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

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

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).

Study Overview

• Status: Completed
• Conditions: Alzheimer's Disease
• Intervention / Treatment: Drug: Active Comparator: A; Drug: Placebo Comparator A; Drug: Active Comparator B; Drug: Placebo Comparator B

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 80
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Garden Grove, California, United States
    • San Francisco, California, United States
  • Florida
    • Orlando, Florida, United States
  • Georgia
    • Atlanta, Georgia, United States
  • Indiana
    • Indianapolis, Indiana, United States
  • New Jersey
    • Eatontown, New Jersey, United States
    • Princeton, New Jersey, United States
  • Utah
    • Salt Lake City, Utah, United States

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion:

1. 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.
2. 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.
3. 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.
4. On stable doses of all other prescribed medications for at least 4 weeks prior to the screening visit.

Exclusion:

1. Any neurological condition that could be contributing to cognitive impairment above and beyond that caused by the subject's Alzheimer's disease (AD).
2. Any psychiatric diagnosis or symptoms, e.g hallucinations, major depression, or delusions, that could interfere with assessment of cognition in the subject.
3. History of transient ischemic attack (TIA), stroke, or seizures within 12 months of Screening.
4. 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.
5. 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: SINGLE_GROUP
• Masking: QUADRUPLE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Active Comparator: A	Drug: Active Comparator: A; 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); Other Names: BAN2401
PLACEBO_COMPARATOR: Placebo Comparator A	Drug: Placebo Comparator A; Placebo Matching Placebo Infusion
ACTIVE_COMPARATOR: Active Comparator: B	Drug: Active Comparator B; Lecanemab Multiple Dose Ascending Intravenous infusions once every 4 weeks at sequentially ascending doses (dose levels: 0.3, 1, 3, and 10 mg/kg); Other Names: BAN2401
PLACEBO_COMPARATOR: Placebo Comparator B	Drug: Placebo Comparator B; Placebo Matching Placebo Infusion

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Eisai Inc.

Publications and helpful links

General Publications

• Logovinsky V, Satlin A, Lai R, Swanson C, Kaplow J, Osswald G, Basun H, Lannfelt L. Safety and tolerability of BAN2401--a clinical study in Alzheimer's disease with a protofibril selective Abeta antibody. Alzheimers Res Ther. 2016 Apr 6;8(1):14. doi: 10.1186/s13195-016-0181-2.

Study record dates

Study Major Dates

• Study Start: August 1, 2010
• Primary Completion (ACTUAL): October 1, 2012
• Study Completion (ACTUAL): February 1, 2013

Study Registration Dates

• First Submitted: October 27, 2010
• First Submitted That Met QC Criteria: October 28, 2010
• First Posted (ESTIMATE): October 29, 2010

Study Record Updates

• Last Update Posted (ACTUAL): November 23, 2020
• Last Update Submitted That Met QC Criteria: November 20, 2020
• Last Verified: February 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Neurodegenerative Diseases; Dementia; Tauopathies; Alzheimer Disease
• Other Study ID Numbers: BAN2401-A001-101