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

This study is currently recruiting participants.
Verified October 2012 by Bristol-Myers Squibb
Sponsor:
Information provided by (Responsible Party):
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT01492374
First received: December 13, 2011
Last updated: October 10, 2012
Last verified: October 2012
History of Changes
  Purpose

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


Condition Intervention Phase
Alzheimer's Disease
 Drug: BMS-241027
Drug: Placebo matching BMS-241027
 Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by Bristol-Myers Squibb:

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

Secondary Outcome Measures:
  • Effects of BMS-241027 on CSF levels of the mid-domain Tau fragment [ Time Frame: Within the first 70 days after first dose ] [ Designated as safety issue: No ]
  • Effects of BMS-241027 on cognitive performance using computerized cognitive tests [ Time Frame: Weeks 3, 6 and 9 ] [ Designated as safety issue: No ]
  • Effects of BMS-241027 on connectivity MRI [ Time Frame: Within the first 70 days after first dose ] [ Designated as safety issue: No ]
  • Maximal observed plasma concentration (Cmax) of BMS-241027 in subjects with mild Alzheimer's disease [ Time Frame: Weeks 1, 4, and 9 ] [ Designated as safety issue: No ]
    Intensive pharmacokinetic parameter Cmax will be derived from subgroups of subjects at Week 7

  • Observed plasma concentration at 24 hours post dose (C24) of BMS-241027 in subjects with mild Alzheimer's disease [ Time Frame: Weeks 1, 4, and 9 ] [ Designated as safety issue: No ]
    Intensive pharmacokinetic parameter C24 will be derived from subgroups of subjects at Week 7

  • Time of maximal observed plasma concentration (Tmax) of BMS-241027 in subjects with mild Alzheimer's disease [ Time Frame: Weeks 1, 4, and 9 ] [ Designated as safety issue: No ]
    Intensive pharmacokinetic parameter Tmax will be derived from subgroups of subjects at Week 7

  • Area under the concentration-time curve in one dosing interval [AUC(TAU)] of BMS-241027 in subjects with mild Alzheimer's disease [ Time Frame: Weeks 1, 4, and 9 ] [ Designated as safety issue: No ]
    Intensive pharmacokinetic parameter AUC(TAU) will be derived from subgroups of subjects at Week 7

  • Safety assessments: based on vital sign measurements, ECGs and clinical laboratory tests [ Time Frame: Within the first 70 day after first dose ] [ Designated as safety issue: Yes ]
  • Effects of BMS-241027 on CSF levels of neurofilaments [ Time Frame: Within the first 70 days after first dose ] [ Designated as safety issue: No ]

Estimated Enrollment: 100
Study Start Date: February 2012
Estimated Study Completion Date: December 2013
Estimated Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm 1: BMS-241027 (0.003 mg/kg) Drug: BMS-241027
Intravenous (IV), 0.003 mg/kg, Once Weekly, 9 weeks
Experimental: Arm 2: BMS-241027 (0.01 mg/kg) Drug: BMS-241027
Intravenous (IV), 0.01 mg/kg, Once Weekly, 9 weeks
Experimental: Arm 3: BMS-241027 (0.03 mg/kg) 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

  Eligibility

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

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01492374

Contacts
Contact: For participation information at a USA site use a phone number below. For site information outside the USA please email: Clinical.Trials@bms.com
Contact: First line of email MUST contain NCT# & Site#. Only trial sites that are recruiting have contact information at this time.

  Show 27 Study Locations
Sponsors and Collaborators
Bristol-Myers Squibb
Investigators
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
  More Information

Additional Information:
BMS Clinical Trials Disclosure  This link exits the ClinicalTrials.gov site
Investigator Inquiry form  This link exits the ClinicalTrials.gov site
For FDA Safety Alerts and Recalls refer to the following link: http://www.fda.gov/MEDWATCH/safety.htm  This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT01492374     History of Changes
Other Study ID Numbers: CN167-003, 2011-004065-33
Study First Received: December 13, 2011
Last Updated: October 10, 2012
Health Authority: United States: Food and Drug Administration
Germany: Federal Institute for Drugs and Medical Devices
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Sweden: Regional Ethical Review Board
Sweden: Medical Products Agency
Canada: Health Canada

Additional relevant MeSH terms:
Alzheimer Disease
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 May 16, 2013