Clinical trial NCT01677572: Multiple Dose Study of Aducanumab (BIIB037) (Recombinant, Fully Human Anti-Aβ IgG1 mAb) in Participants With Prodromal or Mild Alzheimer's Disease
Official title: A Randomized, Double-Blinded, Placebo-Controlled Multiple Dose Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of BIIB037 in Subjects With Prodromal or Mild Alzheimer's Disease
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Alzheimer's Disease
Keywords: Aducanumab
BIIB037
Lead sponsor: Biogen
Sponsor class: INDUSTRY
First posted: 2012-09-03
Enrollment: 197
Sex: ALL
Minimum age (years): 50
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The primary objective of this study is to evaluate the safety and tolerability of multiple doses of Aducanumab (recombinant, fully human anti-Aβ IgG1 mAb) in participants with prodromal or mild Alzheimer's Disease (AD). The secondary objectives of this study are to assess the effect on cerebral amyloid plaque content as measured by florbetapir-fluorine-18 (18F-AV-45F-AV-45) positron emission tomography (PET) imaging, to assess the multiple dose serum concentrations of Aducanumab and to evaluate the immunogenicity of Aducanumab after multiple dose administration in this population.

Detailed description: The study consists of a placebo-controlled period to study week 54, followed by a long-term extension to study week 518. The placebo-controlled period is conducted with a staggered, parallel group design, with the first 3 treatment arms conducted in parallel, 2 further treatment arms subsequently beginning in parallel, 2 additional treatment arms beginning in parallel, and the last 2 treatment arms subsequently beginning in parallel. Qualifying participants can enter the long-term extension period for up to 42 additional doses of active drug for the first 3 years of LTE. Furthermore, up until the last participant in Arms 8 and 9 has had his or her last dose in the fifth year of the LTE, eligible participants will be able to continue treatment beyond the third year of the LTE.

Eligibility criteria: Key Inclusion Criteria:

* Participants must be ambulatory.
* Participants must meet the following core clinical criteria as determined by the Investigator:

Prodromal Alzheimer's Disease (AD) (all of the criteria must apply):

* Mini Mental State Examination (MMSE) scores between 24-30 (inclusive)
* a spontaneous memory complaint
* objective memory loss defined as a free recall score of ≤27 on the Free and Cued Selective Reminding Test (FCSRT)
* a global Clinical Dementia Rating Scale (CDR) score of 0.5
* absence of significant levels of impairment in other cognitive domains
* essentially preserved activities of daily living, and an absence of dementia. OR

Mild Alzheimer's Disease (AD) criteria (all criteria must apply):

* Mini Mental State Examination (MMSE) scores between 20-26 (inclusive)
* a global Clinical Dementia Rating Scale (CDR) of 0.5 or 1.0
* meeting the National Institute on Aging-Alzheimer's Association core clinical criteria for probable AD.
* Participants must have a positive florbetapir positron emission tomography (PET) amyloid scan.
* Participants must consent to apolipoprotein E (ApoE) genotyping.
* Apart from clinical diagnosis of Alzheimer's Disease (AD), participant must be in good health.
* Must have a reliable informant or caregiver.

Key Exclusion Criteria:

* Any medical or neurological condition (other than Alzheimer's Disease) that might be a contributing cause of the participant's cognitive impairment.
* Have had a stroke or Transient Ischemic Attack (TIA) or unexplained loss of consciousness in the past 1 year.
* Clinically significant psychiatric illness in past 6 months.
* Seizure in the past 3 years.
* Poorly controlled diabetes mellitus.
* History of unstable angina, myocardial infarction, chronic heart failure, or clinical significant conduction abnormalities within 1 year prior to Screening.
* Indication of impaired renal or liver function.
* Have human immunodeficiency virus (HIV) infection.
* Have a significant systematic illness or infection in past 30 days.
* Brain MRI showing evidence of acute or sub-acute micro or macrohemorrhage, greater than 4 microhemorrhages, cortical infarct or greater than one 1 lunar infarct.
* Any contraindications to brain MRI or positron emission tomography (PET) scans.
* Negative positron emission tomography (PET) scan with any amyloid-targeting ligand within 48 weeks of Screening.
* Clinically significant 12-lead electrocardiogram (ECG) abnormalities.
* Alcohol or substance abuse in past 1 year.
* Taking blood thinners (except for aspirin at a prophylactic dose or less)
* Have changes in medications or doses of medication in past 4 weeks.

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Primary outcomes:
measure: Number of Participants with Adverse Events
timeFrame: Baseline to week 518
Secondary outcomes:
measure: Change from baseline in florbetapir-fluorine-18 (18F-AV-45F-AV-45) positron emission tomography (PET) imaging in certain brain areas.
timeFrame: Day 1, Weeks 26, 54, End of year 2, 3, and 4
measure: Multiple dose pharmacokinetic (PK) serum concentrations of Aducanumab
timeFrame: Up to week 518
measure: Change from Baseline in Incidence of Anti-Aducanumab Antibodies in Serum.
timeFrame: Up to week 518
Other outcomes:
Locations:
city: Tucson
country: United States
facility: NNS Clinical Research, LLC
state: Arizona
city: Laguna Hills
country: United States
facility: Senior Clinical Trials, Inc.
state: California
city: Lomita
country: United States
facility: Torrance Clinical Research Institute, Inc.
state: California
city: Long Beach
country: United States
facility: Collaborative Neuroscience Network, LLC
state: California
city: Los Angeles
country: United States
facility: University of California, Los Angeles
state: California
city: Oxnard
country: United States
facility: Pacific Neuroscience Medical Group
state: California
city: San Diego
country: United States
facility: Pacific Research Network, Inc.
state: California
city: San Francisco
country: United States
facility: San Francisco Clinical Research Center
state: California
city: Stanford
country: United States
facility: Stanford University Medical Center
state: California
city: New Haven
country: United States
facility: Alzheimer's Disease Research Unit, Yale University
state: Connecticut
city: Washington
country: United States
facility: Georgetown University Hospital
state: District of Columbia
city: Delray Beach
country: United States
facility: Brain Matters Research, Inc.
state: Florida
city: Fort Myers
country: United States
facility: Neuropsychiatric Research Center of Southwest Florida
state: Florida
city: Hallandale Beach
country: United States
facility: MD Clinical Trials, Inc.
state: Florida
city: Miami Springs
country: United States
facility: Galiz Research, LLC
state: Florida
city: Miami
country: United States
facility: Miami Jewish Health Systems
state: Florida
city: Orlando
country: United States
facility: Compass Research, LLC
state: Florida
city: Sunrise
country: United States
facility: Infinity Clinical Research, Inc.
state: Florida
city: Tampa
country: United States
facility: Axiom Clinical Research of Florida
state: Florida
city: Tampa
country: United States
facility: Stedman Clinical Trials, LLC
state: Florida
city: Decatur
country: United States
facility: Neurostudies.net, LLC
state: Georgia
city: Elk Grove Village
country: United States
facility: Alexian Brothers Neurosciences Institute
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University School of Medicine
state: Indiana
city: Saint Louis
country: United States
facility: St. Louis Clinical Trials, LLC
state: Missouri
city: Eatontown
country: United States
facility: Memory Enhancement Center of America, Inc.
state: New Jersey
city: Marlton
country: United States
facility: CRI Lifetree
state: New Jersey
city: Toms River
country: United States
facility: Advanced Memory Research Institute of NJ
state: New Jersey
city: Latham
country: United States
facility: Empire Neurology, PC
state: New York
city: Beachwood
country: United States
facility: Insight Clinical Trials LLC
state: Ohio
city: Portland
country: United States
facility: Summit Research Network (Oregon) Inc.
state: Oregon
city: East Providence
country: United States
facility: Brown Hospital
state: Rhode Island
city: Providence
country: United States
facility: Rhode Island Hospital
state: Rhode Island
Study officials:
affiliation: Biogen
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: Sevigny J, Chiao P, Bussiere T, Weinreb PH, Williams L, Maier M, Dunstan R, Salloway S, Chen T, Ling Y, O'Gorman J, Qian F, Arastu M, Li M, Chollate S, Brennan MS, Quintero-Monzon O, Scannevin RH, Arnold HM, Engber T, Rhodes K, Ferrero J, Hang Y, Mikulskis A, Grimm J, Hock C, Nitsch RM, Sandrock A. The antibody aducanumab reduces Abeta plaques in Alzheimer's disease. Nature. 2016 Sep 1;537(7618):50-6. doi: 10.1038/nature19323.