A Donanemab (LY3002813) Prevention Study in Participants With Alzheimer's Disease (TRAILBLAZER-ALZ 3)

Study Overview
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Brief Summary
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The main purpose of this study is to evaluate the safety and efficacy of donanemab in participants with preclinical Alzheimer's Disease (AD).

Official Title
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A Study of Donanemab Versus Placebo in Participants at Risk for Cognitive and Functional Decline of Alzheimer's Disease

Conditions
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Alzheimer Disease

Intervention / Treatment
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* Drug: Donanemab
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: A Telephone Interview for Cognitive Status - modified (TICS-M) score reflective of intact cognitive functioning. Has a phosphorylated tau (P-tau) result consistent with the presence of amyloid and early-tau pathology. Has a reliable study partner and backup study partner familiar with overall function and behavior, such as day-to-day activities and cognitive abilities. Have adequate literacy, vision, and hearing for neuropsychological testing at screening. Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies Female participants include those who are infertile due to surgical sterilization (hysterectomy, bilateral oophorectomy, or tubal ligation), congenital anomaly such as Mullerian agenesis; or post menopausal (women 55 or older not on hormone therapy and had at least 12 months of spontaneous amenorrhea; or with a diagnosis of menopause prior to starting hormone replacement therapy. Exclusion Criteria: Mild cognitive impairment or dementia, or significant other neurodegenerative disease that can affect cognition. Current serious or unstable illnesses including cardiovascular, hepatic, renal, gastroenterologic, respiratory, endocrinologic, neurologic, psychiatric, immunologic, or hematologic disease that could interfere with the analysis of the study or a life expectancy of approximately ≤5 years. History of cancer with high risk of recurrence and preventing completion of the trial. History of clinically significant multiple or severe drug allergies, or severe posttreatment hypersensitivity reactions (including but not limited to erythema multiforme major, linear immunoglobulin A dermatosis, toxic epidermal necrolysis, and/or exfoliative dermatitis). Have any clinically important abnormality at screening on magnetic resonance imaging (MRI) or clinical laboratory test results that could be detrimental to the participant or study integrity. Have any contraindications for MRI, including claustrophobia or the presence of contraindicated metal (ferromagnetic) implants/cardiac pacemaker. Have a centrally read MRI demonstrating presence of amyloid-related imaging abnormalities (ARIA-E), >4 cerebral microhemorrhages, more than 1 area of superficial siderosis, any macrohemorrhage or severe white matter disease at screening. Have had prior treatment with a passive anti-amyloid immunotherapy <5 half-lives prior to randomization. Have received active immunization against amyloid beta (Aβ) in any other study. Have received active immunization against Aβ in any other study. Current or previous use of prescription medications used as treatment for mild cognitive impairment (MCI) or AD.

Ages Eligible for Study
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Minimum Age: 65 Years
Maximum Age: 80 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
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Donanemab<br>Donanemab administered intravenously (IV) | Drug: Donanemab<br>* Administered intravenously<br>* Other names: LY3002813;|
| Placebo Comparator: Placebo<br>Placebo is administered intravenously | Drug: Placebo<br>* Administered intravenously<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to clinical progression as measured by Clinical Dementia Rating - Global Score (CDR-GS) | Time to clinical progression as measured by CDR-GS. CDR is a clinician-rated scale that provides an overall assessment of the participant's stage on the spectrum of AD dementia. | Estimated Up to Week 182 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline in International Shopping List Test (ISLT) | Change from Baseline in clinical progression as measured by ISLT in participants with preclinical AD. | Baseline, Up to Week 182 | 
| Change from Baseline in Continuous Paired Associate Learning (CPAL) | Change from Baseline in clinical progression as measured by CPAL in participants with preclinical AD. | Baseline, Up to Week 182 | 
| Change from Baseline in International Daily Symbol Substitution Test-Medicines (iDSSTm) | Change from Baseline in clinical progression as measured by iDSSTm in participants with preclinical AD. | Baseline, Up to Week 182 | 
| Change from Baseline in Category Fluency | Change from Baseline in clinical progression as measured by Category Fluency in participants with preclinical AD. | Baseline, Up to Week 182 | 
| Change from Baseline in Face Name Association Test (FNAME) | Change from Baseline in clinical progression as measured by FNAME in participants with preclinical AD. | Baseline, Up to Week 182 | 
| Change from Baseline in Behavioral Pattern Separation-Object test (BPS-O) | Change from Baseline in clinical progression as measured by BPS-O in participants with preclinical AD. | Baseline, Up to Week 182 | 
| Change from Baseline in Cogstate Brief Battery (CBB) | Change from Baseline in clinical progression as measured by CBB in participants with preclinical AD. | Baseline, Up to Week 182 | 
| Change from Baseline in CDR-Sum of Boxes (CDR-SB) | Change from Baseline in clinical progression as measured by CDR-SB in participants with preclinical AD. | Baseline, Up Week 32 | 
| Change from Baseline in Cognitive Function Index (CFI) | Change from Baseline in clinical progression as measured by CFI in participants with preclinical AD. | Baseline, Up to Week 182 | 
| Change from Baseline in Montreal Cognitive Assessment (MoCA) score | Change from Baseline in clinical progression as measured by MoCA score in participants with preclinical AD. | Baseline, Up to Week 182 | 
| Pharmacokinetics (PK): Average Serum Donanemab Concentration at Steady State | PK: Average Serum Donanemab Concentration at Steady State | Baseline through Week 76 | 
| Percentage of Participants with Treatment-emergent Anti-Drug Antibody (ADAs) | Percentage of Participants with Treatment-emergent Anti-Drug Antibody (ADAs) | Baseline through Week 16 |