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

NCT06881836 | Active Not Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: ONO-2020-02jRCT2031240712
• Study Type: interventional
• Target: 240
• Locations: 2 countries
• Sites: 96

Brief Summary

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.

Conditions

Alzheimer Disease

Keywords

Alzheimer Disease; mild to moderate Alzheimer Disease; Dementia; ONO-2020

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (10)

• 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

Study Arms (3)

ONO-2020 Dose 1

EXPERIMENTAL

Participants will receive ONO-2020 Dose 1 administered orally, once a day (QD) for 26 weeks.

Drug: ONO-2020

ONO-2020 Dose 2

EXPERIMENTAL

Participants will receive ONO-2020 Dose 2 administered orally, once a day (QD) for 26 weeks.

Drug: ONO-2020

Placebo

PLACEBO COMPARATOR

Participants will receive Placebo administered orally, once a day (QD) for 26 weeks.

Drug: Placebo

Interventions

ONO-2020 DRUG

ONO-2020 group: Two ONO-2020 tablets will be orally administered once daily.

ONO-2020 Dose 1; ONO-2020 Dose 2

Placebo DRUG

Placebo group: Two ONO-2020 placebo tablets will be orally administered once daily.

Placebo

Eligibility Criteria

• Age: 55 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.
• 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.
• AD numeric clinical stage 4 or stage 5 based on NIA-AA criteria 2024, at screening and baseline visits
• 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.
• Have the ability to comply with procedures for cognitive and other tests in the opinion of the investigator
• If female, postmenopausal for at least 1 year
• 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.
• 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.
• General health status acceptable for participation in the study, and the participant must be able to ingest pills.
• 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.

You may not qualify if:

• 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.
• Participants with a history of stroke, well-documented transient ischemic attack, or pulmonary or cerebral embolism.
• 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.
• Participants with delirium or history of delirium within the 30 days prior to the screening visit.
• 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.
• Clinically significant ECG abnormality as judged by the investigator.
• Confirmed absolute QTcF \>450 msec for males or \>470 msec for females.
• 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.
• 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.
• Participants with estimated creatinine clearance (CrCL, Cockcroft-Gault equation) ≤30 mL/min at screening.
• Participants with a history of treatment, and/or current treatment, with anti-Aβ antibodies
• 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.
• 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

Sponsors & Collaborators

• Ono Pharmaceutical Co. Ltd: lead

Study Sites (96)

University of Alabama at Birmingham

Birmingham, Alabama, 35233, United States

Location

Banner Alzheimer's Institute (BAI)

Phoenix, Arizona, 85006, United States

Location

Clinical Endpoints

Scottsdale, Arizona, 85258, United States

Location

Banner Sun Health Research Institute

Sun City, Arizona, 85351, United States

Location

Center for Neurosciences-Research

Tucson, Arizona, 85718, United States

Location

Profound Research LLC at The Neurology Center of Southern California

Carlsbad, California, 92011, United States

Location

Neurology Center of North Orange County

Fullerton, California, 92835, United States

Location

Stanford University

Palo Alto, California, 94304, United States

Location

Sunwise Clinical Research

Walnut Creek, California, 94596, United States

Location

CenExel Rocky Mountain Clinical Research

Englewood, Colorado, 80113, United States

Location

Brain Matters Research

Delray Beach, Florida, 33445, United States

Location

Velocity Clinical Research, Hallandale Beach

Hallandale, Florida, 33009, United States

Location

Premier Clinical Research Institute; Inc.

Miami, Florida, 33122, United States

Location

Quantum Clinical Trials

Miami Beach, Florida, 33140, United States

Location

Suncoast Clinical Research

New Port Richey, Florida, 34652, United States

Location

Renstar Medical Research

Ocala, Florida, 34470, United States

Location

Charter Research - Orlando

Orlando, Florida, 32803, United States

Location

Accel Research Sites - Brain and Spine Institute

Port Orange, Florida, 32127, United States

Location

USF Health Byrd Alzheimer's Institute

Tampa, Florida, 33613, United States

Location

ForCare Clinical Research

Tampa, Florida, 33647, United States

Location

Charter Research - The Villages

The Villages, Florida, 32162, United States

Location

Conquest Research LLC

Winter Park, Florida, 32789, United States

Location

Sandhill Research, LLC d/b/a Accel Research Sites - NeuroStudies CRU

Decatur, Georgia, 30030, United States

Location

CenExel iResearch, LLC

Savannah, Georgia, 31405, United States

Location

Velocity Clinical Research, Boise

Meridian, Idaho, 83642, United States

Location

Re:Cognition Health-Chicago

Chicago, Illinois, 60611, United States

Location

Charter Research - Chicago

Chicago, Illinois, 60618, United States

Location

Ascension Alexian Brothers Medical Center

Elk Grove Village, Illinois, 60007, United States

Location

University of Kansas Medical Center

Fairway, Kansas, 66205, United States

Location

Univ of Kentucky Sanders-Brown Center on Aging

Lexington, Kentucky, 40504, United States

Location

Boston Clinical Trials

Boston, Massachusetts, 02131, United States

Location

ActivMed Research

Methuen, Massachusetts, 01844, United States

Location

Quest Research Institute

Farmington Hills, Michigan, 48334, United States

Location

Cleveland Clinic Lou Ruvo Center for Brain Health

Las Vegas, Nevada, 89106, United States

Location

Vector Clinical Trials

Las Vegas, Nevada, 89128, United States

Location

The Cognitive and Research Center of New Jersey

Springfield, New Jersey, 07081, United States

Location

Advanced Memory Research Institute of NJ (CenExel AMRI)

Toms River, New Jersey, 08755, United States

Location

Advanced Clinical Institute Inc.

West Long Branch, New Jersey, 07764, United States

Location

Integrative Clinical Trials

Brooklyn, New York, 11229, United States

Location

University at Buffalo

Buffalo, New York, 14203, United States

Location

Velocity Clinical Research; Syracuse

East Syracuse, New York, 13057, United States

Location

The Feinstein Institutes for Medical Research

Manhasset, New York, 11030, United States

Location

NYU Center for Cognitive Neurology

New York, New York, 10016, United States

Location

AD-CARE; University of Rochester

Rochester, New York, 14620, United States

Location

Stony Brook University Hospital

Stony Brook, New York, 11794, United States

Location

New Hope Clinical Research

Charlotte, North Carolina, 28211, United States

Location

Eximia Research-Raleigh

Raleigh, North Carolina, 27607, United States

Location

Velocity Clinical Research at Raleigh Neurology

Raleigh, North Carolina, 27607, United States

Location

NeuroScience Research Center

Canton, Ohio, 44718, United States

Location

University of Cincinnati

Cincinnati, Ohio, 45219, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

The Ohio State University

Columbus, Ohio, 43221, United States

Location

Neurology Diagnostics Research

Dayton, Ohio, 45459, United States

Location

Neuro Behavioral Clinical Research, Inc.

North Canton, Ohio, 44720, United States

Location

Neural Net Research / Center for Cognitive Health

Portland, Oregon, 97225, United States

Location

Oregon Health & Science University

Portland, Oregon, 97239, United States

Location

Penn Medicine

Philadelphia, Pennsylvania, 19104, United States

Location

Rhode Island Hospital

Providence, Rhode Island, 02903, United States

Location

Neurology Clinic, P.C.

Cordova, Tennessee, 38018, United States

Location

Alliance for Multispecialty Research;LLC-Knoxville

Knoxville, Tennessee, 37920, United States

Location

Vanderbilt UMC-Cognitive Med

Nashville, Tennessee, 37212, United States

Location

FutureSearch Trials of Neurology

Austin, Texas, 78731, United States

Location

Horizon Clinical Research Group

Cypress, Texas, 77429, United States

Location

Texas Neurology

Dallas, Texas, 75206, United States

Location

FutureSearch Trials of Dallas LLC

Dallas, Texas, 75251, United States

Location

Re:Cognition Health - Fort Worth

Fort Worth, Texas, 76104, United States

Location

Re:Cognition Health - Houston

Houston, Texas, 77030, United States

Location

Olympus Clinical Research - Katy

Katy, Texas, 77450, United States

Location

Be Well Clinical Studies

Round Rock, Texas, 78681, United States

Location

Central Texas Neurology Consultants

Round Rock, Texas, 78681, United States

Location

Grayline Research Center

Wichita Falls, Texas, 76309, United States

Location

Wasatch Clinical Research; LLC

Salt Lake City, Utah, 84107, United States

Location

Re:Cognition Health - Fairfax

Fairfax, Virginia, 22031, United States

Location

Sentara Neurology Specialists

Norfolk, Virginia, 23510, United States

Location

Northwest Clinical Research Center

Bellevue, Washington, 98007, United States

Location

Kingfisher Cooperative; LLC

Spokane, Washington, 99201, United States

Location

National Center for Geriatrics and Gerontology

Aichi, Japan

Location

Inage Neurology and Memory Clinic

Chiba, Japan

Location

Mabashi Clinic

Chiba, Japan

Location

Southern Tohoku Medical Clinic

Fukushima, Japan

Location

Ikuseikai Shinozuka Hospital

Gunma, Japan

Location

Imon Yukari Neurology Clinic

Hiroshima, Japan

Location

NHO Hiroshima-Nishi Medical Center

Hiroshima, Japan

Location

Himeji Central Hospital Clinic

Hyōgo, Japan

Location

Kobe City Medical Center General Hospital

Hyōgo, Japan

Location

Memory Clinic Toride

Ibaraki, Japan

Location

Kagawa Prefectural Central Hospital

Kagawa, Japan

Location

Meiwakai Izaki Clinic

Nagasaki, Japan

Location

Katayama Medical Clinic

Okayama, Japan

Location

Takesato Hospital

Saitama, Japan

Location

Jichiidai Station Brain Clinic

Tochigi, Japan

Location

Ichiekai Itsuki Hospital

Tokushima, Japan

Location

Federation of National Public Service Personnel Mutual Aid Associations Tachikawa Hospital

Tokyo, Japan

Location

Memory Clinic Ochanomizu

Tokyo, Japan

Location

Tokyo Medical University Hospital

Tokyo, Japan

Location

Tokyo Metropolitan Institute for Geriatrics and Gerontology

Tokyo, Japan

Location

MeSH Terms

Conditions

Alzheimer Disease; Dementia

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders

Study Officials

• Project Leader

  Ono Pharmaceutical Co. Ltd

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 2, 2025
• First Posted: March 18, 2025
• Study Start: April 24, 2025
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): August 1, 2026
• Last Updated: January 28, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (76); JP (20)