A Placebo-Controlled, Double-Blind, Parallel-Group, 18-Month Study With an Op... (NCT03887455)

A Study to Confirm Safety and Efficacy of Lecanemab in Participants With Early Alzheimer's Disease

Overview

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

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:

Study 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:

The 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].

Related Resources

• [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

Comparison 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

Exclusion Criteria

Dose & 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