A Randomized, Double-blind, Placebo-controlled Study to Assess Safety, Tolerability, Pharmacokinetics, Immunogenicity, and Pharmacodynamic Response of Repeated Intravenous Infusions of BAN2401 in Subjects With Mild Cognitive Impairment Due to Alzheimer's Disease and Mild Alzheimer's Disease
- Conditions
- Alzheimer's Disease
- Interventions
- Drug: BAN2401 2.5 mg/kgDrug: BAN2401 5 mg/kgDrug: BAN2401 10 mg/kgDrug: Placebo
- Registration Number
- NCT02094729
- Lead Sponsor
- Eisai Co., Ltd.
- Brief Summary
The purpose of this study is to assess the safety, tolerability, pharmacokinetics, immunogenicity, and pharmacodynamic response of repeated intravenous infusions of BAN2401 in subjects with mild cognitive impairment (MCI) due to Alzheimer's disease (AD) and mild Alzheimer's disease.
- Detailed Description
This is a multicenter, randomized, placebo-controlled, double-blind, multiple ascending dose study in a total of 24 subjects (8 subjects per cohort) with MCI due to AD and mild AD. The study consists of three cohorts to evaluate the safety, tolerability and PK of BAN2401 at three dose levels (2.5, 5, and 10 mg/kg). Each cohort consists of Screening Period before randomization, Treatment Period from randomization to last dose, and Follow-up Period after last dose. Cohorts 1, 2, and 3 will receive 2.5 mg/kg, 5 mg/kg, and 10 mg/kg of BAN2401, respectively.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 26
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description BAN2401 2.5 mg/kg BAN2401 2.5 mg/kg Cohorts 1: Intravenous infusions of 2.5 mg/kg BAN2401 BAN2401 5 mg/kg BAN2401 5 mg/kg Cohorts 2: Intravenous infusions of 5 mg/kg BAN2401 BAN2401 10 mg/kg BAN2401 10 mg/kg Cohorts 3: Intravenous infusions of 10 mg/kg BAN2401 Placebo Placebo Intravenous infusions of placebo for 60 +/- 10 minutes.
- Primary Outcome Measures
Name Time Method Number of Participants with Adverse Events as a Measure of Safety and Tolerability Up to 14 weeks Safety assessment variables will include all adverse events (AEs) including serious and non-serious AEs; laboratory parameters (hematology, blood chemistry, and urinalysis); vital signs; electrocardiograms; and physical examination; as well as a risk of suicide using C-SSRS and brain MRI.
- Secondary Outcome Measures
Name Time Method Pharmacokinetics of BAN2401: Maximum Concentration (Cmax) Up to 14 weeks Cmax after single and repeated administrations based on non-compartmental analysis.
Pharmacokinetics of BAN2401: time attain to Cmax (tmax) Up to 14 weeks tmax after single and repeated administrations based on non-compartmental analysis.
Pharmacokinetics of BAN2401: Area under the curve (AUC) Up to 14 weeks AUC after single and repeated administrations based on non-compartmental analysis.
Pharmacokinetics of BAN2401: Drug Clearance (CL) Up to 14 weeks CL after single and repeated administrations based on non-compartmental analysis.
Pharmacokinetics of BAN2401: apparent volume of distribution at steady state (Vss) Up to 14 weeks Vss after single and repeated administrations based on non-compartmental analysis.
Investigation of the effect of repeated intravenous infusions of BAN2401 on the immunogenicity and CSF biomarkers Up to 14 weeks Summary statistics (mean, standard deviation, median, minimum and maximum) will be calculated for each measurement of CSF concentrations of AB1-40, AB1-42, AB1-x, total tau and p-tau and their percent changes from baseline.
Investigation of the effect of apolipoprotein allele4 (ApoE4) on the safety, tolerability and pharmacodynamic (PD) response of repeated intravenous infusions of BAN2401 Up to 14 weeks