A Randomized, Double-blind, Placebo-controlled, Combined Single Ascending Dose and Multiple Ascending Dose Study

Study Overview
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Brief Summary
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The purpose of this study will be to evaluate the safety and tolerability of lecanemab at sequentially ascending doses in subjects with mild to moderate Alzheimer's disease (AD).

Detailed Description
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This will be a multicenter, double-blind, randomized, placebo-controlled study in subjects with mild to moderate Alzheimer's disease. The study will comprise separate single dose ascending (SAD) and multiple dose ascending (MAD) parts designed to allow the MAD part to be initiated while the SAD part is ongoing.

Official Title
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A Randomized, Double-blind, Placebo-controlled, Combined Single Ascending Dose and Multiple Ascending Dose Study to Assess Safety, Tolerability, Immunogenicity, Pharmacodynamic Response, and Pharmacokinetics of Intravenous Infusions of BAN2401 in Subjects With Mild to Moderate Alzheimer?s Disease

Conditions
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Alzheimer's Disease

Intervention / Treatment
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* Drug: Active Comparator: A
* Drug: Placebo Comparator B
* Drug: Active Comparator B
* Drug: Placebo Comparator A


Participation Criteria
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Eligibility Criteria
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Inclusion: Clinical diagnosis of probable mild to moderate Alzheimer's disease (AD) by National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association Alzheimer's (NINCDS-ADRDA) criteria. A Mini Mental State Examination (MMSE) score of 16 to 28, inclusive, at Screening. Subjects recruited to the first 2 SAD cohorts should have an MMSE of > 22. Where symptomatic treatment of Alzheimer's disease (AD) is clinically indicated, subjects must be on stable treatment (e.g., with an anticholinesterase inhibitor [AChEI] and/or memantine) for at least 12 weeks prior to the Screening visit. On stable doses of all other prescribed medications for at least 4 weeks prior to the screening visit. Exclusion: Any neurological condition that could be contributing to cognitive impairment above and beyond that caused by the subject's Alzheimer's disease (AD). Any psychiatric diagnosis or symptoms, e.g hallucinations, major depression, or delusions, that could interfere with assessment of cognition in the subject. History of transient ischemic attack (TIA), stroke, or seizures within 12 months of Screening. Evidence of infection, tumor, stroke or other clinically significant lesions that could indicate a dementia diagnosis other than AD on brain magnetic resonance imaging (MRI) at Screening. Other significant pathological findings on brain MRI at Screening, including but not limited to: more than 3 micro-hemorrhages, single macro-hemorrhage; evidence of vasogenic edema; evidence of cerebral contusion, encephalomalacia, aneurysms, vascular malformations or space occupying lesions.

Ages Eligible for Study
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Minimum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Active Comparator: A<br> | Drug: Active Comparator: A<br>* Lecanemab Single Dose Ascending Single intravenous infusions at sequentially ascending doses on Day 1 (dose levels: 0.1, 0.3, 1, 3, 10, and 15 mg/kg)<br>* Other names: BAN2401;|
| Placebo Comparator: Placebo Comparator A<br> | Drug: Placebo Comparator A<br>* Placebo Matching Placebo Infusion<br>|
| Active Comparator: Active Comparator: B<br> | Drug: Active Comparator B<br>* Lecanemab Multiple Dose Ascending Intravenous infusions once every 4 weeks at sequentially ascending doses (dose levels: 0.3, 1, 3, and 10 mg/kg)<br>* Other names: BAN2401;|
| Placebo Comparator: Placebo Comparator B<br> | Drug: Placebo Comparator B<br>* Placebo Matching Placebo Infusion<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Single Ascending Dose (SAD) | To evaluate the safety and tolerability of single intravenous (i.v.) infusions of lecanemab at sequentially ascending doses in subjects with mild to moderate Alzheimer's disease (AD) | baseline to Day 180 post-dose | 
| Multiple Ascending Dose(MAD) | To evaluate the safety and tolerability of 4 monthly i.v. infusions of lecanemab at sequentially ascending doses in subjects with AD | baseline to Day 264 post-dose |