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

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 per addendum.

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

Study Overview

• Status: Active, not recruiting
• Conditions: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Neurodegenerative Diseases; Dementia; Alzheimer's Disease
• Intervention / Treatment: Drug: Placebo; Drug: Donanemab; Drug: Dexamethasone

• Study Type: Interventional
• Enrollment (Actual): 1175
• Phase: Phase 3

Contacts and Locations

Study Locations

• United Kingdom
  • Birmingham, United Kingdom, B16 8LT
    • Re:Cognition Health - Birmingham
  • Plymouth, United Kingdom, PL6 8BT
    • Re:Cognition Health - Plymouth
  • Bristol, City of
    • Bristol, Bristol, City of, United Kingdom, BS32 4SY
      • Re:Cognition Health - Bristol
  • Hampshire
    • Winchester, Hampshire, United Kingdom, SO21 1HU
      • Re:Cognition Health - Winchester
  • London, City of
    • London, London, City of, United Kingdom, W1G 9JF
      • Re:Cognition Health - London
  • Reading
    • Guildford, Reading, United Kingdom, GU2 7YD
      • Re:Cognition Health Guildford
• United States
  • Arizona
    • Chandler, Arizona, United States, 85286
      • MD First Research - Chandler
  • California
    • Irvine, California, United States, 92614
      • Irvine Clinical Research
    • Long Beach, California, United States, 90804
      • Healthy Brain Clinic
    • Sherman Oaks, California, United States, 91403
      • California Neuroscience Research Medical Group, Inc.
  • Florida
    • Atlantis, Florida, United States, 33462
      • JEM Research Institute
    • Aventura, Florida, United States, 33180
      • VIN-Julie Schwartzbard
    • Boca Raton, Florida, United States, 33434
      • Excel Medical Clinical Trials
    • Clermont, Florida, United States, 34711
      • K2 Medical Research
    • Delray Beach, Florida, United States, 33445
      • Brain Matters Research
    • Fort Myers, Florida, United States, 33912
      • Neuropsychiatric Research Center of Southwest Florida
    • Greenacres City, Florida, United States, 33467
      • Finlay Medical Research
    • Hollywood, Florida, United States, 33024
      • Infinity Clinical Research, LLC
    • Jacksonville, Florida, United States, 32216
      • Jacksonville Center for Clinical Research
    • Maitland, Florida, United States, 32751
      • K2 Medical Research
    • Maitland, Florida, United States, 32751
      • ClinCloud - Maitland
    • Melbourne, Florida, United States, 32940
      • ClinCloud - Viera
    • New Port Richey, Florida, United States, 34652
      • Suncoast Clinical Research, Inc.
    • Ocala, Florida, United States, 34470
      • Renstar Medical Research
    • Orlando, Florida, United States, 32803
      • Charter Research - Winter Park
    • Port Orange, Florida, United States, 32127
      • Progressive Medical Research
    • Stuart, Florida, United States, 34997
      • Alzheimer's Research and Treatment Center
    • Tampa, Florida, United States, 33607
      • K2 Medical Research - Tampa
    • The Villages, Florida, United States, 32159
      • K2 Summit Research
    • The Villages, Florida, United States, 32162
      • Charter Research - Lady Lake
    • Wellington, Florida, United States, 33414
      • Alzheimer's Research and Treatment Center
    • West Palm Beach, Florida, United States, 33407
      • Palm Beach Neurology
    • Winter Park, Florida, United States, 32789
      • Conquest Research
  • Georgia
    • Columbus, Georgia, United States, 31909
      • Columbus Memory Center, LLC
    • Decatur, Georgia, United States, 30030
      • CenExel iResearch, LLC
    • Gainesville, Georgia, United States, 30501
      • Center for Advanced Research & Education
    • Savannah, Georgia, United States, 31405
      • CenExel iResearch, LLC
  • Massachusetts
    • Waltham, Massachusetts, United States, 02451
      • MedVadis Research Corporation
    • Watertown, Massachusetts, United States, 02472
      • Adams Clinical
  • Michigan
    • Farmington Hills, Michigan, United States, 48334
      • Quest Research Institute
  • New Jersey
    • Springfield, New Jersey, United States, 07081
      • The Cognitive and Research Center of New Jersey
  • Rhode Island
    • Providence, Rhode Island, United States, 02906
      • Butler Hospital
  • Tennessee
    • Cordova, Tennessee, United States, 38018
      • Neurology Clinic, P.C.
  • Texas
    • Beaumont, Texas, United States, 77702
      • Gadolin Research
    • Dallas, Texas, United States, 75231
      • Kerwin Medical Center
    • Houston, Texas, United States, 77054
      • The University of Texas Health Science Center at Houston
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Re:Cognition Health
  • Washington
    • Bellevue, Washington, United States, 98007
      • Northwest Clinical Research Center
    • Tacoma, Washington, United States, 98405
      • Universal Research Group

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 60 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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.

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Donanemab Addendum Arm 1; Participants will receive donanemab by IV infusion. Participants will receive placebo pretreatment to preserve the blind prior to donanemab infusion.	Drug: Placebo; Administered IV; Drug: Donanemab; Administered IV; Other Names: LY3002813
Experimental: Donanemab Addendum Arm 2; Participants will receive donanemab by IV infusion. Participants will receive dexamethasone pretreatment prior to donanemab infusion	Drug: Donanemab; Administered IV; Other Names: LY3002813; Drug: Dexamethasone; Administered IV
Experimental: 1400 mg Donanemab - Standard Regimen; Participants 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.	Drug: Placebo; Administered IV; Drug: Donanemab; Administered IV; Other Names: LY3002813
Experimental: 1400 mg Donanemab - Dose Skipping; Participants 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.	Drug: Placebo; Administered IV; Drug: Donanemab; Administered IV; Other Names: LY3002813
Experimental: 1400 mg Donanemab - Titration; Participants 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.	Drug: Placebo; Administered IV; Drug: Donanemab; Administered IV; Other Names: LY3002813
Experimental: 1400 mg Donanemab - Maximum Concentration (Cmax); Participants 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.	Drug: Placebo; Administered IV; Drug: Donanemab; Administered IV; Other Names: LY3002813

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	24 Weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Any Occurrence of ARIA-E	Outcome data will be provided after the study is completed.	52 Weeks
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.	Baseline, 76 Weeks
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.	24 Weeks
Percentage of Participants With ARIA-H	Outcome data will be provided after the study is completed.	52 Weeks
Percentage of Participants With Maximum Severity of ARIA-E or ARIA-H	Outcome data will be provided after the study is completed.	76 Weeks
Pharmacokinetics (PK): Average Serum Concentration of Donanemab	Outcome data will be provided after the study is completed.	Baseline to 76 Weeks
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.	Baseline to End of Follow-Up (91 Weeks)

Collaborators and Investigators

• Sponsor: Eli Lilly and Company
• Investigators: Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST), Eli Lilly and Company

Publications and helpful links

General Publications

• 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.

Helpful Links

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

Study record dates

Study Major Dates

• Study Start (Actual): February 28, 2023
• Primary Completion (Actual): May 16, 2024
• Study Completion (Estimated): May 1, 2027

Study Registration Dates

• First Submitted: February 13, 2023
• First Submitted That Met QC Criteria: February 13, 2023
• First Posted (Actual): February 22, 2023

Study Record Updates

• Last Update Posted (Estimated): November 14, 2025
• Last Update Submitted That Met QC Criteria: October 30, 2025
• Last Verified: October 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Tauopathies; Alzheimer Disease; Mental Disorders; Dementia; Brain Diseases; Nervous System Diseases; Neurodegenerative Diseases; Central Nervous System Diseases; Neurocognitive Disorders; Polycyclic Compounds; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Steroids, Fluorinated; Pregnadienetriols; Dexamethasone; donanemab
• Other Study ID Numbers: 18648; I5T-MC-AACQ (Other Identifier: Eli Lilly and Company); 2022-502268-18-00 (Other Identifier: EU Trial Number); U1111-1285-9438 (Other Identifier: UTN Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: 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.
• IPD Sharing Time Frame: Data are available 6 months after the primary publication and approval of the indication studied in the US and European Union (EU), whichever is later. Data will be indefinitely available for requesting.
• IPD Sharing Access Criteria: A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No