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

Phase 3

Completed

Conditions: Alzheimer Disease
Mild Cognitive Impairment (MCI)

Interventions: Drug: Donanemab
Drug: Aducanumab

Registration Number: NCT05108922

Lead Sponsor: Eli Lilly and Company

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).

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 148

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Donanemab	Donanemab	Donanemab is administered intravenously (IV) every 4 weeks (Q4W).
Aducanumab	Aducanumab	Aducanumab administered IV per US label.

Primary Outcome Measures

Name	Time	Method
Percentage of Participants Who Reach Complete Amyloid Plaque Clearance on Florbetapir F18 Positron Emission Tomography (PET) Scan (Superiority) on Donanemab Versus Aducanumab	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.
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	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

Name	Time	Method
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	18 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.
Mean Absolute Change From Baseline in Brain Amyloid Plaque on Florbetapir F18 PET Scan (Superiority) on Donanemab Versus Aducanumab	Baseline, 18 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.
Mean Percent Change From Baseline in Brain Amyloid Plaque on Florbetapir F18 PET Scan (Superiority) Donanemab Versus Aducanumab	Baseline, 18 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.
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	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.
Percentage of Participants Who Reach Complete Amyloid Plaque Clearance on Florbetapir F18 Positron Emission Tomography (PET) Scan (Superiority) on Donanemab Versus Aducanumab	18 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.
Mean Absolute 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, 18 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.
Mean Absolute Change From Baseline in Brain Amyloid Plaque on Florbetapir F18 PET Scan (Superiority) on Donanemab 6 Months Versus Aducanumab 12 Months	Baseline, 6 Months and 12 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.
Mean Absolute Change From Baseline in Brain Amyloid Plaque on Florbetapir F18 PET Scan (Non-inferiority) on Donanemab 6 Months Versus Aducanumab 12 Months	Baseline, 6 Months and 12 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.
Time to Reach Complete Amyloid Plaque Clearance on Donanemab Versus Aducanumab	18 Months	Time to reach complete amyloid plaque clearance at 18 months was evaluated.
Mean Absolute Change From Baseline in Brain Amyloid Plaque on Florbetapir F18 PET Scan (Non-inferiority) on Donanemab 6 Months Versus Aducanumab 18 Months	Baseline, 6 Months and 18 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.

Trial Locations

Locations (30): Neurology Center of North Orange County
🇺🇸
Fullerton, California, United States
Josephson Wallack Munshower Neurology, PC
🇺🇸
Indianapolis, Indiana, United States
Conquest Research
🇺🇸
Winter Park, Florida, United States
Kerwin Medical Center
🇺🇸
Dallas, Texas, United States
Clinical Research Professionals
🇺🇸
Chesterfield, Missouri, United States
The Cognitive and Research Center of New Jersey
🇺🇸
Springfield, New Jersey, United States
Neuropsychiatric Research Center of Southwest Florida
🇺🇸
Fort Myers, Florida, United States
Jacksonville Center for Clinical Research
🇺🇸
Jacksonville, Florida, United States
Columbus Memory Center, PC
🇺🇸
Columbus, Georgia, United States
California Neuroscience Research Medical Group, Inc.
🇺🇸
Sherman Oaks, California, United States
Charter Research - Lady Lake
🇺🇸
Lady Lake, Florida, United States
Optimus U Corporation
🇺🇸
Miami, Florida, United States
Las Vegas Medical Research
🇺🇸
Las Vegas, Nevada, United States
JEM Research Institute
🇺🇸
Atlantis, Florida, United States
Donald S. Marks M.D., P.C.
🇺🇸
Plymouth, Massachusetts, United States
The Clinical Trial Center, LLC
🇺🇸
Jenkintown, Pennsylvania, United States
ClinCloud - Maitland
🇺🇸
Maitland, Florida, United States
Merritt Island Medical Research, LLC
🇺🇸
Merritt Island, Florida, United States
Irvine Clinical Research
🇺🇸
Irvine, California, United States
Brain Matters Research
🇺🇸
Stuart, Florida, United States
Infinity Clinical Research, LLC
🇺🇸
Hollywood, Florida, United States
ClinCloud - Viera
🇺🇸
Melbourne, Florida, United States
Brainstorm Research
🇺🇸
Miami, Florida, United States
Neurology Diagnostics, Inc.
🇺🇸
Dayton, Ohio, United States
Adams Clinical
🇺🇸
Watertown, Massachusetts, United States
National Clinical Research, Inc
🇺🇸
Richmond, Virginia, United States
Advanced Memory Research Institute of New Jersey
🇺🇸
Toms River, New Jersey, United States
Abington Neurological Associates, Ltd.
🇺🇸
Abington, Pennsylvania, United States
Institute for Neurodegenerative Disorders
🇺🇸
New Haven, Connecticut, United States
Axiom Clinical Research of Florida
🇺🇸
Tampa, Florida, United States