Back to resultsStudy to Evaluate the Safety, Tolerability and the Effect of BMS-241027 on Cerebrospinal Fluid Biomarkers in Subjects With Mild Alzheimer's Disease
Primary Purpose
Alzheimer's Disease
Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
BMS-241027
BMS-241027
BMS-241027
Placebo matching BMS-241027
Sponsored by
About this trial
This is an interventional treatment trial for Alzheimer's Disease
Eligibility 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
Sites / Locations
- Anaheim Clinical Trials Llc
- Ucsf Memory And Aging Center
- Alpine Clinical Research Center, Inc.
- Associated Neurologists Of Southern Connecticut, P.C.
- Compass Research, Llc
- Palm Beach Neurological Center Advanced Research Consultants
- Alexian Brothers Neurosciences Institute Clinical Research
- Brigham And Women'S Hospital
- Michigan State University
- The Ohio State University
- The Clinical Trial Center, Llc
- Hospital Of The University Of Pennsylvania
- Penn Memory Center
- Lifetree Clinical Research
- Local Institution
- Local Institution
- Local Institution
- Local Institution
- Local Institution
- Local Institution
- Local Institution
- Local Institution
- Local Institution
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Experimental
Experimental
Experimental
Experimental
Arm Label
Arm 1: BMS-241027 (0.003 mg/kg)
Arm 2: BMS-241027 (0.01 mg/kg)
Arm 3: BMS-241027 (0.03 mg/kg)
Arm 4: Placebo matching BMS-241027
Arm Description
Outcomes
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
Biomarker Measures: CSF levels of Tau N-terminal domain fragments
Secondary Outcome Measures
Effects of BMS-241027 on CSF levels of the mid-domain Tau fragment
Effects of BMS-241027 on cognitive performance using computerized cognitive tests
Effects of BMS-241027 on connectivity MRI
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
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
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
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
Safety assessments: based on vital sign measurements, ECGs and clinical laboratory tests
Effects of BMS-241027 on CSF levels of neurofilaments
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01492374
Brief Title
Study to Evaluate the Safety, Tolerability and the Effect of BMS-241027 on Cerebrospinal Fluid Biomarkers in Subjects With Mild Alzheimer's Disease
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
Study Type
Interventional
2. Study Status
Record Verification Date
October 2013
Overall Recruitment Status
Completed
Study Start Date
February 2012 (undefined)
Primary Completion Date
October 2013 (Actual)
Study Completion Date
October 2013 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Bristol-Myers Squibb
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
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
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Alzheimer's Disease
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
40 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Arm 1: BMS-241027 (0.003 mg/kg)
Arm Type
Experimental
Arm Title
Arm 2: BMS-241027 (0.01 mg/kg)
Arm Type
Experimental
Arm Title
Arm 3: BMS-241027 (0.03 mg/kg)
Arm Type
Experimental
Arm Title
Arm 4: Placebo matching BMS-241027
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
BMS-241027
Intervention Description
Intravenous (IV), 0.003 mg/kg, Once Weekly, 9 weeks
Intervention Type
Drug
Intervention Name(s)
BMS-241027
Intervention Description
Intravenous (IV), 0.01 mg/kg, Once Weekly, 9 weeks
Intervention Type
Drug
Intervention Name(s)
BMS-241027
Intervention Description
Intravenous (IV), 0.03 mg/kg, Once Weekly, 9 weeks
Intervention Type
Drug
Intervention Name(s)
Placebo matching BMS-241027
Intervention Description
Intravenous (IV), 0.0 mg/kg, Once Weekly, 9 weeks
Primary Outcome Measure Information:
Title
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
Title
Biomarker Measures: CSF levels of Tau N-terminal domain fragments
Time Frame
Within the first 70 day after first dose
Secondary Outcome Measure Information:
Title
Effects of BMS-241027 on CSF levels of the mid-domain Tau fragment
Time Frame
Within the first 70 days after first dose
Title
Effects of BMS-241027 on cognitive performance using computerized cognitive tests
Time Frame
Weeks 3, 6 and 9
Title
Effects of BMS-241027 on connectivity MRI
Time Frame
Within the first 70 days after first dose
Title
Maximal observed plasma concentration (Cmax) of BMS-241027 in subjects with mild Alzheimer's disease
Description
Intensive pharmacokinetic parameter Cmax will be derived from subgroups of subjects at Week 7
Time Frame
Weeks 1, 4, and 9
Title
Observed plasma concentration at 24 hours post dose (C24) of BMS-241027 in subjects with mild Alzheimer's disease
Description
Intensive pharmacokinetic parameter C24 will be derived from subgroups of subjects at Week 7
Time Frame
Weeks 1, 4, and 9
Title
Time of maximal observed plasma concentration (Tmax) of BMS-241027 in subjects with mild Alzheimer's disease
Description
Intensive pharmacokinetic parameter Tmax will be derived from subgroups of subjects at Week 7
Time Frame
Weeks 1, 4, and 9
Title
Area under the concentration-time curve in one dosing interval [AUC(TAU)] of BMS-241027 in subjects with mild Alzheimer's disease
Description
Intensive pharmacokinetic parameter AUC(TAU) will be derived from subgroups of subjects at Week 7
Time Frame
Weeks 1, 4, and 9
Title
Safety assessments: based on vital sign measurements, ECGs and clinical laboratory tests
Time Frame
Within the first 70 day after first dose
Title
Effects of BMS-241027 on CSF levels of neurofilaments
Time Frame
Within the first 70 days after first dose
10. Eligibility
Sex
All
Minimum Age & Unit of Time
50 Years
Maximum Age & Unit of Time
90 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Bristol-Myers Squibb
Organizational Affiliation
Bristol-Myers Squibb
Official's Role
Study Director
Facility Information:
Facility Name
Anaheim Clinical Trials Llc
City
Anaheim
State/Province
California
ZIP/Postal Code
92801
Country
United States
City
Long Beach
State/Province
California
ZIP/Postal Code
90806
Country
United States
Facility Name
Ucsf Memory And Aging Center
City
San Francisco
State/Province
California
ZIP/Postal Code
94158
Country
United States
Facility Name
Alpine Clinical Research Center, Inc.
City
Boulder
State/Province
Colorado
ZIP/Postal Code
80304
Country
United States
Facility Name
Associated Neurologists Of Southern Connecticut, P.C.
City
Fairfield
State/Province
Connecticut
ZIP/Postal Code
06824
Country
United States
Facility Name
Compass Research, Llc
City
Orlando
State/Province
Florida
ZIP/Postal Code
32806
Country
United States
Facility Name
Palm Beach Neurological Center Advanced Research Consultants
City
Palm Beach Gardens
State/Province
Florida
ZIP/Postal Code
33410
Country
United States
Facility Name
Alexian Brothers Neurosciences Institute Clinical Research
City
Elk Grove Village
State/Province
Illinois
ZIP/Postal Code
60007
Country
United States
Facility Name
Brigham And Women'S Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
Michigan State University
City
East Lansing
State/Province
Michigan
ZIP/Postal Code
48824
Country
United States
Facility Name
The Ohio State University
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43210
Country
United States
Facility Name
The Clinical Trial Center, Llc
City
Jenkintown
State/Province
Pennsylvania
ZIP/Postal Code
19046
Country
United States
Facility Name
Hospital Of The University Of Pennsylvania
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Facility Name
Penn Memory Center
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Facility Name
Lifetree Clinical Research
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84106
Country
United States
Facility Name
Local Institution
City
London
State/Province
Ontario
ZIP/Postal Code
N6C 5J1
Country
Canada
Facility Name
Local Institution
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M3B 2S7
Country
Canada
Facility Name
Local Institution
City
Greenfield Park
State/Province
Quebec
ZIP/Postal Code
J4V 2J2
Country
Canada
Facility Name
Local Institution
City
Toulouse
State/Province
Cedex 9
ZIP/Postal Code
31059
Country
France
Facility Name
Local Institution
City
Lille Cedex
ZIP/Postal Code
59037
Country
France
Facility Name
Local Institution
City
Paris
ZIP/Postal Code
75013
Country
France
Facility Name
Local Institution
City
Berlin
ZIP/Postal Code
14050
Country
Germany
Facility Name
Local Institution
City
Heidelberg
ZIP/Postal Code
69115
Country
Germany
Facility Name
Local Institution
City
Stockholm
ZIP/Postal Code
141 86
Country
Sweden
12. IPD Sharing Statement
Links:
URL
http://www.bms.com/studyconnect/Pages/home.aspx
Description
BMS clinical trial educational resource
Learn more about this trial
Study to Evaluate the Safety, Tolerability and the Effect of BMS-241027 on Cerebrospinal Fluid Biomarkers in Subjects With Mild Alzheimer's Disease
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