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221AD302 Phase 3 Study of Aducanumab (BIIB037) in Early Alzheimer's Disease (EMERGE)

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ClinicalTrials.gov Identifier: NCT02484547
Recruitment Status : Terminated (Study was discontinued based on futility analysis done and not based on safety concerns. Follow-up visits and closing out study activities are completed)
First Posted : June 29, 2015
Results First Posted : September 2, 2021
Last Update Posted : September 2, 2021
Sponsor:
Information provided by (Responsible Party):
Biogen

Tracking Information
First Submitted Date  ICMJE June 18, 2015
First Posted Date  ICMJE June 29, 2015
Results First Submitted Date  ICMJE July 1, 2021
Results First Posted Date  ICMJE September 2, 2021
Last Update Posted Date September 2, 2021
Actual Study Start Date  ICMJE September 15, 2015
Actual Primary Completion Date August 5, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 9, 2021)
Change From Baseline in Clinical Dementia Rating Scale - Sum of Boxes (CDR-SB) Score at Week 78 [ Time Frame: Baseline, Week 78 ]
CDR-SB integrates assessments from 3 domains of cognition (memory, orientation, judgment/problem-solving) and 3 domains of function (community affairs, home/hobbies, personal care). Following caregiver interview and systematic patient examination, the rater assigns a score describing the participant's current performance level in each of these domains of life functioning. Prespecified severity anchors range from none = 0, questionable = 0.5, mild = 1, moderate = 2 to severe = 3 (the personal care domain omits the 0.5 score). "Sum of boxes" scoring methodology sums the score for each of the 6 domains and provides a value ranging from 0 to 18 that can change in increments of 0.5 or greater. Higher scores indicate greater disease severity. Mixed model for repeated measures (MMRM) analysis was used to analyze change from baseline in CDR-SB. A positive change from baseline indicates clinical decline.
Original Primary Outcome Measures  ICMJE
 (submitted: June 26, 2015)
Change from baseline in CDR-SB score [ Time Frame: Week 78 ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: August 9, 2021)
  • Change From Baseline in Mini Mental State Examination (MMSE) Score at Week 78 [ Time Frame: Baseline, Week 78 ]
    The MMSE is a widely used performance-based test of global cognitive status. It consists of 11 tasks that assess orientation, word recall, attention and calculation, language abilities, and visuospatial functions. The scores from the 11 tests are combined to obtain the total score, which ranges from 0 to 30, with lower scores over time indicating increasing cognitive impairment. MMRM analysis was used to analyze change from baseline in MMSE. A negative change from baseline indicates clinical decline.
  • Change From Baseline in Alzheimer's Disease Assessment Scale-Cognitive Subscale (13 Items) (ADAS-Cog 13) at Week 78 [ Time Frame: Baseline, Week 78 ]
    ADAS-Cog13 comprises both cognitive tasks and clinical ratings of cognitive performance. The scale items capture word recall, ability to follow commands, the ability to correctly copy or draw an image, naming, the ability to interact with everyday objects, orientation, word recognition, memory, comprehension of spoken language, word-finding, and language ability, with a measure for delayed word recall and concentration/distractibility. The total score ranges from 0 to 85. An increase in score over time indicates increasing cognitive impairment. MMRM analysis was used to analyze change from baseline in ADAS-Cog 13. A positive change from baseline indicates clinical decline.
  • Change From Baseline in Alzheimer's Disease Cooperative Study-Activities of Daily Living Inventory (Mild Cognitive Impairment Version) (ADCS-ADL-MCI) Score at Week 78 [ Time Frame: Baseline, Week 78 ]
    The ADCS-ADL-MCI consists of 17 instrumental items (e.g., shopping, preparing meals, using household appliances) and 1 basic item (getting dressed). Ratings reflect caregiver observations about the patient's actual functioning over the previous month and provide an assessment of change in the functional state of the participant over time. The total score ranges from 0 to 53, with lower values over time reflecting functional deterioration. MMRM analysis was used to analyze change from baseline in ADAS-ADL-MCI. A negative change from baseline indicates clinical decline.
Original Secondary Outcome Measures  ICMJE
 (submitted: June 26, 2015)
  • Change from baseline in MMSE score [ Time Frame: Week 78 ]
  • Change from baseline in Alzheimer's Disease Assessment Scale-Cognitive Subscale (13 items) (ADAS-Cog 13) [ Time Frame: Week 78 ]
  • Change from baseline in Alzheimer's Disease Cooperative Study-Activities of Daily Living Inventory (Mild Cognitive Impairment version) (ADCS-ADL-MCI) score [ Time Frame: Week 78 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE 221AD302 Phase 3 Study of Aducanumab (BIIB037) in Early Alzheimer's Disease
Official Title  ICMJE A Phase 3 Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study to Evaluate the Efficacy and Safety of Aducanumab (BIIB037) in Subjects With Early Alzheimer's Disease
Brief Summary The primary objective of the study is to evaluate the efficacy of monthly doses of aducanumab in slowing cognitive and functional impairment as measured by changes in the Clinical Dementia Rating-Sum of Boxes (CDR-SB) score as compared with placebo in participants with early AD. Secondary objectives are to assess the effect of monthly doses of aducanumab as compared with placebo on clinical progression as measured by Mini-Mental State Examination (MMSE), AD Assessment Scale-Cognitive Subscale (13 items) [ADAS-Cog 13], and AD Cooperative Study-Activities of Daily Living Inventory (Mild Cognitive Impairment version) [ADCS-ADL-MCI].
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Alzheimer's Disease
Intervention  ICMJE
  • Drug: Aducanumab (BIIB037)
    Low dose
  • Drug: Aducanumab (BIIB037)
    High dose
  • Drug: Placebo
    Placebo
Study Arms  ICMJE
  • Experimental: Low Dose
    Monthly intravenous (IV) infusions
    Interventions:
    • Drug: Aducanumab (BIIB037)
    • Drug: Placebo
  • Experimental: High Dose
    Monthly intravenous (IV) infusions
    Interventions:
    • Drug: Aducanumab (BIIB037)
    • Drug: Placebo
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 Terminated
Actual Enrollment  ICMJE
 (submitted: August 9, 2021)
1643
Original Estimated Enrollment  ICMJE
 (submitted: June 26, 2015)
1350
Actual Study Completion Date  ICMJE August 5, 2019
Actual Primary Completion Date August 5, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Key Inclusion Criteria:

  • Must meet all of the following clinical criteria for MCI due to AD or mild AD and must have:
  • A Clinical Dementia Rating (CDR)-Global Score of 0.5.
  • Objective evidence of cognitive impairment at screening
  • An MMSE score between 24 and 30 (inclusive)
  • Must have a positive amyloid Positron Emission Tomography (PET) scan
  • Must consent to apolipoprotein E (ApoE) genotyping
  • If using drugs to treat symptoms related to AD, doses must be stable for at least 8 weeks prior to screening visit 1
  • Must have a reliable informant or caregiver

Key Exclusion Criteria:

  • Any medical or neurological condition (other than Alzheimer's Disease) that might be a contributing cause of the subject's cognitive impairment
  • Have had a stroke or Transient Ischemic Attack (TIA) or unexplained loss of consciousness in the past 1 year
  • 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
  • Indication of impaired renal or liver function
  • Have human immunodeficiency virus (HIV) infection
  • Have a significant systematic illness or infection in past 30 days
  • Relevant brain hemorrhage, bleeding disorder and cerebrovascular abnormalities
  • Any contraindications to brain magnetic resonance imaging (MRI) or PET scans
  • Alcohol or substance abuse in past 1 year
  • Taking blood thinners (except for aspirin at a prophylactic dose or less)

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 50 Years to 85 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Belgium,   Canada,   Finland,   France,   Germany,   Italy,   Japan,   Netherlands,   Poland,   Spain,   Sweden,   Switzerland,   United States
Removed Location Countries Czech Republic,   United Kingdom
 
Administrative Information
NCT Number  ICMJE NCT02484547
Other Study ID Numbers  ICMJE 221AD302
2015-000967-15 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE 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 August 2021

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