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).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
148
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).
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.
Time frame: 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.
Time frame: 6 Months
Mean Absolute Change From Baseline in Brain Amyloid Plaque on Florbetapir F18 PET Scan (Superiority) on Donanemab Versus Aducanumab
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 frame: Baseline, 6 Months
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Neurology Center of North Orange County
Fullerton, California, United States
Irvine Clinical Research
Irvine, California, United States
California Neuroscience Research Medical Group, Inc.
Sherman Oaks, California, United States
Institute for Neurodegenerative Disorders
New Haven, Connecticut, United States
JEM Research Institute
Atlantis, Florida, United States
Brain Matters Research
Delray Beach, Florida, United States
Neuropsychiatric Research Center of Southwest Florida
Fort Myers, Florida, United States
Infinity Clinical Research, LLC
Hollywood, Florida, United States
Jacksonville Center for Clinical Research
Jacksonville, Florida, United States
Charter Research - Lady Lake
Lady Lake, Florida, United States
...and 21 more locations
Mean Percent Change From Baseline in Brain Amyloid Plaque on Florbetapir F18 PET Scan (Superiority) Donanemab Versus Aducanumab
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 frame: 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
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 frame: Baseline, 6 Months
Mean Absolute Change From Baseline in Brain Amyloid Plaque on Florbetapir F18 PET Scan (Superiority) on Donanemab Versus Aducanumab
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 frame: Baseline, 12 Months
Mean Percent Change From Baseline in Brain Amyloid Plaque on Florbetapir F18 PET Scan (Superiority) Donanemab Versus Aducanumab
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 frame: Baseline, 12 Months
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.
Time frame: 12 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
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.
Time frame: 12 Months
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
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 frame: Baseline, 12 Months
Mean Absolute Change From Baseline in Brain Amyloid Plaque on Florbetapir F18 PET Scan (Superiority) on Donanemab 6 Months Versus Aducanumab 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 frame: Baseline, 6 Months and 12 Months
Mean Absolute Change From Baseline in Brain Amyloid Plaque on Florbetapir F18 PET Scan (Non-inferiority) on Donanemab 6 Months Versus Aducanumab 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 frame: Baseline, 6 Months and 12 Months
Mean Absolute Change From Baseline in Brain Amyloid Plaque on Florbetapir F18 PET Scan (Superiority) on Donanemab Versus Aducanumab
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 frame: Baseline, 18 Months
Time to Reach Complete Amyloid Plaque Clearance on Donanemab Versus Aducanumab
Time to reach complete amyloid plaque clearance at 18 months was evaluated.
Time frame: 18 Months
Mean Percent Change From Baseline in Brain Amyloid Plaque on Florbetapir F18 PET Scan (Superiority) Donanemab Versus Aducanumab
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 frame: Baseline, 18 Months
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.
Time frame: 18 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.
Time frame: 18 Months
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
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 frame: Baseline, 18 Months
Mean Absolute Change From Baseline in Brain Amyloid Plaque on Florbetapir F18 PET Scan (Non-inferiority) on Donanemab 6 Months Versus Aducanumab 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.
Time frame: Baseline, 6 Months and 18 Months