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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

Phase 1
Completed
Conditions
Alzheimer's Disease
Interventions
Drug: BMS-241027
Drug: Placebo matching BMS-241027
Registration Number
NCT01492374
Lead Sponsor
Bristol-Myers Squibb
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

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
40
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
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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
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Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Arm 1: BMS-241027 (0.003 mg/kg)BMS-241027-
Arm 4: Placebo matching BMS-241027Placebo matching BMS-241027-
Arm 2: BMS-241027 (0.01 mg/kg)BMS-241027-
Arm 3: BMS-241027 (0.03 mg/kg)BMS-241027-
Primary Outcome Measures
NameTimeMethod
Safety assessments: based on frequency of Serious Adverse Events (SAEs), frequency of Adverse events (AEs), discontinuation due to AEs and dose reductionWithin the first 70 day after first dose
Biomarker Measures: CSF levels of Tau N-terminal domain fragmentsWithin the first 70 day after first dose
Secondary Outcome Measures
NameTimeMethod
Effects of BMS-241027 on connectivity MRIWithin the first 70 days after first dose
Effects of BMS-241027 on CSF levels of neurofilamentsWithin the first 70 days after first dose
Effects of BMS-241027 on CSF levels of the mid-domain Tau fragmentWithin the first 70 days after first dose
Effects of BMS-241027 on cognitive performance using computerized cognitive testsWeeks 3, 6 and 9
Observed plasma concentration at 24 hours post dose (C24) of BMS-241027 in subjects with mild Alzheimer's diseaseWeeks 1, 4, and 9

Intensive pharmacokinetic parameter C24 will be derived from subgroups of subjects at Week 7

Maximal observed plasma concentration (Cmax) of BMS-241027 in subjects with mild Alzheimer's diseaseWeeks 1, 4, and 9

Intensive pharmacokinetic parameter Cmax 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 diseaseWeeks 1, 4, and 9

Intensive pharmacokinetic parameter Tmax will be derived from subgroups of subjects at Week 7

Safety assessments: based on vital sign measurements, ECGs and clinical laboratory testsWithin the first 70 day after first dose
Area under the concentration-time curve in one dosing interval [AUC(TAU)] of BMS-241027 in subjects with mild Alzheimer's diseaseWeeks 1, 4, and 9

Intensive pharmacokinetic parameter AUC(TAU) will be derived from subgroups of subjects at Week 7

Trial Locations

Locations (15)

Associated Neurologists Of Southern Connecticut, P.C.

🇺🇸

Fairfield, Connecticut, United States

Palm Beach Neurological Center Advanced Research Consultants

🇺🇸

Palm Beach Gardens, Florida, United States

Compass Research, Llc

🇺🇸

Orlando, Florida, United States

Michigan State University

🇺🇸

East Lansing, Michigan, United States

Local Institution

🇸🇪

Stockholm, Sweden

Anaheim Clinical Trials Llc

🇺🇸

Anaheim, California, United States

Ucsf Memory And Aging Center

🇺🇸

San Francisco, California, United States

Brigham And Women'S Hospital

🇺🇸

Boston, Massachusetts, 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

Alexian Brothers Neurosciences Institute Clinical Research

🇺🇸

Elk Grove Village, Illinois, United States

The Clinical Trial Center, Llc

🇺🇸

Jenkintown, Pennsylvania, United States

Alpine Clinical Research Center, Inc.

🇺🇸

Boulder, Colorado, United States

The Ohio State University

🇺🇸

Columbus, Ohio, United States

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