A Study of Donanemab (LY3002813) in Participants With Early Symptomatic Alzheimer's Disease (TRAILBLAZER-ALZ 5)

Study Overview
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Brief Summary
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The reason for this study is to assess the safety and efficacy of donanemab in participants with early Alzheimer's disease. The study duration including screening and follow-up is up to 93 weeks.

Detailed Description
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TRAILBLAZER-ALZ 5 is a Phase 3, double-blind, placebo-controlled study to evaluate the safety and efficacy of donanemab in participants with early symptomatic AD (prodromal AD and mild dementia due to AD) with the presence of brain tau pathology.

Official Title
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Global Study to Investigate Safety and Efficacy of Donanemab in Early Symptomatic Alzheimer's Disease

Conditions
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Alzheimer Disease, Dementia, Brain Diseases, Central Nervous System Diseases, Nervous System Diseases, Tauopathies, 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 MMSE score of 20 to 28 (inclusive) at Day 601 or 1. Meet flortaucipir F18 scan (central read) criteria Meet florbetapir F18 scan (central read) criteria Have a study partner who will provide written informed consent to participate, is in frequent contact with the participant (defined as at least 10 hours per week), and will accompany the participant to the study or be available by telephone at designated times. A second study partner may serve as backup. The study partner(s) is/are required to accompany the participant for signing consent. The study partner must be present on all days the cognitive and functional scales are administered. If a participant has a second study partner, it is preferred that 1 study partner be primarily responsible for the CDR and the ADCS-ADL assessments. Days requiring the following assessments and scales must have a study partner available by telephone if not accompanying participant for the following assessments AEs and concomitant medications CDR, and ADCS-ADL Stable concomitant symptomatic AD medications and other medications that may impact cognition for at least approximately 30 days prior to randomization. Exclusion Criteria: Has significant neurological disease affect 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; or has a life expectancy of <24 months. History of cancer within the last 5 years, except of non-metastatic basal and/or squamous cell carcinoma of the skin, in situ cervical cancer, nonprogressive prostate cancer, or other cancers with low risk of recurrence or spread. Contraindication to MRI or PET scans

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
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Donanemab<br>Participants will receive donanemab intravenously (IV) | Drug: Donanemab<br>* Administered IV<br>* Other names: (LY3002813);|
| Placebo Comparator: Placebo<br>Participants will receive placebo IV | Drug: Placebo<br>* Administered IV<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline on the Integrated Alzheimer's Disease Rating Scale (iADRS) | Change from Baseline on the iADRS in at least one of 'the low-medium tau pathology population or the overall population'. | Baseline, Week 76 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline on the Clinical Dementia Rating Scale-Sum of Boxes (CDR-SB) | Change from Baseline CDR-SB in at least one of 'the low-medium tau pathology population or the overall population'. | Baseline, Week 76 | 
| Change from Baseline on the Alzheimer's Disease Assessment Scale - Cognitive Subscale ADAS-Cog13 Score | Change from Baseline on the ADAS-Cog13 Score in at least one of 'the low-medium tau pathology population or the overall population'. | Baseline, Week 76 | 
| Change from Baseline on the Alzheimer's Disease Cooperative Study - instrumental Activities of Daily Living ADCS-iADL Score | Change from Baseline ADCS-iADL Score in at least one of 'the low-medium tau pathology population or the overall population'. | Baseline, Week 76 | 
| Change from Baseline on the Mini Mental State Examination (MMSE) Score | Change from Baseline on the MMSE Score in at least one of 'the low-medium tau pathology population or the overall population'. | Baseline, Week 76 | 
| Change from Baseline in Amyloid Plaque Deposition as by Florbetapir F18 Positron Emission Tomography (PET) Scan |  | Baseline, Week 76 | 
| Pharmacokinetics (PK): Average Serum Concentration of Donanemab |  | Baseline to Week 76 | 
| Number of Participants with Treatment-Emergent Anti-Drug Antibodies (ADAs) |  | Week 76 | 
| Change from Baseline in Quality of Life in Alzheimer's Disease (QOL-AD) | Change from baseline in the QoL-AD in at least one of 'the low-medium tau pathology population or the overall population'. | Baseline, Week 76 | 
| Change from Baseline in Resource Utilization in Dementia - Lite Version (RUD-Lite) | Change from baseline in the RUD-Lite in at least one of 'the low-medium tau pathology population or the overall population'. | Baseline, Week 76 | 
| Change from Baseline in Neuropsychiatric Inventory (NPI) | Change from baseline in the NPI in at least one of 'the low-medium tau pathology population or the overall population'. | Baseline, Week 76 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Alzheimer's, Dementia, Cognitive Impairment, Amyloid Plaque