Clinical trial NCT05108922: A Study of Donanemab (LY3002813) Compared With Aducanumab in Participants With Early Symptomatic Alzheimer's Disease (TRAILBLAZER-ALZ 4)
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Mild Cognitive Impairment (MCI)
Alzheimer Disease
Keywords: Alzheimer's Disease with MCI or Mild Dementia
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
First posted: 2021-11-05
Enrollment: 148
Sex: ALL
Minimum age (years): 50
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).


Eligibility 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

Primary outcomes:
measure: Percentage of Participants Who Reach Complete Amyloid Plaque Clearance on Florbetapir F18 Positron Emission Tomography (PET) Scan (Superiority) on Donanemab Versus Aducanumab
timeFrame: 6 Months
measure: 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
timeFrame: 6 Months
Secondary outcomes:
measure: Mean Absolute Change From Baseline in Brain Amyloid Plaque on Florbetapir F18 PET Scan (Superiority) on Donanemab Versus Aducanumab
timeFrame: Baseline, 6 Months
measure: Mean Percent Change From Baseline in Brain Amyloid Plaque on Florbetapir F18 PET Scan (Superiority) Donanemab Versus Aducanumab
timeFrame: Baseline, 6 Months
measure: Change From Baseline in Brain Amyloid Plaque on Florbetapir F18 PET Scan in the Low/Medium (Intermediate) Tau Subpopulation (Superiority) on Donanemab Versus Aducanumab
timeFrame: Baseline, 6 Months
measure: Mean Absolute Change From Baseline in Brain Amyloid Plaque on Florbetapir F18 PET Scan (Superiority) on Donanemab Versus Aducanumab
timeFrame: Baseline, 12 Months
measure: Mean Percent Change From Baseline in Brain Amyloid Plaque on Florbetapir F18 PET Scan (Superiority) Donanemab Versus Aducanumab
timeFrame: Baseline, 12 Months
measure: Percentage of Participants Who Reach Complete Amyloid Plaque Clearance on Florbetapir F18 Positron Emission Tomography (PET) Scan (Superiority) on Donanemab Versus Aducanumab
timeFrame: 12 Months
measure: 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
timeFrame: 12 Months
measure: 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
timeFrame: Baseline, 12 Months
measure: Mean Absolute Change From Baseline in Brain Amyloid Plaque on Florbetapir F18 PET Scan (Superiority) on Donanemab 6 Months Versus Aducanumab 12 Months
timeFrame: Baseline, 6 Months and 12 Months
measure: Mean Absolute Change From Baseline in Brain Amyloid Plaque on Florbetapir F18 PET Scan (Non-inferiority) on Donanemab 6 Months Versus Aducanumab 12 Months
timeFrame: Baseline, 6 Months and 12 Months
measure: Mean Absolute Change From Baseline in Brain Amyloid Plaque on Florbetapir F18 PET Scan (Superiority) on Donanemab Versus Aducanumab
timeFrame: Baseline, 18 Months
measure: Time to Reach Complete Amyloid Plaque Clearance on Donanemab Versus Aducanumab
timeFrame: 18 Months
measure: Mean Percent Change From Baseline in Brain Amyloid Plaque on Florbetapir F18 PET Scan (Superiority) Donanemab Versus Aducanumab
timeFrame: Baseline, 18 Months
measure: Percentage of Participants Who Reach Complete Amyloid Plaque Clearance on Florbetapir F18 Positron Emission Tomography (PET) Scan (Superiority) on Donanemab Versus Aducanumab
timeFrame: 18 Months
measure: 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
timeFrame: 18 Months
measure: 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
timeFrame: Baseline, 18 Months
measure: Mean Absolute Change From Baseline in Brain Amyloid Plaque on Florbetapir F18 PET Scan (Non-inferiority) on Donanemab 6 Months Versus Aducanumab 18 Months
timeFrame: Baseline, 6 Months and 18 Months
Other outcomes:
Locations:
city: Fullerton
country: United States
facility: Neurology Center of North Orange County
state: California
city: Irvine
country: United States
facility: Irvine Clinical Research
state: California
city: Sherman Oaks
country: United States
facility: California Neuroscience Research Medical Group, Inc.
state: California
city: New Haven
country: United States
facility: Institute for Neurodegenerative Disorders
state: Connecticut
city: Atlantis
country: United States
facility: JEM Research Institute
state: Florida
city: Delray Beach
country: United States
facility: Brain Matters Research
state: Florida
city: Fort Myers
country: United States
facility: Neuropsychiatric Research Center of Southwest Florida
state: Florida
city: Hollywood
country: United States
facility: Infinity Clinical Research, LLC
state: Florida
city: Jacksonville
country: United States
facility: Jacksonville Center for Clinical Research
state: Florida
city: Lady Lake
country: United States
facility: Charter Research - Lady Lake
state: Florida
city: Maitland
country: United States
facility: ClinCloud - Maitland
state: Florida
city: Melbourne
country: United States
facility: ClinCloud - Viera
state: Florida
city: Merritt Island
country: United States
facility: Merritt Island Medical Research, LLC
state: Florida
city: Miami
country: United States
facility: Optimus U Corporation
state: Florida
city: Miami
country: United States
facility: Brainstorm Research
state: Florida
city: Stuart
country: United States
facility: Brain Matters Research
state: Florida
city: Tampa
country: United States
facility: Axiom Clinical Research of Florida
state: Florida
city: Winter Park
country: United States
facility: Conquest Research
state: Florida
city: Columbus
country: United States
facility: Columbus Memory Center, PC
state: Georgia
city: Indianapolis
country: United States
facility: Josephson Wallack Munshower Neurology, PC
state: Indiana
city: Plymouth
country: United States
facility: Donald S. Marks M.D., P.C.
state: Massachusetts
city: Watertown
country: United States
facility: Adams Clinical
state: Massachusetts
city: Chesterfield
country: United States
facility: Clinical Research Professionals
state: Missouri
city: Las Vegas
country: United States
facility: Las Vegas Medical Research
state: Nevada
city: Springfield
country: United States
facility: The Cognitive and Research Center of New Jersey
state: New Jersey
city: Toms River
country: United States
facility: Advanced Memory Research Institute of New Jersey
state: New Jersey
city: Dayton
country: United States
facility: Neurology Diagnostics, Inc.
state: Ohio
city: Abington
country: United States
facility: Abington Neurological Associates, Ltd.
state: Pennsylvania
city: Jenkintown
country: United States
facility: The Clinical Trial Center, LLC
state: Pennsylvania
city: Dallas
country: United States
facility: Kerwin Medical Center
state: Texas
city: Richmond
country: United States
facility: National Clinical Research, Inc
state: Virginia
Study officials:
affiliation: Eli Lilly and Company
name: 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)
role: STUDY_DIRECTOR
References: