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

Alzheimer Disease Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05108922
• Other study ID #: 18369
• Secondary ID: I5T-MC-AACN
• Status: Completed
• Phase: Phase 3
• Start date: November 16, 2021
• Est. completion date: September 19, 2023

Study information

• Verified date: October 2023
• Source: Eli Lilly and Company
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 148
• Est. completion date: September 19, 2023
• Est. primary completion date: September 9, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 50 Years to 85 Years

Eligibility

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

Related Conditions & MeSH terms

• Alzheimer Disease
• Cognitive Dysfunction
• Mild Cognitive Impairment (MCI)

Intervention

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.
• Aducanumab
Participants received aducanumab administered by IV infusion per US label (prescribing information/routine clinical practice).

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Eli Lilly and Company

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	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.	Baseline, 6 Months
Secondary	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.	Baseline, 6 Months
Secondary	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.	Baseline, 6 Months

External Links

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