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A Study of Donanemab (LY3002813) Compared With Aducanumab in Participants With Early Symptomatic Alzheimer's Disease (TRAILBLAZER-ALZ 4)

Sponsor
Eli Lilly and Company (Industry)
Overall Status
Active, not recruiting
CT.gov ID
NCT05108922
Collaborator
(none)
200
Enrollment
31
Locations
2
Arms
31.5
Anticipated Duration (Months)
6.5
Patients Per Site
0.2
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The main purpose of this study is to compare donanemab to aducanumab on amyloid plaque clearance in participants with early symptomatic Alzheimer's Disease (AD).

Condition or Disease Intervention/Treatment Phase
Phase 3

Study Design

Study Type:
Interventional
Anticipated Enrollment :
200 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase 3, Open-Label, Parallel-Group, 2-Arm Study to Investigate Amyloid Plaque Clearance With Donanemab Compared With Aducanumab-avwa in Participants With Early Symptomatic Alzheimer's Disease
Actual Study Start Date :
Nov 16, 2021
Anticipated Primary Completion Date :
Aug 30, 2022
Anticipated Study Completion Date :
Jul 2, 2024

Arms and Interventions

Arm Intervention/Treatment
Experimental: Donanemab

Donanemab is administered intravenously (IV) every 4 weeks (Q4W)

Drug: Donanemab
Administered IV
Other Names:
  • LY3002813

    		•
    Active Comparator: Aducanumab

    Aducanumab administered IV per label

    Drug: Aducanumab
    Administered IV

    Outcome Measures

    Primary Outcome Measures

    1. Percentage of Participants Who Reach Complete Amyloid Plaque Clearance on Florbetapir F18 Positron Emission Tomography (PET) Scan (Superiority) on donanemab versus aducanumab [6 Months]

      Percentage of Participants Who Reach Complete Amyloid Plaque Clearance on Florbetapir F18 PET Scan (Superiority) on donanemab versus aducanumab

    2. Percentage of Participants Who Reach Complete Amyloid Plaque Clearance on Florbetapir F18 PET Scan in the Intermediate Subpopulation (Superiority) on donanemab versus aducanumab [6 Months]

      Percentage of Participants Who Reach Complete Amyloid Plaque Clearance on Florbetapir F18 PET Scan in the intermediate subpopulation (Superiority) on donanemab versus aducanumab

    Secondary Outcome Measures

    1. Mean Absolute Change from Baseline in Brain Amyloid Plaque on Florbetapir F18 PET Scan (Superiority) on donanemab versus aducanumab [Baseline, 6 Months]

      Mean Absolute Change from Baseline in Brain Amyloid Plaque on Florbetapir F18 PET Scan (Superiority) on donanemab versus aducanumab

    2. Mean Absolute Change from Baseline in Brain Amyloid Plaque on Florbetapir F18 PET Scan (Superiority) on donanemab versus aducanumab [Baseline, 12 Months]

      Mean Absolute Change from Baseline in Brain Amyloid Plaque on Florbetapir F18 PET Scan (Superiority) on donanemab versus aducanumab

    3. Mean Absolute Change from Baseline in Brain Amyloid Plaque on Florbetapir F18 PET Scan (Superiority) on donanemab versus aducanumab [Baseline, 18 Months]

      Mean Absolute Change from Baseline in Brain Amyloid Plaque on Florbetapir F18 PET Scan (Superiority) on donanemab versus aducanumab

    4. Mean Absolute Change from Baseline in Brain Amyloid Plaque on Florbetapir F18 PET Scan (Noninferiority) on donanemab 6 months versus aducanumab 12 months [Baseline, 6 Months, 12 Months]

      Mean Absolute Change from Baseline in Brain Amyloid Plaque on Florbetapir F18 PET Scan (Noninferiority) on donanemab 6 months versus aducanumab 12 months

    5. Mean Absolute Change from Baseline in Brain Amyloid Plaque on Florbetapir F18 PET Scan (Noninferiority) donanemab 6 months versus aducanumab 18 months [Baseline, 6 Months, 18 Months]

      Mean Absolute Change from Baseline in Brain Amyloid Plaque on Florbetapir F18 PET Scan (Noninferiority) donanemab 6 months versus aducanumab 18 months

    6. Time to Reach Complete Amyloid Plaque Clearance on donanemab versus aducanumab [Baseline to 18 Months]

      Time to reach complete amyloid plaque clearance on donanemab versus aducanumab

    7. Mean Percent Change from Baseline in Brain Amyloid Plaque on Florbetapir F18 PET Scan (Superiority) donanemab versus aducanumab [Baseline, 6 Months]

      Mean Percent Change from Baseline in Brain Amyloid Plaque on Florbetapir F18 PET Scan (Superiority) donanemab versus aducanumab

    8. Mean Percent Change from Baseline in Brain Amyloid Plaque on Florbetapir F18 PET Scan (Superiority) on donanemab versus aducanumab [Baseline, 12 Months]

      Mean Percent Change from Baseline in Brain Amyloid Plaque on Florbetapir F18 PET Scan (Superiority) on donanemab versus aducanumab

    9. Mean Percent Change from Baseline in Brain Amyloid Plaque on Florbetapir F18 PET Scan (Superiority) on donanemab versus aducanumab [Baseline, 18 Months]

      Mean Percent Change from Baseline in Brain Amyloid Plaque on Florbetapir F18 PET Scan (Superiority) on donanemab versus aducanumab

    10. Percentage of Participants Who Reach Complete Amyloid Plaque Clearance on Florbetapir F18 PET Scan (Superiority) on donanemab versus aducanumab [12 Months]

      Percentage of Participants Who Reach Complete Amyloid Plaque Clearance on Florbetapir F18 PET Scan (Superiority) on donanemab versus aducanumab

    11. Percentage of Participants Who Reach Complete Amyloid Plaque Clearance on Florbetapir F18 PET Scan (Superiority) on donanemab versus aducanumab [18 Months]

      Percentage of Participants Who Reach Complete Amyloid Plaque Clearance on Florbetapir F18 PET Scan (Superiority) on donanemab versus aducanumab

    12. Percentage of Participants Who Reach Complete Amyloid Plaque Clearance on Florbetapir F18 PET Scan in the Intermediate Tau Subpopulation (Superiority) on donanemab versus aducanumab [12 Months]

      Percentage of Participants Who Reach Complete Amyloid Plaque Clearance on Florbetapir F18 PET Scan in the Intermediate Tau Subpopulation (Superiority) on donanemab versus aducanumab

    13. Percentage of Participants Who Reach Complete Amyloid Plaque Clearance on Florbetapir F18 PET Scan in the Intermediate Tau Subpopulation (Superiority) on donanemab versus aducanumab [18 Months]

      Percentage of Participants Who Reach Complete Amyloid Plaque Clearance on Florbetapir F18 PET Scan in the Intermediate Tau Subpopulation (Superiority) on donanemab versus aducanumab

    14. Mean Absolute Change from Baseline in Brain Amyloid Plaque on Florbetapir F18 PET Scan in the Intermediate Tau Subpopulation (Superiority) on donanemab versus aducanumab [Baseline, 6 Months]

      Mean Absolute Change from Baseline in Brain Amyloid Plaque on Florbetapir F18 PET Scan in the Intermediate Tau Subpopulation (Superiority) on donanemab versus aducanumab

    15. Mean Absolute Change from Baseline in Brain Amyloid Plaque on Florbetapir F18 PET Scan in the Intermediate Tau Subpopulation (Superiority) on donanemab versus aducanumab [Baseline, 12 Months]

      Mean Absolute Change from Baseline in Brain Amyloid Plaque on Florbetapir F18 PET Scan in the Intermediate Tau Subpopulation (Superiority) on donanemab versus aducanumab

    16. Mean Absolute Change from Baseline in Brain Amyloid Plaque on Florbetapir F18 PET Scan in the Intermediate Tau Subpopulation (Superiority) on donanemab versus aducanumab [Baseline, 18 Months]

      Mean Absolute Change from Baseline in Brain Amyloid Plaque on Florbetapir F18 PET Scan in the Intermediate Tau Subpopulation (Superiority) on donanemab versus aducanumab

    17. Change from Baseline in Brain Amyloid Plaque Reduction on Florbetapir F18 PET Scan (Superiority) donanemab 6 months versus aducanumab 12 months [Baseline, 6 Months, 12 Months]

      Change from Baseline in Brain Amyloid Plaque Reduction on Florbetapir F18 PET Scan (Superiority) donanemab 6 months versus aducanumab 12 months

    Eligibility Criteria

    Criteria

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

    • Gradual and progressive change in memory function reported by the participant or informant for ≥6 months.

    • Meet florbetapir F18 PET scan criteria.

    • A Clinical Dementia Rating (CDR)-Global Score of 0.5 or 1.

    • Must consent to apolipoprotein E (ApoE) genotyping

    • Must have a mini mental state examination (MMSE) score between 20 and 30

    • Have a study partner who will provide written informed consent to participate, is in frequent contact with the participant (defined as at least 10 hours per week), and will accompany the participant to study visits or be available by telephone at designated times.

    • Have adequate literacy, vision, and hearing for neuropsychological testing in the opinion of the investigator at the time of screening.

    • Women not of childbearing potential may participate

    Exclusion Criteria:

    • Significant neurological disease affecting the central nervous system (other than AD), that may affect cognition or ability to complete the study, including but not limited to, other dementias, serious infection of the brain, Parkinson's disease, multiple concussions, history of transient ischemic attack or stroke, or epilepsy or recurrent seizures (except febrile childhood seizures).

    • Current serious or unstable medical illnesses including cardiovascular, hepatic, renal, gastroenterologic, respiratory, endocrinologic, psychiatric (including actively suicidal or deemed at risk of suicide, or current alcohol or substance abuse), immunologic, infectious, or hematologic disease and other conditions that, in the investigator's opinion, could interfere with the analyses in this study; or has a life expectancy of approximately

    ≤24 months.

    • History of clinically significant multiple or severe drug allergies, or severe posttreatment hypersensitivity reactions (including but not limited to erythema multiforme major, linear immunoglobulin A dermatosis, toxic epidermal necrolysis, and/or exfoliative dermatitis).

    • History of bleeding disorder or use of medications with platelet anti-aggregant or anti-coagulant properties (unless aspirin at ≤325 milligram (mg).

    • Have had prior or current treatment with donanemab or aducanumab

    • Have known allergies to donanemab or aducanumab, related compounds, or any components of the formulation

    • Prior or current participation in any immunotherapy study targeting Amyloid beta

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Neurology Center of North Orange County Fullerton California United States 92835
    2 Irvine Clinical Research Irvine California United States 92614
    3 California Neuroscience Research Medical Group, Inc. Sherman Oaks California United States 91403
    4 Institute for Neurodegenerative Disorders New Haven Connecticut United States 06510
    5 JEM Research Institute Atlantis Florida United States 33462
    6 Brain Matters Research Delray Beach Florida United States 33445
    7 Neuropsychiatric Research Center of Southwest Florida Fort Myers Florida United States 33912
    8 Infinity Clinical Research, LLC Hollywood Florida United States 33024
    9 Jacksonville Center for Clinical Research Jacksonville Florida United States 32216
    10 Charter Research - Lady Lake Lady Lake Florida United States 32159
    11 ClinCloud - Maitland Maitland Florida United States 32751
    12 ClinCloud - Viera Melbourne Florida United States 32940
    13 Merritt Island Medical Research, LLC Merritt Island Florida United States 32952
    14 Optimus U Corporation Miami Florida United States 33125
    15 Brainstorm Research Miami Florida United States 33176
    16 Brain Matters Research Stuart Florida United States 34997
    17 Axiom Clinical Research of Florida Tampa Florida United States 33609
    18 Conquest Research Winter Park Florida United States 32789
    19 Columbus Memory Center, PC Columbus Georgia United States 31909
    20 Josephson Wallack Munshower Neurology, PC Indianapolis Indiana United States 46256
    21 Donald S. Marks M.D., P.C. Plymouth Massachusetts United States 02360
    22 Adams Clinical Watertown Massachusetts United States 02472
    23 Clinical Research Professionals Chesterfield Missouri United States 63005
    24 Las Vegas Medical Research Las Vegas Nevada United States 89113
    25 The Cognitive and Research Center of New Jersey Springfield New Jersey United States 07081
    26 Advanced Memory Research Institute of New Jersey Toms River New Jersey United States 08755
    27 Neurology Diagnostics, Inc. Dayton Ohio United States 45459
    28 Abington Neurological Associates, Ltd. Abington Pennsylvania United States 19001
    29 The Clinical Trial Center, LLC Jenkintown Pennsylvania United States 19046
    30 Kerwin Medical Center Dallas Texas United States 75231
    31 National Clinical Research, Inc Richmond Virginia United States 23294

    Sponsors and Collaborators

    • Eli Lilly and Company

    Investigators

    • Study Director: Call 1-877-CTLILLY (1-877-285-2559) or 1-317-615-4559 Mon - Fri 9 am - 5 pm Eastern time (UTC/GMT) - 5 hours, EST), Eli Lilly and Company

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    Eli Lilly and Company
    ClinicalTrials.gov Identifier:
    NCT05108922
    Other Study ID Numbers:
    • 18369
    • I5T-MC-AACN
    First Posted:
    Nov 5, 2021
    Last Update Posted:
    Aug 18, 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
    Keywords provided by Eli Lilly and Company
    Mild Cognitive Impairment due to Alzheimer's Disease
    Additional relevant MeSH terms:
    Alzheimer Disease
    Cognitive Dysfunction

    Study Results

    No Results Posted as of Aug 18, 2022