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Active not recruitingPhase 3

A Donanemab (LY3002813) Study in Participants With Preclinical Alzheimer's Disease (TRAILBLAZER-ALZ 3)

A Study of Donanemab Versus Placebo in Participants at Risk for Cognitive and Functional Decline of Alzheimer's Disease

Lead sponsor

Eli Lilly and Company

Asset

Donanemab

Listed sites

216

Recruiting sites

Enrollment

2,996

estimated

Study population

Alzheimer’s disease

Key I/E criteria

•Amyloid biomarker required•Tau biomarker required•Study partner/caregiver required•MRI contraindications excluded•Brain MRI excludes superficial siderosis

Primary endpoint

•Clinical Progression of Composite Endpoint

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 ID18284

Secondary IDI5T-MC-AACMEli Lilly and Company

NCT IDNCT05026866

Timeline

Milestones

Study start2021-08-27actual

Study first posted2021-08-30actual

Last update posted2026-01-21actual

Primary completion2027-11estimated (month precision)

Study completion2027-11estimated (month precision)

Assets

Drug assets

Donanemab

Study populations

Who this study enrolls

Alzheimer’s disease

Eligibility

Who can enroll

Minimum age55 Years

Maximum age80 Years

SexAll

Healthy volunteersNot accepted

Inclusion criteria

•A Telephone Interview for Cognitive Status - modified (TICS-M) score reflective of intact cognitive functioning.

•Has a phosphorylated tau (P-tau) result consistent with the presence of amyloid pathology.

•Has a reliable study partner and backup study partner familiar with overall function and behavior, such as day-to-day activities and cognitive abilities.

•Have adequate literacy, vision, and hearing for neuropsychological testing at screening.

•Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies

•Female participants include those who are infertile due to surgical sterilization (hysterectomy, bilateral oophorectomy, or tubal ligation), congenital anomaly such as Mullerian agenesis; or post menopausal (women 55 or older not on hormone therapy and had at least 12 months of spontaneous amenorrhea; or with a diagnosis of menopause prior to starting hormone replacement therapy.

Treatment Extension: (Study Period II Placebo Group Only)

•Are actively participating in Study AACM at the conclusion of Study Period III

Exclusion criteria

•Mild cognitive impairment or dementia, or significant other neurodegenerative disease that can affect cognition.

•Current serious or unstable illnesses including cardiovascular, hepatic, renal, gastroenterologic, respiratory, endocrinologic, neurologic, psychiatric, immunologic, or hematologic disease that could interfere with the analysis of the study or a life expectancy of approximately ≤5 years.

•History of cancer with high risk of recurrence and preventing completion of the trial.

•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).

•Have any clinically important abnormality at screening on magnetic resonance imaging (MRI) or clinical laboratory test results that could be detrimental to the participant or study integrity.

•Have any contraindications for MRI, including claustrophobia or the presence of contraindicated metal (ferromagnetic) implants/cardiac pacemaker.

•Have a centrally read MRI demonstrating presence of amyloid-related imaging abnormalities (ARIA-E), >4 cerebral microhemorrhages, more than 1 area of superficial siderosis, any macrohemorrhage or severe white matter disease at screening.

•Have had prior treatment with a passive anti-amyloid immunotherapy <5 half-lives prior to randomization.

•Have received active immunization against amyloid beta (Aβ) in any other study.

•Have received active immunization against Aβ in any other study.

•Current or previous use of prescription medications used as treatment for mild cognitive impairment (MCI) or AD.

Addendum 7 Exclusion Criteria:

•Same as the main study except contraindications for florbetapir F 18 PET are exclusionary.

Endpoints (18)

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.

Coverage by outcome category

Global cognition

Disease progression

Other (unclassified)

Memory

Safety / tolerability / PK

Global cognition

6 endpoints

Primary/protocol endpoint

Time to Clinical Progression of Composite Endpoint as Measured by Clinical Dementia Rating (CDR) in the Primary Study Population (Baseline CDR-Global Score [GS 0])

Time frame:Estimated up to Week 332

time to event, event

Secondary/protocol endpoint

Change from Baseline in Cognitive Composite in the Primary Study Population (Baseline CDR-GS 0)

Time frame:Baseline, Up to Week 332

change from baseline, improvement

Secondary/protocol endpoint

Change from Baseline in CDR-Sum of Boxes (CDR-SB) n the Primary Study Population (Baseline CDR-GS 0)

Time frame:Baseline, Up Week 332

Clinical Dementia Rating-Sum of Boxes (CDR-SB)

change from baseline, improvement

Secondary/protocol endpoint

Change from Baseline in Cognitive Function Index (CFI) in the Primary Study Population (Baseline CDR-GS 0)

Time frame:Baseline, Up to Week 332

change from baseline, improvement

Secondary/protocol endpoint

Change from Baseline in Montreal Cognitive Assessment (MoCA) Score in the Primary Study Population (Baseline CDR-GS 0)

Time frame:Baseline, Up to Week 332

Montreal Cognitive Assessment (MoCA)

change from baseline, improvement

Secondary/protocol endpoint

Time to Clinical Progression as Measured by At Least 0.5 Change on CDR-SB in Primary Study Population (Baseline CDR-GS 0)

Time frame:Estimated up to Week 332

Clinical Dementia Rating-Sum of Boxes (CDR-SB)

time to event, event

Memory

2 endpoints

Secondary/protocol endpoint

Change from Baseline in Continuous Paired Associate Learning (CPAL ) in the Primary Study Population (Baseline CDR-GS 0)

Time frame:Baseline, Up to Week 332

change from baseline, improvement

Secondary/protocol endpoint

Time to Clinical Progression as Measured by CDR Memory Box in Primary Study Population (Baseline CDR-GS 0)

Time frame:Estimated up to Week 332

time to event, event

Disease progression

6 endpoints

Secondary/protocol endpoint

Change from Baseline in International Shopping List Test (ISLT) in the Primary Study Population (Baseline CDR-GS 0)

Time frame:Baseline, Up to Week 332

change from baseline, improvement

Secondary/protocol endpoint

Change from Baseline in International Daily Symbol Substitution Test-Medicines (iDSSTm) in the Primary Study Population (Baseline CDR-GS 0)

Time frame:Baseline, Up to Week 332

change from baseline, improvement

Secondary/protocol endpoint

Change from Baseline in Category Fluency in the Primary Study Population (Baseline CDR-GS 0)

Time frame:Baseline, Up to Week 332

change from baseline, improvement

Secondary/protocol endpoint

Time to Clinical Progression of Composite Endpoint as Measured by CDR in the Overall Study Population (Baseline CDR-GS 0 or 0.5)

Time frame:Baseline, Up to Week 332

time to event, event

Secondary/protocol endpoint

Time to Clinical Progression as Measured by CDR Judgment and Problem Solving Box in the Primary Study Population (Baseline CDR-GS 0)

Time frame:Estimated up to Week 332

time to event, event

Secondary/protocol endpoint

Time to Clinical Progression of Composite Endpoint as Measured by CDR in Subpopulation Positive Based on Secondary Diagnostic Test

Time frame:Estimated up to Week 332

time to event, event

Safety / tolerability / PK

1 endpoint

Secondary/protocol endpoint

Pharmacokinetics (PK): Average Serum Donanemab Concentration at Steady State

Time frame:Baseline through Week 76

concentration, descriptive

Other (unclassified)

3 endpoints

Secondary/protocol endpoint/low confidence

Change from Baseline in Mild Behavioral Impairment Checklist (MBI-C) in the Primary Study Population (Baseline CDR-GS 0)

Time frame:Baseline, Up to Week 332

change from baseline, improvement

Secondary/protocol endpoint/low confidence

Change from Baseline in Plasma P-tau217

Time frame:Baseline, Up to Week 332

Phosphorylated tau 217 (p-tau217)

change from baseline, improvement

Secondary/protocol endpoint/low confidence

Percentage of Participants with Treatment-emergent Anti-Drug Antibody (ADAs)

Time frame:Baseline through Week 16

threshold achievement, improvement

Publications (1)

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

Yaari R, Holdridge KC, Williamson M, Wessels AM, Shcherbinin S, Kotari V, Reiman EM, Tariot PN, Alexander R, Langbaum JB, Sims JR. Donanemab in preclinical Alzheimer's disease: Screening and baseline data from TRAILBLAZER-ALZ 3. Alzheimers Dement. 2025 Sep;21(9):e70662. doi: 10.1002/alz.70662.
PMID40955720via DERIVED

Provenance

Sources

Trial identity, design, statusClinicalTrials.gov API v2

Snapshot dateJuly 21, 2026

Endpoint classificationDelfa ADRD endpoint taxonomy

Results tableno registry results posted yet

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.