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

Brief Summary

Official Title: “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. 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 subjects and 2 dose levels (5 and 10 mg/kg) are given monthly to separate groups of subjects. Subjects 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.

  • Study Type: Interventional
  • Study Design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment
  • Study Primary Completion Date: October 2017

Interventions Used in this Clinical Trial

  • 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

Arms, Groups and Cohorts in this Clinical Trial

  • Experimental: BAN2401 2.5 mg/kg biweekly
    • 2.5 mg/kg biweekly
  • Experimental: BAN2401 5.0 mg/kg biweekly
    • 5.0 mg/kg biweekly
  • Experimental: BAN2401 10 mg/kg biweekly
    • 10 mg/kg biweekly
  • Experimental: BAN2401 5.0 mg/kg monthly
    • 5.0 mg/kg monthly
  • Experimental: BAN2401 10 mg/kg monthly
    • 10 mg/kg monthly ——————————————————————————–

Outcome Measures for this Clinical Trial

Primary Measures

  • Change from baseline in the derived Composite Clinical Score at 12 months
    • Time Frame: Baseline and 12 months
      Safety Issue?: No

Secondary Measures

  • Change from baseline in the derived Composite Clinical Score at 18 months
    • Time Frame: Baseline and 18 months
      Safety Issue?: No
  • Change from baseline in total hippocampal volume at 6, 12, and 18 Months using volumetric magnetic resonance imaging (vMRI)
    • Time Frame: Baseline and 6, 12, and 18 months
      Safety Issue?: No
  • Change from baseline at 12 and 18 months in brain amyloid levels as measured by amyloid Positron Emission Tomography (PET)
    • Time Frame: Baseline and 12 and 18 months
      Safety Issue?: No

Criteria for Participation in this Clinical Trial

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

4. 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

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. Positive amyloid load as indicated by PET assessment

2. Age between 50 and 90 years, inclusive

3. Mini Mental State Examination (MMSE) score equal to or greater than 22, and equal to or less than 30, at Screening and Baseline

4. Body Mass Index (BMI) less than 35 at Screening

5. Females must not be pregnant or lactating, and specified contraceptive precautions must be followed

6. Subjects on acetylcholinesterase inhibitor or memantine therapy for Alzheimer's disease (AD) must be on a stable dose for at least 12 weeks prior to baseline

7. Subjects must have identified caregivers/informants

8. Subjects must provide written informed consent

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. 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

5. 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

6. A prolonged QT/QTc interval (QTc greater than 450 ms) as demonstrated by a repeated electrocardiogram (ECG)

7. Certain other specified medical conditions

8. Severe visual or hearing impairment that would prevent the subject from performing psychometric tests accurately

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 50 Years

Maximum Age for this Clinical Trial: 90 Years

Are Healthy Volunteers Accepted for this Clinical Trial: No

Clinical Trial Investigator Information

  • Lead Sponsor
    • Eisai Inc.
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Chad Swanson, Study Director, Eisai Inc.
  • Overall Contact(s)
    • Eisai Medical Services, (888) 422-4743

Source

Clinical Trials content is provided directly by the US National Institutes of Health via ClinicalTrials.gov and is not reviewed separately by ClinicalTrialsFeeds.org. Every page of information about a specific clinical trial contains a unique identifier which can be used to find further details directly from the National Institutes of Health.

The URL of this page is:
http://clinicaltrialsfeeds.org/clinical-trials/show/NCT01767311