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

Phase 3

Active, not recruiting

• Conditions: Alzheimer's Disease; Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders
• Interventions: Drug: Donanemab; Drug: Placebo; Drug: Dexamethasone

• Registration Number: NCT05738486
• Lead Sponsor: Eli Lilly and Company

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 300 additional participants will be enrolled per addendum.

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

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2023-02-13
• Study First Submitted QC: 2023-02-13
• Study First Posted: 2023-02-22
• Study Start: 2023-02-28
• Primary Completion: 2024-05-16
• Status Verified: 2025-05
• Study Completion: 2025-05
• Last Update Submitted: 2025-05-07
• Last Update Posted: 2025-05-11

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 1100

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Donanemab Dose Level 1	Donanemab	Participants will receive donanemab by intravenously (IV) infusion. Participants will receive placebo at certain intervals to preserve the blind.
Donanemab Dose Level 1	Placebo	Participants will receive donanemab by intravenously (IV) infusion. Participants will receive placebo at certain intervals to preserve the blind.
Donanemab Dose Level 2	Donanemab	Participants will receive donanemab by IV infusion. Participants will receive placebo at certain intervals to preserve the blind.
Donanemab Dose Level 2	Placebo	Participants will receive donanemab by IV infusion. Participants will receive placebo at certain intervals to preserve the blind.
Donanemab Dose Level 3	Donanemab	Participants will receive donanemab by IV infusion. Participants will receive placebo at certain intervals to preserve the blind.
Donanemab Dose Level 3	Placebo	Participants will receive donanemab by IV infusion. Participants will receive placebo at certain intervals to preserve the blind.
Donanemab Dose Level 4	Donanemab	Participants will receive donanemab by IV infusion. Participants will receive placebo at certain intervals to preserve the blind.
Donanemab Dose Level 4	Placebo	Participants will receive donanemab by IV infusion. Participants will receive placebo at certain intervals to preserve the blind.
Donanemab Addendum Arm 1	Donanemab	Participants will receive donanemab by IV infusion. Participants will receive placebo pretreatment to preserve the blind prior to donanemab infusion.
Donanemab Addendum Arm 1	Placebo	Participants will receive donanemab by IV infusion. Participants will receive placebo pretreatment to preserve the blind prior to donanemab infusion.
Donanemab Addendum Arm 2	Donanemab	Participants will receive donanemab by IV infusion. Participants will receive dexamethasone pretreatment prior to donanemab infusion
Donanemab Addendum Arm 2	Dexamethasone	Participants will receive donanemab by IV infusion. Participants will receive dexamethasone pretreatment prior to donanemab infusion

Primary Outcome Measures

Name	Time	Method
Percentage of Participants with Any Occurrence of Amyloid-Related Imaging Abnormality-Edema/Effusion (ARIA-E)	24 Weeks

Secondary Outcome Measures

Name	Time	Method
Percentage of Participants with Maximum Severity of ARIA-E or ARIA-H	52 Weeks
Pharmacokinetics (PK): Average Serum Concentration of Donanemab	Baseline to 52 Weeks
Number of Participants with Anti-Drug Antibodies (ADAs) Against Donanemab, including Treatment Emergent ADAs and Neutralizing Antibodies	Baseline to End of Follow-Up (91 Weeks)
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

Trial Locations

Locations (46)

MD First Research - Chandler; 🇺🇸 Chandler, Arizona, United States

Irvine Clinical Research; 🇺🇸 Irvine, California, United States

Healthy Brain Clinic; 🇺🇸 Long Beach, California, United States

California Neuroscience Research Medical Group, Inc.; 🇺🇸 Sherman Oaks, California, United States

JEM Research Institute; 🇺🇸 Atlantis, Florida, United States

VIN-Julie Schwartzbard; 🇺🇸 Aventura, Florida, United States

Excel Medical Clinical Trials; 🇺🇸 Boca Raton, Florida, United States

K2 Medical Research; 🇺🇸 Maitland, Florida, United States

Brain Matters Research; 🇺🇸 Delray Beach, Florida, United States

Neuropsychiatric Research Center of Southwest Florida; 🇺🇸 Fort Myers, Florida, United States

Scroll for more (36 remaining)