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

Bristol-Myers Squibb (BMS)

Status and phase: Completed; Phase 1

Conditions: Alzheimer's Disease

Treatments: Drug: BMS-241027; Drug: Placebo matching BMS-241027

Study type: Interventional

Funder types: Industry

Identifiers

NCT01492374

CN167-003

2011-004065-33 (EudraCT Number)

Details and patient eligibility

About

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

Enrollment: 40 patients

Sex: All

Ages: 50 to 90 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

---

40 participants in 4 patient groups

Arm 1: BMS-241027 (0.003 mg/kg)

Experimental group

Treatment:

Drug: BMS-241027

Drug: BMS-241027

Drug: BMS-241027

Arm 2: BMS-241027 (0.01 mg/kg)

Experimental group

Treatment:

Drug: BMS-241027

Drug: BMS-241027

Drug: BMS-241027

Arm 3: BMS-241027 (0.03 mg/kg)

Experimental group

Treatment:

Drug: BMS-241027

Drug: BMS-241027

Drug: BMS-241027

Arm 4: Placebo matching BMS-241027

Experimental group

Treatment:

Drug: Placebo matching BMS-241027