A Study of Aducanumab in Participants With Mild Cognitive Impairment Due to Alzheimer's Disease or With Mild Alzheimer's Disease Dementia to Evaluate the Safety of Continued Dosing in Participants With Asymptomatic Amyloid-Related Imaging Abnormalities
- Conditions
- Alzheimer's DiseaseCognitive Dysfunction
- Interventions
- Drug: Placebo
- Registration Number
- NCT03639987
- Lead Sponsor
- Biogen
- Brief Summary
The primary objective of the study is to assess the safety impact of continuing aducanumab dosing in asymptomatic Amyloid-related Imaging Abnormalities (ARIA) in participants with mild cognitive impairment (MCI) due to Alzheimer's disease (AD) or with mild AD dementia. The secondary objective of the study is to characterize ARIA, from both the imaging and the clinical perspective and to characterize the safety, tolerability, pharmacokinetics (PK), and immunogenicity of aducanumab.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 52
- Ability of the participant or his/her legally authorized representative to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use confidential health information in accordance with national and local participant privacy regulations.
- Must have at least 6 years of education or work experience to exclude mental deficits other than MCI due to AD or mild AD dementia.
- Must have evidence of cerebral Aβ accumulation, based on a positive PET scan of the brain. Previously obtained positron emission tomography (PET) scan (within 12 months of screening) is permissible. Previous PET scan images must be submitted to the central imaging vendor to confirm that study inclusion criteria are met.
- Must consent to apolipoprotein E (ApoE) genotyping.
- Must meet all of the following clinical criteria for MCI due to AD or mild AD dementia according to NIA-AA criteria [Albert 2011; McKhann 2011], and must have the following: MCI due to AD (a CDR global score of 0.5, and an MMSE score between 24 and 30 (inclusive)), or Mild AD dementia (a CDR global score of 0.5 or 1, and as MMSE score between 20 and 26 (inclusive)).
Key
- Any uncontrolled medical or neurological/neurodegenerative condition (other than AD) that, in the opinion of the Investigator, might be a contributing cause of the participant's cognitive impairment (e.g., substance abuse, vitamin B12 deficiency, abnormal thyroid function, stroke or other cerebrovascular condition, Lewy body dementia, frontotemporal dementia, head trauma).
- Clinically significant unstable psychiatric illness (e.g., uncontrolled major depression, uncontrolled schizophrenia, uncontrolled bipolar affective disorder) within 6 months prior to Screening.
- Transient ischemic attack or stroke or any unexplained loss of consciousness within 1 year prior to Screening.
- Vaccinations within 10 days prior to randomization (Day 1).
- Female participants who are pregnant or currently breastfeeding.
NOTE: Other protocol defined Inclusion/Exclusion criteria may apply
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Group 1 Placebo Aducanumab, intravenous infusion, every 4 weeks for up to Week 52 during the randomized treatment period. The dose will be titrated to a desirable dose. Participants will be managed for drug continuation and suspension. Following a 4-week follow-up period, eligible participants will continue to receive aducanumab, intravenous infusion, every 4 weeks for an additional 104 weeks in the long-term extension period. Group 1 Aducanumab Aducanumab, intravenous infusion, every 4 weeks for up to Week 52 during the randomized treatment period. The dose will be titrated to a desirable dose. Participants will be managed for drug continuation and suspension. Following a 4-week follow-up period, eligible participants will continue to receive aducanumab, intravenous infusion, every 4 weeks for an additional 104 weeks in the long-term extension period. Group 2 Aducanumab Aducanumab, intravenous infusion, every 4 weeks for up to Week 52 during the randomized treatment period. The dose will be titrated to a desirable dose. Participants will be managed for drug continuation and suspension. Following a 4-week follow-up period, eligible participants will continue to receive aducanumab, intravenous infusion, every 4 weeks for an additional 104 weeks in the long-term extension period.
- Primary Outcome Measures
Name Time Method Number of Participants With Clinically Impactful Amyloid-related Imaging Abnormalities (ARIA) up to Week 54
- Secondary Outcome Measures
Name Time Method Number of Participants With Antiaducanumab Antibodies in Serum up to Week 54 Time to Resolution of Symptomatic ARIA up to Week 54 Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) up to Week 54 An AE is any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An SAE is any untoward medical occurrence that at any dose: results in death, in the view of the Investigator, places the participant at immediate risk of death (a life-threatening event), however, this does not include an event that, had it occurred in a more severe form, might have caused death; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; results in a congenital anomaly/birth defect or is a medically important event.
Change From Baseline in the Montreal Cognitive Assessment (MoCA) at Week 54 Baseline, Week 54 Number of Participants With Aducanumab Concentration in Serum up to Week 54 Time to Onset of ARIA as Obtained on MRI up to Week 54 Number of Participants With ARIA by Severity as Obtained on Magnetic Resonance Imaging (MRI) up to Week 54 ARIA by severity was obtained on Magnetic Resonance Imaging (MRI).
Time to Resolution of ARIA as Obtained on MRI up to Week 54 Number of Participants With Symptomatic ARIA by Severity up to Week 54 ARIA by severity was obtained on Magnetic Resonance Imaging (MRI).
Time to Onset of Symptomatic ARIA up to Week 54
Trial Locations
- Locations (21)
Neurology Center of North Orange County
🇺🇸Fullerton, California, United States
Pacific Research Network, Inc
🇺🇸San Diego, California, United States
Neuropsychiatric Research Center of Southwest Florida
🇺🇸Fort Myers, Florida, United States
Baylor College Of Medicine
🇺🇸Houston, Texas, United States
Pacific Neuroscience Medical Group
🇺🇸Oxnard, California, United States
Brain Matters Research
🇺🇸Delray Beach, Florida, United States
California Neuroscience Research Medical Group Inc.
🇺🇸Sherman Oaks, California, United States
Bioclinica Orlando
🇺🇸The Villages, Florida, United States
Las Vegas Medical Research
🇺🇸Las Vegas, Nevada, United States
Medical Research Health and Education Foundation, Inc
🇺🇸Columbus, Georgia, United States
Josephson, Wallack, Munshower Neurology, P.C.
🇺🇸Indianapolis, Indiana, United States
Advanced Memory Research Institute of NJ, PC
🇺🇸Toms River, New Jersey, United States
Neurology Clinic, PC
🇺🇸Cordova, Tennessee, United States
Clinical Trial Network
🇺🇸Houston, Texas, United States
National Clinical Research Inc.-Richmond
🇺🇸Richmond, Virginia, United States
Kingfisher Cooperative, LLC
🇺🇸Spokane, Washington, United States
Center for Neurosciences
🇺🇸Tucson, Arizona, United States
Banner Alzheimer's Institute
🇺🇸Phoenix, Arizona, United States
Lynn Health Science Institute
🇺🇸Oklahoma City, Oklahoma, United States
JEM Research Institute
🇺🇸Atlantis, Florida, United States
Senior Adult Specialty Research
🇺🇸Austin, Texas, United States