Clarity AD

Active not recruitingPhase 3

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

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

Lead sponsor

Eisai Inc.

Asset

Lecanemab

Listed sites

247

Recruiting sites

Enrollment

1,906

actual

Study population

Alzheimer’s disease

Key I/E criteria

•MCI due to AD / mild AD dementia•Amyloid biomarker required•CDR global 0.5-1•MMSE 22-30•Study partner/caregiver required

Primary endpoints

•Clinical Dementia Rating-Sum of Boxes (CDR-SB)•Treatment-emergent Adverse Events (TEAEs)•Exposure to Lecanemab

Footprint

Where this trial recruits

Site locations as reported to ClinicalTrials.gov. Site count is not enrollment count; per-site enrollment is not available from source.

Identifiers

Registered as

Eudract number2018-004739-58

Secondary ID2024-510887-22CTIS

Org study IDBAN2401-G000-301

NCT IDNCT03887455

Timeline

Milestones

Study first posted2019-03-25actual

Study start2019-03-27actual

Last update posted2026-04-07actual

Primary completion2029-06-30estimated

Study completion2029-06-30estimated

Assets

Drug assets

Lecanemab

Study populations

Who this study enrolls

Alzheimer’s disease

Eligibility

Who can enroll

Minimum age50 Years

Maximum age90 Years

SexAll

Healthy volunteersNot accepted

Inclusion criteria

Core Study: Inclusion Criteria

Diagnosis: Mild Cognitive Impairment (MCI) due to Alzheimer's disease - intermediate likelihood:

•Meet the National Institute of Aging - Alzheimer's Association (NIA-AA) core clinical criteria for MCI due to Alzheimer's disease - intermediate likelihood

•Have a global Clinical Dementia Rating (CDR) score of 0.5 and CDR Memory Box score of 0.5 or greater at Screening and Baseline

•Report a history of subjective memory decline with gradual onset and slow progression over the last 1 year before Screening; must be corroborated by an informant

Mild Alzheimer's disease dementia:

•Meet the NIA-AA core clinical criteria for probable Alzheimer's disease dementia

•Have a global CDR score of 0.5 to 1.0 and a CDR Memory Box score of 0.5 or greater at Screening and Baseline

Key Inclusion Criteria that must be met by all participants:

•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 (subscale) II (WMS-IV LMII)

•Positive biomarker for brain amyloid pathology

•Male or female participants aged greater than or equal to (>=) 50 and less than or equal to (<=) 90 years, at the time of informed consent

•Mini mental state examination (MMSE) score >=22 at Screening and Baseline and <=30 at Screening and Baseline

•Body mass index (BMI) greater than (>)17 and less than (<) 35 at Screening

•If receiving an approved Alzheimer's disease treatment such as acetylcholinesterase inhibitor (AChEIs) or memantine or both for Alzheimer's disease, must be on a stable dose for at least 12 weeks prior to Baseline. Treatment-naive participants for Alzheimer's disease can be entered into the study. Unless otherwise stated, participants must have been on stable doses of all other (that is, non-Alzheimer's disease-related) permitted concomitant medications for at least 4 weeks prior to Baseline. Use of memantine will not be allowed for participants in Japan

•Have an identified study partner (defined as a person able to support the participant for the duration of the study and who spends at least 8 hours per week with the participant)

•Provide written informed consent. If a participant lacks capacity to consent in the investigator's opinion, the participant'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). In countries where local laws, regulations, and customs do not permit participants who lack capacity to consent to participate in this study (example, Germany and Spain), they will not be enrolled

Extension Phase: Inclusion Criteria:

•Participants who have completed the Core Study (except de novo participants)

•Must continue to have a study partner who is willing and able to provide follow-up information on the participant throughout the course of the Extension Phase

•Provide written informed consent for the Extension Phase. If a participant lacks capacity to consent in the investigator's opinion, the participant's assent should be obtained, if required and 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). In countries where local laws, regulations, and customs do not permit participants who lack capacity to consent to participate in this study (example, Germany and Spain), they will not be enrolled

•Participants entering the SC (vial) substudy at Extension Phase Week 1, must be willing to participate, or continue participating in the amyloid positron emission tomography (PET) substudy. All participants must have an amyloid PET scan within 4 weeks before starting SC BAN2401

•Participants enrolling into the SC autoinjector substudy must have had at least 6 months exposure to BAN2401 10 mg/kg IV biweekly or at least 12 months exposure of BAN2401 Dose 1 subcutaneously weekly.

•Participants enrolling into the SC Dose 3 autoinjector substudy must have previously received BAN2401 by either IV administration and/or SC autoinjector administration and must have completed Visit 82 (Extension Week 79) at a minimum, regardless of previous route of administration

Extension Phase Part B: Inclusion Criteria:

• Must have completed Week 207 in the Extension Phase

Exclusion criteria

•Any neurological condition that may be contributing to cognitive impairment above and beyond that caused by the participant's Alzheimer's disease

•History of transient ischemic attacks (TIA), stroke, or seizures within 12 months of Screening

•Any psychiatric diagnosis or symptoms (example, hallucinations, major depression, or delusions) that could interfere with study procedures in the participant

•Geriatric Depression Scale (GDS) score >=8 at Screening

•Contraindications to MRI scanning, including cardiac pacemaker/defibrillator, ferromagnetic metal implants (example in skull and cardiac devices other than those approved as safe for use in MRI scanners)

•Evidence of other clinically significant lesions on brain MRI at Screening that could indicate a dementia diagnosis other than Alzheimer's disease

•Other significant pathological findings on brain MRI at screening, including but not limited to: more than 4 microhemorrhages (defined as 10 millimeter [mm] or less at the greatest diameter); a single macrohemorrhage >10 mm at greatest diameter; an area of superficial siderosis; evidence of vasogenic edema; evidence of cerebral contusion, encephalomalacia, aneurysms, vascular malformations, or infective lesions; evidence of multiple lacunar infarcts or stroke involving a major vascular territory, severe small vessel, or white matter disease; space occupying lesions; or brain tumors (however, lesions diagnosed as meningiomas or arachnoid cysts and <1 centimeter [cm] at their greatest diameter need not be exclusionary)

•Any immunological disease which is not adequately controlled, or which requires treatment with immunoglobulins, systemic monoclonal antibodies (or derivatives of monoclonal antibodies), systemic immunosuppressants, or plasmapheresis during the study

•Participants with a bleeding disorder that is not under adequate control (including a platelet count <50,000 or international normalized ratio [INR] >1.5 for participants who are not on anticoagulant treatment, example, warfarin). Participants who are on anticoagulant therapy should have their anticoagulant status optimized and be on a stable dose for 4 weeks before Screening. Participants who are on anticoagulant therapy are not permitted to participate in cerebrospinal fluid (CSF) assessments

•Any other medical conditions (example, cardiac, respiratory, gastrointestinal, renal disease) which are not stably and adequately controlled, or which in the opinion of the investigator(s) could affect the participant's safety or interfere with the study assessments

•Participation in a clinical study involving any therapeutic monoclonal antibody, protein derived from a monoclonal antibody, immunoglobulin therapy, or vaccine within 6 months before screening unless it can be documented that the participant was randomized to placebo

•Participation in a clinical study involving any anti-amyloid therapies (including any monoclonal antibody therapies and any β-site amyloid precursor protein cleaving enzyme [BACE] inhibitor therapies) unless it can be documented that the participant only received placebo

•Participants who have any known prior exposure to lecanemab

•Participants who were dosed in a clinical study involving any new chemical entities for AD within 6 months prior to screening unless it can be documented that the participant was in a placebo treatment arm

Extension Phase: Exclusion Criteria

•Participants who discontinued early from the Core Study

•Participants who develop the following conditions from the time of Screening for the Core Study to the start of the Extension Phase

•Any neurological condition that may be contributing to cognitive impairment above and beyond that caused by the participant's AD

•Any psychiatric diagnosis or symptoms, (example, hallucinations, major depression, or delusions) that could interfere with study procedures in the participant

•Contraindications to MRI scanning, including cardiac pacemaker/defibrillator, ferromagnetic metal implants (example, in skull and cardiac devices other than those approved as safe for use in MRI scanners)

•Other significant pathological findings on brain MRI during the Core Study including but not limited to: cerebral contusion, encephalomalacia, aneurysms, vascular malformations, or infective lesions; evidence of multiple lacunar infarcts or stroke involving a major vascular territory, severe small vessel, or white matter disease; space occupying lesions; or brain tumors will be exclusionary if based on the opinion of the investigator, with consultation of medical monitor, these findings may interfere with the study procedures or safety

•Hypersensitivity to BAN2401 or any of the excipients, or to any monoclonal antibody treatment

•Any immunological disease which is not adequately controlled, or which requires chronic treatment with immunoglobulins, systemic monoclonal antibodies (or derivatives of monoclonal antibodies), systemic immunosuppressants, or plasmapheresis during the study

•Any other clinically significant abnormalities in physical examination, vital signs, laboratory tests, or ECG, which in the opinion of the investigator require further investigation or treatment or which may interfere with study procedures or safety

•Malignant neoplasms (except for basal or squamous cell carcinoma in situ of the skin, or localized prostate cancer in male participants) that are not stably and adequately controlled or which, based on the opinion of the investigator, may interfere with the participant's safety or participation in the study

•Severe visual or hearing impairment that would prevent the participant from performing psychometric tests accurately

Extension Phase Part B: Exclusion Criteria

-In countries where lecanemab is authorized for use in APOE4 noncarriers and heterozygous carriers only, APOE4 homozygous carriers will not be eligible for participation in Extension Phase Part B. Any APOE4 homozygous carriers that are already participating in Extension Phase Part B in such countries will be discontinued from the study.

Endpoints (12)

What's being measured

Protocol endpoints and posted registry outcome measures, grouped into outcome categories. Composite endpoints show their component event types. Standard codes (LOINC, SNOMED CT) are shown where available.

Coverage by outcome category

Other (unclassified)

Global cognition

Neuroimaging

Function / daily living

Amyloid biomarkers

Global cognition

2 endpoints

Primary/protocol endpoint

Core Study: Change from Baseline in the CDR-SB at 18 Months

Time frame:Baseline, 18 months

Clinical Dementia Rating-Sum of Boxes (CDR-SB)

change from baseline, improvement

Primary/protocol endpoint

Extension Phase: Change from Core Study Baseline in CDR-SB

Time frame:Baseline up to Month 66

Clinical Dementia Rating-Sum of Boxes (CDR-SB)

descriptive

Function / daily living

1 endpoint

Secondary/protocol endpoint

Core Study: Change From Baseline in Alzheimer's Disease Cooperative Study-Activities of Daily Living Scale for Mild Cognitive Impairment (ADCS MCI-ADL) at 18 Months

Time frame:Baseline, 18 months

change from baseline, improvement

Amyloid biomarkers

1 endpoint

Secondary/protocol endpoint

Core Study: Change From Baseline in Amyloid Positron Emission Tomography (PET) Using Centiloids at 18 Months

Time frame:Baseline, 18 months

Amyloid PET Centiloid

change from baseline, improvement

Neuroimaging

2 endpoints

Primary/protocol endpoint

Extension Phase: Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs)

Time frame:From first dose of study drug up to approximately 51 months (including 3 months follow up) for the extension phase

event count, event

Secondary/protocol endpoint

Core Study: Number of Participants Reporting One or More TEAEs

Time frame:From first dose of study drug up to approximately 21 months (including 3 months follow-up)

event count, event

Other (unclassified)

6 endpoints

Primary/protocol endpoint/low confidence

Extension Phase Part B: Number of Participants Exposed to Lecanemab

Time frame:From 48th month in extension phase part A to the end of extension phase part B (up to 24 months)

event count, event