Clinical trial NCT06881836: A Study of ONO-2020 in Participants With Mild to Moderate Alzheimer's Disease
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Alzheimer Disease
Keywords: Alzheimer Disease
mild to moderate Alzheimer Disease
Dementia
ONO-2020
Lead sponsor: Ono Pharmaceutical Co. Ltd
Sponsor class: INDUSTRY
First posted: 2025-03-18
Enrollment: 240
Sex: ALL
Minimum age (years): 55
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Incidence, severity, and type of treatment emergent adverse events (TEAEs)
timeFrame: From baseline up to 26 weeks
measure: Clinically abnormal findings in Columbia Suicide Severity Rating Scale (C-SSRS)
timeFrame: From baseline up to 26 weeks
measure: Change from baseline through week 26 in Alzheimer's Disease Assessment Scale-Cognitive Subscale 12 (ADAS-cog 12) score
timeFrame: From baseline up to 26 weeks
Secondary outcomes:
measure: Change from baseline through week 26 in ADAS-cog 12 score in mild AD participants
timeFrame: From baseline up to 26 weeks
measure: Change from baseline through week 26 in ADAS-cog 12 score in moderate AD participants
timeFrame: From baseline up to 26 weeks
measure: Change from baseline through week 26 in ADAS-cog 11 and 13 scores
timeFrame: From baseline up to 26 weeks
measure: Change from baseline through week 26 in Alzheimer's Disease Cooperative Study Group-Activities of Daily Living (ADCS-ADL) score
timeFrame: From baseline up to 26 weeks
measure: Change from baseline through week 26 in Quick Dementia Rating System (QDRS)
timeFrame: From baseline up to 26 weeks
measure: Change from baseline through week 26 in Mini-Mental State Examination (MMSE) score
timeFrame: From baseline up to 26 weeks
measure: Change from baseline through week 26 in Neuropsychiatric Inventory Questionnaire (NPI-Q)
timeFrame: From baseline up to 26 weeks
measure: Change from baseline through week 26 in Quality of Life-Alzheimer's Disease (QoL-AD) Scale
timeFrame: From baseline up to 26 weeks
measure: Change from baseline through week 26 in Zarit Burden Interview Scale (ZBI)
timeFrame: From baseline up to 26 weeks
measure: Change in plasma concentration of ONO-2020 by dose level and time point
timeFrame: Day 1, Week 2, Week 10, and Week 26
Other outcomes:
Locations:
city: Walnut Creek
country: United States
facility: Sunwise Clinical Research
state: California
city: Delray Beach
country: United States
facility: Brain Matters Research
state: Florida
city: Fort Myers
country: United States
facility: Neuropsychiatric Research Center of Southwest Florida
state: Florida
city: Hallandale Beach
country: United States
facility: Velocity Clinical Research, Hallandale Beach
state: Florida
city: Decatur
country: United States
facility: Sandhill Research, LLC d/b/a Accel Research Sites - NeuroStudies CRU
state: Georgia
city: Methuen
country: United States
facility: ActivMed Research
state: Massachusetts
city: Las Vegas
country: United States
facility: Vector Clinical Trials
state: Nevada
city: Raleigh
country: United States
facility: Velocity Clinical Research at Raleigh Neurology
state: North Carolina
city: Chiba
country: Japan
facility: Inage Neurology and Memory Clinic
city: Chiba
country: Japan
facility: Mabashi Clinic
city: Gunma
country: Japan
facility: Ikuseikai Shinozuka Hospital
city: Hiroshima
country: Japan
facility: Imon Yukari Neurology Clinic
city: Hiroshima
country: Japan
facility: NHO Hiroshima-Nishi Medical Center
city: Hyogo
country: Japan
facility: Himeji Central Hospital Clinic
city: Ibaraki
country: Japan
facility: Memory Clinic Toride
city: Kagawa
country: Japan
facility: Kagawa Prefectural Central Hospital
city: Nagasaki
country: Japan
facility: Meiwakai Izaki Clinic
city: Okayama
country: Japan
facility: Katayama Medical Clinic
city: Tochigi
country: Japan
facility: Jichiidai Station Brain Clinic
city: Tokushima
country: Japan
facility: Ichiekai Itsuki Hospital
city: Tokyo
country: Japan
facility: Federation of National Public Service Personnel Mutual Aid Associations Tachikawa Hospital
city: Tokyo
country: Japan
facility: Memory Clinic Ochanomizu
city: Tokyo
country: Japan
facility: Tokyo Medical University Hospital
city: Tokyo
country: Japan
facility: Tokyo Metropolitan Institute for Geriatrics and Gerontology
Study officials:
affiliation: Ono Pharmaceutical Co. Ltd
name: Project Leader
role: STUDY_DIRECTOR
References: