ONO-2020 for Alzheimer's Disease (NCT06881836)

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ONO-2020 for Alzheimer's Disease (NCT06881836)

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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) production

Therapeutic 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 cells

This 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 months

Age 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.

[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/)

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📊 Evidence Profile Foundational

Evidence Balance

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Certainty

100%

Debates

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Incoming

496

Outgoing

520

0 supporting 0 contradicting 0 neutral

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📗 Cite This Artifact

ONO-2020 for Alzheimer's Disease (NCT06881836)

ONO-2020 for Mild to Moderate Alzheimer's Disease (NCT06881836)

Trial Overview

Mechanism of Action

Epigenetic Dysregulation in Alzheimer's Disease

ONO-2020 for Mild to Moderate Alzheimer's Disease (NCT06881836)

Trial Overview

Mechanism of Action

Epigenetic Dysregulation in Alzheimer's Disease

Therapeutic Rationale

Study Design

Trial Structure

Treatment Arms

Primary Endpoints

Secondary Endpoints

Cognitive Outcomes

Functional Outcomes

Pharmacokinetics

Biomarkers

Eligibility Criteria

Inclusion Criteria

Key Exclusion Criteria

Age Range

Trial Locations

United States (54 sites)

Japan (16 sites)

Clinical Context

Epigenetic Therapeutics in Alzheimer's

Comparison to Current AD Therapies

Ono Pharmaceutical

External Links

References

💬 Discussion

📗 Cite This Artifact

ONO-2020 for Alzheimer's Disease (NCT06881836)

ONO-2020 for Mild to Moderate Alzheimer's Disease (NCT06881836)

Trial Overview

Mechanism of Action

Epigenetic Dysregulation in Alzheimer's Disease

ONO-2020 for Mild to Moderate Alzheimer's Disease (NCT06881836)

Trial Overview

Mechanism of Action

Epigenetic Dysregulation in Alzheimer's Disease

Therapeutic Rationale

Study Design

Trial Structure

Treatment Arms

Primary Endpoints

Secondary Endpoints

Cognitive Outcomes

Functional Outcomes

Pharmacokinetics

Biomarkers

Eligibility Criteria

Inclusion Criteria

Key Exclusion Criteria

Age Range

Trial Locations

United States (54 sites)

Japan (16 sites)

Clinical Context

Epigenetic Therapeutics in Alzheimer's

Comparison to Current AD Therapies

Ono Pharmaceutical

Related Pages

External Links

References

💬 Discussion