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

• ClinicalTrials.gov Identifier: NCT02094729
• Recruitment Status: Completed
• First Posted: March 24, 2014
• Last Update Posted: June 8, 2015
• Sponsor: Eisai Co., Ltd.
• Information provided by (Responsible Party): Eisai Inc. ( Eisai Co., Ltd. )

Tracking Information

• First Submitted Date: January 9, 2014
• First Posted Date: March 24, 2014
• Last Update Posted Date: June 8, 2015
• Study Start Date: September 2013
• Actual Primary Completion Date: March 2015 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 19, 2014)

Number of Participants with Adverse Events as a Measure of Safety and Tolerability [ Time Frame: 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.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: February 6, 2015)

• Pharmacokinetics of BAN2401: Maximum Concentration (Cmax) [ Time Frame: Up to 14 weeks ]
  Cmax after single and repeated administrations based on non-compartmental analysis.
• Pharmacokinetics of BAN2401: time attain to Cmax (tmax) [ Time Frame: Up to 14 weeks ]
  tmax after single and repeated administrations based on non-compartmental analysis.
• Pharmacokinetics of BAN2401: Area under the curve (AUC) [ Time Frame: Up to 14 weeks ]
  AUC after single and repeated administrations based on non-compartmental analysis.
• Pharmacokinetics of BAN2401: Drug Clearance (CL) [ Time Frame: 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) [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: Up to 14 weeks ]

Original Secondary Outcome Measures (submitted: March 19, 2014)

• Pharmacokinetics of E2006: Maximum Concentration (Cmax) [ Time Frame: Up to 14 weeks ]
  Cmax after single and repeated administrations based on non-compartmental analysis.
• Pharmacokinetics of E2006: time attain to Cmax (tmax) [ Time Frame: Up to 14 weeks ]
  tmax after single and repeated administrations based on non-compartmental analysis.
• Pharmacokinetics of E2006: Area under the curve (AUC) [ Time Frame: Up to 14 weeks ]
  AUC after single and repeated administrations based on non-compartmental analysis.
• Pharmacokinetics of E2006: Drug Clearance (CL) [ Time Frame: Up to 14 weeks ]
  CL after single and repeated administrations based on non-compartmental analysis.
• Pharmacokinetics of E2006: apparent volume of distribution at steady state (Vss) [ Time Frame: 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 [ Time Frame: Up to 14 weeks ]
  Summary statistics (mean, standard deviation, median, minimum and maximum) will be calculated for each measurement of CSF concentrations of A?1-40, A?1-42, A?1-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 [ Time Frame: Up to 14 weeks ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• Official Title: 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
• 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.
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
• Condition: Alzheimer's Disease

Intervention

• Drug: BAN2401 2.5 mg/kg
  Cohorts 1: Intravenous infusions of 2.5 mg/kg BAN2401 for 60 +/- 10 minutes.
• Drug: BAN2401 5 mg/kg
  Cohorts 2: Intravenous infusions of 5 mg/kg BAN2401 for 60 +/- 10 minutes.
• Drug: BAN2401 10 mg/kg
  Cohorts 3: Intravenous infusions of 10 mg/kg BAN2401 for 60 +/- 10 minutes
• Drug: Placebo
  Intravenous infusions of placebo for 60 +/- 10 minutes.

Study Arms

• Experimental: BAN2401 2.5 mg/kg
  Cohorts 1: Intravenous infusions of 2.5 mg/kg BAN2401
  Intervention: Drug: BAN2401 2.5 mg/kg
• Experimental: BAN2401 5 mg/kg
  Cohorts 2: Intravenous infusions of 5 mg/kg BAN2401
  Intervention: Drug: BAN2401 5 mg/kg
• Experimental: BAN2401 10 mg/kg
  Cohorts 3: Intravenous infusions of 10 mg/kg BAN2401
  Intervention: Drug: BAN2401 10 mg/kg
• Placebo Comparator: Placebo
  Intravenous infusions of placebo for 60 +/- 10 minutes.
  Intervention: Drug: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: June 4, 2015): 26
• Original Estimated Enrollment (submitted: March 19, 2014): 24
• Actual Study Completion Date: May 2015
• Actual Primary Completion Date: March 2015 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria

MCI due to AD

1. Subjects who have clinical and cognitive symptoms consistent with the National Institute on Aging-Alzheimer's Association (NIA-AA) core criteria for MCI
2. Subjects who have a Clinical Dementia Rating (CDR) of 0.5 and a memory box score of 0.5 or greater at Screening
3. Subjects who report a history of subjective memory decline with slow progression at least 1 year before Screening, or subjects whose information provider or attending physician reports a history of memory decline with slow progression at least 1 year before Screening

4. Subjects with objective impairment in episodic memory as indicated by 1-1.5 standard deviations below age-adjusted mean in the Wechsler Memory Scale-Revised (WMS-R) logical memory II (delayed recall) at Screening:

   • less than or equal to 15 for age 50 to 64 years
   • less than or equal to 12 for age 65 to 69 years
   • less than or equal to 11 for age 70 to 74 years
   • less than or equal to 9 for age 75 to 79 years
   • less than or equal to 7 for age 80 to 90 years

   Mild AD

5. Subjects who meet the NIA-AA core clinical criteria for probable AD

6. Subjects who have a CDR of 0.5 or 1.0 and a memory box score of 0.5 or greater at Screening

   All subjects

7. Male or female subjects aged between 50 and 90 years, inclusive, at obtaining informed consent
8. Subjects who have an Mini Mental State Examination (MMSE) score greater than or equal to 22 and less than or equal to 30 at Screening
9. Body Mass Index (BMI) less than 35 kg/m2 at Screening
10. Females must not be pregnant or lactating, and specified contraceptive precautions must be followed
11. Subjects must have identified caregivers/informants
12. Must have an informant or a caregiver who will provide written informed consent voluntarily and is able to spend 3 days a week with the subject (4 hours per day), and is able to support the subject during the study period by providing necessary patient information, assisting treatment compliance, and accompanying the subject to all scheduled visits (if needed) throughout the study.
13. Provide voluntary written informed consent (obtaining as much as possible from subjects, but mandatory from their legal guardians).
14. Willing and able to comply with all aspects of the protocol.

Exclusion Criteria

1. Any neurological condition that may affect cognitive impairment
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. Any medical devices contraindicated for MRI scanning (e.g., cardiac pacemaker/defibrillator, ferromagnetic metal implants, any devices other than those approved as safe for use in MRI scanners)
5. Evidence of infection, tumor, stroke or other clinically significant lesions that could indicate a dementia diagnosis other than AD on brain MRI at Screening
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 interval (QTcF greater than or equal to 450 ms) as demonstrated by a repeated ECG at Screening
8. Any other clinically significant conditions (e.g., cardiac, respiratory, gastrointestinal, renal disease) that in the opinion of the investigator(s) could affect the subject's safety or interfere with the study assessments
9. Severe visual or hearing impairment that would prevent the subject from performing psychometric tests accurately.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 50 Years to 90 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Japan

Administrative Information

• NCT Number: NCT02094729
• Other Study ID Numbers: BAN2401-J081-104
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Eisai Inc. ( Eisai Co., Ltd. )
• Original Responsible Party: Same as current
• Current Study Sponsor: Eisai Co., Ltd.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Eisai Inc.
• Verification Date: June 2015