CompletedPhase 3Results posted

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

Lead sponsor

Eli Lilly and Company

Assets

Aducanumab / Donanemab

Listed sites

Recruiting sites

Enrollment

148

actual

Study population

Alzheimer’s disease, MCI / preclinical Alzheimer’s

Key I/E criteria

•MMSE 20-30•Study partner/caregiver required

Primary endpoint

•Amyloid PET Centiloid

Footprint

Where this trial recruits

Site locations as reported to ClinicalTrials.gov. Site count is not enrollment count; per-site enrollment is not available from source.

Identifiers

Registered as

Org study ID18369

Secondary IDI5T-MC-AACNEli Lilly and Company

NCT IDNCT05108922

Timeline

Milestones

Study first posted2021-11-05actual

Study start2021-11-16actual

Primary completion2022-09-09actual

Study completion2023-09-19actual

Results first posted2023-11-02actual

Last update posted2024-11-29actual

Assets

Drug assets

Aducanumab Donanemab

Study populations

Who this study enrolls

Alzheimer’s diseaseMCI / preclinical Alzheimer’s

Eligibility

Who can enroll

Minimum age50 Years

Maximum age85 Years

SexAll

Healthy volunteersNot accepted

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

Endpoints (38)

What's being measured

Protocol endpoints and posted registry outcome measures, grouped into outcome categories. Composite endpoints show their component event types. Standard codes (LOINC, SNOMED CT) are shown where available.

Amyloid biomarkers

38 endpoints

Primary/protocol endpoint

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

Time frame:6 Months

Amyloid PET Centiloid

threshold achievement, improvement

Primary/protocol endpoint

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

Time frame:6 Months

Amyloid PET Centiloid

threshold achievement, improvement

Primary/registry result

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

Time frame:6 Months

Amyloid PET Centiloid

threshold achievement, improvement

Posted result

Group	Value (number), Percentage of participants	Reported bounds
Aducanumabn=64 Participants	1.6	-0.0 - 4.6
Donanemabn=66 Participants	37.9	-26.2 - 49.6

Odds Ratio (OR)29.2695% CI5.30 - 100.0p<0.001Regression, Logistic

Analysis was based on logistic regression model with treatment, Apolipoprotein (ApoE) ε4 Carrier Status, baseline amyloid Level, baseline age as factors.

Primary/registry result

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

Time frame:6 Months

Amyloid PET Centiloid

threshold achievement, improvement

Posted result

Group	Value (number), Percentage of participants	Reported bounds
Aducanumabn=26 Participants	3.8	-0.0 - 11.2
Donanemabn=26 Participants	38.5	-19.8 - 57.2

Odds Ratio (OR)15.1895% CI2.04 - 100.0p0.008Regression, Logistic

Analysis was based on logistic regression model with treatment, ApoE ε4 Carrier Status, baseline amyloid Level, baseline age as factors.

Secondary/protocol endpoint

Mean Absolute Change From Baseline in Brain Amyloid Plaque on Florbetapir F18 PET Scan (Superiority) on Donanemab Versus Aducanumab

Time frame:Baseline, 6 Months

Amyloid PET Centiloid

change from baseline, improvement

Secondary/protocol endpoint

Mean Percent Change From Baseline in Brain Amyloid Plaque on Florbetapir F18 PET Scan (Superiority) Donanemab Versus Aducanumab

Time frame:Baseline, 6 Months

Amyloid PET Centiloid

percent change from baseline, improvement

Secondary/protocol endpoint

Change From Baseline in Brain Amyloid Plaque on Florbetapir F18 PET Scan in the Low/Medium (Intermediate) Tau Subpopulation (Superiority) on Donanemab Versus Aducanumab

Time frame:Baseline, 6 Months

Amyloid PET Centiloid

change from baseline, improvement

Secondary/protocol endpoint

Mean Absolute Change From Baseline in Brain Amyloid Plaque on Florbetapir F18 PET Scan (Superiority) on Donanemab Versus Aducanumab

Time frame:Baseline, 12 Months

Amyloid PET Centiloid

change from baseline, improvement

Secondary/protocol endpoint

Mean Percent Change From Baseline in Brain Amyloid Plaque on Florbetapir F18 PET Scan (Superiority) Donanemab Versus Aducanumab

Time frame:Baseline, 12 Months

Amyloid PET Centiloid

percent change from baseline, improvement

Secondary/protocol endpoint

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

Time frame:12 Months

Amyloid PET Centiloid

threshold achievement, improvement

Secondary/protocol endpoint

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

Time frame:12 Months

Amyloid PET Centiloid

threshold achievement, improvement

Secondary/protocol endpoint

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

Time frame:Baseline, 12 Months

Amyloid PET Centiloid

change from baseline, improvement

Secondary/protocol endpoint

Mean Absolute Change From Baseline in Brain Amyloid Plaque on Florbetapir F18 PET Scan (Superiority) on Donanemab 6 Months Versus Aducanumab 12 Months

Time frame:Baseline, 6 Months and 12 Months

Amyloid PET Centiloid

change from baseline, improvement

Secondary/protocol endpoint

Mean Absolute Change From Baseline in Brain Amyloid Plaque on Florbetapir F18 PET Scan (Non-inferiority) on Donanemab 6 Months Versus Aducanumab 12 Months

Time frame:Baseline, 6 Months and 12 Months

Amyloid PET Centiloid

change from baseline, improvement

Secondary/protocol endpoint

Mean Absolute Change From Baseline in Brain Amyloid Plaque on Florbetapir F18 PET Scan (Superiority) on Donanemab Versus Aducanumab

Time frame:Baseline, 18 Months

Amyloid PET Centiloid

change from baseline, improvement

Secondary/protocol endpoint

Time to Reach Complete Amyloid Plaque Clearance on Donanemab Versus Aducanumab

Time frame:18 Months

time to event, event

Secondary/protocol endpoint

Mean Percent Change From Baseline in Brain Amyloid Plaque on Florbetapir F18 PET Scan (Superiority) Donanemab Versus Aducanumab

Time frame:Baseline, 18 Months

Amyloid PET Centiloid

percent change from baseline, improvement

Secondary/protocol endpoint

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

Time frame:18 Months

Amyloid PET Centiloid

threshold achievement, improvement

Secondary/protocol endpoint

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

Time frame:18 Months

Amyloid PET Centiloid

threshold achievement, improvement

Secondary/protocol endpoint

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

Time frame:Baseline, 18 Months

Amyloid PET Centiloid

change from baseline, improvement

Secondary/protocol endpoint

Mean Absolute Change From Baseline in Brain Amyloid Plaque on Florbetapir F18 PET Scan (Non-inferiority) on Donanemab 6 Months Versus Aducanumab 18 Months

Time frame:Baseline, 6 Months and 18 Months

Amyloid PET Centiloid

change from baseline, improvement

Secondary/registry result

Mean Absolute Change From Baseline in Brain Amyloid Plaque on Florbetapir F18 PET Scan (Superiority) on Donanemab Versus Aducanumab

Time frame:Baseline, 6 Months

Amyloid PET Centiloid

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), Centiloids	Standard error
Aducanumabn=64 Participants	-16.413	3.7685
Donanemabn=66 Participants	-62.104	3.6898

LS Mean difference (Final Values)-45.69195% CI-54.84 - -36.54p<0.001ANCOVA

Secondary/registry result

Mean Percent Change From Baseline in Brain Amyloid Plaque on Florbetapir F18 PET Scan (Superiority) Donanemab Versus Aducanumab

Time frame:Baseline, 6 Months

Amyloid PET Centiloid

percent change from baseline, improvement

Posted result

Group	Value (least_squares_mean), Percent change	Standard error
Aducanumabn=64 Participants	-16.956	4.0253
Donanemabn=66 Participants	-65.169	3.9412

LS Mean difference (Final Values)-48.21395% CI-57.99 - -38.44p<0.001ANCOVA

Secondary/registry result

Change From Baseline in Brain Amyloid Plaque on Florbetapir F18 PET Scan in the Low/Medium (Intermediate) Tau Subpopulation (Superiority) on Donanemab Versus Aducanumab

Time frame:Baseline, 6 Months

Amyloid PET Centiloid

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), Centiloids	Standard error
Aducanumabn=26 Participants	-23.824	7.7028
Donanemabn=26 Participants	-64.076	7.3359

LS Mean difference (Final Values)-40.25295% CI-61.87 - -18.64p<0.001ANCOVA

Secondary/registry result

Mean Absolute Change From Baseline in Brain Amyloid Plaque on Florbetapir F18 PET Scan (Superiority) on Donanemab Versus Aducanumab

Time frame:Baseline, 12 Months

Amyloid PET Centiloid

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), Centiloids	Standard error
Aducanumabn=65 Participants	-56.06	2.977
Donanemabn=67 Participants	-80.03	2.973

LS Mean difference (Final Values)-23.9795% CI-32.35 - -15.60p<0.001Mixed Models Analysis

Secondary/registry result

Mean Percent Change From Baseline in Brain Amyloid Plaque on Florbetapir F18 PET Scan (Superiority) Donanemab Versus Aducanumab

Time frame:Baseline, 12 Months

Amyloid PET Centiloid

percent change from baseline, improvement

Posted result

Group	Value (least_squares_mean), Percent change	Standard error
Aducanumabn=65 Participants	-56.97	3.081
Donanemabn=67 Participants	-82.79	3.077

LS Mean difference (Final Values)-25.8295% CI-34.49 - -17.15p<0.001Mixed Models Analysis

Secondary/registry result

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

Time frame:12 Months

Amyloid PET Centiloid

threshold achievement, improvement

Posted result

Group	Value (number), Percentage of participants	Reported bounds
Aducanumabn=65 Participants	24.59	-
Donanemabn=67 Participants	70.00	-

Odds Ratio (OR)8.3895% CI3.37 - 20.81p<0.001Regression, Logistic

Secondary/registry result

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

Time frame:12 Months

Amyloid PET Centiloid

threshold achievement, improvement

Posted result

Group	Value (number), percentage of participants	Reported bounds
Aducanumabn=27 Participants	18.52	-
Donanemabn=26 Participants	76.00	-

Odds Ratio (OR)37.7395% CI5.71 - 99.99p<.001Regression, Logistic

Secondary/registry result

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

Time frame:Baseline, 12 Months

Amyloid PET Centiloid

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), Centiloids	Standard error
Aducanumabn=27 Participants	-57.77	4.419
Donanemabn=26 Participants	-84.53	4.565

LS Mean difference (Final Values)-26.7595% CI-39.78 - -13.73p<0.001Mixed Models Analysis

Secondary/registry result

Mean Absolute Change From Baseline in Brain Amyloid Plaque on Florbetapir F18 PET Scan (Superiority) on Donanemab 6 Months Versus Aducanumab 12 Months

Time frame:Baseline, 6 Months and 12 Months

Amyloid PET Centiloid

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), Centiloids	Standard error
Aducanumabn=65 Participants	-56.056	2.9768
Donanemabn=67 Participants	-63.987	2.8142

LS Mean difference (Final Values)-7.93195% CI-16.060 - 0.199p0.0558Mixed Models Analysis

Secondary/registry result

Mean Absolute Change From Baseline in Brain Amyloid Plaque on Florbetapir F18 PET Scan (Non-inferiority) on Donanemab 6 Months Versus Aducanumab 12 Months

Time frame:Baseline, 6 Months and 12 Months

Amyloid PET Centiloid

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), Centiloids	Standard error
Aducanumabn=65 Participants	-56.056	2.9768
Donanemabn=67 Participants	-63.987	2.8142

LS Mean difference (Final Values)-7.93195% CI-16.060 - 0.199Mixed Models Analysis

Secondary/registry result

Mean Absolute Change From Baseline in Brain Amyloid Plaque on Florbetapir F18 PET Scan (Superiority) on Donanemab Versus Aducanumab

Time frame:Baseline, 18 Months

Amyloid PET Centiloid

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), Centiloids	Standard error
Aducanumabn=65 Participants	-72.18	2.883
Donanemabn=67 Participants	-84.22	2.905

LS Mean difference (Final Values)-12.0495% CI-20.19 - -3.88p0.004Mixed Models Analysis

Secondary/registry result

Time to Reach Complete Amyloid Plaque Clearance on Donanemab Versus Aducanumab

Time frame:18 Months

time to event, event

Posted result

Group	Value (median), days	Reported bounds
Aducanumabn=65 Participants	568.00	-542.00 - NA
Donanemabn=67 Participants	359.00	-343.00 - 377.00

p<0.001Log Rank

Secondary/registry result

Mean Percent Change From Baseline in Brain Amyloid Plaque on Florbetapir F18 PET Scan (Superiority) Donanemab Versus Aducanumab

Time frame:Baseline, 18 Months

Amyloid PET Centiloid

percent change from baseline, improvement

Posted result

Group	Value (least_squares_mean), percent change	Standard error
Aducanumabn=65 Participants	-72.84	3.011
Donanemabn=67 Participants	-86.29	3.030

LS Mean difference (Final Values)-13.4595% CI-21.96 - -4.93p0.002Mixed Models Analysis

Secondary/registry result

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

Time frame:18 Months

Amyloid PET Centiloid

threshold achievement, improvement

Posted result

Group	Value (number), percentage of participants	Reported bounds
Aducanumabn=65 Participants	43.10	-
Donanemabn=67 Participants	76.79	-

Odds Ratio (OR)4.6895% CI1.93 - 11.34p<0.001Regression, Logistic

Secondary/registry result

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

Time frame:18 Months

Amyloid PET Centiloid

threshold achievement, improvement

Posted result

Group	Value (number), percentage of participants	Reported bounds
Aducanumabn=27 Participants	43.48	-
Donanemabn=26 Participants	72.00	-

Odds Ratio (OR)6.3495% CI1.32 - 30.54p0.022Regression, Logistic

Secondary/registry result

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

Time frame:Baseline, 18 Months

Amyloid PET Centiloid

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), Centiloids	Standard error
Aducanumabn=27 Participants	-72.24	4.374
Donanemabn=26 Participants	-86.57	4.408

LS Mean difference (Final Values)-14.3395% CI-27.07 - -1.59p0.028Mixed Models Analysis

Secondary/registry result

Mean Absolute Change From Baseline in Brain Amyloid Plaque on Florbetapir F18 PET Scan (Non-inferiority) on Donanemab 6 Months Versus Aducanumab 18 Months

Time frame:Baseline, 6 Months and 18 Months

Amyloid PET Centiloid

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), Centiloids	Standard error
Aducanumabn=65 Participants	-72.178	2.8834
Donanemabn=67 Participants	-64.347	2.8645

LS Mean difference (Final Values)7.83195% CI-0.226 - 15.889Mixed Models Analysis

Publications (2)

Bibliography

Records linked to this trial through ClinicalTrials.gov references, PubMed NCT search, and curated study seeds. 'Canonical' marks design/result papers; others are registry references or candidates.

Registry references + supporting bibliography

Provenance

Sources

Trial identity, design, statusClinicalTrials.gov API v2

Snapshot dateJuly 21, 2026

Endpoint classificationDelfa ADRD endpoint taxonomy

Results tableClinicalTrials.gov results section

Trial facts come from public ClinicalTrials.gov records. Endpoint categories are Delfa's classification of those records, not a ClinicalTrials.gov field. All figures reflect the July 21, 2026 snapshot.