Multiple Dose Study of Aducanumab (BIIB037) (Recombinant, Fully Human Anti-Aβ IgG1 mAb) in Participants With Prodromal or Mild Alzheimer's Disease
- Conditions
- Alzheimer's Disease
- Interventions
- Registration Number
- NCT01677572
- Lead Sponsor
- Biogen
- 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.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 197
- 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
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Low-dose #1 Aducanumab Aducanumab (recombinant, fully human anti-Aβ IgG1 mAb) Intravenous doses of low-dose level #1 Aducanumab administered approximately 4 weeks apart over approximately 52 weeks (a total of 14 doses). Qualifying participants can continue into the long-term extension at a dose administered approximately 4 weeks apart for up to an additional 112 doses. Low-dose #2 Aducanumab Aducanumab (recombinant, fully human anti-Aβ IgG1 mAb) Intravenous doses of low-dose level #2 Aducanumab administered approximately 4 weeks apart over approximately 52 weeks (a total of 14 doses). Qualifying participants can continue into the long-term extension at a dose administered approximately 4 weeks apart for up to an additional 112 doses. Placebo (low dose group) Aducanumab (recombinant, fully human anti-Aβ IgG1 mAb) Intravenous doses of placebo administered approximately 4 weeks apart over approximately 52 weeks (a total of 14 doses). Qualifying participants can continue into the long-term extension at a dose approximately 4 weeks apart for up to an additional 112 doses. Mid-dose Aducanumab Aducanumab (recombinant, fully human anti-Aβ IgG1 mAb) Intravenous doses of mid-dose Aducanumab administered approximately 4 weeks apart over approximately 52 weeks (a total of 14 doses). Qualifying participants can continue into the long-term extension at a dose administered approximately 4 weeks apart for up to an additional 112 doses. Placebo (mid dose group) Aducanumab (recombinant, fully human anti-Aβ IgG1 mAb) Intravenous doses of placebo administered approximately 4 weeks apart over approximately 52 weeks (a total of 14 doses). Qualifying participants can continue into the long-term extension at a dose administered approximately 4 weeks apart for up to an additional 112 doses. High-dose Aducanumab Aducanumab (recombinant, fully human anti-Aβ IgG1 mAb) Intravenous doses of high-dose Aducanumab administered approximately 4 weeks apart over approximately 52 weeks (a total of 14 doses). Qualifying participants can continue into the long-term extension at a dose administered approximately 4 weeks apart for up to an additional 112 doses. Placebo (high dose group) Aducanumab (recombinant, fully human anti-Aβ IgG1 mAb) Intravenous doses of placebo administered approximately 4 weeks apart over approximately 52 weeks (a total of 14 doses). Qualifying participants can continue into the long-term extension at a dose administered approximately 4 weeks apart for up to an additional 112 doses. Aducanumab Titration Aducanumab (recombinant, fully human anti-Aβ IgG1 mAb) Intravenous doses of Aducanumab administered approximately 4 weeks apart over approximately 52 weeks (a total of 14 doses). Qualifying participants can continue into the long-term extension at a dose approximately 4 weeks apart for up to an additional 112 doses. Placebo (mid dose group) Placebo Intravenous doses of placebo administered approximately 4 weeks apart over approximately 52 weeks (a total of 14 doses). Qualifying participants can continue into the long-term extension at a dose administered approximately 4 weeks apart for up to an additional 112 doses. Placebo (low dose group) Placebo Intravenous doses of placebo administered approximately 4 weeks apart over approximately 52 weeks (a total of 14 doses). Qualifying participants can continue into the long-term extension at a dose approximately 4 weeks apart for up to an additional 112 doses. Placebo (high dose group) Placebo Intravenous doses of placebo administered approximately 4 weeks apart over approximately 52 weeks (a total of 14 doses). Qualifying participants can continue into the long-term extension at a dose administered approximately 4 weeks apart for up to an additional 112 doses. Placebo (Titration Group) Placebo Intravenous doses of placebo administered approximately 4 weeks apart over approximately 52 weeks (a total of 14 doses). Qualifying participants can continue into the long-term extension at a dose approximately 4 weeks apart for up to an additional 112 doses.
- Primary Outcome Measures
Name Time Method Number of Participants with Adverse Events Baseline to week 518
- Secondary Outcome Measures
Name Time Method Change from Baseline in Incidence of Anti-Aducanumab Antibodies in Serum. Up to week 518 Multiple dose pharmacokinetic (PK) serum concentrations of Aducanumab Up to week 518 Change from baseline in florbetapir-fluorine-18 (18F-AV-45F-AV-45) positron emission tomography (PET) imaging in certain brain areas. Day 1, Weeks 26, 54, End of year 2, 3, and 4
Trial Locations
- Locations (32)
Infinity Clinical Research, Inc.
🇺🇸Sunrise, Florida, United States
Senior Clinical Trials, Inc.
🇺🇸Laguna Hills, California, United States
University of California, Los Angeles
🇺🇸Los Angeles, California, United States
Brain Matters Research, Inc.
🇺🇸Delray Beach, Florida, United States
Neuropsychiatric Research Center of Southwest Florida
🇺🇸Fort Myers, Florida, United States
Miami Jewish Health Systems
🇺🇸Miami, Florida, United States
Pacific Research Network, Inc.
🇺🇸San Diego, California, United States
San Francisco Clinical Research Center
🇺🇸San Francisco, California, United States
Summit Research Network (Oregon) Inc.
🇺🇸Portland, Oregon, United States
Axiom Clinical Research of Florida
🇺🇸Tampa, Florida, United States
Stedman Clinical Trials, LLC
🇺🇸Tampa, Florida, United States
Collaborative Neuroscience Network, LLC
🇺🇸Long Beach, California, United States
Torrance Clinical Research Institute, Inc.
🇺🇸Lomita, California, United States
NNS Clinical Research, LLC
🇺🇸Tucson, Arizona, United States
Stanford University Medical Center
🇺🇸Stanford, California, United States
Pacific Neuroscience Medical Group
🇺🇸Oxnard, California, United States
Georgetown University Hospital
🇺🇸Washington, District of Columbia, United States
MD Clinical Trials, Inc.
🇺🇸Hallandale Beach, Florida, United States
Galiz Research, LLC
🇺🇸Miami Springs, Florida, United States
Alexian Brothers Neurosciences Institute
🇺🇸Elk Grove Village, Illinois, United States
Neurostudies.net, LLC
🇺🇸Decatur, Georgia, United States
Indiana University School of Medicine
🇺🇸Indianapolis, Indiana, United States
St. Louis Clinical Trials, LLC
🇺🇸Saint Louis, Missouri, United States
Memory Enhancement Center of America, Inc.
🇺🇸Eatontown, New Jersey, United States
Advanced Memory Research Institute of NJ
🇺🇸Toms River, New Jersey, United States
CRI Lifetree
🇺🇸Marlton, New Jersey, United States
Empire Neurology, PC
🇺🇸Latham, New York, United States
Insight Clinical Trials LLC
🇺🇸Beachwood, Ohio, United States
Brown Hospital
🇺🇸East Providence, Rhode Island, United States
Alzheimer's Disease Research Unit, Yale University
🇺🇸New Haven, Connecticut, United States
Compass Research, LLC
🇺🇸Orlando, Florida, United States
Rhode Island Hospital
🇺🇸Providence, Rhode Island, United States