Clincosm LogoSign in Get a demo

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

Sponsor
Bristol-Myers Squibb (Industry)
Overall Status
Completed
CT.gov ID
NCT01492374
Collaborator
(none)
40
Enrollment
24
Locations
4
Arms
20
Duration (Months)
1.7
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

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

Condition or Disease Intervention/Treatment Phase
Phase 1

Study Design

Study Type:
Interventional
Actual Enrollment :
40 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
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 Start Date :
Feb 1, 2012
Actual Primary Completion Date :
Oct 1, 2013
Actual Study Completion Date :
Oct 1, 2013

Arms and Interventions

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

Drug: BMS-241027
Intravenous (IV), 0.003 mg/kg, Once Weekly, 9 weeks
Experimental: Arm 2: BMS-241027 (0.01 mg/kg)

Drug: BMS-241027
Intravenous (IV), 0.01 mg/kg, Once Weekly, 9 weeks
Experimental: Arm 3: BMS-241027 (0.03 mg/kg)

Drug: BMS-241027
Intravenous (IV), 0.03 mg/kg, Once Weekly, 9 weeks
Experimental: Arm 4: Placebo matching BMS-241027

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

Outcome Measures

Primary Outcome Measures

  1. 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]

  2. Biomarker Measures: CSF levels of Tau N-terminal domain fragments [Within the first 70 day after first dose]

Secondary Outcome Measures

  1. Effects of BMS-241027 on CSF levels of the mid-domain Tau fragment [Within the first 70 days after first dose]

  2. Effects of BMS-241027 on cognitive performance using computerized cognitive tests [Weeks 3, 6 and 9]

  3. Effects of BMS-241027 on connectivity MRI [Within the first 70 days after first dose]

  4. 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

  5. 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

  6. 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

  7. 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

  8. Safety assessments: based on vital sign measurements, ECGs and clinical laboratory tests [Within the first 70 day after first dose]

  9. Effects of BMS-241027 on CSF levels of neurofilaments [Within the first 70 days after first dose]

Eligibility Criteria

Criteria

Ages Eligible for Study:
50 Years to 90 Years
Sexes Eligible for Study:
All
Accepts 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

Contacts and Locations

Locations

Site City State Country Postal Code
1 Anaheim Clinical Trials Llc Anaheim California United States 92801
2 Long Beach California United States 90806
3 Ucsf Memory And Aging Center San Francisco California United States 94158
4 Alpine Clinical Research Center, Inc. Boulder Colorado United States 80304
5 Associated Neurologists Of Southern Connecticut, P.C. Fairfield Connecticut United States 06824
6 Compass Research, Llc Orlando Florida United States 32806
7 Palm Beach Neurological Center Advanced Research Consultants Palm Beach Gardens Florida United States 33410
8 Alexian Brothers Neurosciences Institute Clinical Research Elk Grove Village Illinois United States 60007
9 Brigham And Women'S Hospital Boston Massachusetts United States 02115
10 Michigan State University East Lansing Michigan United States 48824
11 The Ohio State University Columbus Ohio United States 43210
12 The Clinical Trial Center, Llc Jenkintown Pennsylvania United States 19046
13 Hospital Of The University Of Pennsylvania Philadelphia Pennsylvania United States 19104
14 Penn Memory Center Philadelphia Pennsylvania United States 19104
15 Lifetree Clinical Research Salt Lake City Utah United States 84106
16 Local Institution London Ontario Canada N6C 5J1
17 Local Institution Toronto Ontario Canada M3B 2S7
18 Local Institution Greenfield Park Quebec Canada J4V 2J2
19 Local Institution Toulouse Cedex 9 France 31059
20 Local Institution Lille Cedex France 59037
21 Local Institution Paris France 75013
22 Local Institution Berlin Germany 14050
23 Local Institution Heidelberg Germany 69115
24 Local Institution Stockholm Sweden 141 86

Sponsors and Collaborators

  • Bristol-Myers Squibb

Investigators

  • Study Director: Bristol-Myers Squibb, Bristol-Myers Squibb

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

Publications

None provided.
Responsible Party:
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT01492374
Other Study ID Numbers:
  • CN167-003
  • 2011-004065-33
First Posted:
Dec 15, 2011
Last Update Posted:
Jul 24, 2014
Last Verified:
Oct 1, 2013
Additional relevant MeSH terms:
Alzheimer Disease

Study Results

No Results Posted as of Jul 24, 2014