Clinical trial NCT01492374: 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
Overall status: COMPLETED
Phase: PHASE1
Conditions: Alzheimer's Disease
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
First posted: 2011-12-15
Enrollment: 40
Sex: ALL
Minimum age (years): 50
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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


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

Primary outcomes:
measure: Safety assessments: based on frequency of Serious Adverse Events (SAEs), frequency of Adverse events (AEs), discontinuation due to AEs and dose reduction
timeFrame: Within the first 70 day after first dose
measure: Biomarker Measures: CSF levels of Tau N-terminal domain fragments
timeFrame: Within the first 70 day after first dose
Secondary outcomes:
measure: Effects of BMS-241027 on CSF levels of the mid-domain Tau fragment
timeFrame: Within the first 70 days after first dose
measure: Effects of BMS-241027 on cognitive performance using computerized cognitive tests
timeFrame: Weeks 3, 6 and 9
measure: Effects of BMS-241027 on connectivity MRI
timeFrame: Within the first 70 days after first dose
measure: Maximal observed plasma concentration (Cmax) of BMS-241027 in subjects with mild Alzheimer's disease
timeFrame: Weeks 1, 4, and 9
measure: Observed plasma concentration at 24 hours post dose (C24) of BMS-241027 in subjects with mild Alzheimer's disease
timeFrame: Weeks 1, 4, and 9
measure: Time of maximal observed plasma concentration (Tmax) of BMS-241027 in subjects with mild Alzheimer's disease
timeFrame: Weeks 1, 4, and 9
measure: Area under the concentration-time curve in one dosing interval [AUC(TAU)] of BMS-241027 in subjects with mild Alzheimer's disease
timeFrame: Weeks 1, 4, and 9
measure: Safety assessments: based on vital sign measurements, ECGs and clinical laboratory tests
timeFrame: Within the first 70 day after first dose
measure: Effects of BMS-241027 on CSF levels of neurofilaments
timeFrame: Within the first 70 days after first dose
Other outcomes:
Locations:
city: Anaheim
country: United States
facility: Anaheim Clinical Trials Llc
state: California
city: Long Beach
country: United States
state: California
city: San Francisco
country: United States
facility: Ucsf Memory And Aging Center
state: California
city: Boulder
country: United States
facility: Alpine Clinical Research Center, Inc.
state: Colorado
city: Fairfield
country: United States
facility: Associated Neurologists Of Southern Connecticut, P.C.
state: Connecticut
city: Orlando
country: United States
facility: Compass Research, Llc
state: Florida
city: Palm Beach Gardens
country: United States
facility: Palm Beach Neurological Center Advanced Research Consultants
state: Florida
city: Elk Grove Village
country: United States
facility: Alexian Brothers Neurosciences Institute Clinical Research
state: Illinois
city: Boston
country: United States
facility: Brigham And Women'S Hospital
state: Massachusetts
city: East Lansing
country: United States
facility: Michigan State University
state: Michigan
city: Columbus
country: United States
facility: The Ohio State University
state: Ohio
city: Jenkintown
country: United States
facility: The Clinical Trial Center, Llc
state: Pennsylvania
city: Philadelphia
country: United States
facility: Hospital Of The University Of Pennsylvania
state: Pennsylvania
city: Philadelphia
country: United States
facility: Penn Memory Center
state: Pennsylvania
city: Salt Lake City
country: United States
facility: Lifetree Clinical Research
state: Utah
city: London
country: Canada
facility: Local Institution
state: Ontario
city: Toronto
country: Canada
facility: Local Institution
state: Ontario
city: Greenfield Park
country: Canada
facility: Local Institution
state: Quebec
city: Toulouse
country: France
facility: Local Institution
state: Cedex 9
city: Lille Cedex
country: France
facility: Local Institution
city: Paris
country: France
facility: Local Institution
city: Berlin
country: Germany
facility: Local Institution
city: Heidelberg
country: Germany
facility: Local Institution
city: Stockholm
country: Sweden
facility: Local Institution
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References: