Alzheimer's Disease
Conditions
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
Interventions
DRUGBMS-241027
Intravenous (IV), 0.003 mg/kg, Once Weekly, 9 weeks
DRUGPlacebo matching BMS-241027
Intravenous (IV), 0.0 mg/kg, Once Weekly, 9 weeks
Sponsors
Bristol-Myers Squibb
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
50 Years to 90 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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 |
| Biomarker Measures: CSF levels of Tau N-terminal domain fragments | Within the first 70 day after first dose |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Effects of BMS-241027 on connectivity MRI | Within the first 70 days after first dose | — |
| Maximal observed plasma concentration (Cmax) of BMS-241027 in subjects with mild Alzheimer's disease | Weeks 1, 4, and 9 | 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 | Weeks 1, 4, and 9 | Intensive pharmacokinetic parameter C24 will be derived from subgroups of subjects at Week 7 |
| Effects of BMS-241027 on CSF levels of the mid-domain Tau fragment | Within the first 70 days after first dose | — |
| Area under the concentration-time curve in one dosing interval [AUC(TAU)] of BMS-241027 in subjects with mild Alzheimer's disease | Weeks 1, 4, and 9 | 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 | Within the first 70 day after first dose | — |
| Effects of BMS-241027 on CSF levels of neurofilaments | Within the first 70 days after first dose | — |
| Time of maximal observed plasma concentration (Tmax) of BMS-241027 in subjects with mild Alzheimer's disease | Weeks 1, 4, and 9 | Intensive pharmacokinetic parameter Tmax will be derived from subgroups of subjects at Week 7 |
| Effects of BMS-241027 on cognitive performance using computerized cognitive tests | Weeks 3, 6 and 9 | — |
Countries
Canada, France, Germany, Sweden, United States
Outcome results
None listed