临床试验/NCT03887455

NCT03887455进行中（未招募）3 期

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

Eisai Inc.235 个研究点分布在 1 个国家目标入组 1,906 人开始时间: 2019年3月27日最近更新: 2025年10月14日

适应症

干预措施

试验速览

阶段: 3 期
状态: 进行中（未招募）
发起方: Eisai Inc.
入组人数: 1,906
试验地点: 235
主要终点: Core Study: Change from Baseline in the CDR-SB at 18 Months

研究概览研究设计入排标准研究组 & 干预措施结局指标研究者研究点记录与标识符相似试验相关资讯

研究概览

简要总结

This study will be conducted to evaluate the efficacy of lecanemab in participants with early Alzheimer's disease (EAD) by determining the superiority of lecanemab compared with placebo on the change from baseline in the Clinical Dementia Rating-Sum of Boxes (CDR-SB) at 18 months of treatment in the Core Study. This study will also evaluate the long-term safety and tolerability of lecanemab in participants with EAD in the Extension Phase and whether the long-term effects of lecanemab as measured by the CDR-SB at the end of the Core Study is maintained over time in the Extension Phase. Extension Phase Part B will continue dosing with lecanemab in countries where lecanemab may not be commercially available.

详细描述

All administrations of study drug will be administered in the clinic or in the home; However, home administrations of intravenous (IV) study drug will be allowed per sponsor approval according to country and local guidelines during the COVID-19 pandemic and following its resolution, where permitted.

研究设计

研究类型: Interventional
分配方式: Randomized
干预模型: Parallel
主要目的: Treatment
盲法: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

入排标准

年龄范围: 50 Years 至 90 Years（Adult, Older Adult）
性别: All
接受健康志愿者: 否

入选标准

•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 subcutaneous (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 subcutaneous BAN2401
•Participants enrolling into the subcutaneous autoinjector substudy must have had at least 6 months exposure to BAN2401 10 mg/kg intravenously biweekly or BAN2401 Dose 1 subcutaneously weekly.
•Participants enrolling into the subcutaneous Dose 3 autoinjector substudy must have previously received BAN2401 by either intravenous administration and/or subcutaneous 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
•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
•Severe visual or hearing impairment that would prevent the participant from performing psychometric tests accurately

排除标准

未提供

研究组 & 干预措施

Core Study: Lecanemab 10 mg/kg biweekly

Experimental

干预措施: Lecanemab IV (Drug)

Core Study: Placebo

Placebo Comparator

干预措施: Placebo (Drug)

Extension Phase: Lecanemab 10 mg/kg biweekly

Experimental

干预措施: Lecanemab IV (Drug)

Extension Phase: Lecanemab Subcutaneous Injection Dose 1

Experimental

This will include approximately 40 de novo participants (those that did not participate in the core study) with early Alzheimer disease (AD).

干预措施: Lecanemab SC (Drug)

Extension Phase: Lecanemab Subcutaneous Injection Dose 2

Experimental

干预措施: Lecanemab SC (Drug)

Extension Phase: Lecanemab Subcutaneous Injection Dose 3

Experimental

干预措施: Lecanemab SC (Drug)

Extension Phase: Lecanemab Subcutaneous Injection Dose 4

Experimental

干预措施: Lecanemab SC (Drug)

Extension Phase: Lecanemab 10 mg/kg Intravenous Infusion Once Every 4 Weeks

Experimental

干预措施: Lecanemab IV (Drug)

Extension Phase B

Experimental

Participants will receive Lecanemab 10 mg/kg intravenous infusion once every 2 weeks, or 4 weeks, or Dose 3, or Dose 4 subcutaneous injection weekly.

干预措施: Lecanemab IV (Drug)

Extension Phase B

Experimental

Participants will receive Lecanemab 10 mg/kg intravenous infusion once every 2 weeks, or 4 weeks, or Dose 3, or Dose 4 subcutaneous injection weekly.

干预措施: Lecanemab SC (Drug)

结局指标

主要结局

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

时间窗: Baseline, 18 months

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

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

A TEAE is defined as an adverse event that emerges during treatment or within 30 days of the last dose of study drug, having been absent at pretreatment (Baseline) or reemerges during treatment, having been present at pretreatment (Baseline) but stopped before treatment, or worsens in severity during treatment relative to the pretreatment state, when the adverse event was continuous. Number of participants with TEAEs (serious and non-serious adverse events) will be reported based on their regular measurement of vital signs, safety assessments of laboratory tests, antidrug antibody assessments, suicidality assessments, magnetic resonance imaging and electrocardiogram parameter values.

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

时间窗: Baseline up to Month 66

Extension Phase Part B: Number of Participants Exposed to Lecanemab

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

次要结局

Core Phase: Change From Baseline in Amyloid Positron Emission Tomography (PET) Using Centiloids at 18 Months(Baseline, 18 months)
Core Study: Change from Baseline in Alzheimer Disease Assessment Scale - Cognitive Subscale 14 (ADAS-cog14) at 18 Months(Baseline, 18 months)
Core Phase: Change From Baseline in Alzheimer's Disease Composite Score (ADCOMS) at 18 Months(Baseline, 18 months)
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(Baseline, 18 months)
Extension Phase Part B: Number of Participants Reporting Adverse Events(From 48th month in extension phase part A to the end of extension phase part B (up to 24 months))

研究者

发起方

Eisai Inc.

申办方类型

Industry

责任方

Sponsor

研究点 (235)

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