ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 1 of 1 for:    NCT01767311
Previous Study | Return to List | Next Study

A Study to Evaluate Safety, Tolerability, and Efficacy of BAN2401 in Subjects With Early Alzheimer's Disease

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT01767311
Recruitment Status : Completed
First Posted : January 14, 2013
Last Update Posted : September 5, 2018
Sponsor:
Information provided by (Responsible Party):
Eisai Inc.

January 8, 2013
January 14, 2013
September 5, 2018
December 20, 2012
July 19, 2018   (Final data collection date for primary outcome measure)
  • Core Study: Change from Baseline in the Alzheimer's Disease Composite Score (ADCOMS) at 12 months [ Time Frame: Baseline and 12 months ]
  • Core Study and Extension Phase: Safety will be assessed by monitoring and recording all adverse events (AEs) and serious adverse events (SAEs) [ Time Frame: From the time the participant signs the informed consent form until 3 months after the last dose of study drug or through the last visit, whichever is longer; up to 78 months ]
    Safety assessments will consist of monitoring and recording all AEs and SAEs; regular monitoring of hematology, blood chemistry, and urine values; periodic measurement of vital signs and electrocardiograms (ECGs); safety magnetic resonance imaging (MRI); and performance of physical examinations.
Change from baseline in the derived Composite Clinical Score at 12 months [ Time Frame: 12 months ]
Complete list of historical versions of study NCT01767311 on ClinicalTrials.gov Archive Site
  • Core Study: Change from Baseline at 18 Months in Brain Amyloid Pathophysiology as Measured by Amyloid Positron Emission Tomography (PET) [ Time Frame: Baseline and 18 Months ]
  • Core Study: Change from Baseline in the ADCOMS at 18 Months [ Time Frame: Baseline and 18 Months ]
  • Core Study: Change from Baseline in Clinical Dementia Rating - Sum of Boxes (CDR-SB) at 18 Months [ Time Frame: Baseline and 18 Months ]
  • Core Study: Change from Baseline in Alzheimer Disease Assessment Scale - Cognitive Subscale (ADAS-cog) at 18 Months [ Time Frame: Baseline and 18 Months ]
  • Core Study: Change from Baseline in Cerebrospinal fluid (CSF) Biomarkers (Aβ[1-42], t-tau, and p-tau) at 18 Months [ Time Frame: Baseline and 18 Months ]
  • Core Study: Change from Baseline in Total Hippocampal Volume at 18 Months as Measured by Volumetric Magnetic Resonance Imaging (vMRI) [ Time Frame: Baseline and 18 months ]
  • Core Study: Change from Baseline at 12 Months in Brain Amyloid Pathophysiology as Measured by Amyloid PET [ Time Frame: Baseline and 12 Months ]
  • Core Study: Change from baseline at 12 months on clinical status for the following assessments: ADCOMS, CDR-SB, and ADAS-cog [ Time Frame: Baseline and 12 Months ]
  • Core Study: Change from Baseline in CSF Biomarkers (Aβ[1-42], t-tau, and p-tau) at 12 Months [ Time Frame: Baseline and 12 Months ]
  • Core Study: Change from Baseline in Total Hippocampal Volume at 6 and 12 Months as Measured by vMRI [ Time Frame: Baseline, 6 and 12 Months ]
  • Core Study: Change from Baseline in Left and Right Hippocampal Volume at 6, 12, and 18 Months as Measured by vMRI [ Time Frame: Baseline and 6, 12 and 18 Months ]
  • Core Study: Change from Baseline in Whole Brain Volume at 6, 12, and 18 Months as Measured by vMRI [ Time Frame: Baseline and 6, 12 and 18 Months ]
  • Core Study: Change from Baseline in Total Ventricular Volume at 6, 12, and 18 Months as Measured by vMRI [ Time Frame: Baseline and 6, 12 and 18 Months ]
  • Extension Phase: Change from Baseline in ADCOMS at Each Visit [ Time Frame: Baseline and up to 60 months ]
  • Change from baseline in the derived Composite Clinical Score at 18 months [ Time Frame: 18 months ]
  • Change from baseline in total hippocampal volume at 6 months using vMRI [ Time Frame: 6 months ]
  • Change from baseline in total hippocampal volume at 12 months using vMRI [ Time Frame: 12 months ]
  • Change from baseline in total hippocampal volume at 18 months using vMRI [ Time Frame: 18 months ]
  • Change from baseline at 12 months in brain amyloid levels as measured by amyloid PET [ Time Frame: 12 months ]
  • Change from baseline at 18 months in brain amyloid levels as measured by amyloid PET [ Time Frame: 18 months ]
Not Provided
Not Provided
 
A Study to Evaluate Safety, Tolerability, and Efficacy of BAN2401 in Subjects With Early Alzheimer's Disease
A Placebo-controlled, Double-blind, Parallel-group, Bayesian Adaptive Randomization Design and Dose Regimen-finding Study to Evaluate Safety, Tolerability and Efficacy of BAN2401 in Subjects With Early Alzheimer's Disease
This is a multinational, multicenter, double-blind, placebo-controlled, parallel-group study using a Bayesian design with response adaptive randomization across placebo or 5 active arms of BAN2401 to determine clinical efficacy and to explore the dose response of BAN2401 using a composite clinical score (ADCOMS). BAN2401-G000-201 is an 18-month study in which 3 dose levels (2.5, 5, and 10 mg/kg) are given biweekly (once every 2 weeks) to separate groups of participants and 2 dose levels (5 and 10 mg/kg) are given monthly (once every 4 weeks) to separate groups of participants. Participants will be from 2 clinical subgroups: mild cognitive impairment (MCI) due to Alzheimer's disease (AD) or mild Alzheimer's disease dementia. Frequent interim analyses will be conducted to continually update randomization allocation on the basis of the primary clinical endpoint. In the event of early success in the Core Study at any interim analysis (IA) or at the Bayesian analysis at 12 months of treatment, an open label extension (OLE) Phase will be implemented to allow for up to 60 months (5 years) of additional treatment. The OLE will not be conducted if early success is not achieved at any IA or at the Bayesian analysis at 12 months of treatment.
Not Provided
Interventional
Phase 2
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Alzheimer's Disease
  • Drug: BAN2401 2.5 mg/kg
    2.5 mg/kg biweekly (once every 2 weeks) administered as a 60 minute i.v. infusion
  • Drug: BAN2401 5.0 mg/kg
    5.0 mg/kg biweekly (once every 2 weeks) administered as a 60 minute i.v. infusion
  • Drug: BAN2401 10 mg/kg
    10 mg/kg biweekly (once every 2 weeks) administered as a 60 minute i.v. infusion.
  • Drug: BAN2401 5.0 mg/kg
    5.0 mg/kg monthly (once every 4 weeks) administered as a 60 minute i.v. infusion. All participants will receive biweekly infusions, participants will have placebo infusion alternating with BAN2401
  • Drug: BAN2401 10 mg/kg
    10 mg/kg monthly (once every 4 weeks) administered as a 60 minute i.v. infusion. All participants will receive biweekly infusions, participants will have placebo infusion alternating with BAN2401
  • Drug: Placebo
    biweekly (once every 2 weeks) administered as a 60 minute i.v. infusion
  • Experimental: BAN2401 2.5 mg/kg biweekly
    2.5 mg/kg biweekly
    Intervention: Drug: BAN2401 2.5 mg/kg
  • Experimental: BAN2401 5.0 mg/kg biweekly
    5.0 mg/kg biweekly
    Intervention: Drug: BAN2401 5.0 mg/kg
  • Experimental: BAN2401 10 mg/kg biweekly
    10 mg/kg biweekly
    Intervention: Drug: BAN2401 10 mg/kg
  • Experimental: BAN2401 5.0 mg/kg monthly
    5.0 mg/kg monthly
    Intervention: Drug: BAN2401 5.0 mg/kg
  • Experimental: BAN2401 10 mg/kg monthly
    10 mg/kg monthly
    Intervention: Drug: BAN2401 10 mg/kg
  • Placebo Comparator: Placebo
    Matching placebo biweekly
    Intervention: Drug: Placebo
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
800
Same as current
July 19, 2018
July 19, 2018   (Final data collection date for primary outcome measure)

Key Inclusion Criteria for Mild Cognitive Impairment due to Alzheimer's Disease - Intermediate likelihood:

  1. Subjects who meet the National Institute of Aging - Alzheimer's Association (NIA-AA) core clinical criteria for mild cognitive impairment 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 one year before Screening; MUST be corroborated by an informant

Key Inclusion Criteria for Mild Alzheimer's Disease Dementia:

  1. Subjects who meet the NIA-AA core clinical criteria for probable Alzheimer's disease dementia
  2. Subjects who have a CDR score of 0.5-1.0 and a Memory Box score of 0.5 or greater at Screening and Baseline

Inclusion Criteria that must be met by all subjects:

  1. Subjects with 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 II (WMS-IV LMII):

    1. Less than or equal to 15 for age 50 to 64 years
    2. Less than or equal to 12 for age 65 to 69 years
    3. Less than or equal to 11 for age 70 to 74 years
    4. Less than or equal to 9 for age 75 to 79 years
    5. Less than or equal to 7 for age 80 to 90 years
  2. Positive amyloid load as indicated by PET or CSF assessment

    1. PET assessment of imaging agent uptake into brain
    2. CSF assessment of Aβ(1-42)
  3. Age between 50 and 90 years, inclusive
  4. Mini Mental State Examination (MMSE) score equal to or greater than 22, and equal to or less than 30, at Screening and Baseline
  5. Body Mass Index (BMI) greater than 17 and less than 35 at Screening or Baseline
  6. Females must not be lactating or pregnant at Screening or Baseline (as documented by a negative beta-human chorionic gonadotropin assay [ß-hCG]). A separate baseline assessment is required if a negative screening pregnancy test was obtained more than 72 hours before the first dose of study drug.
  7. Subjects on acetylcholinesterase inhibitor or memantine therapy or both for Alzheimer's disease (AD) must be on a stable dose for at least 12 weeks prior to Baseline. Treatment naive subjects can be entered into the study. Unless otherwise stated, subjects must have been on stable doses of all other permitted concomitant medications (ie, non-AD related) for at least 4 weeks prior to Baseline.
  8. Subjects must have identified caregivers/informants
  9. Subjects must provide written informed consent

Extension Phase:

- Have completed Visit 42 (Week 79) of the Core Study and fall within a 4-month window from Visit 40 (Week 75) beginning at the time the decision is made to proceed with the extension

Key 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 (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. GDS score ≥8 at Screening
  5. Contraindications to MRI scanning, including cardiac pacemaker/ defibrillator, ferromagnetic metal implants, e,g., in skull and cardiac devices other than those approved as safe for use in MR scanners
  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/QTc interval (QTc greater than 450 ms) as demonstrated by a repeated electrocardiogram (ECG)
  8. Certain other specified medical conditions
  9. Severe visual or hearing impairment that would prevent the subject from performing psychometric tests accurately

Extension Phase:

Participants who previously completed the Core Study prior to the implementation of the open label extension (OLE), or those who discontinue from the study drug or from the Core Study are not eligible to participate in the OLE Phase.

Sexes Eligible for Study: All
50 Years to 90 Years   (Adult, Older Adult)
No
Contact information is only displayed when the study is recruiting subjects
Canada,   France,   Germany,   Italy,   Japan,   Korea, Republic of,   Netherlands,   Spain,   Sweden,   United Kingdom,   United States
 
 
NCT01767311
BAN2401-G000-201
2012-002843-11 ( EudraCT Number )
Yes
Studies a U.S. FDA-regulated Drug Product: Yes
Not Provided
Eisai Inc.
Eisai Inc.
Not Provided
Study Director: Chad Swanson, PhD Eisai Inc.
Eisai Inc.
July 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP