NCT05738486

Brief 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. 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.

Trial Health

78
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
1,175

participants targeted

Target at P75+ for phase_3

Timeline
12mo left

Started Feb 2023

Typical duration for phase_3

Geographic Reach
2 countries

49 active sites

Status
active not recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress76%
Feb 2023May 2027

First Submitted

Initial submission to the registry

February 13, 2023

Completed
9 days until next milestone

First Posted

Study publicly available on registry

February 22, 2023

Completed
6 days until next milestone

Study Start

First participant enrolled

February 28, 2023

Completed
1.2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

May 16, 2024

Completed
1.5 years until next milestone

Results Posted

Study results publicly available

November 14, 2025

Completed
1.5 years until next milestone

Study Completion

Last participant's last visit for all outcomes

May 1, 2027

Expected
Last Updated

November 14, 2025

Status Verified

October 1, 2025

Enrollment Period

1.2 years

First QC Date

February 13, 2023

Results QC Date

May 16, 2025

Last Update Submit

October 30, 2025

Conditions

Outcome Measures

Primary Outcomes (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.

    24 Weeks

Secondary Outcomes (7)

  • Percentage of Participants With Any Occurrence of ARIA-E

    52 Weeks

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

    Baseline, 76 Weeks

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

    24 Weeks

  • Percentage of Participants With ARIA-H

    52 Weeks

  • Percentage of Participants With Maximum Severity of ARIA-E or ARIA-H

    76 Weeks

  • +2 more secondary outcomes

Study Arms (6)

1400 mg Donanemab - Standard Regimen

EXPERIMENTAL

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: DonanemabDrug: Placebo

1400 mg Donanemab - Dose Skipping

EXPERIMENTAL

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: DonanemabDrug: Placebo

1400 mg Donanemab - Titration

EXPERIMENTAL

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: DonanemabDrug: Placebo

1400 mg Donanemab - Maximum Concentration (Cmax)

EXPERIMENTAL

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: DonanemabDrug: Placebo

Donanemab Addendum Arm 1

EXPERIMENTAL

Participants will receive donanemab by IV infusion. Participants will receive placebo pretreatment to preserve the blind prior to donanemab infusion.

Drug: DonanemabDrug: Placebo

Donanemab Addendum Arm 2

EXPERIMENTAL

Participants will receive donanemab by IV infusion. Participants will receive dexamethasone pretreatment prior to donanemab infusion

Drug: DonanemabDrug: Dexamethasone

Interventions

Administered IV

Also known as: LY3002813
1400 mg Donanemab - Dose Skipping1400 mg Donanemab - Maximum Concentration (Cmax)1400 mg Donanemab - Standard Regimen1400 mg Donanemab - TitrationDonanemab Addendum Arm 1Donanemab Addendum Arm 2

Administered IV

1400 mg Donanemab - Dose Skipping1400 mg Donanemab - Maximum Concentration (Cmax)1400 mg Donanemab - Standard Regimen1400 mg Donanemab - TitrationDonanemab Addendum Arm 1

Administered IV

Donanemab Addendum Arm 2

Eligibility Criteria

Age60 Years - 85 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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.

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (49)

MD First Research - Chandler

Chandler, Arizona, 85286, United States

Location

Irvine Clinical Research

Irvine, California, 92614, United States

Location

Healthy Brain Clinic

Long Beach, California, 90804, United States

Location

California Neuroscience Research Medical Group, Inc.

Sherman Oaks, California, 91403, United States

Location

JEM Research Institute

Atlantis, Florida, 33462, United States

Location

VIN-Julie Schwartzbard

Aventura, Florida, 33180, United States

Location

Excel Medical Clinical Trials

Boca Raton, Florida, 33434, United States

Location

K2 Medical Research

Clermont, Florida, 34711, United States

Location

Brain Matters Research

Delray Beach, Florida, 33445, United States

Location

Neuropsychiatric Research Center of Southwest Florida

Fort Myers, Florida, 33912, United States

Location

Finlay Medical Research

Greenacres City, Florida, 33467, United States

Location

Infinity Clinical Research, LLC

Hollywood, Florida, 33024, United States

Location

Jacksonville Center for Clinical Research

Jacksonville, Florida, 32216, United States

Location

ClinCloud - Maitland

Maitland, Florida, 32751, United States

Location

K2 Medical Research

Maitland, Florida, 32751, United States

Location

ClinCloud - Viera

Melbourne, Florida, 32940, United States

Location

Suncoast Clinical Research, Inc.

New Port Richey, Florida, 34652, United States

Location

Renstar Medical Research

Ocala, Florida, 34470, United States

Location

Charter Research - Winter Park

Orlando, Florida, 32803, United States

Location

Progressive Medical Research

Port Orange, Florida, 32127, United States

Location

Alzheimer's Research and Treatment Center

Stuart, Florida, 34997, United States

Location

K2 Medical Research - Tampa

Tampa, Florida, 33607, United States

Location

K2 Summit Research

The Villages, Florida, 32159, United States

Location

Charter Research - Lady Lake

The Villages, Florida, 32162, United States

Location

Alzheimer's Research and Treatment Center

Wellington, Florida, 33414, United States

Location

Palm Beach Neurology

West Palm Beach, Florida, 33407, United States

Location

Conquest Research

Winter Park, Florida, 32789, United States

Location

Columbus Memory Center, LLC

Columbus, Georgia, 31909, United States

Location

CenExel iResearch, LLC

Decatur, Georgia, 30030, United States

Location

Center for Advanced Research & Education

Gainesville, Georgia, 30501, United States

Location

CenExel iResearch, LLC

Savannah, Georgia, 31405, United States

Location

MedVadis Research Corporation

Waltham, Massachusetts, 02451, United States

Location

Adams Clinical

Watertown, Massachusetts, 02472, United States

Location

QUEST Research Institute

Farmington Hills, Michigan, 48334, United States

Location

The Cognitive and Research Center of New Jersey

Springfield, New Jersey, 07081, United States

Location

Butler Hospital

Providence, Rhode Island, 02906, United States

Location

Neurology Clinic, P.C.

Cordova, Tennessee, 38018, United States

Location

Gadolin Research

Beaumont, Texas, 77702, United States

Location

Kerwin Medical Center

Dallas, Texas, 75231, United States

Location

The University of Texas Health Science Center at Houston

Houston, Texas, 77054, United States

Location

Re:Cognition Health

Fairfax, Virginia, 22031, United States

Location

Northwest Clinical Research Center

Bellevue, Washington, 98007, United States

Location

Universal Research Group

Tacoma, Washington, 98405, United States

Location

Re:Cognition Health - Bristol

Bristol, Bristol, City of, BS32 4SY, United Kingdom

Location

Re:Cognition Health - Winchester

Winchester, Hampshire, SO21 1HU, United Kingdom

Location

Re:Cognition Health - London

London, London, City of, W1G 9JF, United Kingdom

Location

Re:Cognition Health Guildford

Guildford, Reading, GU2 7YD, United Kingdom

Location

Re:Cognition Health - Birmingham

Birmingham, B16 8LT, United Kingdom

Location

Re:Cognition Health - Plymouth

Plymouth, PL6 8BT, United Kingdom

Location

Related Publications (1)

  • 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.

Related Links

MeSH Terms

Conditions

Alzheimer DiseaseDementiaBrain DiseasesCentral Nervous System DiseasesNervous System DiseasesNeurodegenerative DiseasesNeurocognitive DisordersMental Disorders

Interventions

donanemabDexamethasone

Condition Hierarchy (Ancestors)

Tauopathies

Intervention Hierarchy (Ancestors)

PregnadienetriolsPregnadienesPregnanesSteroidsFused-Ring CompoundsPolycyclic CompoundsSteroids, Fluorinated

Results Point of Contact

Title
Chief Medical Officer
Organization
Eli Lilly and Company

Study Officials

  • 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

    STUDY DIRECTOR

Publication Agreements

PI is Sponsor Employee
No
Restriction Type
GT60
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
DOUBLE
Who Masked
PARTICIPANT, INVESTIGATOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Model Details: Phase 3b
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

February 13, 2023

First Posted

February 22, 2023

Study Start

February 28, 2023

Primary Completion

May 16, 2024

Study Completion (Estimated)

May 1, 2027

Last Updated

November 14, 2025

Results First Posted

November 14, 2025

Record last verified: 2025-10

Data Sharing

IPD Sharing
Will share

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.

Shared Documents
STUDY PROTOCOL, SAP, CSR
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.
Access Criteria
A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.
More information

Locations