Mild cognitive impairment due to Alzheimer's disease or mild Alzheimer's disease dementia
Conditions
Interventions
Product Name: BAN2401
Product Code: BAN2401
Pharmaceutical Form: Solution for injection
Pharmaceutical form of the placebo: Solution for injection
Sponsors
Eisai Limited
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Mild Cognitive Impairment due to Alzheimer’s Disease – Intermediate Likelihood: 1. Subjects meeting the National Institute of Aging – Alzheimer’s Association (NIA-AA) core clinical criteria for MCI 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 1 year before Screening; MUST be corroborated by an informant 4.Subjects who meet the NIA-AA core clinical criteria for probable Alzheimer's disease dementia 5.Subjects who have CDR score of 0.5 to 1.0 and Memory Box score of 0.5 or greater at Screening and Baseline Key Inclusion Criteria 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 WMS-IV LMII, as follows: a)=15 for age 50 to 64 years b)=12 for age 65 to 69 years c)=11 for age 70 to 74 years d)=9 for age 75 to 79 years e)=7 for age 80 to 90 years 7. Positive amyloid load as indicated by 1 of the following: a.PET assessment b.CSF assessment of Aß(1-42) Subjects may consent to both the PET and CSF assessments, but need a positive amyloid result in only one of the 2 procedures to confirm eligibility . Subjects who initially consent for only one of the amyloid screening assessments will only be allowed to subsequently consent for the second assessment should the first assessment result be positive or they have not yet been informed of the results of the first assessment. Subjects who consent to Amyloid PET or CSF Amyloid are not required to participate in the respective substudies. 8.Male or female subjects aged between 50 and 90 years, inclusive 9.MMSE score equal to or greater than 22, and equal to or less than 30 at Screening and Baseline, except for the following countries, where MMSE score must be equal to or greater than 22 and equal to or less than 28 at Screening and Baseline: UK, ES, DE, SE, FR, and the NL 10.Body Mass Index >17 and <35 at Screening 11.Females must not be lactating or pregnant at Screening or Baseline All females will be considered to be of childbearing potential unless they are postmenopausal or have been sterilized surgically 12.Females of childbearing potential must not have had unprotected sexual intercourse within 30 days before study entry and must agree to use a highly effective method of contraception throughout the entire study period and for 35 days after study drug discontinuation. If currently abstinent, the subject must agree to use a double-barrier method as described above if she becomes sexually active during the study period or f
Exclusion criteria
Exclusion criteria: 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, stroke, or seizures within 12 months of Screening 3.Any psychiatric diagnosis or symptoms, that could interfere with study procedures 4.GDS score =8 at Screening 5.Contraindications to MRI scanning, including cardiac pacemaker/ defibrillator, ferromagnetic metal implants 6.Evidence of other clinically significant lesions that could indicate a dementia diagnosis other than AD on MRI at Screening. 7.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 450 ms) as demonstrated by a repeated electrocardiogram 14.Known to be HIV positive 15.Any other clinically significant abnormalities in physical examination, vital signs, laboratory tests or ECG at Screening or Baseline which in the opinion of the principal investigator (PI), require further investigation or treatment or which may interfere with study procedures or safety 16.Uncontrolled Type 1 or Type 2 diabetes mellitus 17.Uncontrolled hypertension with a history of blood pressure consistently above 165/100 mm Hg at Screening 18.History of uncontrolled cardiovascular disease within 6 months of Screening 19.Subjects with malignant neoplasms within 3 years of Screening (except for basal or squamous cell carcinoma in situ of the skin, or
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 1. To evaluate the efficacy of BAN2401 compared to placebo by establishing the ED90 (as defined in the protocol) for BAN2401 on the Alzheimer's Disease Composite Score (ADCOMS) at 12 months of treatment in subjects with Early Alzheimer’s Disease (EAD), defined as mild cognitive impairment (MCI) due to Alzheimer’s disease (AD) – intermediate likelihood or mild Alzheimer’s disease dementia. 2. To assess the safety and tolerability of 3 doses and 2 dose regimens of BAN2401 in subjects with EAD. ; Secondary Objective: Key Secondary Objectives: 1. To evaluate the effects of BAN2401 compared to placebo on brain amyloid pathophysiology at 18 months of treatment in subjects with EAD as measured by amyloid positron emission tomography (PET) 2. To evaluate the efficacy of BAN2401 compared to placebo on the ADCOMS at 18 months of treatment in subjects with EAD 3. To evaluate the efficacy of BAN2401 compared to placebo on the Clinical Dementia Rating – Sum of Boxes (CDR-SB) at 18 months of treatment in subjects with EAD 4. To evaluate the efficacy of BAN2401 compared to placebo on Alzheimer Disease Assessment Scale - Cognitive Subscale (ADAS-cog) in subjects with EAD at 18 months 5. To evaluate the effects of BAN2401 compared to placebo at 18 months on clinical status separately within subjects with MCI and mild AD dementia for the following assessments: ADCOMS, CDR-SB, and ADAScog (Due to character limit it's not possible to include all texts. Please refer to relevant section of protocol) ;Primary end point(s): • Change from baseline in the ADCOMS;Timepoint(s) of evaluation of this end point: At 12 months only. | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: The ADCOMS at 18 months, vMRI at 6, 12, and 18 months. Amyloid PET at 12 and 18 months.; Secondary end point(s): Key Secondary Endpoints: • Change from baseline at 18 months in brain amyloid pathophysiology as measured by amyloid PET (revised per Amendments 09 and 10) • Change from baseline in the ADCOMS at 18 months (revised per Amendment 09) • Change from baseline in CDR-SB at 18 months (revised per Amendments 09 and 10) • Change from baseline in ADAS-cog at 18 months (revised per Amendments 09 and 10) • Change from baseline in CSF biomarkers (Aß[1-42], t-tau, and p-tau) at 18 months (revised per Amendment 10) • Change from baseline in total hippocampal volume at 18 months using vMRI (revised per Amendments 09 and 10) Secondary Endpoints: • Change from baseline at 12 months in brain amyloid pathophysiology as measured by amyloid PET (revised per Amendment 10) • Change from baseline at 12 months on clinical status for the following assessments: ADCOMS, CDR-SB, and ADAS-cog (revised per Amendment 10) • Change from baseline in CSF biomarkers (Aß[1-42], t-tau, and p-tau) at 12 months (revised per Amendment 10) • Change from baseline in total hippocampal at 6 and 12 months, and in left and right hippocampus, whole brain, and total ventricular volume as measured by vMRI at 6, 12, and 18 months (revised per Amendment 10) Exploratory Endpoints: • Change from baseline in clinical status at time points not analyzed in Key Secondary and Secondary sections for each of the followi | — |
Countries
Canada, Germany, Italy, Japan, Korea, Republic of, Netherlands, Spain, Sweden, United Kingdom, United States
Contacts
Public ContactMedical Information
Eisai Limited
Outcome results
None listed