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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05108922
Recruitment Status : Completed
First Posted : November 5, 2021
Results First Posted : November 2, 2023
Last Update Posted : November 2, 2023
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company

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

Condition or disease Intervention/treatment Phase
Mild Cognitive Impairment (MCI) Alzheimer Disease Drug: Donanemab Drug: Aducanumab Phase 3

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 148 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 : November 16, 2021
Actual Primary Completion Date : September 9, 2022
Actual Study Completion Date : September 19, 2023

Resource links provided by the National Library of Medicine

Drug Information available for: Aducanumab

Arms and Interventions
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Arm Intervention/treatment
Experimental: Donanemab
Donanemab is administered intravenously (IV) every 4 weeks (Q4W).
 Drug: Donanemab
Participants received 700 milligram (mg) donanemab administered by intravenous (IV) infusion every 4 weeks (Q4W) for first three doses and then 1400 mg IV Q4W.
Other Name: LY3002813
Active Comparator: Aducanumab
Aducanumab administered IV per US label.
 Drug: Aducanumab
Participants received aducanumab administered by IV infusion per US label (prescribing information/routine clinical practice).


Outcome Measures
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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 [ Time Frame: 6 Months ]
    Amyloid deposition in the brain is one of the defining neuropathologic findings of Alzheimer's disease (AD). Amyloid PET scan assesses cerebral amyloid load using florbetapir tracer which is standardized into centiloids for evaluation of AD. Florbetapir exhibits high affinity specific binding to amyloid plaques. Centiloid values on centiloid scale is based on mean composite Standardized Uptake Value Ratio (SUVR) in cingulate, frontal, parietal and temporal cortexes using whole cerebellum as reference region. SUVR is ratio of tracer uptake in each of cingulate, frontal, parietal and temporal cortexes relative to cerebellum. Complete brain amyloid plaque clearance is a binary outcome and is defined as a centiloid value <24.1 from the florbetapir F18 PET scan.

  2. Percentage of Participants Who Reach Complete Amyloid Plaque Clearance on Florbetapir F18 PET Scan in the Low/Medium (Intermediate) Subpopulation (Superiority) on Donanemab Versus Aducanumab [ Time Frame: 6 Months ]
    Complete brain amyloid plaque clearance is a binary outcome and is defined as a centiloid value <24.1 from the florbetapir F18 PET scan.


Secondary Outcome Measures :
  1. Mean Absolute Change From Baseline in Brain Amyloid Plaque on Florbetapir F18 PET Scan (Superiority) on Donanemab Versus Aducanumab [ Time Frame: Baseline, 6 Months ]
    Florbetapir PET imaging was used as a quantitative amyloid biomarker. Quantitative amyloid burden was first formalized as the average Standardized Uptake Value Ratio (SUVR) in six predetermined cortical areas of the brain relative to the cerebellum as a reference region. Larger SUVR reflects the larger cortical amyloid burden relative to cerebellum. SUVR values were further calibrated to a centiloid (CL) scale. The Centiloid scale anchor points are 0 and 100, where 0 represents a high-certainty amyloid negative scan and 100 represents the amount of global amyloid deposition found in a typical AD scan. A negative change indicates an improvement from baseline.

  2. Mean Percent Change From Baseline in Brain Amyloid Plaque on Florbetapir F18 PET Scan (Superiority) Donanemab Versus Aducanumab [ Time Frame: Baseline, 6 Months ]
    Florbetapir PET imaging was used as a quantitative amyloid biomarker. Quantitative amyloid burden was first formalized as the average Standardized Uptake Value Ratio (SUVR) in six predetermined cortical areas of the brain relative to the cerebellum as a reference region. Larger SUVR reflects the larger cortical amyloid burden relative to cerebellum. SUVR values were further calibrated to a centiloid (CL) scale. The Centiloid scale anchor points are 0 and 100, where 0 represents a high-certainty amyloid negative scan and 100 represents the amount of global amyloid deposition found in a typical AD scan. A negative change indicates an improvement from baseline.

  3. Change From Baseline in Brain Amyloid Plaque on Florbetapir F18 PET Scan in the Low/Medium (Intermediate) Tau Subpopulation (Superiority) on Donanemab Versus Aducanumab [ Time Frame: Baseline, 6 Months ]
    Florbetapir PET imaging was used as a quantitative amyloid biomarker. Quantitative amyloid burden was first formalized as the average Standardized Uptake Value Ratio (SUVR) in six predetermined cortical areas of the brain relative to the cerebellum as a reference region. Larger SUVR reflects the larger cortical amyloid burden relative to cerebellum. SUVR values were further calibrated to a centiloid (CL) scale. The Centiloid scale anchor points are 0 and 100, where 0 represents a high-certainty amyloid negative scan and 100 represents the amount of global amyloid deposition found in a typical AD scan. A negative change indicates an improvement from baseline.


Eligibility Criteria
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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 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
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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): NCT05108922


Locations
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Sponsors and Collaborators
Eli Lilly and Company
Investigators
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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)

Documents provided by Eli Lilly and Company:
Study Protocol  [PDF] May 17, 2022
Statistical Analysis Plan  [PDF] September 24, 2021

More Information
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Additional Information:

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Responsible Party: Eli Lilly and Company
ClinicalTrials.gov Identifier: NCT05108922    
Other Study ID Numbers: 18369
I5T-MC-AACN ( Other Identifier: Eli Lilly and Company )
First Posted: November 5, 2021    Key Record Dates
Results First Posted: November 2, 2023
Last Update Posted: November 2, 2023
Last Verified: October 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Anonymized individual patient level data will be provided in a secure access environment upon approval of a research proposal and a signed data sharing agreement.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Clinical Study Report (CSR)
Time Frame: Data are available 6 months after the primary publication and approval of the indication studied in the US and European Union (EU), whichever is later. Data will be indefinitely available for requesting.
Access Criteria: A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.
URL: http://vivli.org/

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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:
Alzheimer's Disease with MCI or Mild Dementia
Additional relevant MeSH terms:
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Alzheimer Disease
Cognitive Dysfunction
Dementia
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
 Tauopathies
Neurodegenerative Diseases
Neurocognitive Disorders
Mental Disorders
Cognition Disorders