessment of the etiology of the participant's cognitive status.
3. MMSE score of 15 to 24, inclusive, and MMSE score cannot deviate more than 3 points in either direction between the screening and baseline visits.
4. AD numeric clinical stage 4 or stage 5 based on NIA-AA criteria 2024, at screening and baseline visits
5. Participants receiving concurrent AD treatment (acetylcholinesterase inhibitors and /or memantine) must be on a stable dose for at least 90 days prior to randomization, and the participant must be willing to remain on the same dose for the duration of the study.
6. Have the ability to comply with procedures for cognitive and other tests in the opinion of the investigator
7. If female, postmenopausal for at least 1 year
8. Non-vasectomized male participants with female partners of childbearing potential must agree to use an effective method of contraception from dosing on Day 1 until 3 months after the last administration of study intervention and agree not to donate sperm until 3 months after the last administration of study intervention.
9. Participant must have a Caregiver who has frequent contact with the participant (defined as at least 8 hours per week spread across 3~4 visits per week) to provide support to the participant to ensure compliance with study requirements. The Caregiver must be willing to consent to participate in this study, to provide a rating of the extent and severity of change of the participant's memory, problem-solving abilities, or activities of daily living from prior abilities.
10. General health status acceptable for participation in the study, and the participant must be able to ingest pills.
11. Participant and his/her Caregiver have provided full written informed consent prior to the performance of any protocol-specified procedure; or if a participant is unable to provide informed consent due to cognitive status, he/she has provided assent, and a legally acceptable representative (LAR) has provided full written informed consent on behalf of the participant.

Exclusion Criteria:

1. Participants with dementia or other memory impairment not due to Alzheimer's disease, including, but not limited to, dementia with Lewy bodies, vascular dementia, Parkinson's disease, Huntington disease, corticobasal degeneration, Creutzfeldt-Jakob disease, progressive supranuclear palsy, frontotemporal degeneration, normal pressure hydrocephalus, hypoxia, severe sleep apnea or other chronic sleep disturbance, or baseline intellectual disability.
2. Participants with a history of stroke, well-documented transient ischemic attack, or pulmonary or cerebral embolism.
3. History of significant psychiatric illness such as schizophrenia or bipolar affective disorder, or history or current major depressive disorder in the past year and any other significant psychiatric illness that in the opinion of the investigator could interfere with participation in the study.
4. Participants with delirium or history of delirium within the 30 days prior to the screening visit.
5. Have suicide ideation according to the investigator's clinical judgment as per the Columbia-Suicide Severity Rating Scale (C-SSRS) at screening or have made a suicide attempt in the 6 months prior to screening.
6. Clinically significant ECG abnormality as judged by the investigator.
7. Confirmed absolute QTcF >450 msec for males or >470 msec for females.
8. Positive results at screening for active viral infections that include human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), and hepatitis C virus (HCV) RNA PCR test.
9. Participants with total bilirubin, alanine transaminase (ALT) or aspartate transaminase (AST) greater than 1.5×upper limit of normal (ULN), or international normalized ratio (INR) greater than 1.7 at screening.
10. Participants with estimated creatinine clearance (CrCL, Cockcroft-Gault equation) ≤30 mL/min at screening.
11. Participants with a history of treatment, and/or current treatment, with anti-Aβ antibodies
12. Changes in any medications that, in the opinion of the investigator, may potentially impair participants' ability to perform cognitive testing or study procedures during the study period (from Screening to EOT), and their dosing should be stable for at least 1 month before Screening (such as benzodiazepines and sedatives/hypnotics). All concomitant medications must be kept as stable as medically possible during the study.
13. Participants who have taken any investigational products, or used investigational medical devices, within 3 months or five half-lives of the therapy (whichever is longer) with respect to first dosing and throughout the study

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ONO-2020 Dose 1; Participants will receive ONO-2020 Dose 1 administered orally, once a day (QD) for 26 weeks.	Drug: ONO-2020; ONO-2020 group: Two ONO-2020 tablets will be orally administered once daily.
Experimental: ONO-2020 Dose 2; Participants will receive ONO-2020 Dose 2 administered orally, once a day (QD) for 26 weeks.	Drug: ONO-2020; ONO-2020 group: Two ONO-2020 tablets will be orally administered once daily.
Placebo Comparator: Placebo; Participants will receive Placebo administered orally, once a day (QD) for 26 weeks.	Drug: Placebo; Placebo group: Two ONO-2020 placebo tablets will be orally administered once daily.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence, severity, and type of treatment emergent adverse events (TEAEs)	The number and percentage of subjects reporting each TEAE will be summarized by both system organ class (SOC) and preferred term (PT).	From baseline up to 26 weeks
Clinically abnormal findings in Columbia Suicide Severity Rating Scale (C-SSRS)	The number and percentage of subjects with clinically abnormal finding will be tabulated at each time point.	From baseline up to 26 weeks
Change from baseline through week 26 in Alzheimer's Disease Assessment Scale-Cognitive Subscale 12 (ADAS-cog 12) score		From baseline up to 26 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline through week 26 in ADAS-cog 12 score in mild AD participants		From baseline up to 26 weeks
Change from baseline through week 26 in ADAS-cog 12 score in moderate AD participants		From baseline up to 26 weeks
Change from baseline through week 26 in ADAS-cog 11 and 13 scores		From baseline up to 26 weeks
Change from baseline through week 26 in Alzheimer's Disease Cooperative Study Group-Activities of Daily Living (ADCS-ADL) score		From baseline up to 26 weeks
Change from baseline through week 26 in Quick Dementia Rating System (QDRS)		From baseline up to 26 weeks
Change from baseline through week 26 in Mini-Mental State Examination (MMSE) score		From baseline up to 26 weeks
Change from baseline through week 26 in Neuropsychiatric Inventory Questionnaire (NPI-Q)		From baseline up to 26 weeks
Change from baseline through week 26 in Quality of Life-Alzheimer's Disease (QoL-AD) Scale		From baseline up to 26 weeks
Change from baseline through week 26 in Zarit Burden Interview Scale (ZBI)		From baseline up to 26 weeks
Change in plasma concentration of ONO-2020 by dose level and time point	The plasma concentrations of ONO-2020 will be listed, and descriptive summary statistics of them will be calculated by dose level and time point.	Day 1, Week 2, Week 10, and Week 26

Collaborators and Investigators

• Sponsor: Ono Pharmaceutical Co. Ltd
• Investigators: Study Director: Project Leader, Ono Pharmaceutical Co. Ltd

Study record dates

Study Major Dates

• Study Start (Actual): April 24, 2025
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): August 1, 2026

Study Registration Dates

• First Submitted: March 2, 2025
• First Submitted That Met QC Criteria: March 11, 2025
• First Posted (Actual): March 18, 2025

Study Record Updates

• Last Update Posted (Actual): January 28, 2026
• Last Update Submitted That Met QC Criteria: January 26, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: Dementia; Alzheimer Disease; mild to moderate Alzheimer Disease; ONO-2020
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Mental Disorders; Neurocognitive Disorders; Tauopathies; Neurodegenerative Diseases; Alzheimer Disease; Dementia
• Other Study ID Numbers: ONO-2020-02; jRCT2031240712 (Registry Identifier: Japan Registry of Clinical Trials)

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