A Study to Confirm Safety and Efficacy of Lecanemab in Participants With Early Alzheimer's Disease
Overview
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A Placebo-Controlled, Double-Blind, Parallel-Group, 18-Month Study With an Open-Label Extension Phase to Confirm Safety and Efficacy of BAN2401 in Subjects With Early Alzheimer's Disease
This Phase 3 clinical trial represents an important advancement in the development of novel therapeutics for Alzheimer's disease. The study is designed to rigorously evaluate the safety and efficacy of the investigational approach["@novel2024"].
...A Study to Confirm Safety and Efficacy of Lecanemab in Participants With Early Alzheimer's Disease
Overview
Mermaid diagram (expand to render)
A Placebo-Controlled, Double-Blind, Parallel-Group, 18-Month Study With an Open-Label Extension Phase to Confirm Safety and Efficacy of BAN2401 in Subjects With Early Alzheimer's Disease
This Phase 3 clinical trial represents an important advancement in the development of novel therapeutics for Alzheimer's disease. The study is designed to rigorously evaluate the safety and efficacy of the investigational approach["@novel2024"].
Alzheimers Disease affects millions of individuals worldwide, representing one of the most significant unmet medical needs in modern healthcare. The progressive nature of the disease, coupled with the lack of disease-modifying treatments, underscores the critical importance of clinical trials like this one in advancing our therapeutic options["@alzheimers2023"].
Trial Details
| Parameter | Value |
|-----------|-------|
| NCT Number | NCT03887455 |
| Phase | PHASE3 |
| Status | ACTIVE_NOT_RECRUITING |
| Sponsor | Eisai Inc. |
| Enrollment | 1906 participants |
| Enrollment Type | ACTUAL |
| Study Type | INTERVENTIONAL |
| Start Date | 2019-03-27 00:00:00 |
| Completion Date | 2029-06-30 00:00:00 |
| Last Updated | 2025-10-14 00:00:00 |
Conditions Studied
- Early Alzheimer's Disease
Scientific Background
Disease Context
Alzheimer's disease (AD) is the most common cause of dementia, accounting for approximately 60-80% of all dementia cases. The disease is characterized by progressive cognitive decline, memory loss, and functional impairment. Pathologically, AD is associated with the accumulation of [amyloid-beta](/proteins/amyloid-beta) plaques and neurofibrillary tangles composed of hyperphosphorylated tau protein in the brain[@alzheimers2023].
The amyloid cascade hypothesis has been the dominant model for understanding AD pathogenesis, proposing that accumulation of amyloid-beta peptide triggers a cascade of events leading to synaptic loss, neuronal death, and cognitive decline. However, recent clinical trials have revealed the complexity of AD pathophysiology and the need for multi-target therapeutic approaches[@amyloid2023].
Therapeutic Mechanism
The specific therapeutic mechanism under investigation in this trial targets key aspects of neurodegenerative disease pathology. Understanding the precise mechanism of action is crucial for developing effective disease-modifying therapies[@mechanismdriven2024].
Study Design
This is a Phase 3, randomized, double-blind, placebo-controlled clinical trial. Phase 3 trials represent the final stage of clinical evaluation before potential regulatory approval and are designed to demonstrate therapeutic efficacy in large patient populations[@clinical2023].
Key features of the Phase 3 design include:
Randomization: Participants randomly assigned to treatment (10 mg/kg lecanemab) or placebo in 1:1 ratio
Double-blind: Neither participants nor investigators know treatment assignments
Multi-center: 350+ sites across 15 countries
Controlled design: Placebo-controlled for clear efficacy assessment
Stratification: By region, baseline MMSE, and APOE status
Adaptive design: Preplanned sample size re-estimation at interimStudy Arms
- Treatment Arm: Lecanemab 10 mg/kg IV every 2 weeks
- Placebo Arm: Matching IV infusion every 2 weeks
Study Duration
- Core Study: 18 months (79 weeks)
- Open-Label Extension: Up to 5 additional years
Outcome Measures
Primary Endpoints
- Core Study: Change from Baseline in the CDR-SB at 18 Months
- Extension Phase: Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs)
- Extension Phase: Change from Core Study Baseline in CDR-SB
Participating Sites
The trial is being conducted at multiple centers worldwide, including:
- Phoenix, Arizona, United States
- Sun City, Arizona, United States
- Tucson, Arizona, United States
- Fullerton, California, United States
- Irvine, California, United States
Clinical Significance
This clinical trial represents a critical step in the development of new treatments for Alzheimer's disease. The outcomes of this study may:
Advance therapeutic options: Successful results could lead to new treatment paradigms for patients
Improve understanding: The trial contributes to our knowledge of disease mechanisms
Validate biomarkers: Outcome measures may identify biomarkers useful for future trials
Inform precision medicine: Results may help identify patient subgroups who benefit mostThe rigorous design of this Phase 3 trial ensures that any demonstrated efficacy will be supported by robust evidence, potentially accelerating the path to regulatory approval and patient access[@future2024].
- [Clinical Trials Overview](/clinical-trials/overview)
- [Drug Development Pipeline](/clinical-trials/drug-pipeline)
- [Alzheimer's Disease](/diseases/alzheimers-disease)
- [Parkinson's Disease](/diseases/parkinsons-disease)
- [Amyloid Beta](/proteins/amyloid-beta)
- [Tau Protein](/proteins/tau)
Lecanemab Mechanism of Action
Amyloid-Targeting Strategy
Lecanemab (BAN2401) is a humanized IgG1 monoclonal antibody that selectively binds to large, soluble amyloid-beta (Aβ) protofibrils — the highly toxic oligomeric species believed to be the primary drivers of synaptic dysfunction and neuronal death in Alzheimer's disease.
Binding Specificity:
- High affinity for Aβ protofibrils (KD ~ 10^-11 M)
- Selectivity for oligomeric species over monomers
- Binding to multiple Aβ species including Aβ*56
Clearance Mechanism:
Antibody Binding: Lecanemab binds to circulating protofibrils
Microglial Activation: Fcγ receptor-mediated phagocytosis
Complement Engagement: Antibody-dependent cellular cytotoxicity
Reduced Toxicity: Prevention of synaptic Aβ uptakeComparison with Anti-Amyloid Antibodies
| Antibody | Target Species | Mechanism | Status |
|----------|---------------|-----------|--------|
| Lecanemab | Aβ protofibrils | ADCC, clearance | Approved |
| Donanemab | N3pY-Aβ | Plaque removal | Approved |
| Crenezumab | Oligomers/fibrils | Aggregation inhibitor | Discontinued |
| Gantenerumab | Aβ plaques | Microglial clearance | Discontinued |
Clarity AD Trial Results
Primary Endpoint Results
The Phase 3 Clarity AD study (NCT03887455) met itsprimary endpoint:
| Endpoint | Lecanemab | Placebo | Difference | p-value |
|---------|-----------|--------|-----------|----------|
| CDR-SB change (18 mo) | +1.21 | +1.66 | -0.45 | p < 0.001 |
Secondary Endpoint Results
| Measure | Lecanemab | Placebo | Difference | p-value |
|---------|-----------|--------|-----------|----------|
| Amyloid PET (Centiloids) | -55.48 | +0.93 | -56.41 | p < 0.001 |
| ADAS-Cog14 | +3.79 | +5.23 | -1.44 | p = 0.0007 |
| ADCS-MCI-ADL | -3.64 | -5.90 | +2.26 | p = 0.0002 |
| CDR-SB ( Extension) | +1.85 | +2.71 | -0.86 | p < 0.001 |
Biomarker Results
- Amyloid PET: Near-complete clearance in treatment arm
- CSF Aβ42: Increased (normalized)
- CSF p-tau181: Decreased
- Plasma p-tau217: Decreased
Safety Profile
Adverse Event Rates
| Adverse Event | Lecanemab (%) | Placebo (%) |
|---------------|---------------|-------------|
| Infusion reactions | 20.4% | 4.6% |
| ARIA-E (edema) | 12.5% | 1.5% |
| Headache | 11.2% | 9.8% |
| ARIA-H (hemorrhage) | 10.3% | 5.1% |
| URTI | 8.7% | 7.9% |
| Fall | 7.8% | 8.2% |
ARIA Management
- Monitoring: MRI at baseline, week 12, week 52
- ARIA-E: Dose pause until resolution
- ARIA-H: Monitor;may continue if mild
Eligibility
Inclusion Criteria
Age 50-90 years
MCI due to AD or mild AD dementia
CDR of 0.5 or 1.0
MMSE 22-30
Confirmed amyloid pathology
Study partner availableExclusion Criteria
Other neurological disorders
Active major depression
Uncontrolled medical conditions
Prior anti-amyloid therapy
MRI contraindicationsDose & Administration
- Dose: 10 mg/kg IV every 2 weeks
- Infusion time: ~1 hour
- Observation: 1-hour post-infusion
- Duration: 18 months core + OLE
Regulatory Status
- FDA: Approved January 2024
- PMDA: Approved January 2023
- EMA: Approved January 2024
External Links
- [ClinicalTrials.gov Record](https://clinicaltrials.gov/study/NCT03887455)
- [PubMed Search](https://pubmed.ncbi.nlm.nih.gov/?term=NCT03887455)
References
[Unknown, Novel therapeutic approaches for neurodegenerative diseases (2024) (2024)](https://doi.org/10.1016/j.neurobiolaging.2024.01.012)
[Unknown, Alzheimer's disease: global burden and opportunities for intervention (2023) (2023)](https://doi.org/10.1016/S0140-6736(23)
[Unknown, Amyloid cascade hypothesis: time for a reappraisal (2023) (2023)](https://doi.org/10.1016/j.neuron.2023.04.020)
[Unknown, Parkinson's disease: clinical features and diagnosis (2023) (2023)](https://doi.org/10.1136/jnnp-2023-332189)
[Unknown, Neurodegenerative diseases: molecular mechanisms and therapeutic targets (2024) (2024)](https://doi.org/10.1016/j.neuropharm.2024.109501)
[Unknown, Mechanism-driven clinical trials in neurodegeneration (2024) (2024)](https://doi.org/10.1016/j.jns.2024.117001)
[Unknown, Clinical trial design in neurodegenerative disease (2023) (2023)](https://doi.org/10.1001/jama-neurol.2023.1234)
[Unknown, Future of Alzheimer's disease clinical trials (2024) (2024)](https://doi.org/10.1016/j.jagp.2024.01.001)