Study to Evaluate the Safety, Tolerability and the Effect of BMS-241027 on Cerebrospinal Fluid Biomarkers in Subjects With Mild Alzheimer's Disease

A Multi-Center, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety, Tolerability and the Effect of BMS-241027 on Cerebrospinal Fluid Biomarkers in Subjects With Mild Alzheimer's Disease

The purpose of the study is to evaluate safety and the pharmacodynamic effects of BMS-241027 on cerebrospinal fluid (CSF) Tau, connectivity magnetic resonance imaging (MRI), and computerized cognitive tests in mild Alzheimer's disease (AD) subjects, following 9 weekly intravenous (IV) infusions of BMS-241027

Study Overview

• Status: Completed
• Conditions: Alzheimer's Disease
• Intervention / Treatment: Drug: BMS-241027; Drug: BMS-241027; Drug: BMS-241027; Drug: Placebo matching BMS-241027

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 1

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • London, Ontario, Canada, N6C 5J1
      • Local Institution
    • Toronto, Ontario, Canada, M3B 2S7
      • Local Institution
  • Quebec
    • Greenfield Park, Quebec, Canada, J4V 2J2
      • Local Institution
• France
  • Lille Cedex, France, 59037
    • Local Institution
  • Paris, France, 75013
    • Local Institution
  • Cedex 9
    • Toulouse, Cedex 9, France, 31059
      • Local Institution
• Germany
  • Berlin, Germany, 14050
    • Local Institution
  • Heidelberg, Germany, 69115
    • Local Institution
• Sweden
  • Stockholm, Sweden, 141 86
    • Local Institution
• United States
  • California
    • Anaheim, California, United States, 92801
      • Anaheim Clinical Trials Llc
    • Long Beach, California, United States, 90806
    • San Francisco, California, United States, 94158
      • UCSF Memory and Aging Center
  • Colorado
    • Boulder, Colorado, United States, 80304
      • Alpine Clinical Research Center, Inc.
  • Connecticut
    • Fairfield, Connecticut, United States, 06824
      • Associated Neurologists of Southern Connecticut, P.C.
  • Florida
    • Orlando, Florida, United States, 32806
      • Compass Research, LLC
    • Palm Beach Gardens, Florida, United States, 33410
      • Palm Beach Neurological Center Advanced Research Consultants
  • Illinois
    • Elk Grove Village, Illinois, United States, 60007
      • Alexian Brothers Neurosciences Institute Clinical Research
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Brigham and Women's Hospital
  • Michigan
    • East Lansing, Michigan, United States, 48824
      • Michigan State University
  • Ohio
    • Columbus, Ohio, United States, 43210
      • The Ohio State University
  • Pennsylvania
    • Jenkintown, Pennsylvania, United States, 19046
      • The Clinical Trial Center, LLC
    • Philadelphia, Pennsylvania, United States, 19104
      • Hospital of the University of Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Penn Memory Center
  • Utah
    • Salt Lake City, Utah, United States, 84106
      • Lifetree Clinical Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 48 years to 88 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Mild AD Subjects meeting National Institute of Neurological Disorders and Stroke - Alzheimer's Disease Related Disorders Association(NINCDS-ADRDA) and Diagnostic and Statistical Manual of Mental Disorders-Forth Edition, Text Revision (DSM-IV-TR) criteria
• Mini-Mental State Exam (MMSE) Score between 20 & 26 (inclusive)
• CSF consistent with AD pathology
• Screening brain MRI - normal - commensurate with age or demonstrate atrophy consistent with AD diagnosis (dx); reveal no more than mild white matter disease; up to 2 lacunar infarcts acceptable except in anterior thalamus, genu of internal capsule or basal forebrain; reveal no cortical infarcts; reveal no more than 4 microbleeds; reveal no focal asymmetric lobar atrophy or other findings suggesting primary cause of dementia is attributed to a cause other than AD; reveal no macrohemorrhages (>10 mm)
• Subjects must have reliable study partners
• Men and Women of Non Child Bearing Potentia (WONCBP), ages 50-90 years

Exclusion Criteria:

• Subjects with any other medical condition other than mild AD that could explain subjects' memory or cognitive deficits
• Subjects diagnosed with moderate or severe AD per DSM-IV criteria
• Subjects with a history (hx) of stroke
• Subjects with a hx of GI illnesses
• Subjects with Vitamin B12 or folate deficiency
• Subjects with any unstable cardiovascular (CV), pulmonary, Gastrointestinal (GI) or hepatic disease within 30 days prior to screening
• Subjects with active liver dx or history of hepatic intolerance
• Subjects with a Geriatric Depression Scale score of ≥ 6 at screening
• Subjects treated for or have had a diagnosis of schizophrenia
• Subjects treated for or have had a diagnosis of bipolar disease within 3 years prior to screening
• Subjects with a history of generalized peripheral neuropathy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm 1: BMS-241027 (0.003 mg/kg)	Drug: BMS-241027; Intravenous (IV), 0.003 mg/kg, Once Weekly, 9 weeks; Drug: BMS-241027; Intravenous (IV), 0.01 mg/kg, Once Weekly, 9 weeks; Drug: BMS-241027; Intravenous (IV), 0.03 mg/kg, Once Weekly, 9 weeks
Experimental: Arm 2: BMS-241027 (0.01 mg/kg)	Drug: BMS-241027; Intravenous (IV), 0.003 mg/kg, Once Weekly, 9 weeks; Drug: BMS-241027; Intravenous (IV), 0.01 mg/kg, Once Weekly, 9 weeks; Drug: BMS-241027; Intravenous (IV), 0.03 mg/kg, Once Weekly, 9 weeks
Experimental: Arm 3: BMS-241027 (0.03 mg/kg)	Drug: BMS-241027; Intravenous (IV), 0.003 mg/kg, Once Weekly, 9 weeks; Drug: BMS-241027; Intravenous (IV), 0.01 mg/kg, Once Weekly, 9 weeks; Drug: BMS-241027; Intravenous (IV), 0.03 mg/kg, Once Weekly, 9 weeks
Experimental: Arm 4: Placebo matching BMS-241027	Drug: Placebo matching BMS-241027; Intravenous (IV), 0.0 mg/kg, Once Weekly, 9 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Safety assessments: based on frequency of Serious Adverse Events (SAEs), frequency of Adverse events (AEs), discontinuation due to AEs and dose reduction	Within the first 70 day after first dose
Biomarker Measures: CSF levels of Tau N-terminal domain fragments	Within the first 70 day after first dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Effects of BMS-241027 on CSF levels of the mid-domain Tau fragment		Within the first 70 days after first dose
Effects of BMS-241027 on cognitive performance using computerized cognitive tests		Weeks 3, 6 and 9
Effects of BMS-241027 on connectivity MRI		Within the first 70 days after first dose
Maximal observed plasma concentration (Cmax) of BMS-241027 in subjects with mild Alzheimer's disease	Intensive pharmacokinetic parameter Cmax will be derived from subgroups of subjects at Week 7	Weeks 1, 4, and 9
Observed plasma concentration at 24 hours post dose (C24) of BMS-241027 in subjects with mild Alzheimer's disease	Intensive pharmacokinetic parameter C24 will be derived from subgroups of subjects at Week 7	Weeks 1, 4, and 9
Time of maximal observed plasma concentration (Tmax) of BMS-241027 in subjects with mild Alzheimer's disease	Intensive pharmacokinetic parameter Tmax will be derived from subgroups of subjects at Week 7	Weeks 1, 4, and 9
Area under the concentration-time curve in one dosing interval [AUC(TAU)] of BMS-241027 in subjects with mild Alzheimer's disease	Intensive pharmacokinetic parameter AUC(TAU) will be derived from subgroups of subjects at Week 7	Weeks 1, 4, and 9
Safety assessments: based on vital sign measurements, ECGs and clinical laboratory tests		Within the first 70 day after first dose
Effects of BMS-241027 on CSF levels of neurofilaments		Within the first 70 days after first dose

Collaborators and Investigators

• Sponsor: Bristol-Myers Squibb

Publications and helpful links

Helpful Links

• BMS clinical trial educational resource

Study record dates

Study Major Dates

• Study Start: February 1, 2012
• Primary Completion (Actual): October 1, 2013
• Study Completion (Actual): October 1, 2013

Study Registration Dates

• First Submitted: December 13, 2011
• First Submitted That Met QC Criteria: December 13, 2011
• First Posted (Estimate): December 15, 2011

Study Record Updates

• Last Update Posted (Estimate): July 24, 2014
• Last Update Submitted That Met QC Criteria: July 23, 2014
• Last Verified: October 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Neurodegenerative Diseases; Dementia; Tauopathies; Alzheimer Disease
• Other Study ID Numbers: CN167-003; 2011-004065-33 (EudraCT Number)