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 has been completed.
Sponsor:
Information provided by (Responsible Party):
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT01492374
First received: December 13, 2011
Last updated: July 23, 2014
Last verified: October 2013
  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:


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 ]

Enrollment: 40
Study Start Date: February 2012
Study Completion Date: October 2013
Primary Completion Date: October 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
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: NCT01492374

  Show 24 Study Locations
Sponsors and Collaborators
Bristol-Myers Squibb
Investigators
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
  More Information

Additional Information:
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: July 23, 2014
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
Brain Diseases
Central Nervous System Diseases
Delirium, Dementia, Amnestic, Cognitive Disorders
Dementia
Mental Disorders
Nervous System Diseases
Neurodegenerative Diseases
Tauopathies

ClinicalTrials.gov processed this record on October 23, 2014