Alzheimer's Disease
Conditions
Interventions
investigational material(s)
Generic name etc : BAN2401
INN of investigational material : Lecanemab
Therapeutic category code : 119 Other agents affecting central nervous system
Dosage and Administrati
Sponsors
Eisai Co., Ltd.
Biogen
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 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: 4.Subjects who meet the NIA-AA core clinical criteria for probable Alzheimer's disease dementia 5.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: 6.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): a.Less than or equal to 15 for age 50 to 64 years b.Less than or equal to 12 for age 65 to 69 years c.Less than or equal to 11 for age 70 to 74 years d.Less than or equal to 9 for age 75 to 79 years e.Less than or equal to 7 for age 80 to 90 years 7.Positive amyloid load as indicated by PET or CSF assessment 8.Age between 50 and 90 years, inclusive 9.Mini Mental State Examination (MMSE) score equal to or greater than 22, and equal to or less than 30, at Screening and Baseline 10.Body Mass Index (BMI) greater than 17 and less than 35 at Screening 11.Females must not be pregnant or lactating, and specified contraceptive precautions must be followed 12.Subjects on acetylcholinesterase inhibitor or memantine therapy for Alzheimer's disease (AD) must be on a stable dose for at least 12 weeks prior to baseline 13.Subjects must have identified caregivers/informants 14.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: a.Alzheimer's Related Imaging Abnormality-Edema (ARIA-E) b.Amyloid related imaging abnormality hemorrhage (ARIA-H) (superficial siderosis, macrohemorrhage, or symptomatic microhemorrhage) c.Prohibited or restricted medications that were prohibited during Core Study conduct but are no longer prohibited in the Extension Phase d.Subjects who were APOE4 positive and receiving treatment with lecanemab 10 mg/kg biweekly e.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 a
Exclusion criteria
Exclusion criteria: 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 Key Exclusion Criteria (Extension Phase): 1.Subjects who discontinued from the study drug or from the Core Study for reasons other than the following: a.ARIA-E b.ARIA-H (superficial siderosis, macrohemorrhage, or symptomatic microhemorrhage) c.Prohibited or restricted medications that were prohibited during Core Study conduct but are no longer prohibited in the Extension Phase d.Subjects who were APOE4 positive and receiving treatment with lecanemab 10 mg/kg biweekly e.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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Core Study: Change from Baseline in the Alzheimer's Disease Composite Score (ADCOMS) at 12 months Core Study and Extension Phase: Safety will be assessed by monitoring and recording all adverse events (AEs) and serious adverse events (SAEs) | — |
Secondary
| Measure | Time frame |
|---|---|
| Core Study: Change from Baseline at 18 Months in Brain Amyloid Pathophysiology as Measured by Amyloid Positron Emission Tomography (PET) Core Study: Change from Baseline in the ADCOMS at 18 Months Core Study: Change from Baseline in Clinical Dementia Rating - Sum of Boxes (CDR-SB) at 18 Months Core Study: Change from Baseline in Alzheimer Disease Assessment Scale - Cognitive Subscale (ADAS-cog) at 18 Months Core Study: Change from Baseline in Cerebrospinal fluid (CSF) Biomarkers (Abeta[1-42], t-tau, and p-tau) at 18 Months Core Study: Change from Baseline in Total Hippocampal Volume at 18 Months as Measured by Volumetric Magnetic Resonance Imaging (vMRI) Core Study: Change from Baseline at 12 Months in Brain Amyloid Pathophysiology as Measured by Amyloid PET Core Study: Change from baseline at 12 months on clinical status for the following assessments: ADCOMS, CDR-SB, and ADAS-cog Core Study: Change from Baseline in CSF Biomarkers (Abeta[1-42], t-tau, and p-tau) at 12 Months Core Study: Change from Baseline in Total Hippocampal Volume at 6 and 12 Months as Measured by vMRI Core Study: Change from Baseline in Left and Right Hippocampal Volume at 6, 12, and 18 Months as Measured by vMRI Core Study: Change from Baseline in Whole Brain Volume at 6, 12, and 18 Months as Measured by vMRI Core Study: Change from Baseline in Total Ventricular Volume at 6, 12, and 18 Months as Measured by vMRI Change From Baselines in Brain Amyloid Levels as Measured by Amyloid PET at 3 months (Visit 50 [Extension Week 13], Cohort 1) or 6 months (Visit 57 [Extension Week 27], Cohort 2), 12 months and Annually Thereafter in the Extension Phase Extension Phase: Change from end of Core Study in Brain Amyloid Levels as Measured by Amyloid PET at the Baseline of Extension Phase Extension Phase: Percentage of Amyloid Positive Participants Over Time | — |
Countries
Asia except Japan, Europe, Japan, North America
Outcome results
None listed