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

Study Overview
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Brief Summary
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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.

Official Title
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A Phase 2, Multicenter, Randomized, Parallel-Group, Double-Blind, Controlled Study of Aducanumab (BIIB037) in Subjects With Mild Cognitive Impairment Due to Alzheimer's Disease or With Mild Alzheimer's Disease Dementia to Evaluate the Safety of Continued Dosing in Subjects With Asymptomatic Amyloid-Related Imaging Abnormalities

Conditions
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Cognitive Dysfunction, Alzheimer's Disease

Intervention / Treatment
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* Drug: Aducanumab
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion/ Exclusion Criteria Key Inclusion Criteria: 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 Exclusion Criteria: 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

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1<br>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. | Drug: Aducanumab<br>* Administered as specified in the treatment arm.<br>* Other names: BIIB037;Drug: Placebo<br>* Administered as specified in the treatment arm.<br>|
| Experimental: Group 2<br>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. | Drug: Aducanumab<br>* Administered as specified in the treatment arm.<br>* Other names: BIIB037;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Clinically Impactful Amyloid-related Imaging Abnormalities (ARIA) |  | up to Week 54 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With ARIA by Severity as Obtained on Magnetic Resonance Imaging (MRI) | ARIA by severity was obtained on Magnetic Resonance Imaging (MRI). | up to Week 54 | 
| Time to Onset of ARIA as Obtained on MRI |  | up to Week 54 | 
| Time to Resolution of ARIA as Obtained on MRI |  | up to Week 54 | 
| Number of Participants With Symptomatic ARIA by Severity | ARIA by severity was obtained on Magnetic Resonance Imaging (MRI). | up to Week 54 | 
| Time to Onset of Symptomatic ARIA |  | 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) | 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. | up to Week 54 | 
| 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 | 
| Number of Participants With Antiaducanumab Antibodies in Serum |  | up to Week 54 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Aducanumab, BIIB037