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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

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ClinicalTrials.gov Identifier: NCT03639987
Recruitment Status : Recruiting
First Posted : August 21, 2018
Last Update Posted : March 20, 2019
Sponsor:
Information provided by (Responsible Party):
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.

Condition or disease Intervention/treatment Phase
Cognitive Dysfunction Alzheimer's Disease Drug: Aducanumab Drug: Placebo Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 500 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : December 20, 2018
Estimated Primary Completion Date : July 9, 2021
Estimated Study Completion Date : November 13, 2023


Arm Intervention/treatment
Experimental: Group 1
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
Administered as specified in the treatment arm.
Other Name: BIIB037

Drug: Placebo
Administered as specified in the treatment arm.

Experimental: Group 2
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
Administered as specified in the treatment arm.
Other Name: BIIB037




Primary Outcome Measures :
  1. Number of Clinically Impactful Amyloid-related Imaging Abnormalities (ARIA) [ Time Frame: Baseline up to Week 54 ]
    Clinically impactful ARIA is defined as symptoms and/or signs associated with ARIA that meet pre-defined criteria as assessed by an independent adjudication committee.


Secondary Outcome Measures :
  1. Number of Participants With ARIA by Severity as Obtained on Magnetic Resonance Imaging (MRI) [ Time Frame: Baseline up to Week 54 ]
    Severity of ARIA is graded as mild, moderate and severe.

  2. Time to Onset of ARIA as Obtained on MRI [ Time Frame: Baseline up to Week 54 ]
    Time to onset of ARIA is defined as the time from first dose until the first subsequent documentation of onset of ARIA as obtained on MRI.

  3. Time to Resolution of ARIA as Obtained on MRI [ Time Frame: Baseline up to Week 54 ]
    Time to resolution of ARIA is defined as the time from first onset until the first subsequent documentation of resolution of ARIA as obtained on MRI.

  4. Number of Participants With Symptomatic ARIA by Severity [ Time Frame: Baseline up to Week 54 ]
    Severity of symptomatic ARIA to be graded as mild, moderate and severe.

  5. Time to Onset of Symptomatic ARIA [ Time Frame: Baseline up to Week 54 ]
    Time to onset of symptomatic ARIA is defined as the time from first dose until the first subsequent documentation of onset of ARIA.

  6. Time to Resolution of Symptomatic ARIA [ Time Frame: Baseline up to Week 54 ]
    Time to resolution of symptomatic ARIA is defined as the time from first onset until the first subsequent documentation of resolution of symptomatic ARIA.

  7. Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: Baseline up to Week 54 ]
    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, is a life-threatening event, requires inpatient hospitalization or prolongation of existing hospitalization, results in a significant disability/incapacity or congenital anomaly, is a medically important event.

  8. Change From Baseline in the Montreal Cognitive Assessment (MoCA) at Week 54 [ Time Frame: Baseline, Week 54 ]
    MoCA is used to assess changes in cognition.

  9. Aducanumab Concentration in Serum [ Time Frame: Pre-dose on Day 1 of Weeks 1, 16, 24, 32, 44, 54, 56, 70, 80, 104 ]
  10. Number of Participants With Antiaducanumab Antibodies in Serum [ Time Frame: Pre-dose on Day 1 of Weeks 1, 16, 24, 32, 44, 54, 56, 70, 80, 104 ]
    Presence of serum antiaducanumab antibodies will be determined using a validated assay.



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Ages Eligible for Study:   50 Years to 85 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03639987


Contacts
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Contact: US Biogen Clinical Trial Center 866-633-4636 clinicaltrials@biogen.com
Contact: Global Biogen Clinical Trial Center clinicaltrials@biogen.com

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Sponsors and Collaborators
Biogen
Investigators
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Study Director: Medical Director Biogen

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Responsible Party: Biogen
ClinicalTrials.gov Identifier: NCT03639987     History of Changes
Other Study ID Numbers: 221AD205
2018-002102-31 ( EudraCT Number )
First Posted: August 21, 2018    Key Record Dates
Last Update Posted: March 20, 2019
Last Verified: March 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
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Alzheimer Disease
Dementia
Cognitive Dysfunction
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Tauopathies
Neurodegenerative Diseases
Neurocognitive Disorders
Mental Disorders
Cognition Disorders