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

Study Overview
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Brief Summary
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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.

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

Conditions
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Alzheimer's Disease, Dementia, Brain Diseases, Central Nervous System Diseases, Nervous System Diseases, Neurodegenerative Diseases, Neurocognitive Disorders, Mental Disorders

Intervention / Treatment
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* Drug: Donanemab
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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 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 Contraindication to MRI or PET scans Have had prior treatment with a passive anti-amyloid immunotherapy.

Ages Eligible for Study
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Minimum Age: 60 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Phase 3b
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Donanemab Dose Level 1<br>Participants will receive donanemab by intravenously (IV) infusion. Participants will receive placebo at certain intervals to preserve the blind. | Drug: Donanemab<br>* Administered IV<br>* Other names: LY3002813;Drug: Placebo<br>* Administered IV<br>|
| Experimental: Donanemab Dose Level 2<br>Participants will receive donanemab by IV infusion. Participants will receive placebo at certain intervals to preserve the blind. | Drug: Donanemab<br>* Administered IV<br>* Other names: LY3002813;Drug: Placebo<br>* Administered IV<br>|
| Experimental: Donanemab Dose Level 3<br>Participants will receive donanemab by IV infusion. Participants will receive placebo at certain intervals to preserve the blind. | Drug: Donanemab<br>* Administered IV<br>* Other names: LY3002813;Drug: Placebo<br>* Administered IV<br>|
| Experimental: Donanemab Dose Level 4<br>Participants will receive donanemab by IV infusion. Participants will receive placebo at certain intervals to preserve the blind. | Drug: Donanemab<br>* Administered IV<br>* Other names: LY3002813;Drug: Placebo<br>* Administered IV<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants with Any Occurence of Amyloid-Related Imaging Abnormality-Edema/Effusion (ARIA-E) |  | 24 Weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants with Any Occurence 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 |  | 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) |