A Study of Donanemab (LY3002813) Compared With Aducanumab in Participants With Early Symptomatic Alzheimer's Disease (TRAILBLAZER-ALZ 4)
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
2 other identifiers
interventional
148
1 country
31
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).
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_3
Started Nov 2021
31 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
October 26, 2021
CompletedFirst Posted
Study publicly available on registry
November 5, 2021
CompletedStudy Start
First participant enrolled
November 16, 2021
CompletedPrimary Completion
Last participant's last visit for primary outcome
September 9, 2022
CompletedStudy Completion
Last participant's last visit for all outcomes
September 19, 2023
CompletedResults Posted
Study results publicly available
November 2, 2023
CompletedNovember 29, 2024
November 1, 2024
10 months
October 26, 2021
September 7, 2023
November 4, 2024
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
Percentage of Participants Who Reach Complete Amyloid Plaque Clearance on Florbetapir F18 Positron Emission Tomography (PET) Scan (Superiority) on Donanemab Versus Aducanumab
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.
6 Months
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
Complete brain amyloid plaque clearance is a binary outcome and is defined as a Centiloid value \<24.1 from the florbetapir F18 PET scan.
6 Months
Secondary Outcomes (17)
Mean Absolute Change From Baseline in Brain Amyloid Plaque on Florbetapir F18 PET Scan (Superiority) on Donanemab Versus Aducanumab
Baseline, 6 Months
Mean Percent Change From Baseline in Brain Amyloid Plaque on Florbetapir F18 PET Scan (Superiority) Donanemab Versus Aducanumab
Baseline, 6 Months
Change From Baseline in Brain Amyloid Plaque on Florbetapir F18 PET Scan in the Low/Medium (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 (Superiority) on Donanemab Versus Aducanumab
Baseline, 12 Months
Mean Percent Change From Baseline in Brain Amyloid Plaque on Florbetapir F18 PET Scan (Superiority) Donanemab Versus Aducanumab
Baseline, 12 Months
- +12 more secondary outcomes
Study Arms (2)
Donanemab
EXPERIMENTALDonanemab is administered intravenously (IV) every 4 weeks (Q4W).
Aducanumab
ACTIVE COMPARATORAducanumab administered IV per US label.
Interventions
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.
Participants received aducanumab administered by IV infusion per US label (prescribing information/routine clinical practice).
Eligibility Criteria
You may qualify if:
- 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
You may not qualify if:
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (31)
Neurology Center of North Orange County
Fullerton, California, 92835, United States
Irvine Clinical Research
Irvine, California, 92614, United States
California Neuroscience Research Medical Group, Inc.
Sherman Oaks, California, 91403, United States
Institute for Neurodegenerative Disorders
New Haven, Connecticut, 06510, United States
JEM Research Institute
Atlantis, Florida, 33462, United States
Brain Matters Research
Delray Beach, Florida, 33445, United States
Neuropsychiatric Research Center of Southwest Florida
Fort Myers, Florida, 33912, United States
Infinity Clinical Research, LLC
Hollywood, Florida, 33024, United States
Jacksonville Center for Clinical Research
Jacksonville, Florida, 32216, United States
Charter Research - Lady Lake
Lady Lake, Florida, 32159, United States
ClinCloud - Maitland
Maitland, Florida, 32751, United States
ClinCloud - Viera
Melbourne, Florida, 32940, United States
Merritt Island Medical Research, LLC
Merritt Island, Florida, 32952, United States
Optimus U Corporation
Miami, Florida, 33125, United States
Brainstorm Research
Miami, Florida, 33176, United States
Brain Matters Research
Stuart, Florida, 34997, United States
Axiom Clinical Research of Florida
Tampa, Florida, 33609, United States
Conquest Research
Winter Park, Florida, 32789, United States
Columbus Memory Center, PC
Columbus, Georgia, 31909, United States
Josephson Wallack Munshower Neurology, PC
Indianapolis, Indiana, 46256, United States
Donald S. Marks M.D., P.C.
Plymouth, Massachusetts, 02360, United States
Adams Clinical
Watertown, Massachusetts, 02472, United States
Clinical Research Professionals
Chesterfield, Missouri, 63005, United States
Las Vegas Medical Research
Las Vegas, Nevada, 89113, United States
The Cognitive and Research Center of New Jersey
Springfield, New Jersey, 07081, United States
Advanced Memory Research Institute of New Jersey
Toms River, New Jersey, 08755, United States
Neurology Diagnostics, Inc.
Dayton, Ohio, 45459, United States
Abington Neurological Associates, Ltd.
Abington, Pennsylvania, 19001, United States
The Clinical Trial Center, LLC
Jenkintown, Pennsylvania, 19046, United States
Kerwin Medical Center
Dallas, Texas, 75231, United States
National Clinical Research, Inc
Richmond, Virginia, 23294, United States
Related Publications (1)
Salloway S, Pain A, Lee E, Papka M, Ferguson MB, Wang H, Hu H, Lu M, Oru E, Ardayfio PA, Hoban DB, Collins EC, Brooks DA, Sims JR. TRAILBLAZER-ALZ 4: A phase 3 trial comparing donanemab with aducanumab on amyloid plaque clearance in early, symptomatic Alzheimer's disease. Alzheimers Dement. 2025 May;21(5):e70293. doi: 10.1002/alz.70293.
PMID: 40390253DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Results Point of Contact
- Title
- Chief Medical Officer
- Organization
- Eli Lilly and Company
Study Officials
- 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
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- GT60
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
October 26, 2021
First Posted
November 5, 2021
Study Start
November 16, 2021
Primary Completion
September 9, 2022
Study Completion
September 19, 2023
Last Updated
November 29, 2024
Results First Posted
November 2, 2023
Record last verified: 2024-11
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP, 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.
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.