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

• ClinicalTrials.gov Identifier: NCT04241068
• Recruitment Status: Active, not recruiting
• First Posted: January 27, 2020
• Last Update Posted: April 4, 2024
• Sponsor: Biogen
• Information provided by (Responsible Party): Biogen

Tracking Information

• First Submitted Date: January 22, 2020
• First Posted Date: January 27, 2020
• Last Update Posted Date: April 4, 2024
• Actual Study Start Date: March 2, 2020
• Actual Primary Completion Date: January 19, 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 14, 2022)

• Core Treatment Period: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: Up to Week 100 ]
  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.
• Core Treatment Period: Number of Participants with AEs Leading to Treatment Discontinuation or Study Withdrawal [ Time Frame: Up to Week 100 ]
  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.
• Core Treatment Period: Number of Participants with Amyloid-related Imaging Abnormality-Edema (ARIA-E) [ Time Frame: Up to Week 100 ]
  Magnetic resonance imaging (MRI) readings will be used to assess ARIA-E severity as mild, moderate and severe.
• Core Treatment Period: Number of Participants with Amyloid-related Imaging Abnormality- Hemorrhage or Superficial Siderosis (ARIA-H) [ Time Frame: Up to Week 100 ]
  MRI readings will be used to assess severity of ARIA-H microhemorrhages and superficial siderosis.
• Core Treatment Period: Number of Participants With Antidrug Antibodies (ADAs) in Serum [ Time Frame: Up to Week 100 ]
  Presence of serum ADAs will be determined using a validated assay.

Original Primary Outcome Measures (submitted: January 22, 2020)

• Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: Up to Week 118 ]
  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.
• Number of Participants with AEs Leading to Treatment Discontinuation or Study Withdrawal [ Time Frame: Up to Week 118 ]
  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.
• Number of Participants with Amyloid-related Imaging Abnormality-Edema (ARIA-E) [ Time Frame: Up to Week 102 ]
  Magnetic resonance imaging (MRI) readings will be used to assess ARIA-E severity as mild, moderate and severe.
• Number of Participants with Amyloid-related Imaging Abnormality- Hemorrhage or Superficial Siderosis (ARIA-H) [ Time Frame: Up to Week 102 ]
  MRI readings will be used to assess severity of ARIA-H microhemorrhages and superficial siderosis.
• Number of Participants With Anti-aducanumab Antibodies in Serum [ Time Frame: Up to Week 102 ]
  Presence of serum anti-aducanumab antibodies will be determined using a validated assay.

• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• 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
• 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).
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Alzheimer's Disease

Intervention

Drug: Aducanumab

Administered as specified in the treatment arm.

Other Name: BIIB037

Study Arms

Experimental: Aducanumab

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.

Intervention: Drug: Aducanumab

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: December 22, 2021): 1696
• Original Estimated Enrollment (submitted: January 22, 2020): 2400
• Estimated Study Completion Date: August 28, 2024
• Actual Primary Completion Date: January 19, 2024 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 50 Years to 90 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia, Austria, Belgium, Canada, Denmark, Finland, France, Germany, Italy, Japan, Korea, Republic of, Netherlands, Poland, Portugal, Spain, Sweden, Switzerland, Taiwan, United Kingdom, United States

Administrative Information

• NCT Number: NCT04241068
• Other Study ID Numbers: 221AD304; 2019-004368-22 ( EudraCT Number )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: In accordance with Biogen's Clinical Trial Transparency and Data Sharing Policy on https://www.biogentrialtransparency.com/
• URL: https://vivli.org/

• Current Responsible Party: Biogen
• Original Responsible Party: Same as current
• Current Study Sponsor: Biogen
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Medical Director; Biogen

• PRS Account: Biogen
• Verification Date: April 2024