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Trial record 3 of 7 for:    aducanumab AND BIIB037

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 15, 2019
Sponsor:
Information provided by (Responsible Party):
Biogen

Tracking Information
First Submitted Date  ICMJE August 17, 2018
First Posted Date  ICMJE August 21, 2018
Last Update Posted Date March 15, 2019
Actual Study Start Date  ICMJE December 20, 2018
Estimated Primary Completion Date July 9, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 6, 2018)
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.
Original Primary Outcome Measures  ICMJE
 (submitted: August 17, 2018)
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 are life threatening, require hospitalization, and/or result in persistent or significant disability as assessed by the independent Adjudication Committee.
Change History Complete list of historical versions of study NCT03639987 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: September 6, 2018)
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • Aducanumab Concentration in Serum [ Time Frame: Pre-dose on Day 1 of Weeks 1, 16, 24, 32, 44, 54, 56, 70, 80, 104 ]
  • 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: August 17, 2018)
  • 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.
  • 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.
  • 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.
  • Number of Participants With Symptomatic ARIA by Severity [ Time Frame: Baseline up to Week 54 ]
    Severity of symptomatic ARIA is graded as mild, moderate and severe. Where mild =symptoms barely noticeable to participant or does not make participant uncomfortable; does not influence performance or functioning; prescription drug not ordinarily needed for relief of symptoms but may be given because of personality of participant. Moderate =symptoms of a sufficient severity to make participant uncomfortable; performance of daily activity is influenced; participant is able to continue in study; treatment for symptoms may be needed. Severe =symptoms cause severe discomfort; incapacitation or significant impact on participant's daily life; severity may cause cessation of treatment with study treatment; treatment for symptoms may be given and/or participant hospitalized.
  • 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.
  • 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.
  • 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.
  • Change From Baseline in the Montreal Cognitive Assessment (MoCA) at Week 54 [ Time Frame: Baseline, Week 54 ]
    MoCA is used to assess any changes in cognition. The MoCA is a 1-page 30-point test administered in approximately 10 minutes. The MoCA assesses short term memory, visuospatial abilities, multiple aspects of executive functions, attention, concentration, working memory, and language, as well as orientation to time and place. The total possible score ranges from 0 to 30, with lower numbers indicating lower cognition performance.
  • Aducanumab Concentration in Serum [ Time Frame: Pre-dose on Day 1 of Weeks 1, 16, 24, 32, 44, 54, 56, 70, 80, 104 ]
  • 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. A standard 3-tier antidrug antibody (ADA) approach will be used (i.e., screening assay, confirmatory assay, and titration assay).
Current Other Outcome Measures  ICMJE Not Provided
Original Other Outcome Measures  ICMJE Not Provided
 
Descriptive Information
Brief Title  ICMJE 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
Official Title  ICMJE 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
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 Provided
Study Type  ICMJE Interventional
Study Phase Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE
  • Cognitive Dysfunction
  • Alzheimer's Disease
Intervention  ICMJE
  • Drug: Aducanumab
    Administered as specified in the treatment arm.
    Other Name: BIIB037
  • Drug: Placebo
    Administered as specified in the treatment arm.
Study Arms
  • 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.
    Interventions:
    • Drug: Aducanumab
    • Drug: Placebo
  • 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.
    Intervention: Drug: Aducanumab
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: August 17, 2018)
500
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date November 13, 2023
Estimated Primary Completion Date July 9, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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

Sex/Gender
Sexes Eligible for Study: All
Ages 50 Years to 85 Years   (Adult, Older Adult)
Accepts Healthy Volunteers No
Contacts  ICMJE
Contact: US Biogen Clinical Trial Center 866-633-4636 clinicaltrials@biogen.com
Contact: Global Biogen Clinical Trial Center clinicaltrials@biogen.com
Listed Location Countries  ICMJE Australia,   Canada,   Italy,   Spain,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03639987
Other Study ID Numbers  ICMJE 221AD205
2018-002102-31 ( 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
IPD Sharing Statement Not Provided
Responsible Party Biogen
Study Sponsor  ICMJE Biogen
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Medical Director Biogen
PRS Account Biogen
Verification Date March 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP