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

Alzheimer's Disease Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01492374
• Other study ID #: CN167-003
• Secondary ID: 2011-004065-33
• Status: Completed
• Phase: Phase 1
• First received: December 13, 2011
• Last updated: July 23, 2014
• Start date: February 2012
• Est. completion date: October 2013

Study information

• Verified date: October 2013
• Source: Bristol-Myers Squibb
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationGermany: Federal Institute for Drugs and Medical DevicesFrance: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)Sweden: Regional Ethical Review BoardSweden: Medical Products AgencyCanada: Health Canada
• Study type: Interventional

Clinical Trial 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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 40
• Est. completion date: October 2013
• Est. primary completion date: October 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 50 Years to 90 Years

Eligibility

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 Design

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

Related Conditions & MeSH terms

• Alzheimer Disease
• Alzheimer's Disease

Intervention

Drug:
• BMS-241027
Intravenous (IV), 0.003 mg/kg, Once Weekly, 9 weeks
• BMS-241027
Intravenous (IV), 0.01 mg/kg, Once Weekly, 9 weeks
• BMS-241027
Intravenous (IV), 0.03 mg/kg, Once Weekly, 9 weeks
• Placebo matching BMS-241027
Intravenous (IV), 0.0 mg/kg, Once Weekly, 9 weeks

Locations

Country	Name	City	State
Canada	Local Institution	Greenfield Park	Quebec
Canada	Local Institution	London	Ontario
Canada	Local Institution	Toronto	Ontario
France	Local Institution	Lille Cedex
France	Local Institution	Paris
France	Local Institution	Toulouse	Cedex 9
Germany	Local Institution	Berlin
Germany	Local Institution	Heidelberg
Sweden	Local Institution	Stockholm
United States	Anaheim Clinical Trials Llc	Anaheim	California
United States	Brigham And Women'S Hospital	Boston	Massachusetts
United States	Alpine Clinical Research Center, Inc.	Boulder	Colorado
United States	The Ohio State University	Columbus	Ohio
United States	Michigan State University	East Lansing	Michigan
United States	Alexian Brothers Neurosciences Institute Clinical Research	Elk Grove Village	Illinois
United States	Associated Neurologists Of Southern Connecticut, P.C.	Fairfield	Connecticut
United States	The Clinical Trial Center, Llc	Jenkintown	Pennsylvania
United States	Compass Research, Llc	Orlando	Florida
United States	Palm Beach Neurological Center Advanced Research Consultants	Palm Beach Gardens	Florida
United States	Hospital Of The University Of Pennsylvania	Philadelphia	Pennsylvania
United States	Penn Memory Center	Philadelphia	Pennsylvania
United States	Lifetree Clinical Research	Salt Lake City	Utah
United States	Ucsf Memory And Aging Center	San Francisco	California

Sponsors (1)

Lead Sponsor	Collaborator
Bristol-Myers Squibb

Countries where clinical trial is conducted

United States,  Canada,  France,  Germany,  Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Yes
Primary	Biomarker Measures: CSF levels of Tau N-terminal domain fragments		Within the first 70 day after first dose	Yes
Secondary	Effects of BMS-241027 on CSF levels of the mid-domain Tau fragment		Within the first 70 days after first dose	No
Secondary	Effects of BMS-241027 on cognitive performance using computerized cognitive tests		Weeks 3, 6 and 9	No
Secondary	Effects of BMS-241027 on connectivity MRI		Within the first 70 days after first dose	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	Safety assessments: based on vital sign measurements, ECGs and clinical laboratory tests		Within the first 70 day after first dose	Yes
Secondary	Effects of BMS-241027 on CSF levels of neurofilaments		Within the first 70 days after first dose	No

External Links

•   BMS clinical trial educational resource
•   BMS Clinical Trial Information
•   FDA Safety Alerts and Recalls
•   Investigator Inquiry form