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

Phase 2

Recruiting

• Conditions: Alzheimer Disease
• Interventions: Drug: ONO-2020; Drug: Placebo

• Registration Number: NCT06881836
• Lead Sponsor: Ono Pharmaceutical Co. Ltd

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.

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 Timeline

• Study First Submitted: 2025-03-02
• Study First Submitted QC: 2025-03-11
• Study First Posted: 2025-03-18
• Study Start: 2025-04-24
• Status Verified: 2025-06
• Last Update Submitted: 2025-06-24
• Last Update Posted: 2025-06-26
• Primary Completion: 2026-07
• Study Completion: 2026-08-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 240

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
ONO-2020 Dose 1	ONO-2020	Participants will receive ONO-2020 Dose 1 administered orally, once a day (QD) for 26 weeks.
ONO-2020 Dose 2	ONO-2020	Participants will receive ONO-2020 Dose 2 administered orally, once a day (QD) for 26 weeks.
Placebo	Placebo	Participants will receive Placebo administered orally, once a day (QD) for 26 weeks.

Primary Outcome Measures

Name	Time	Method
Incidence, severity, and type of treatment emergent adverse events (TEAEs)	From baseline up to 26 weeks	The number and percentage of subjects reporting each TEAE will be summarized by both system organ class (SOC) and preferred term (PT).
Clinically abnormal findings in Columbia Suicide Severity Rating Scale (C-SSRS)	From baseline up to 26 weeks	The number and percentage of subjects with clinically abnormal finding will be tabulated at each time point.
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

Name	Time	Method
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 Quick Dementia Rating System (QDRS)	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 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	Day 1, Week 2, Week 10, and Week 26	The plasma concentrations of ONO-2020 will be listed, and descriptive summary statistics of them will be calculated by dose level and time point.

Trial Locations

Locations (50)

Profound Research LLC at The Neurology Center of Southern California; 🇺🇸 Carlsbad, California, United States

Ark Clinical Research; 🇺🇸 Fountain Valley, California, United States

Sunwise Clinical Research; 🇺🇸 Walnut Creek, California, United States

Brain Matters Research; 🇺🇸 Delray Beach, Florida, United States

Neuropsychiatric Research Center of Southwest Florida; 🇺🇸 Fort Myers, Florida, United States

Velocity Clinical Research, Hallandale Beach; 🇺🇸 Hallandale Beach, Florida, United States

Quantum Clinical Trials; 🇺🇸 Miami Beach, Florida, United States

Suncoast Clinical Research; 🇺🇸 New Port Richey, Florida, United States

Renstar Medical Research; 🇺🇸 Ocala, Florida, United States

Accel Research Sites - Brain and Spine Institute; 🇺🇸 Port Orange, Florida, United States

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