A Study to Evaluate Safety and Tolerability of Aducanumab in Participants With Alzheimer's Disease Who Had Previously Participated in the Aducanumab Studies 221AD103, 221AD301, 221AD302 and 221AD205

Study Overview
=================
Brief Summary
-----------------
The primary objective is to evaluate the safety and tolerability of aducanumab over 100 weeks of treatment after a wash-out period imposed by discontinuation of feeder studies in participants who had previously received aducanumab (i.e. previously treated participants) or who had previously received placebo (i.e. treatment-naïve participants).

Official Title
-----------------
Phase 3b Open-Label, Multicenter, Safety Study of BIIB037 (Aducanumab) in Subjects With Alzheimer's Disease Who Had Previously Participated in the Aducanumab Studies 221AD103, 221AD301, 221AD302 and 221AD205

Conditions
-----------------
Alzheimer's Disease

Intervention / Treatment
-----------------
* Drug: Aducanumab


Participation Criteria
=================
Eligibility Criteria
-----------------
Key Inclusion Criteria: Core Treatment Period: Participant was participating in an aducanumab clinical study at the time of the announcement of early termination (feeder studies). Has one care partner who, in the Investigator's opinion, has adequate contact with the participant as to be able to provide accurate information about the participant's cognitive and functional abilities. LTE Treatment Period: Participant must have completed the Core study period (Week 102) and adequately tolerated 10 mg/kg of aducanumab during the Core study period in the opinion of the Investigator. Has one informant/care partner who, in the Investigator's opinion, has frequent and sufficient contact with the participant as to be able to provide accurate information about the participant's cognitive and functional abilities. Key Exclusion Criteria: Core Treatment Period: Any medical or neurological condition (other than Alzheimer's Disease) that might be a contributing cause of the participant's cognitive impairment. Stroke or any unexplained loss of consciousness within 1 year prior to Screening. Clinically significant unstable psychiatric illness in past 6 months. History of unstable angina, myocardial infarction, advanced chronic heart failure, or clinically significant conduction abnormalities within 1 year prior to Screening. A seizure event that occurred after the last visit of the feeder study and before Screening for this study. Evidence of impaired liver function as shown by an abnormal liver function profile at Screening. History of or known seropositivity for HIV. Clinically significant systemic illness or serious infection within 30 days prior to or during Screening. Contraindications to having a brain magnetic resonance imaging (MRI). LTE Treatment Period: Any medical or psychiatric contraindication or clinically significant abnormality that, in the opinion of the Investigator, will substantially increase the risk associated with the participant's enrollment in and completion of the study. Note- Other protocol defined Inclusion/Exclusion criteria may apply.

Ages Eligible for Study
-----------------
Minimum Age: 50 Years
Maximum Age: 90 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Aducanumab<br>Participants will be administered aducanumab 10 milligrams per kilogram (mg/kg) by intravenous (IV) infusions every four weeks (Q4W) for a duration of 100 weeks during the Core Treatment Period. Eligible participants will continue to receive aducanumab 10 mg/kg IV infusion, Q4W, for 52 weeks during the Long-Term Extension (LTE) Treatment Period. | Drug: Aducanumab<br>* Administered as specified in the treatment arm.<br>* Other names: BIIB037;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Core Treatment Period: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) | An AE is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. A SAE is any untoward medical occurrence that at any dose results in death, life-threatening event, requires inpatient hospitalization, significant disability/incapacity or congenital anomaly. | Up to Week 100 | 
| Core Treatment Period: Number of Participants with AEs Leading to Treatment Discontinuation or Study Withdrawal | An AE is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. | Up to Week 100 | 
| Core Treatment Period: Number of Participants with Amyloid-related Imaging Abnormality-Edema (ARIA-E) | Magnetic resonance imaging (MRI) readings will be used to assess ARIA-E severity as mild, moderate and severe. | Up to Week 100 | 
| Core Treatment Period: Number of Participants with Amyloid-related Imaging Abnormality- Hemorrhage or Superficial Siderosis (ARIA-H) | MRI readings will be used to assess severity of ARIA-H microhemorrhages and superficial siderosis. | Up to Week 100 | 
| Core Treatment Period: Number of Participants With Antidrug Antibodies (ADAs) in Serum | Presence of serum ADAs will be determined using a validated assay. | Up to Week 100 |