A Study to Evaluate Safety, Tolerability, and Efficacy of Lecanemab in Subjects With Early Alzheimer's Disease

A Placebo-Controlled, Double-Blind, Parallel-Group, Bayesian Adaptive Randomization Design and Dose Regimen-finding Study With an Open-Label Extension Phase to Evaluate Safety, Tolerability and Efficacy of BAN2401 in Subjects With Early Alzheimer's Disease

This is a multinational, multicenter, double-blind, placebo-controlled, parallel-group study using a Bayesian design with response adaptive randomization across placebo or 5 active arms of lecanemab to determine clinical efficacy and to explore the dose response of lecanemab using a composite clinical score (ADCOMS). BAN2401-G000-201 Core study is an 18-month study in which 3 dose levels (2.5, 5, and 10 mg/kg) are given biweekly (once every 2 weeks) to separate groups of participants and 2 dose levels (5 and 10 mg/kg) are given monthly (once every 4 weeks) to separate groups of participants. Participants will be from 2 clinical subgroups: mild cognitive impairment (MCI) due to Alzheimer's disease (AD) or mild Alzheimer's disease dementia. Frequent interim analyses will be conducted to continually update randomization allocation on the basis of the primary clinical endpoint. Any participant who completes the study treatment (Visit 42 [Week 79] of the Core study) or discontinues the Core Study will be eligible to participate in the Extension Phase, provided they meet the Extension Phase inclusion and exclusion criteria. Participants will receive 10 mg/kg biweekly for up to 60 months or until the drug is commercially available in the country, where the subject resides, or until the benefit-to-risk ratio from treatment with lecanemab is no longer considered favorable, whichever comes first. The Follow-up Visit in the Extension Phase will take place 3 months after the last dose of study drug.

Study Overview

• Status: Completed
• Conditions: Alzheimer's Disease
• Intervention / Treatment: Drug: Lecanemab 2.5 mg/kg; Drug: Lecanemab 5.0 mg/kg; Drug: Lecanemab 5.0 mg/kg; Drug: Lecanemab 10 mg/kg; Drug: Lecanemab 10 mg/kg; Drug: Lecanemab 10 mg/kg; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 856
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Québec, Canada
    • Facility #1
  • Nova Scotia
    • Kentville, Nova Scotia, Canada
      • Facility #1
  • Ontario
    • Kingston, Ontario, Canada
      • Facility #1
    • London, Ontario, Canada
      • Facility #2
    • Ottawa, Ontario, Canada
      • Facility #1
    • Peterborough, Ontario, Canada
      • Facility #1
    • Toronto, Ontario, Canada
      • Facility #1
  • Quebec
    • Greenfield Park, Quebec, Canada
      • Facility #1
    • Montreal, Quebec, Canada
      • Facility #1
    • Verdun, Quebec, Canada
      • Facility #1
• France
  • Bron, France
    • Facility #1
  • Paris, France
    • Facility #1
  • Rennes, France
    • Facility #1
  • Villeurbanne, France
    • Facility #1
  • Bas Rhin
    • Strasbourg, Bas Rhin, France
      • Facility #1
  • Haute Garonne
    • Toulouse, Haute Garonne, France
      • Facility #1
  • Paris
    • Paris, Paris, France
      • Facility #1
• Germany
  • Berlin, Germany
    • Facility #1
  • Berlin, Germany
    • Facility #2
  • Berlin, Germany
    • Facility #3
  • Günzburg, Germany
    • Facility #1
  • Hamburg, Germany
    • Facility #1
  • Heidelberg, Germany
    • Facility #1
  • Leipzig, Germany
    • Facility #1
  • Mannheim, Germany
    • Facility #1
  • München, Germany
    • Facility #1
  • Tübingen, Germany
    • Facility #1
  • Baden-Wurttemberg
    • Gunzburg, Baden-Wurttemberg, Germany
      • Facility #1
  • Bavaria
    • Karlstadt am Main, Bavaria, Germany
      • Facility #1
  • Lower Saxony
    • Hanover, Lower Saxony, Germany
      • Facility #1
  • Saxony
    • Mittweida, Saxony, Germany
      • Facility #1
  • State of Berlin
    • Hoppegarten, State of Berlin, Germany
      • Facility #1
• Italy
  • Brescia, Italy
    • Facility #1
  • Genova, Italy
    • Facility #1
  • Milan, Italy
    • Facility #1
  • Parma, Italy
    • Facility #1
  • Perugia, Italy
    • Facility #1
  • Pisa, Italy
    • Facility #1
  • Roma, Italy
    • Facility #1
  • Roma, Italy
    • Facility #2
  • Roma, Italy
    • Facility #3
• Japan
  • Hiroshima
    • Otake-shi, Hiroshima, Japan
      • Eisai Trial Site #1
  • Hyōgo
    • Himeji-shi, Hyōgo, Japan
      • Eisai Trial Site #1
    • Himeji-shi, Hyōgo, Japan
      • Eisai Trial Site #2
    • Himeji-shi, Hyōgo, Japan
      • Eisai Trial Site #3
    • Kobe, Hyōgo, Japan
      • Eisai Trial Site #1
    • Nishinomiya-shi, Hyōgo, Japan
      • Eisai Trial Site #1
  • Kyoto
    • Kyoto, Kyoto, Japan
      • Eisai Trial Site #1
  • Okayama-ken
    • Kurashiki-shi, Okayama-ken, Japan
      • Eisai Trial Site #1
  • Osaka
    • Osaka, Osaka, Japan
      • Eisai Trial Site #1
  • Saitama
    • Saitama-shi, Saitama, Japan
      • Eisai Trial Site #1
  • Tokyo-To
    • Itabashi-ku, Tokyo-To, Japan
      • Eisai Trial Site #1
    • Shinjuku-ku, Tokyo-To, Japan
      • Eisai Trial Site #1
    • Shinjuku-ku, Tokyo-To, Japan
      • Eisai Trial Site #2
• Netherlands
  • Amsterdam, Netherlands
    • Facility #1
• South Korea
  • Seoul, South Korea
    • Facility #2
  • Seoul, South Korea
    • Facility #3
  • Seoul, South Korea
    • Facility #4
  • Gyeonggi-do
    • Seongnam-si, Gyeonggi-do, South Korea
      • Facility #1
  • Gyeongsangnam-do
    • Pusan, Gyeongsangnam-do, South Korea
      • Facility #1
• Spain
  • Alicante, Spain
    • Facility #1
  • Barcelona, Spain
    • Facility #1
  • Madrid, Spain
    • Facility #1
  • Madrid, Spain
    • Facility #2
  • Seville, Spain
    • Facility #1
  • Barcelona
    • Sant Cugat Del Vallés, Barcelona, Spain
      • Facility #1
  • Guipuzcoa
    • Donostia / San Sebastian, Guipuzcoa, Spain
      • Facility #1
  • Vizcaya
    • Barakaldo, Vizcaya, Spain
      • Facility #1
• Sweden
  • Malmo, Sweden
    • Facility #1
  • Mölndal, Sweden
    • Facility #1
  • Stockholm, Sweden
    • Facility #1
  • Uppsala, Sweden
    • Facility #1
• United Kingdom
  • Bath, United Kingdom
    • Facility #1
  • London, United Kingdom
    • Facility #2
  • Swindon, United Kingdom
    • Facility #1
  • Greater London
    • London, Greater London, United Kingdom
      • Facility #1
  • Middlesex
    • Isleworth, Middlesex, United Kingdom
      • Facility #1
  • Renfrewshire
    • Glasgow, Renfrewshire, United Kingdom
      • Facility #1
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • Facility #1
  • Arizona
    • Phoenix, Arizona, United States, 85004
      • Facility #1
    • Tucson, Arizona, United States, 85724
      • Facility #1
  • California
    • Carson, California, United States, 90746
      • Facility #1
    • Lomita, California, United States, 90717
      • Facility #1
    • Long Beach, California, United States, 90806
      • Facility #1
    • Los Alamitos, California, United States, 90720
      • Facility #1
    • Los Angeles, California, United States, 90024
      • Facility #1
    • Los Angeles, California, United States, 90024
      • Facility #2
    • Los Angeles, California, United States, 90024
      • Facility #3
    • Orange, California, United States
      • Facility #1
    • Oxnard, California, United States, 93030
      • Facility #1
    • San Diego, California, United States, 92123
      • Facility #1
  • Colorado
    • Denver, Colorado, United States, 80239-3133
      • Facility #1
  • Connecticut
    • New Haven, Connecticut, United States, 06510
      • Facility #1
    • New Haven, Connecticut, United States, 06510
      • Facility #2
  • Florida
    • Atlantis, Florida, United States, 33462
      • Facility #1
    • Boca Raton, Florida, United States, 33431
      • Facility #1
    • Boca Raton, Florida, United States, 33486
      • Facility #2
    • Bradenton, Florida, United States, 34205
      • Facility #1
    • Deerfield Beach, Florida, United States, 33064
      • Facility #1
    • Delray Beach, Florida, United States, 33445
      • Facility #1
    • Fort Myers, Florida, United States, 33912
      • Facility #1
    • Hallandale, Florida, United States, 33009
      • Facility #1
    • Hialeah, Florida, United States, 33016
      • Facility #1
    • Lake Worth, Florida, United States, 33449
      • Facility #1
    • Leesburg, Florida, United States, 34748
      • Facility #1
    • Leesburg, Florida, United States, 34749
      • Facility #2
    • Miami, Florida, United States, 33133
      • Facility #1
    • Miami, Florida, United States, 33137
      • Facility #2
    • Miami, Florida, United States, 33145
      • Facility #3
    • Miami Springs, Florida, United States, 33166
      • Facility #1
    • Naples, Florida, United States, 34102
      • Facility #1
    • Ocala, Florida, United States, 34471
      • Facility #1
    • Orlando, Florida, United States, 32806
      • Facility #1
    • Palm Beach Gardens, Florida, United States, 33410
      • Facility #1
    • St. Petersburg, Florida, United States, 33713
      • Facility #1
    • Sunrise, Florida, United States, 33351
      • Facility #1
    • Tampa, Florida, United States, 33609
      • Facility #3
    • Tampa, Florida, United States, 33613
      • Facility #1
    • Tampa, Florida, United States, 33613
      • Facility #2
    • The Villages, Florida, United States
      • Facility #1
  • Georgia
    • Atlanta, Georgia, United States, 30308
      • Facility #2
    • Atlanta, Georgia, United States, 30329
      • Facility #1
    • Columbus, Georgia, United States, 31909
      • Facility #1
    • Decatur, Georgia, United States, 30033
      • Facility #1
  • Illinois
    • Chicago, Illinois, United States, 60640
      • Facility #1
    • Elk Grove Village, Illinois, United States, 60007
      • Facility #1
  • Indiana
    • Elkhart, Indiana, United States, 46514
      • Facility #1
    • Indianapolis, Indiana, United States, 46202
      • Facility #1
  • Kansas
    • Wichita, Kansas, United States, 67214
      • Facility #1
  • Kentucky
    • Lexington, Kentucky, United States, 40504
      • Facility #1
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Facility #1
    • Boston, Massachusetts, United States, 02118
      • Facility #2
    • Burlington, Massachusetts, United States, 01805
      • Facility #1
    • Newton, Massachusetts, United States, 02459
      • Facility #1
  • Michigan
    • Ann Arbor, Michigan, United States, 48105-2945
      • Facility #1
    • East Lansing, Michigan, United States
      • Facility #1
    • Farmington Hills, Michigan, United States, 48334
      • Facility #1
    • Lansing, Michigan, United States, 48824
      • Facility #1
    • West Bloomfield, Michigan, United States, 48322
      • Facility #1
  • Missouri
    • St Louis, Missouri, United States, 63118
      • Facility #1
  • New Jersey
    • Eatontown, New Jersey, United States, 07724
      • Facility #1
    • Toms River, New Jersey, United States, 08755
      • Facility #1
  • New York
    • Albany, New York, United States, 12206
      • Facility #1
    • Amherst, New York, United States, 14226
      • Facility #1
    • Latham, New York, United States, 12110
      • Facility #1
    • New York, New York, United States, 10016
      • Facility #1
    • New York, New York, United States, 10021
      • Facility #2
    • Rochester, New York, United States, 14620
      • Facility #1
    • Rochester, New York, United States, 14623
      • Facility #2
  • North Carolina
    • Charlotte, North Carolina, United States, 28211
      • Facility #1
  • Ohio
    • Centerville, Ohio, United States, 45459
      • Facility #1
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73112
      • Facility #1
    • Oklahoma City, Oklahoma, United States, 73116
      • Facility #2
  • Oregon
    • Portland, Oregon, United States, 97210
      • Facility #2
    • Portland, Oregon, United States, 97239
      • Facility #1
  • Pennsylvania
    • Abington, Pennsylvania, United States, 19001
      • Facility #1
    • Jenkintown, Pennsylvania, United States, 19046
      • Facility #1
  • Rhode Island
    • East Providence, Rhode Island, United States, 02914
      • Facility #1
  • Tennessee
    • Knoxville, Tennessee, United States, 37920
      • Facility #1
  • Texas
    • Austin, Texas, United States, 78757
      • Facility #1
    • Dallas, Texas, United States, 75214
      • Facility #1
    • Dallas, Texas, United States
      • Facility #2
    • Houston, Texas, United States, 77074
      • Facility #1
    • San Antonio, Texas, United States, 78229
      • Facility #1
    • San Antonio, Texas, United States, 78229
      • Facility #2
    • San Antonio, Texas, United States, 78229
      • Facility #3
  • Vermont
    • Bennington, Vermont, United States, 05201
      • Facility #1
  • Virginia
    • Richmond, Virginia, United States, 23294
      • Facility #1
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Facility #1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria (Core Study) for Mild Cognitive Impairment due to Alzheimer's Disease

- Intermediate likelihood:

1. Subjects who meet the National Institute of Aging - Alzheimer's Association (NIA-AA) core clinical criteria for mild cognitive impairment due to Alzheimer's disease - intermediate likelihood
2. Subjects who have a CDR score of 0.5 and a Memory Box score of 0.5 or greater at Screening and Baseline
3. Subjects who report a history of subjective memory decline with gradual onset and slow progression over the last one year before Screening; MUST be corroborated by an informant

Key Inclusion Criteria (Core Study) for Mild Alzheimer's Disease Dementia:

1. Subjects who meet the NIA-AA core clinical criteria for probable Alzheimer's disease dementia
2. Subjects who have a CDR score of 0.5-1.0 and a Memory Box score of 0.5 or greater at Screening and Baseline

Inclusion Criteria (Core Study) that must be met by all subjects:

1. Subjects with objective impairment in episodic memory as indicated by at least 1 standard deviation below age-adjusted mean in the Wechsler Memory Scale - IV Logical Memory II (WMS-IV LMII):

   1. Less than or equal to 15 for age 50 to 64 years
   2. Less than or equal to 12 for age 65 to 69 years
   3. Less than or equal to 11 for age 70 to 74 years
   4. Less than or equal to 9 for age 75 to 79 years
   5. Less than or equal to 7 for age 80 to 90 years

2. Positive amyloid load as indicated by PET or CSF assessment

   1. PET assessment of imaging agent uptake into brain
   2. CSF assessment of Aβ(1-42)
3. Age between 50 and 90 years, inclusive
4. Mini Mental State Examination (MMSE) score equal to or greater than 22, and equal to or less than 30, at Screening and Baseline
5. Body Mass Index (BMI) greater than 17 and less than 35 at Screening or Baseline
6. Females must not be lactating or pregnant at Screening or Baseline (as documented by a negative beta-human chorionic gonadotropin assay [ß-hCG]). A separate baseline assessment is required if a negative screening pregnancy test was obtained more than 72 hours before the first dose of study drug.
7. Subjects on acetylcholinesterase inhibitor or memantine therapy or both for AD must be on a stable dose for at least 12 weeks prior to Baseline. Treatment naive subjects can be entered into the study. Unless otherwise stated, subjects must have been on stable doses of all other permitted concomitant medications (ie, non-AD related) for at least 4 weeks prior to Baseline.
8. Subjects must have identified caregivers/informants
9. Subjects must provide written informed consent

Inclusion Criteria (Extension Phase):

1. Subjects who have completed Visit 42 (Week 79) of the Core Study or who discontinued study drug during the Core Study due to any of the following reasons:

   1. Alzheimer's Related Imaging Abnormality-Edema (ARIA-E)
   2. Amyloid related imaging abnormality hemorrhage (ARIA-H) (superficial siderosis, macrohemorrhage, or symptomatic microhemorrhage)
   3. Prohibited or restricted medications that were prohibited during Core Study conduct but are no longer prohibited in the Extension Phase
   4. Subjects who were APOE4 positive and receiving treatment with lecanemab 10 mg/kg biweekly
   5. Any reason for discontinuation not related to prohibited medications, including any AE that was considered not related to study drug, and that was not severe or life-threatening
2. Must continue to have an identified caregiver or informant who is willing and able to provide follow-up information on the subject throughout the course of the Extension Phase
3. Provide written informed consent. If a subject lacks capacity to consent in the investigator's opinion, the subject's assent should be obtained, if required in accordance with local laws, regulations and customs, plus the written informed consent of a legal representative should be obtained (capacity to consent and definition of legal representative should be determined in accordance with applicable local laws and regulations).
4. Must be able to physically attend clinic visits and be willing and able to comply with all aspects of the protocol

Key Exclusion Criteria (Core study):

1. Any neurological condition that may be contributing to cognitive impairment above and beyond that caused by the subject's AD
2. History of transient ischemic attacks (TIA), stroke, or seizures within 12 months of Screening
3. Any psychiatric diagnosis or symptoms, (e.g., hallucinations, major depression, or delusions) that could interfere with study procedures in the subject
4. Geriatric Depression Scale (GDS) score ≥8 at Screening
5. Contraindications to MRI scanning, including cardiac pacemaker/ defibrillator, ferromagnetic metal implants, e,g., in skull and cardiac devices other than those approved as safe for use in MR scanners
6. Evidence of other clinically significant lesions that could indicate a dementia diagnosis other than AD on brain MRI at Screening, or other significant pathological findings on brain MRI at Screening
7. A prolonged QT/QTc interval (QTc greater than 450 ms) as demonstrated by a repeated electrocardiogram (ECG)
8. Certain other specified medical conditions
9. Severe visual or hearing impairment that would prevent the subject from performing psychometric tests accurately

Exclusion Criteria (Extension Phase):

1. Subjects who discontinued from the study drug or from the Core Study for reasons other than the following:

   1. ARIA-E
   2. ARIA-H (superficial siderosis, macrohemorrhage, or symptomatic microhemorrhage)
   3. Prohibited or restricted medications that were prohibited during Core Study conduct but are no longer prohibited in the Extension Phase
   4. Subjects who were APOE4 positive and receiving treatment with lecanemab 10 mg/kg biweekly
   5. AE that was considered not related to study drug, and that was not severe or life-threatening
2. Females of childbearing potential who do not agree to use a highly effective method of contraception
3. Severe visual or hearing impairment that would prevent the subject from performing psychometric tests accurately.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

7

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Core Study: Lecanemab 2.5 mg/kg biweekly; 2.5 mg/kg biweekly	Drug: Lecanemab 2.5 mg/kg; 2.5 mg/kg biweekly (once every 2 weeks) administered as i.v. infusion; Other Names: BAN2401
Experimental: Core Study: Lecanemab 5.0 mg/kg biweekly; 5.0 mg/kg biweekly	Drug: Lecanemab 5.0 mg/kg; 5.0 mg/kg biweekly (once every 2 weeks) administered as i.v. infusion; Other Names: BAN2401; Drug: Lecanemab 5.0 mg/kg; 5.0 mg/kg monthly (once every 4 weeks) administered as i.v. infusion. All participants will receive biweekly infusions, participants will have placebo infusion alternating with BAN2401; Other Names: BAN2401
Experimental: Core Study: Lecanemab 10 mg/kg biweekly; 10 mg/kg biweekly	Drug: Lecanemab 10 mg/kg; 10 mg/kg biweekly (once every 2 weeks) administered as i.v. infusion.; Other Names: BAN2401; Drug: Lecanemab 10 mg/kg; 10 mg/kg monthly (once every 4 weeks) administered as i.v. infusion. All participants will receive biweekly infusions, participants will have placebo infusion alternating with BAN2401; Other Names: BAN2401; Drug: Lecanemab 10 mg/kg; 10 mg/kg biweekly (once every 2 weeks), once every 4 weeks (Q4W) or once every 3 months (Q3M) i.v. infusion.; Other Names: BAN2401
Experimental: Core Study: Lecanemab 5.0 mg/kg monthly; 5.0 mg/kg monthly	Drug: Lecanemab 5.0 mg/kg; 5.0 mg/kg biweekly (once every 2 weeks) administered as i.v. infusion; Other Names: BAN2401; Drug: Lecanemab 5.0 mg/kg; 5.0 mg/kg monthly (once every 4 weeks) administered as i.v. infusion. All participants will receive biweekly infusions, participants will have placebo infusion alternating with BAN2401; Other Names: BAN2401
Experimental: Core Study: Lecanemab 10 mg/kg monthly; 10 mg/kg monthly	Drug: Lecanemab 10 mg/kg; 10 mg/kg biweekly (once every 2 weeks) administered as i.v. infusion.; Other Names: BAN2401; Drug: Lecanemab 10 mg/kg; 10 mg/kg monthly (once every 4 weeks) administered as i.v. infusion. All participants will receive biweekly infusions, participants will have placebo infusion alternating with BAN2401; Other Names: BAN2401; Drug: Lecanemab 10 mg/kg; 10 mg/kg biweekly (once every 2 weeks), once every 4 weeks (Q4W) or once every 3 months (Q3M) i.v. infusion.; Other Names: BAN2401
Placebo Comparator: Core Study: Lecanemab-matched Placebo; Matching placebo biweekly	Drug: Placebo; biweekly (once every 2 weeks) administered as i.v. infusion
Experimental: Extension Phase: Lecanemab 10 mg/kg; All participants who fulfill Extension Phase inclusion and exclusion criteria will have the option to participate in the Extension Phase to receive lecanemab 10 mg/kg biweekly for up to 60 months or until the benefit-to-risk ratio from treatment with lecanemab is no longer considered favorable, whichever comes first. Additionally, participants who have received Extension Phase treatment for at least 18 months may opt to enter the dosing regimen substudy during which they will receive either lecanemab 10 mg/kg once every 4 weeks (Q4W) or once every 3 months (Q3M).	Drug: Lecanemab 10 mg/kg; 10 mg/kg biweekly (once every 2 weeks) administered as i.v. infusion.; Other Names: BAN2401; Drug: Lecanemab 10 mg/kg; 10 mg/kg monthly (once every 4 weeks) administered as i.v. infusion. All participants will receive biweekly infusions, participants will have placebo infusion alternating with BAN2401; Other Names: BAN2401; Drug: Lecanemab 10 mg/kg; 10 mg/kg biweekly (once every 2 weeks), once every 4 weeks (Q4W) or once every 3 months (Q3M) i.v. infusion.; Other Names: BAN2401

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Core Study Phase: Change From Baseline in Alzheimer's Disease Composite Score (ADCOMS) at Month 12	The ADCOMS is a composite score that comprises 4/14 items from the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog), 2 items from the Mini Mental State Examination (MMSE), and all items from the Clinical Dementia Rating (CDR). Composite score is derived from the variables from the 12 items, and ranges from 0 to 1.97, where higher score means greater impairment. Change from baseline was analyzed using Bayesian analysis. Data presented are posterior mean and posterior standard deviation.	Core Study Phase: at Month 12
Core Study Phase: Number of Participants With All Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)	A TEAE is defined as an AE that emerged during treatment or within 90 days following the last dose of study drug, having been absent at pretreatment (Baseline) or reemerged during treatment, having been present at pretreatment (Baseline) but stopped before treatment, or worsened in severity during treatment relative to the pretreatment state, when the AE was continuous. A SAE is any untoward medical occurrence that at any dose: results in death; is life-threatening (that is, the participant is at immediate risk of death from the adverse event as it occurs, this does not include an event that, has it occurred in a more severe form or is allowed to continue, might have cause death); requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability or incapacity; is a congenital anomaly or birth defect (in the child of a participant who is exposed to the study drug).	From first dose of the study drug (Week 1) up to 90 days after last dose of study drug (up to 21 months)
OLE Phase: Number of Participants With All TEAEs and SAEs	A TEAE is defined as an AE that emerged during treatment or within 30 days following the last dose of study drug, having been absent at pretreatment (Baseline) or reemerged during treatment, having been present at pretreatment (Baseline) but stopped before treatment, or worsened in severity during treatment relative to the pretreatment state, when the AE was continuous. A SAE is any untoward medical occurrence that at any dose: results in death; is life-threatening (that is, the participant is at immediate risk of death from the adverse event as it occurs, this does not include an event that, has it occurred in a more severe form or is allowed to continue, might have cause death); requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability or incapacity; is a congenital anomaly or birth defect (in the child of a participant who is exposed to the study drug).	From first dose of the study drug (Week 1) up to 30 days after last dose of study drug (up to 61 months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Core Study Phase: Change From Baseline at Months 12 and 18 in Brain Amyloid Pathophysiology as Measured by Amyloid Positron Emission Tomography (PET)	Amyloid plaque load was identified by PET using 2 tracers (florbetapir and flutemetamol). The imaging uptake was determined via standard uptake value ratio (SUVr) versus a reference region. The SUVr is a quantitative tool and refers to the ratio of the global cortical average as compared to a reference region of choice. Whole cerebellum mask was used as the reference region of choice in this study. PET SUVr values were converted to Centiloid units. Centiloid scale anchor points are 0 and 100, where 0 represents a high-certainty amyloid negative scan and 100 represents the amount of global amyloid deposition.	Core Study Phase: at Months 12 and 18
Core Study Phase: Change From Baseline in ADCOMS at Month 18	The ADCOMS is a composite score that comprises 4/14 items from the ADAS-cog, 2 items from the MMSE, and all items from the CDR. Composite score is derived from the variables from the 12 items, and ranges from 0 to 1.97, where higher score means greater impairment.	Core Study Phase: at Month 18
Core Study Phase: Change From Baseline in Clinical Dementia Rating- Sum of Boxes (CDR-SB) at Months 12 and 18	The CDR is a clinical scale that describes 5 degrees of impairment in performance on each of 6 categories of function including memory, orientation, judgment and problem solving, community affairs, home and hobbies, and personal care. The ratings of degree of impairment obtained on each of the 6 categories of function are synthesized into 1 global rating of dementia CDR score (ranging from 0 to 3). A sum of boxes score provides an additional measure of change where each category has a maximum possible score of 3 points and the total score is a sum of the category scores giving a total possible score of 0 to 18 with higher scores indicating more impairment.	Core Study Phase: at Months 12 and 18
Core Study Phase: Change From Baseline in Alzheimer Disease Assessment Scale - Cognitive Subscale (ADAS-Cog) at Months 12 and 18	The ADAS-Cog is a cognitive scale which evaluates 14 items- memory (word recall, delayed word recall, and word recognition), reasoning (following commands), language (naming, comprehension), orientation, ideational praxis (placing letter in envelope), constructional praxis (copying geometric designs), spoken language, language comprehension, word finding difficulty, ability to remember test instructions, maze, and number cancellation. The total score ranges from 0 to 90. Higher score indicates greater cognitive impairment.	Core Study Phase: at Months 12 and 18
Core Study Phase: Change From Baseline in Cerebrospinal Fluid (CSF) Biomarker Levels at Months 12 and 18	The measurement of the amyloid proteins- Aβ(1-42) (amyloid beta monomer from amino acid 1 to 42), total (t)-tau, and phospho (p)-tau in CSF have been shown to be important biomarkers for alzheimer's disease.	Core Study Phase: at Months 12 and 18
Core Study Phase: Change From Baseline in Total Hippocampal Volume at Months 6, 12 and 18	Total hippocampal volume is measured by volumetric magnetic resonance imaging (vMRI). Volumetric imaging is a 3D technique where all the MRI signals are collected from the entire tissue sample and imaged as a whole entity, therefore providing a high signal to noise ratio. Total hippocampal volume is calculated by summing up right and left hippocampal volumes.	Core Study Phase: at Months 6, 12 and 18
Core Study Phase: Change From Baseline in Left and Right Hippocampal Volume at Months 6, 12 and 18	Left and right hippocampal volume is measured by vMRI. Volumetric imaging is a 3D technique where all the MRI signals are collected from the entire tissue sample and imaged as a whole entity, therefore providing a high signal to noise ratio. Left and right hippocampal volumes represent a summary measure in the left and right hippocampal regions.	Core Study Phase: at Months 6, 12 and 18
Core Study Phase: Change From Baseline in Whole Brain Volume at Months 6, 12 and 18	Whole brain volume is measured by vMRI. Volumetric imaging is a 3D technique where all the MRI signals are collected from the entire tissue sample and imaged as a whole entity, therefore providing a high signal to noise ratio. Whole brain volume represents a summary measure of total brain parenchyma which includes the cerebrum, basal ganglia, diencephalon, and cerebellum.	Core Study Phase: at Months 6, 12 and 18
Core Study Phase: Change From Baseline in Total Ventricular Volume at Months 6, 12 and 18	Total ventricular volume is measured by vMRI. Volumetric imaging is a 3D technique where all the MRI signals are collected from the entire tissue sample and imaged as a whole entity, therefore providing a high signal to noise ratio. Total ventricular volume represents a summary measure of total including right and left lateral ventricles, third ventricle and fourth ventricle of brain.	Core Study Phase: at Months 6, 12 and 18
OLE Phase: Change From OLE Baseline in Brain Amyloid Levels as Measured by Amyloid PET	Amyloid plaque load was identified by PET using 2 tracers (florbetapir and flutemetamol). The imaging uptake was determined via standard uptake value ratio (SUVr) versus a reference region. The SUVr is a quantitative tool and refers to the ratio of the global cortical average as compared to a reference region of choice. Whole cerebellum mask was used as the reference region of choice in this study. PET SUVr values were converted to Centiloid units. Centiloid scale anchor points are 0 and 100, where 0 represents a high-certainty amyloid negative scan and 100 represents the amount of global amyloid deposition. Change from OLE baseline was analyzed using the Mixed Model for Repeated Measures (MMRM) with Core Study treatment group, visit, Core Study treatment group by visit interaction, APOE4 status as fixed effects, and OLE baseline value and Gap duration as covariates.	OLE Phase: at Months 3, 6, 12, 24, 36 and 48
OLE Phase: Change From End of Core Study at the Baseline of OLE Phase in Brain Amyloid Levels as Measured by Amyloid PET	Amyloid plaque load was identified by PET using 2 tracers (florbetapir and flutemetamol). The imaging uptake was determined via standard uptake value ratio (SUVr) versus a reference region. The SUVr is a quantitative tool and refers to the ratio of the global cortical average as compared to a reference region of choice. Whole cerebellum mask was used as the reference region of choice in this study. PET SUVr values were converted to Centiloid units. Centiloid scale anchor points are 0 and 100, where 0 represents a high-certainty amyloid negative scan and 100 represents the amount of global amyloid deposition. Change from end of core study at the baseline of OLE phase was summarized using change from core study baseline at each visit.	Core Study: Baseline and at Month 18, OLE Phase: Baseline
OLE Phase: Percentage of Amyloid Positive Participants Over Time	Percentage of amyloid positive participants over time was reported. Participants who had Amyloid PET (using Centiloid scales) values greater than or equal to 30.00 were considered as amyloid positive.	OLE Phase: Baseline, at Months 3, 6, 12, 24, 36 and 48

Collaborators and Investigators

• Sponsor: Eisai Inc.
• Collaborators: Biogen

Publications and helpful links

General Publications

• Devanarayan V, Ye Y, Charil A, Andreozzi E, Sachdev P, Llano DA, Tian L, Zhu L, Hampel H, Kramer L, Dhadda S, Irizarry M; Alzheimer's Disease Neuroimaging Initiative (ADNI). Predicting clinical progression trajectories of early Alzheimer's disease patients. Alzheimers Dement. 2024 Mar;20(3):1725-1738. doi: 10.1002/alz.13565. Epub 2023 Dec 13.
• Berry DA, Dhadda S, Kanekiyo M, Li D, Swanson CJ, Irizarry M, Kramer LD, Berry SM. Lecanemab for Patients With Early Alzheimer Disease: Bayesian Analysis of a Phase 2b Dose-Finding Randomized Clinical Trial. JAMA Netw Open. 2023 Apr 3;6(4):e237230. doi: 10.1001/jamanetworkopen.2023.7230.
• McDade E, Cummings JL, Dhadda S, Swanson CJ, Reyderman L, Kanekiyo M, Koyama A, Irizarry M, Kramer LD, Bateman RJ. Lecanemab in patients with early Alzheimer's disease: detailed results on biomarker, cognitive, and clinical effects from the randomized and open-label extension of the phase 2 proof-of-concept study. Alzheimers Res Ther. 2022 Dec 21;14(1):191. doi: 10.1186/s13195-022-01124-2.
• Dhadda S, Kanekiyo M, Li D, Swanson CJ, Irizarry M, Berry S, Kramer LD, Berry DA. Consistency of efficacy results across various clinical measures and statistical methods in the lecanemab phase 2 trial of early Alzheimer's disease. Alzheimers Res Ther. 2022 Dec 9;14(1):182. doi: 10.1186/s13195-022-01129-x.
• Swanson CJ, Zhang Y, Dhadda S, Wang J, Kaplow J, Lai RYK, Lannfelt L, Bradley H, Rabe M, Koyama A, Reyderman L, Berry DA, Berry S, Gordon R, Kramer LD, Cummings JL. A randomized, double-blind, phase 2b proof-of-concept clinical trial in early Alzheimer's disease with lecanemab, an anti-Abeta protofibril antibody. Alzheimers Res Ther. 2021 Apr 17;13(1):80. doi: 10.1186/s13195-021-00813-8.

Study record dates

Study Major Dates

• Study Start (Actual): December 20, 2012
• Primary Completion (Actual): December 10, 2024
• Study Completion (Actual): December 10, 2024

Study Registration Dates

• First Submitted: January 8, 2013
• First Submitted That Met QC Criteria: January 10, 2013
• First Posted (Estimated): January 14, 2013

Study Record Updates

• Last Update Posted (Actual): March 4, 2026
• Last Update Submitted That Met QC Criteria: March 2, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: Alzheimer's Disease; BAN2401; Lecanemab
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Mental Disorders; Neurocognitive Disorders; Dementia; Tauopathies; Neurodegenerative Diseases; Alzheimer Disease; lecanemab
• Other Study ID Numbers: BAN2401-G000-201; 2012-002843-11 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No