Clinical trial NCT00112073: AAB-001 in Patients With Mild to Moderate Alzheimer's Disease
Official title: A Phase IIA, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Multiple Ascending Dose, Safety, Tolerability, Pharmacokinetic, Pharmacodynamic, and Immunogenicity Trial of AAB-001 in Patients With Mild to Moderate AD
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Alzheimer's Disease
Keywords: Alzheimer's disease
immunotherapy
beta amyloid
Lead sponsor: JANSSEN Alzheimer Immunotherapy Research & Development, LLC
Sponsor class: INDUSTRY
Collaborators: name: Pfizer
First posted: 2005-05-30
Enrollment: 234
Sex: ALL
Minimum age (years): 50
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to assess the safety and tolerability of multiple doses of AAB-001 passive immunization in patients with mild to moderate Alzheimer's disease (AD).

Detailed description: The humanized monoclonal antibody, AAB-001, which binds to and clears beta amyloid peptide, is designed to provide antibodies to beta amyloid directly to the patient, rather than requiring the patient to mount his/her own individual response. It is believed that this approach may eliminate the need for the patient to mount an immune response to beta amyloid. Animal studies have shown that this approach is equally effective in clearing beta amyloid from the brain as traditional active immunization methods.

This is a multicenter, double-blind, placebo controlled, randomized, outpatient, multiple ascending dose study in male and female patients aged 50 to 85 years with mild to moderate AD. Approximately 30 study sites will be involved. Patients will be randomized to receive either AAB-001 or placebo. Each patient's participation will last approximately 2 years.

Eligibility criteria: Inclusion Criteria:

* Diagnosis of probable AD
* Age from 50 to 85 years
* Rosen Modified Hachinski Ischemic score less than or equal to 4
* Magnetic resonance imaging (MRI) scan consistent with the diagnosis of AD
* Fluency in English
* Stable doses of medications

Exclusion Criteria:

* Significant neurological disease other than AD
* Major psychiatric disorder
* Significant systemic illness
* History of stroke or seizure
* Weight greater than 120 kg (264 lbs.)
* History of autoimmune disease
* Smoking more than 20 cigarettes per day
* Anticonvulsants, anti-Parkinson's, anticoagulant, or narcotic medications
* Prior treatment with experimental immunotherapeutics or vaccines for AD
* Presence of pacemakers or foreign metal objects in the eyes, skin, or body

Primary outcomes:
measure: safety assessments
timeFrame: 18 months
Secondary outcomes:
measure: blood levels of administered study drug
timeFrame: 18 months
measure: cognitive and functional assessments
timeFrame: 18 months
Other outcomes:
Locations:
city: Sun City
country: United States
facility: Cleo Roberts Center for Clinical Research / Sun Health Research Institute
state: Arizona
city: Irvine
country: United States
facility: UC Irvine
state: California
city: Los Alamitos
country: United States
facility: Pharmacology Research Institute
state: California
city: Northridge
country: United States
facility: Pharmacology Research Institute
state: California
city: San Diego
country: United States
facility: UCSD Shiley-Marcos Alzheimer's Disease Research Center
state: California
city: San Francisco
country: United States
facility: Memory & Aging Center, UCSF
state: California
city: New Haven
country: United States
facility: Yale University School of Medicine
state: Connecticut
city: Washington
country: United States
facility: Georgetown University Medical Center
state: District of Columbia
city: Delray Beach
country: United States
facility: Brain Matters Research, Inc.
state: Florida
city: Jacksonville
country: United States
facility: Mayo Clinic - Department of Neurology
state: Florida
city: Chicago
country: United States
facility: Rush Presbyterian St. Luke's Medical Center
state: Illinois
city: Indianapolis
country: United States
facility: Department of Neurology - Indiana University Medical Center
state: Indiana
city: Boston
country: United States
facility: Behavioral Neurology
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan Health System, Department of Neurology
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic Department of Neurology - Alzheimer's Disease Research Center
state: Minnesota
city: Long Branch
country: United States
facility: The Memory Enhancement Center
state: New Jersey
city: New York City
country: United States
facility: Sergievsky Center, Columbia University
state: New York
city: Rochester
country: United States
facility: University of Rochester / Monroe Community Hospital
state: New York
city: Durham
country: United States
facility: Department of Psychiatry and Behavioral Sciences
state: North Carolina
city: Portland
country: United States
facility: Oregon Health and Science University
state: Oregon
city: Pittsburgh
country: United States
facility: University of Pittsburgh
state: Pennsylvania
city: Providence
country: United States
facility: Memory and Aging Program, Butler Hospital
state: Rhode Island
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center
state: Texas
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
city: Bennington
country: United States
facility: Clinical Neuroscience Research Associates, Inc.
state: Vermont
city: Seattle
country: United States
facility: University of Washington
state: Washington
Study officials:
References:
citation: Arrighi HM, Barakos J, Barkhof F, Tampieri D, Jack C Jr, Melancon D, Morris K, Ketter N, Liu E, Brashear HR. Amyloid-related imaging abnormalities-haemosiderin (ARIA-H) in patients with Alzheimer's disease treated with bapineuzumab: a historical, prospective secondary analysis. J Neurol Neurosurg Psychiatry. 2016 Jan;87(1):106-12. doi: 10.1136/jnnp-2014-309493. Epub 2015 Feb 10.
citation: Blennow K, Zetterberg H, Rinne JO, Salloway S, Wei J, Black R, Grundman M, Liu E; AAB-001 201/202 Investigators. Effect of immunotherapy with bapineuzumab on cerebrospinal fluid biomarker levels in patients with mild to moderate Alzheimer disease. Arch Neurol. 2012 Aug;69(8):1002-10. doi: 10.1001/archneurol.2012.90.