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ENVISION: A Study to Verify the Clinical Benefit of Aducanumab in Participants With Early Alzheimer's Disease

Sponsor
Biogen (Industry)
Overall Status
Recruiting
CT.gov ID
NCT05310071
Collaborator
(none)
1,512
Enrollment
20
Locations
2
Arms
53
Anticipated Duration (Months)
75.6
Patients Per Site
1.4
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The primary objective of this study is to verify the clinical benefit of monthly doses of aducanumab in slowing cognitive and functional impairment as measured by changes in the Clinical Dementia Rating Scale Sum of Boxes (CDR-SB) score as compared with placebo in participants with early Alzheimer's disease.

Condition or Disease Intervention/Treatment Phase
Phase 4

Study Design

Study Type:
Interventional
Anticipated Enrollment :
1512 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
A Phase 3b/4 Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study to Verify the Clinical Benefit of Aducanumab (BIIB037) in Participants With Alzheimer's Disease
Actual Study Start Date :
Jun 2, 2022
Anticipated Primary Completion Date :
Dec 27, 2025
Anticipated Study Completion Date :
Oct 31, 2026

Arms and Interventions

Arm Intervention/Treatment
Experimental: Aducanumab

Participants will receive aducanumab, up to 10 milligrams per kilograms (mg/kg), monthly (once every four weeks), administered as intravenous (IV) infusion.

Drug: Aducanumab
Administered as specified in the treatment arm.
Other Names:
  • BIIB037
  • Aducanumab-avwa
  • Aduhelm

    		•
    Placebo Comparator: Placebo

    Participants will receive placebo, monthly (once every four weeks), administered as IV infusion.

    Drug: Placebo
    Administered as specified in the treatment arm.

    Outcome Measures

    Primary Outcome Measures

    1. Change From Baseline in CDR-SB Score at Week 78 [Baseline, Week 78]

      The CDR 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 participant examination, the rater assigns a score describing the participant's current performance level in each of these domains of life functioning. The "Sum of boxes" scoring methodology (CDR-SB) sums the score for each of the 6 domains and provides a value ranging from 0 to 18 with higher scores indicating greater impairment. Positive change from baseline indicates greater impairment.

    Secondary Outcome Measures

    1. Change From Baseline in Integrated Alzheimer's Disease Rating Scale (iADRS) Score at Weeks 78 and 106 [Baseline, Weeks 78 and 106]

      The iADRS composite captures decline in both cognition and daily function. The iADRS is a simple linear combination of Alzheimer's disease assessment scale, cognitive subscale (ADAS-Cog13) and the Alzheimer's disease cooperative study scale for activities of daily living in mild cognitive impairment (ADCS-ADL-MCI). The iADRS scale ranges from 0-138, higher scores indicating better performance.

    2. Change From Baseline in ADCS-ADL-MCI Score at Weeks 78 and 106 [Baseline, Weeks 78 and 106]

      The ADCS-ADL-MCI is a functional evaluation scale for MCI participants, based on information provided by an informant who rates 18 areas of daily living, with total score ranging from 0-53. Higher scores indicate greater independent, healthy functioning. Positive change from baseline indicates healthy functioning.

    3. Change From Baseline in ADAS-Cog13 Score at Weeks 78 and 106 [Baseline, Weeks 78 and 106]

      The ADCS-ADAS-Cog13 is a brief objective cognitive assessment of the severity of cognitive symptoms of Alzheimer's disease. The ADAS-Cog13 score ranges from 0 to 85, with higher scores indicating worse performance.

    4. Change From Baseline in Mini-Mental State Examination (MMSE) Score at Weeks 78 and 106 [Baseline, Weeks 78 and 106]

      The MMSE is a brief cognitive screening tool that provides clinicians the ability to rapidly assess cognitive ability in less than 10 minutes. The MMSE score ranges from 0-30, with higher scores indicating better performance.

    5. Change From Baseline in Neuropsychiatric Inventory-10 (NPI-10) Score at Weeks 78 and 106 [Baseline, Weeks 78 and 106]

      The NPI-10 is a questionnaire administered to the informant, designed to obtain information on the presence of neuropsychiatric symptoms and behaviors in a participant with Alzheimer's disease. Ten areas are assessed: delusions, hallucinations, agitation/aggression, depression, anxiety, elation/euphoria, apathy/indifference, disinhibition, irritability and aberrant motor behavior. The NPI total score ranges from 0 to 120. Higher scores indicates greater impairment.

    6. Change From Baseline in Amyloid Positron Emission Tomography (PET) Signal at Weeks 78 and 104 [Baseline, Weeks 78 and 104]

      The cerebral amyloid plaque level was measured by amyloid PET imaging.

    7. Change From Baseline in Tau PET Signal at Weeks 78 and 104 [Baseline, Weeks 78 and 104]

      The cerebral tau level was measured by tau PET imaging.

    8. Change From Baseline in CDR-SB Score at Week 106 [Baseline, Week 106]

      The CDR 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 participant examination, the rater assigns a score describing the participant's current performance level in each of these domains of life functioning. The "Sum of boxes" scoring methodology (CDR-SB) sums the score for each of the 6 domains and provides a value ranging from 0 to 18 with higher scores indicating greater impairment. Positive change from baseline indicates greater impairment.

    9. Change From Baseline in Global Statistical Test (GST) Composite Z-Score [Baseline, Weeks 78 and 106]

      The GST is a composite z-score defined as the average of standardized z-scores of the CDR-SB, ADASCog13, and ADCS-ADL-MCI. A positive change from baseline indicates improvement.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    60 Years to 85 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Key Inclusion Criteria:

    • The participant must have confirmed amyloid beta pathology by cerebrospinal fluid (CSF) or amyloid PET

    • Must have a history of subjective memory decline with gradual onset and slow progression over the 6 months before Screening, confirmed by study partner

    • The participant must have 1 informant/care partner who, in the Investigator's opinion, has frequent and sufficient contact with the participant (at least 10 hours/week in person or by phone) as to be able to provide accurate information about the participant's cognitive and functional abilities over time

    • Must meet all of the following clinical criteria for MCI due to Alzheimer's disease or mild Alzheimer's disease according to National Institute on Aging and Alzheimer's Association (NIA-AA) criteria

    1. Have an MMSE score between 22 and 30 inclusive

    2. Have a CDR memory score >0.5

    3. Have a Clinical Dementia Rating Scale Global Score (CDR-GS) of 0.5 or 1.0

    4. Have a Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) score of 85 or lower indicative of objective cognitive impairment

    • Apart from a clinical diagnosis of early Alzheimer's disease, the participant must be in good health as determined by the Investigator based on medical history and screening assessments

    • Must consent to apolipoprotein E (ApoE) genotyping. (Note: Participants are not required to be ApoE ε4 carriers)

    Key Exclusion Criteria:

    • Any uncontrolled medical or neurological/neurodegenerative condition (other than Alzheimer's disease) that, in the opinion of the Investigator, might be a contributing cause of the participant's cognitive impairment

    • Clinically significant and/or unstable psychiatric illness within 6 months prior to Screening

    • Transient ischemic attack or stroke or any unexplained loss of consciousness within 1 year prior to Screening

    • History of severe allergic or anaphylactic reactions or of hypersensitivity to any of the inactive ingredients in the drug product

    • Participation in any study with purported disease-modifying effect in Alzheimer's disease within 12 months prior to Screening unless documentation of receipt of placebo is available

    • Current use or previous use of medications with a purported disease-modifying effect in Alzheimer's disease, outside of investigational studies

    • Use of any medications that, in the opinion of the Investigator, may contribute to cognitive impairment, put the participant at higher risk for AEs, or impair the participant's ability to perform cognitive testing or complete study procedures

    • Use of any investigational drug

    • Prior exposure to aducanumab either commercially or by participation in a previous study with aducanumab. (Participants are eligible if they did not receive active aducanumab.)

    • A negative PET scan result with any amyloid-targeting ligand within 12 months prior to Screening

    NOTE: Other protocol defined Inclusion/Exclusion criteria may apply

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Syrentis Clinical Research Santa Ana California United States 92705
    2 California Neuroscience Research Medical Group Inc. Sherman Oaks California United States 91403
    3 Institute for Neurodegenerative Diseases New Haven Connecticut United States 06510
    4 Research Center for Clinical Studies, Inc. Norwalk Connecticut United States 06851
    5 JEM Research Institute Atlantis Florida United States 33462
    6 Brain Matters Research Delray Beach Florida United States 33445
    7 Infinity Clinical Research, LLC Hollywood Florida United States 33024
    8 K2 Medical Research Orlando Florida United States 32751
    9 Headlands Orlando Orlando Florida United States 32819
    10 Brain Matters Research (Kane Center) Stuart Florida United States 34997
    11 Hattiesburg Clinic, PA Hattiesburg Mississippi United States 39402
    12 Las Vegas Medical Research Las Vegas Nevada United States 89113
    13 ActivMed Practices and Research Portsmouth New Hampshire United States 03801
    14 Advanced Memory Research Institute of NJ Toms River New Jersey United States 08755
    15 Neurology Clinic, PC Cordova Tennessee United States 38018
    16 Senior Adult Specialty Research Austin Texas United States 78757
    17 Kerwin Research Center and Memory Care Dallas Texas United States 75231
    18 The Memory Clinic Bennington Vermont United States 05201
    19 National Clinical Research Inc. - Richmond Richmond Virginia United States 23294
    20 Kingfisher Cooperative, LLC Spokane Washington United States 99202

    Sponsors and Collaborators

    • Biogen

    Investigators

    • Study Director: Medical Director, Biogen

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Biogen
    ClinicalTrials.gov Identifier:
    NCT05310071
    Other Study ID Numbers:
    • 221AD305
    First Posted:
    Apr 4, 2022
    Last Update Posted:
    Aug 10, 2022
    Last Verified:
    Aug 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:
    Alzheimer Disease

    Study Results

    No Results Posted as of Aug 10, 2022