Evaluating ONO-2020 for 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 study is testing if a new drug called ONO-2020 can help improve memory and thinking skills in people with mild to moderate Alzheimer's disease.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 240 (estimated)
• Ages: 55 Years to 85 Years
• Sex: All
• Sponsor: Ono Pharmaceutical Co. Ltd (Industry-sponsored)
• Locations: 12 sites (Decatur, Georgia and 11 other locations)
• Trial ID: NCT06881836 on ClinicalTrials.gov

What this trial studies

This Phase 2, double-blind, placebo-controlled study investigates the safety, tolerability, pharmacokinetics, and efficacy of ONO-2020 in individuals diagnosed with mild to moderate Alzheimer's disease. Participants will be randomly assigned to receive either ONO-2020 or a placebo for 26 weeks, followed by a 4-week follow-up period. The study aims to assess whether ONO-2020, an epigenetic regulator, can enhance cognitive functions such as memory in Alzheimer's patients. A total of 240 participants will be enrolled, with some undergoing additional biomarker evaluations.

Who should consider this trial

Good fit: Ideal candidates are individuals diagnosed with mild to moderate Alzheimer's disease who meet specific cognitive and biomarker criteria.

Not a fit: Patients with severe Alzheimer's disease or those not meeting the inclusion criteria may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could improve cognitive functions in patients with Alzheimer's disease.

How similar studies have performed: Other studies have explored similar epigenetic approaches in Alzheimer's disease, but the specific use of ONO-2020 is novel.

Eligibility criteria

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

Where this trial is running

Decatur, Georgia and 11 other locations

• Sandhill Research, LLC d/b/a Accel Research Sites - NeuroStudies CRU — Decatur, Georgia, United States (Recruiting)
• ActivMed Research — Methuen, Massachusetts, United States (Recruiting)
• Inage Neurology and Memory Clinic — Chiba, Japan (Not_yet_recruiting)
• Mabashi Clinic — Chiba, Japan (Not_yet_recruiting)
• Ikuseikai Shinozuka Hospital — Gunma, Japan (Not_yet_recruiting)
• Imon Yukari Neurology Clinic — Hiroshima, Japan (Not_yet_recruiting)
• NHO Hiroshima-Nishi Medical Center — Hiroshima, Japan (Not_yet_recruiting)
• Meiwakai Izaki Clinic — Nagasaki, Japan (Not_yet_recruiting)
• Katayama Medical Clinic — Okayama, Japan (Not_yet_recruiting)
• Federation of National Public Service Personnel Mutual Aid Associations Tachikawa Hospital — Tokyo, Japan (Not_yet_recruiting)
• Memory Clinic Ochanomizu — Tokyo, Japan (Not_yet_recruiting)
• Tokyo Metropolitan Institute for Geriatrics and Gerontology — Tokyo, Japan (Not_yet_recruiting)

Study contacts

• Study coordinator: Ono Pharma USA, Inc.

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