Mild cognitive impairment due to Alzheimer's disease or mild Alzheimer's disease dementia MedDRA version: 20.0 Level: LLT Classification code 10001896 Term: Alzheimer's disease System Organ Class: 10029205 - Nervous system disorders MedDRA version: 20.0 Level: PT Classification code 10074616 Term: Prodromal Alzheimer's disease System Organ Class: 10029205 - Nervous system disorders
Conditions
Interventions
Product Name: BAN2401
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: BAN2401
CAS Number: 1260393-98-3
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: range
Conce
Sponsors
Eisai Limited
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Diagnosis MCI due to AD–intermediate likelihood: 1. Meet the NIA-AA core clinical criteria for MCI due to AD–intermediate likelihood. 2. Have a global CDR score of 0.5 and a CDR Memory Box score of 0.5 or greater at Screening and Baseline. 3. 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. 4. Meet the NIA-AA core clinical criteria for probable AD dementia. 5. 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 subjects: 6. 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: a. =15 for age 50-64 years b. =12 for age 65-69 yrs c. =11 for age 70-74 yrs d. =9 for age 75-79 yrs e. =7 for age 80-90 yrs 7. Positive biomarker for brain amyloid pathology as indicated by at least 1 of the following: a. PET assessment of imaging agent uptake into brain. Note: amyloid PET screens will be performed according to local regulatory guidelines and thus may be restricted for those subjects who are not suitable for lumbar puncture (LP) to obtain CSF for testing of eligibility. b. CSF assessment of t-tau/Aß[1-42] NOTE1: Subjects who are on anticoagulant therapy may not participate in CSF assessments. NOTE2: Subjects may consent to both the PET and CSF assessments, but to confirm eligibility, a positive amyloid result is needed in only 1 of the 2 procedures (ie, the subject will be eligible even if 1 of the 2 results does not meet its eligibility criterion). Subjects who consent to amyloid PET or CSF at Screening for the purposes of eligibility are not required to participate in the amyloid PET, tau PET, or CSF longitudinal substudies. Use of a historical amyloid positive PET (conducted within 12 months before the planned date of randomization) is acceptable for determination of eligibility provided the subject did not participate in any clinical studies involving anti-amyloid therapies subsequent to the PET assessment. Historical PET will not suffice for the baseline assessment if the subject wishes to consent to the amyloid PET longitudinal substudy. The historical imaging data must be made available to the sponsor to confirm amyloid positivity. 8. Male or female subjects aged =50 and =90 years, at the time of informed consent. 9. MMSE score greater than or equal to 22 at Screening and Baseline and less than or equal to 30 at Screening and Baseline. 10. Body mass index (BMI) greater than 17 and less than 35 at Screening. 11. If receiving an approved AD treatment, such as AChEIs, or memantine, or both for AD, must be on a stable dose for at least 12 weeks prior to Baseline. Treatment-naïve subjects for AD can be entered into the study. Unless otherwise stated, subjects must have been on stable doses of all other (ie, non-AD-related) permitted concomitant medications for at least 4 weeks prior to Baseline. Use of memantine will not be allowed for Japanese subjects. 12. Have an identified study partner (defined as a person able to support the subject for the duration of the study and who spends at least 8 hours per week with the subject). The study partner must provide separate written informed consent. In addition, this person must be willing and able to provide follow-up information on the subject throughout the course of the study. Th
Exclusion criteria
Exclusion criteria: 1. Females who are breastfeeding or pregnant at Screening or Baseline 2. Females of childbearing potential who: a. Within 28 days before study entry, did not use a highly effective method of contraception (see protocol for full details) b. Do not agree to use a highly effective method of contraception (as described in the protocol) throughout the entire study period and for 28 days after study drug discontinuation. 3. Any neurological condition that may be contributing to cognitive impairment above and beyond that caused by the subject's AD. 4. History of transient ischemic attacks, stroke, or seizures within 12 months of Screening. 5. Any psychiatric diagnosis or symptoms that could interfere with study procedures in the subject. 6. GDS score greater than or equal to 8 at Screening. 7. Contraindications to MRI scanning, including cardiac pacemaker/defibrillator, ferromagnetic metal implants. 8. Evidence of other clinically significant lesions on brain MRI at Screening that could indicate a dementia diagnosis other than AD. 9. Other significant pathological findings on brain MRI at Screening, including but not limited to: more than 4 microhemorrhages (defined as 10 mm or less at the greatest diameter); a single macrohemorrhage greater than 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 less than 1 cm at their greatest diameter need not be exclusionary). 10. Hypersensitivity to BAN2401 or any of the excipients, or to any monoclonal antibody treatment. 11. 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. 12. Subjects with a bleeding disorder that is not under adequate control (including a platelet count 1.5 for subjects who are not on anticoagulant treatment. Subjects who are on anticoagulant therapy should have their anticoagulant status optimized and be on a stable dose for 4 weeks before Screening. Subjects who are on anticoagulant therapy are not permitted to participate in CSF assessments. 13. Have thyroid stimulating hormone (TSH) above normal range. Other tests of thyroid function with results outside the normal range should only be exclusionary if they are considered clinically significant by the investigator. This applies to all subjects whether or not they are taking thyroid supplements. 14. Abnormally low serum vitamin B12 levels for the testing laboratory 15. Known to be HIV positive. 16. Any other clinically significant abnormalities in physical examination, vital signs, laboratory tests, or ECG at Screening or Baseline which in the opinion of the investigator require further investigation 17. Subjects with malignant neoplasms within 3 years of Screening (see protocol for exceptions). 18. Answer "yes" to C-SSRS suicidal ideation Type 4 or 5, or any suicidal behavior assessment within 6 months before Screening, at Screening, or at the Baseline Visit, or has been hospitalized or treated for suicidal behavior in the past 5 years be
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Core • To evaluate the efficacy of BAN2401 in subjects with early Alzheimer’s disease (EAD) by determining the superiority of BAN2401 compared with placebo on the change from baseline in the Clinical Dementia Rating–Sum of Boxes (CDR-SB) at 18 months of treatment. Extension • To evaluate the long-term safety and tolerability of BAN2401 in subjects with EAD in the Extension Phase. • To evaluate whether the long-term effects of BAN2401 as measured by the CDR-SB at the end of the Core Study is maintained over time in the Extension Phase;Secondary Objective: Key Secondary Objective - To determine whether BAN2401 is superior to placebo in reducing brain amyloid levels as measured by amyloid positron emission tomography (PET) using Centiloids at 18 months - To evaluate the efficacy of BAN2401 in subjects with EAD by determining the superiority of BAN2401 compared with placebo on the change from baseline in the AD Assessment Scale–Cognitive Subscale14 (ADAS-cog14) at 18 months of treatment - To evaluate the efficacy of BAN2401 in subjects with EAD by determining the superiority of BAN2401 compared with placebo on the change from baseline in the AD composite score (ADCOMS) at 18 months of treatment - To evaluate the efficacy of BAN2401 in subjects with EAD by determining the superiority of BAN2401 compared with placebo on the change from baseline in the Alzheimer''s Disease Cooperative Study-Activities of Daily Living Scale for Mild Cognitive Impairment (ADCS MCI-ADL) at 18 months of treatment. For all other objectives see protocol.;Primary end point(s): Core • Change from baseline in the CDR-SB at 18 months . Extension • Incidence of AEs and changes in vital signs, ECGs, laboratory safety tests, suicidality assessments, ADAs, and MRI safety parameters • Change from Core Study baseline in CDR-SB;Timepoint(s) of evaluation of this end point: Core • 18 months | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The key secondary endpoints for this study are: - Change from baseline in amyloid PET using Centiloids at 18 months for brain amyloid levels - Change from baseline in ADAS-cog14 at 18 months - Change from baseline in ADCOMS at 18 months - Change from baseline in ADCS MCI-ADL at 18 months OTHER SECONDARY ENDPOINTS Refer to protocol BM Endpoints Refer to protocol;Timepoint(s) of evaluation of this end point: Core • 18 months | — |
Countries
Canada, China, France, Germany, Italy, Japan, Korea, Republic of, Russian Federation, Spain, Sweden, United Kingdom, United States
Contacts
Public ContactMedical Information
Eisai Limited
Outcome results
None listed