ONO-2020 for Mild to Moderate Alzheimer's Disease (NCT06881836)
ClinicalTrials.gov Identifier: [NCT06881836](https://clinicaltrials.gov/study/NCT06881836)
Trial Overview
flowchart TD
ONO_2020_for_Alzheimer_s_Disea["ONO-2020 for Alzheimer's Disease (NCT06881836)"] -->|"references"| synaptic_plasticity_genes["synaptic plasticity genes"]
ONO_2020_for_Alzheimer_s_Disea["ONO-2020 for Alzheimer's Disease (NCT06881836)"] -->|"references"| HDAC["HDAC"]
style ONO_2020_for_Alzheimer_s_Disea fill:#4fc3f7,stroke:#333,color:#000
| Attribute | Details |
|-----------|---------|
| Phase | Phase 2 |
| Status | Active, Not Recruiting |
| Sponsor | Ono Pharmaceutical Co. Ltd. |
| Intervention | ONO-2020 (epigenetic regulator) |
| Indication | Mild to Moderate Alzheimer's Disease |
| Enrollment | 240 participants |
| Study Duration | 26 weeks (+ 4-week follow-up) |
| Study Design | Double-blind, Placebo-controlled, Parallel assignment |
| Randomization | 1:1:1 (two dose levels + placebo) |
| Registry | jRCT2031240712 (Japan) |
Mechanism of Action
ONO-2020 is a novel epigenetic regulator being developed by Ono Pharmaceutical for the treatment of Alzheimer's disease. Epigenetic regulators represent an emerging therapeutic approach that targets the underlying gene expression dysregulation observed in neurodegenerative diseases[@ballard2023].
Epigenetic Dysregulation in Alzheimer's Disease
...ONO-2020 for Mild to Moderate Alzheimer's Disease (NCT06881836)
ClinicalTrials.gov Identifier: [NCT06881836](https://clinicaltrials.gov/study/NCT06881836)
Trial Overview
Mermaid diagram (expand to render)
| Attribute | Details |
|-----------|---------|
| Phase | Phase 2 |
| Status | Active, Not Recruiting |
| Sponsor | Ono Pharmaceutical Co. Ltd. |
| Intervention | ONO-2020 (epigenetic regulator) |
| Indication | Mild to Moderate Alzheimer's Disease |
| Enrollment | 240 participants |
| Study Duration | 26 weeks (+ 4-week follow-up) |
| Study Design | Double-blind, Placebo-controlled, Parallel assignment |
| Randomization | 1:1:1 (two dose levels + placebo) |
| Registry | jRCT2031240712 (Japan) |
Mechanism of Action
ONO-2020 is a novel epigenetic regulator being developed by Ono Pharmaceutical for the treatment of Alzheimer's disease. Epigenetic regulators represent an emerging therapeutic approach that targets the underlying gene expression dysregulation observed in neurodegenerative diseases[@ballard2023].
Epigenetic Dysregulation in Alzheimer's Disease
The [epigenetic regulation](/mechanisms/epigenetic-regulation) of gene expression is increasingly recognized as a key contributor to Alzheimer's disease pathogenesis. Several epigenetic changes have been documented in AD:
- [DNA methylation](/entities/dna-methylation) alterations — Global hypomethylation coupled with gene-specific hypermethylation patterns
- Histone modification changes — Acetylation and methylation patterns that affect chromatin structure and gene transcription
- Non-coding RNA dysregulation — miRNAs and lncRNAs that modulate gene expression post-transcriptionally
These epigenetic changes can lead to:
Downregulation of synaptic plasticity genes — Impaired memory formation and neuronal communication
Dysregulation of inflammatory responses — Chronic [neuroinflammation](/mechanisms/neuroinflammation-alzheimers) that drives disease progression
Altered [tau](/proteins/tau) phosphorylation pathways — Increased [tau aggregation](/mechanisms/tau-aggregation) and neurofibrillary tangle formation
Impaired amyloid processing — Changes in [APP metabolism](/mechanisms/amyloid-precursor-protein-processing) and [Aβ](/proteins/amyloid-beta) productionTherapeutic Rationale
By targeting epigenetic regulators, ONO-2020 aims to:
Restore normal gene expression patterns — Correct dysregulated transcription of key neuronal genes
Promote neuroprotective pathways — Upregulate genes that support neuronal survival and function
Reduce pathological protein accumulation — Modify expression of genes involved in amyloid and tau metabolism
Modulate neuroinflammation — Regulate immune gene expression in glial cellsThis represents a disease-modifying approach rather than merely symptomatic treatment, addressing the upstream molecular dysregulation believed to drive Alzheimer's disease progression.
Study Design
Trial Structure
- Screening Period: Up to 6 weeks (42 days)
- Treatment Period: 26 weeks (orally, once daily)
- Follow-up: 4 weeks after treatment discontinuation
- Total Duration: Approximately 36 weeks per participant
Treatment Arms
| Arm | Description |
|-----|-------------|
| ONO-2020 Dose 1 | Low dose, orally once daily for 26 weeks |
| ONO-2020 Dose 2 | High dose, orally once daily for 26 weeks |
| Placebo | Matching placebo orally once daily for 26 weeks |
Primary Endpoints
- Safety and Tolerability — Incidence, severity, and type of treatment-emergent adverse events (TEAEs)
- Psychiatric Safety — Clinically abnormal findings in Columbia Suicide Severity Rating Scale (C-SSRS)
- Cognitive Efficacy — Change from baseline through week 26 in Alzheimer's Disease Assessment Scale-Cognitive Subscale 12 (ADAS-cog 12) score
Secondary Endpoints
Cognitive Outcomes
- Change in ADAS-cog 12 in mild AD participants
- Change in ADAS-cog 12 in moderate AD participants
- Change in ADAS-cog 11 and 13 scores
- Change in Mini-Mental State Examination (MMSE) score
- Change in Quick Dementia Rating System (QDRS)
Functional Outcomes
- Change in Alzheimer's Disease Cooperative Study Group-Activities of Daily Living (ADCS-ADL) score
- Change in Neuropsychiatric Inventory Questionnaire (NPI-Q)
- Change in Quality of Life-Alzheimer's Disease (QoL-AD) Scale
- Change in Zarit Burden Interview Scale (ZBI)
Pharmacokinetics
- Plasma concentration of ONO-2020 by dose level and time point (Day 1, Week 2, Week 10, Week 26)
Biomarkers
- CSF biomarker evaluation in up to 45 participants
Eligibility Criteria
Inclusion Criteria
Diagnosis of Alzheimer's disease per NIA-AA criteria with positive AD-specific biomarker (abnormal Core 1 or Core 2 biomarkers)
MRI or CT scan within 1 year prior to enrollment
MMSE score of 15 to 24 (inclusive), with ≤3 point deviation between screening and baseline
NIA-AA clinical stage 4 or 5 at screening and baseline
Stable dose of AD treatment (acetylcholinesterase inhibitors and/or memantine) for ≥90 days prior to randomization
Ability to comply with cognitive testing procedures
Postmenopausal female for ≥1 year, or male with appropriate contraception
Caregiver with ≥8 hours/week contact to support compliance
Able to ingest pills; acceptable overall health status
Written informed consent (or assent with LAR consent if cognitively impaired)Key Exclusion Criteria
Dementia not due to AD (DLB, vascular dementia, PD, Huntington's, etc.)
History of stroke, TIA, or pulmonary/cerebral embolism
Schizophrenia, bipolar disorder, or major depressive disorder in past year
Delirium within 30 days of screening
Suicidal ideation or suicide attempt within 6 months
Clinically significant ECG abnormality or QTcF >450msec (males) / >470msec (females)
HIV, hepatitis B or C positive
Liver function tests >1.5× ULN
Creatinine clearance ≤30 mL/min
Prior treatment with anti-Aβ antibodies
Investigational products within 3 monthsAge Range
- Minimum: 55 years
- Maximum: 85 years
Trial Locations
United States (54 sites)
| State | Sites |
|-------|-------|
| Alabama | University of Arizona at Birmingham |
| Arizona | Banner Alzheimer's Institute (Phoenix), Scottsdale, Sun City, Tucson |
| California | Carlsbad, Fullerton, Palo Alto (Stanford), Walnut Creek |
| Colorado | Englewood |
| Florida | Delray Beach, Hallandale Beach, Miami (×3), New Port Richey, Ocala, Orlando, Port Orange, Tampa (×2), The Villages, Winter Park |
| Georgia | Decatur, Savannah |
| Idaho | Meridian |
| Illinois | Chicago (×3), Elk Grove Village |
| Kansas | Fairway (University of Kansas) |
| Kentucky | Lexington (Sanders-Brown Center on Aging) |
| Massachusetts | Boston, Methuen |
| Michigan | Farmington Hills |
| Nevada | Las Vegas (×2) |
| New Jersey | Springfield, Toms River, West Long Branch |
| New York | Brooklyn, Buffalo, East Syracuse, Manhasset (Feinstein Institutes), New York (NYU), Rochester, Stony Brook |
| North Carolina | Charlotte, Raleigh (×2) |
| Ohio | Canton, Cincinnati, Columbus, Dayton, North Canton |
| Oregon | Portland (×2) |
| Pennsylvania | Philadelphia (Penn Medicine) |
| Rhode Island | Providence |
| Tennessee | Cordova, Knoxville, Nashville (Vanderbilt) |
| Texas | Austin, Cypress, Dallas (×2), Fort Worth, Houston, Katy, Round Rock (×2), Wichita Falls |
| Utah | Salt Lake City |
| Virginia | Fairfax, Norfolk |
| Washington | Bellevue, Spokane |
Japan (16 sites)
- National Center for Geriatrics and Gerontology (Aichi)
- Inage Neurology and Memory Clinic (Chiba)
- Mabashi Clinic (Chiba)
- Southern Tohoku Medical Clinic (Fukushima)
- Ikuseikai Shinozuka Hospital (Gunma)
- Hiroshima medical centers (×3)
- Kobe City Medical Center (Hyōgo)
- Memory Clinic Toride (Ibaraki)
- Kagawa Prefectural Central Hospital
- Meiwakai Izaki Clinic (Nagasaki)
- Okayama Medical Clinic
- Takesato Hospital (Saitama)
- Jichiidai Station Brain Clinic (Tochigi)
- Ichiekai Itsuki Hospital (Tokushima)
- Tokyo sites (×4): Tachikawa Hospital, Memory Clinic Ochanomizu, Tokyo Medical University Hospital, Tokyo Metropolitan Institute for Geriatrics and Gerontology
Clinical Context
Epigenetic Therapeutics in Alzheimer's
ONO-2020 enters a growing field of epigenetic-based approaches for neurodegenerative diseases:
| Compound | Company | Mechanism | Stage |
|----------|---------|-----------|-------|
| ONO-2020 | Ono Pharmaceutical | Epigenetic regulator | Phase 2 |
| Various [HDAC](/entities/hdac-enzymes) inhibitors | Multiple | Histone deacetylase inhibition | Various |
Comparison to Current AD Therapies
Current FDA-approved AD treatments include:
- [Lecanemab](/entities/lecanemab) (Leqembi) — Anti-amyloid monoclonal antibody (anti-Aβ protofibrils)
- [Donanemab](/entities/donanemab) (Kisunla) — Anti-amyloid monoclonal antibody (anti-Aβ plaque)
- Aducanumab (Aduhelm) — Anti-amyloid monoclonal antibody
- Symptomatic treatments — [Cholinesterase inhibitors](/entities/cholinesterase-inhibitors) ([donepezil](/entities/donepezil), [rivastigmine](/entities/rivastigmine), galantamine) and memantine
ONO-2020 represents a
different mechanistic class targeting epigenetic regulation rather than amyloid clearance or symptomatic benefit.
Ono Pharmaceutical
Ono Pharmaceutical Co. Ltd. is a major Japanese pharmaceutical company headquartered in Osaka, Japan. The company has a diverse pipeline in:
- Oncology — Immuno-oncology and targeted therapies
- Immunology — Autoimmune and inflammatory diseases
- Neurology — CNS disorders including Alzheimer's disease
ONO-2020 represents their lead candidate in the CNS space for Alzheimer's disease, reflecting a strategic expansion beyond their traditional therapeutic areas.
Related Pages
- [Epigenetic Regulation in Neurodegeneration](/mechanisms/epigenetic-regulation)
- [DNA Methylation and Neurodegeneration](/mechanisms/epigenetics-ad)
- [Alzheimer's Disease Clinical Trials](/clinical-trials)
- [Alzheimer's Disease Overview](/diseases/alzheimers-disease)
- [Neuroinflammation in AD](/mechanisms/neuroinflammation-alzheimers)
- [Tau Pathology in AD](/mechanisms/tau-aggregation)
- [Amyloid Cascade Hypothesis](/mechanisms/amyloid-cascade)
External Links
- [ClinicalTrials.gov: NCT06881836](https://clinicaltrials.gov/study/NCT06881836)
- [Ono Pharmaceutical R&D Pipeline](https://www.ono-pharma.com)
References
[Ballard et al., The underlying mechanisms of cognitive decline in Alzheimer's disease (2023) (2023)](https://pubmed.ncbi.nlm.nih.gov/37112345/)