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Alzheimer's DiseasePhase 3NCT05738486

A Study of Different Donanemab (LY3002813) Dosing Regimens in Adults With Early Alzheimer's Disease (TRAILBLAZER-ALZ 6)

A Phase 3 study testing Donanemab and Dexamethasone in people with Alzheimer's Disease and Dementia, run by Eli Lilly and Company at 49 sites in 2 countries.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial summary

This study will investigate different donanemab dosing regimens and their effect on the frequency and severity of ARIA-E in adults with early symptomatic Alzheimer's disease (AD) and explore participant characteristics that might predict risk of ARIA. Read more about this study

Who is it for?
Ages 60 to 85 years
Conditions the study is for
Alzheimer's Disease, Dementia, Brain Diseases
What is being tested?
Donanemab and Dexamethasone
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
1,175 participants
Where
49 sitesin 2 countries
Study dates
28 Feb 2023to May 2027
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 60 to 85 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Gradual and progressive change in memory function reported by the participant or informant for ≥6 months.
  • A mini mental state examination (MMSE) score of 20 to 28 (inclusive) at screening.
  • Have an amyloid PET scan result from central read, consistent with the presence of amyloid pathology.

Who cannot join

  • Have 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, or epilepsy or recurrent seizures, except febrile childhood seizures.
  • Has current serious or unstable illnesses including cardiovascular, hepatic, renal, gastroenterologic, respiratory, endocrinologic, neurologic (other than AD), psychiatric, immunologic, or hematologic disease and other conditions that, in the investigator's opinion, could interfere with the analyses in this study.
  • A life expectancy of <24 months.
  • Contraindication to MRI or PET scans
  • Have had prior treatment with a passive anti-amyloid immunotherapy.
  • Have a presence or history of malignant neoplasms within the past 5 years prior to Visit 1.
Show all 11Show fewer
  • Exceptions:
  • non-metastatic basal- or squamous-cell skin cancer
  • Stage 0 non-invasive carcinoma of the cervix
  • Stage 0 non-invasive prostate cancer, or
  • other cancers with low risk of recurrence or spread

Trial locations and contacts

49 sites in 2 countries.

49 sites in 2 countries

United States43 sites
  • JEM Research Institute

    Atlantis, Florida, 33462

  • VIN-Julie Schwartzbard

    Aventura, Florida, 33180

  • Gadolin Research

    Beaumont, Texas, 77702

  • Northwest Clinical Research Center

    Bellevue, Washington, 98007

  • Excel Medical Clinical Trials

    Boca Raton, Florida, 33434

  • MD First Research - Chandler

    Chandler, Arizona, 85286

  • K2 Medical Research

    Clermont, Florida, 34711

  • Columbus Memory Center, LLC

    Columbus, Georgia, 31909

  • Neurology Clinic, P.C.

    Cordova, Tennessee, 38018

  • Kerwin Medical Center

    Dallas, Texas, 75231

  • CenExel iResearch, LLC

    Decatur, Georgia, 30030

  • Brain Matters Research

    Delray Beach, Florida, 33445

  • Re:Cognition Health

    Fairfax, Virginia, 22031

  • QUEST Research Institute

    Farmington Hills, Michigan, 48334

  • Neuropsychiatric Research Center of Southwest Florida

    Fort Myers, Florida, 33912

  • Center for Advanced Research & Education

    Gainesville, Georgia, 30501

  • Finlay Medical Research

    Greenacres City, Florida, 33467

  • Infinity Clinical Research, LLC

    Hollywood, Florida, 33024

  • The University of Texas Health Science Center at Houston

    Houston, Texas, 77054

  • Irvine Clinical Research

    Irvine, California, 92614

  • Jacksonville Center for Clinical Research

    Jacksonville, Florida, 32216

  • Healthy Brain Clinic

    Long Beach, California, 90804

  • ClinCloud - Maitland

    Maitland, Florida, 32751

  • K2 Medical Research

    Maitland, Florida, 32751

  • ClinCloud - Viera

    Melbourne, Florida, 32940

  • Suncoast Clinical Research, Inc.

    New Port Richey, Florida, 34652

  • Renstar Medical Research

    Ocala, Florida, 34470

  • Charter Research - Winter Park

    Orlando, Florida, 32803

  • Progressive Medical Research

    Port Orange, Florida, 32127

  • Butler Hospital

    Providence, Rhode Island, 02906

  • CenExel iResearch, LLC

    Savannah, Georgia, 31405

  • California Neuroscience Research Medical Group, Inc.

    Sherman Oaks, California, 91403

  • The Cognitive and Research Center of New Jersey

    Springfield, New Jersey, 07081

  • Alzheimer's Research and Treatment Center

    Stuart, Florida, 34997

  • Universal Research Group

    Tacoma, Washington, 98405

  • K2 Medical Research - Tampa

    Tampa, Florida, 33607

  • K2 Summit Research

    The Villages, Florida, 32159

  • Charter Research - Lady Lake

    The Villages, Florida, 32162

  • MedVadis Research Corporation

    Waltham, Massachusetts, 02451

  • Adams Clinical

    Watertown, Massachusetts, 02472

  • Alzheimer's Research and Treatment Center

    Wellington, Florida, 33414

  • Palm Beach Neurology

    West Palm Beach, Florida, 33407

  • Conquest Research

    Winter Park, Florida, 32789

Other trials in United States

United Kingdom6 sites
  • Re:Cognition Health - Birmingham

    Birmingham, B16 8LT

  • Re:Cognition Health - Bristol

    Bristol, Bristol, City of, BS32 4SY

  • Re:Cognition Health Guildford

    Guildford, Reading, GU2 7YD

  • Re:Cognition Health - London

    London, London, City of, W1G 9JF

  • Re:Cognition Health - Plymouth

    Plymouth, PL6 8BT

  • Re:Cognition Health - Winchester

    Winchester, Hampshire, SO21 1HU

Other trials in United Kingdom

About this study

Official title: Investigating the Effect of Different Donanemab Dosing Regimens on ARIA-E and Amyloid Lowering in Adults With Early Symptomatic Alzheimer's Disease

This study will investigate different donanemab dosing regimens and their effect on the frequency and severity of ARIA-E in adults with early symptomatic Alzheimer's disease (AD) and explore participant characteristics that might predict risk of ARIA.

Approximately 375 additional participants will be enrolled in addendum 2.

Addendum 3 includes a subset of participants from the main study to receive a single dose.

The study will last approximately 91 weeks and include up to 26 visits in the main study.

Being tested
Donanemab, Placebo, Dexamethasone
Medical subject headings
Alzheimer Disease, Dementia, Brain Diseases, Central Nervous System Diseases, Nervous System Diseases, Neurodegenerative Diseases, Neurocognitive Disorders, Mental Disorders

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • DonanemabDrug

    Also called LY3002813

    Administered IV

  • PlaceboDrug

    Administered IV

  • DexamethasoneDrug

    Administered IV

Study groups in NCT05738486
Study groupRoleWhat they receive
1400 mg Donanemab - Standard RegimenExperimentalParticipants received: * 700 milligrams (mg) donanemab administered intravenously (IV) at baseline, week 4, and 8. * placebo administered IV at week 2, 6, 10, and 14. * 1400 mg of donanemab administered IV at week 12, 16, 20, and 24. Participants enrolled to addendum 3 will receive a single dose at least 12 months after their last dose
Receives: Drug: Donanemab; Drug: Placebo
1400 mg Donanemab - Dose SkippingExperimentalParticipants received: * 700 mg donanemab administered IV at baseline. * placebo administered IV at week 2, 4, 6, 10, and 14. * 1400 mg of donanemab administered IV at week 8, 12, 16, 20, and 24. Participants enrolled to addendum 3 will receive a single dose at least 12 months after their last dose
Receives: Drug: Donanemab; Drug: Placebo
1400 mg Donanemab - TitrationExperimentalParticipants received: * 350 mg donanemab administered IV at baseline. * placebo administered IV at week 2, 6, 10, and 14. * 700 mg donanemab administered IV at week 4. * 1050 mg of donanemab administered IV at week 8. * 1400 mg of donanemab administered IV at week 12, 16, 20, and 24. Participants enrolled to addendum 3 will receive a single dose at least 12 months after their last dose
Receives: Drug: Donanemab; Drug: Placebo
1400 mg Donanemab - Maximum Concentration (Cmax)ExperimentalParticipants received: * 350 mg donanemab administered IV at baseline, weeks 2, 4, 6, 8, and 10. * 700 mg donanemab administered IV at weeks 12 and 14. * 1400 mg of donanemab administered IV at weeks 16, 20, and 24. Participants enrolled to addendum 3 will receive a single dose at least 12 months after their last dose
Receives: Drug: Donanemab; Drug: Placebo
Donanemab Addendum 2 Arm 1ExperimentalParticipants will receive donanemab by IV infusion. Participants will receive placebo pretreatment to preserve the blind prior to donanemab infusion.
Receives: Drug: Donanemab; Drug: Placebo
Donanemab Addendum 2 Arm 2ExperimentalParticipants will receive donanemab by IV infusion. Participants will receive dexamethasone pretreatment prior to donanemab infusion
Receives: Drug: Donanemab; Drug: Dexamethasone

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Percentage of Participants With Any Occurrence of Amyloid-Related Imaging Abnormality-Edema/Effusion (ARIA-E)

    Percentage of participants with occurrence of ARIA-E at Week 24 is reported here.

    Measured: 24 Weeks

Secondary outcomes (7)
  1. Percentage of Participants With Any Occurrence of ARIA-E

    Outcome data will be provided after the study is completed.

    Measured: 52 Weeks

  2. Change From Baseline in Brain Amyloid Plaque Deposition As Measured By Amyloid Positron Emission Tomography (PET) Scan

    Outcome data will be provided after the study is completed.

    Measured: Baseline, 76 Weeks

  3. Percentage of Participants With Any Occurrence of Amyloid-Related Imaging Abnormality-Hemorrhage/Hemosiderin Deposits (ARIA-H)

    Percentage of participants with occurrence of ARIA-H at Week 24 is reported here.

    Measured: 24 Weeks

  4. Percentage of Participants With ARIA-H

    Outcome data will be provided after the study is completed.

    Measured: 52 Weeks

  5. Percentage of Participants With Maximum Severity of ARIA-E or ARIA-H

    Outcome data will be provided after the study is completed.

    Measured: 76 Weeks

  6. Pharmacokinetics (PK): Average Serum Concentration of Donanemab

    Outcome data will be provided after the study is completed.

    Measured: Baseline to 76 Weeks

  7. Number of Participants With Anti-Drug Antibodies (ADAs) Against Donanemab, Including Treatment Emergent ADAs and Neutralizing Antibodies

    Outcome data will be provided after the study is completed.

    Measured: Baseline to End of Follow-Up (91 Weeks)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted22 Feb 2023
  2. Study start28 Feb 2023
  3. Primary completion16 May 2024
  4. Study completionMay 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
Phase 3b
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
1,175 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05738486
Sponsor's protocol ID
18648
Other IDs
I5T-MC-AACQ, 2022-502268-18-00, U1111-1285-9438
Status last verified
Oct 2025
First submitted
13 Feb 2023
Last updated
18 Jun 2026
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: Anonymized individual patient level data will be provided in a secure access environment upon approval of a research proposal and a signed data sharing agreement.

Publications

  • Boustani M, Klein EG, Zimmer JA, Wang H, Engle SE, Phipps A, Japha M, Schilling T, Hartry A; Alzheimer's Disease Neuroimaging Initiative. Further data to address the Alzheimer's coverage with evidence development questions. Alzheimers Dement. 2026 Aug;22(8):e71724. doi: 10.1002/alz.71724.

    PubMed 42552749
  • Wang H, Nery ESM, Ardayfio P, Khanna R, Svaldi DO, Shcherbinin S, Xu W, Andersen SW, Hauck PM, Brooks DA, Collins EC, Salloway S, Mintun MA, Sims JR. The effect of modified donanemab titration on amyloid-related imaging abnormalities with edema/effusions and amyloid reduction: 18-month results from TRAILBLAZER-ALZ 6. J Prev Alzheimers Dis. 2025 Sep;12(8):100266. doi: 10.1016/j.tjpad.2025.100266. Epub 2025 Jul 5.

    PubMed 40619285
  • Wang H, Serap Monkul Nery E, Ardayfio P, Khanna R, Otero Svaldi D, Gueorguieva I, Shcherbinin S, Andersen SW, Hauck PM, Engle SE, Brooks DA, Collins EC, Fox NC, Greenberg SM, Salloway S, Mintun MA, Sims JR. Modified titration of donanemab reduces ARIA risk and maintains amyloid reduction. Alzheimers Dement. 2025 Apr;21(4):e70062. doi: 10.1002/alz.70062.

    PubMed 40172303

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Donanemab and Dexamethasone in people with Alzheimer's Disease and Dementia, run by Eli Lilly and Company at 49 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 18 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 49 sites in United States, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 14 Nov 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percentage of Participants With Any Occurrence of Amyloid-Related Imaging Abnormality-Edema/Effusion (ARIA-E) (time frame: 24 Weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05738486, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Jun 2026.

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