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

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by Eisai Inc.
Sponsor:
Information provided by (Responsible Party):
Eisai Inc. ( Eisai Co., Ltd. )
ClinicalTrials.gov Identifier:
NCT02094729
First received: January 9, 2014
Last updated: June 25, 2014
Last verified: June 2014
  Purpose

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.


Condition Intervention Phase
Alzheimer's Disease
Drug: BAN2401 2.5 mg /kg
Drug: BAN2401 5 mg /kg
Drug: BAN2401 10 mg /kg
Drug: Placebo
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Eisai Inc.:

Primary Outcome Measures:
  • Number of Participants with Adverse Events as a Measure of Safety and Tolerability [ Time Frame: Up to 14 weeks ] [ Designated as safety issue: Yes ]
    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:
  • Pharmacokinetics of BAN-2401: Maximum Concentration (Cmax) [ Time Frame: Up to 14 weeks ] [ Designated as safety issue: No ]
    Cmax after single and repeated administrations based on non-compartmental analysis.

  • Pharmacokinetics of BAN-2401: time attain to Cmax (tmax) [ Time Frame: Up to 14 weeks ] [ Designated as safety issue: No ]
    tmax after single and repeated administrations based on non-compartmental analysis.

  • Pharmacokinetics of BAN-2401: Area under the curve (AUC) [ Time Frame: Up to 14 weeks ] [ Designated as safety issue: No ]
    AUC after single and repeated administrations based on non-compartmental analysis.

  • Pharmacokinetics of BAN-2401: Drug Clearance (CL) [ Time Frame: Up to 14 weeks ] [ Designated as safety issue: No ]
    CL after single and repeated administrations based on non-compartmental analysis.

  • Pharmacokinetics of BAN-2401: apparent volume of distribution at steady state (Vss) [ Time Frame: Up to 14 weeks ] [ Designated as safety issue: No ]
    Vss after single and repeated administrations based on non-compartmental analysis.

  • Investigation of the effect of repeated intravenous infusions of BAN-2401 on the immunogenicity and CSF biomarkers [ Time Frame: Up to 14 weeks ] [ Designated as safety issue: No ]
    Summary statistics (mean, standard deviation, median, minimum and maximum) will be calculated for each measurement of CSF concentrations of Aβ1-40, Aβ1-42, Aβ1-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 ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 24
Study Start Date: September 2013
Estimated Study Completion Date: February 2015
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: BAN2401 2.5 mg /kg
Cohorts 1: Intravenous infusions of 2.5 mg /kg BAN2401
Drug: BAN2401 2.5 mg /kg
Cohorts 1: Intravenous infusions of 2.5 mg /kg BAN2401 for 60 +/- 10 minutes.
Experimental: BAN2401 5 mg /kg
Cohorts 2: Intravenous infusions of 5 mg /kg BAN2401
Drug: BAN2401 5 mg /kg
Cohorts 2: Intravenous infusions of 5 mg /kg BAN2401 for 60 +/- 10 minutes.
Experimental: BAN2401 10 mg /kg
Cohorts 3: Intravenous infusions of 10 mg /kg BAN2401
Drug: BAN2401 10 mg /kg
Cohorts 3: Intravenous infusions of 10 mg /kg BAN2401 for 60 +/- 10 minutes
Placebo Comparator: Placebo
Intravenous infusions of placebo for 60 +/- 10 minutes.
Drug: Placebo
Intravenous infusions of placebo for 60 +/- 10 minutes.

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.

  Eligibility

Ages Eligible for Study:   50 Years to 90 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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).

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02094729

Contacts
Contact: Customer Joy Department. EJ ML_CLNCL@hhc.eisai.co.jp

Locations
Japan
Recruiting
Kobe, Hyogo, Japan
Recruiting
Sendai, Miyagi, Japan
Recruiting
Kurashiki, Okayama, Japan
Recruiting
Koto-ku, Tokyo, Japan
Sponsors and Collaborators
Eisai Co., Ltd.
  More Information

No publications provided

Responsible Party: Eisai Inc. ( Eisai Co., Ltd. )
ClinicalTrials.gov Identifier: NCT02094729     History of Changes
Other Study ID Numbers: BAN2401-J081-104
Study First Received: January 9, 2014
Last Updated: June 25, 2014
Health Authority: Japan: Ministry of Health, Labor and Welfare

Keywords provided by Eisai Inc.:
mild cognitive impairment
Alzheimer's disease

Additional relevant MeSH terms:
Alzheimer Disease
Cognition Disorders
Mild Cognitive Impairment
Dementia
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Tauopathies
Neurodegenerative Diseases
Delirium, Dementia, Amnestic, Cognitive Disorders
Mental Disorders

ClinicalTrials.gov processed this record on August 26, 2014