A Study of LY3372689 to Assess the Safety, Tolerability, and Efficacy in Participants With Alzheimer's Disease

Study Overview
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Brief Summary
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The purpose of this study is to assess the safety, tolerability and effect of study drug LY3372689 in participants with early symptomatic Alzheimer's Disease

Official Title
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Assessment of Safety, Tolerability, and Efficacy of LY3372689 in Early Symptomatic Alzheimer's Disease

Conditions
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Alzheimer Disease

Intervention / Treatment
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* Drug: LY3372689
* Drug: LY3372689
* 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 participants or informants for ≥ 6 months MMSE score of 22 to 30 (inclusive) at baseline CDR global score of 0.5 to 1.0 (inclusive), with a memory box score ≥0.5. Meet 18F flortaucipir positron emission tomography (PET) scan (central analysis) criteria Have a study partner who will provide written informed consent to participate Exclusion Criteria: Contraindication to MRI or PET scans Have known allergies to LY3372689, related compounds, or any components of the formulations

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: Based on a common closed study design. Participants final endpoint time will be between 76-124 weeks.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LY3372689 High Dose<br>LY3372689 given orally | Drug: LY3372689<br>* given orally<br>|
| Experimental: LY3372689 Low Dose<br>LY3372689 given orally | Drug: LY3372689<br>* given orally<br>|
| Placebo Comparator: Placebo<br>Placebo given orally | Drug: Placebo<br>* given orally<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline to End Time Point in Integrated Alzheimer's Disease Rating Scale (iADRS) | Change from Baseline to End Time Point in iADRS will be measured in participants with early symptomatic Alzheimer's Disease (AD) with demonstrated presence of moderate levels of tau pathology | Baseline, 76 to 124 Weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline to End Time Point in iADRS | Change from baseline to end point time in iADRS will be measured in the full study population (moderate + high levels of tau pathology) with early symptomatic AD | Baseline, 76 to 124 Weeks | 
| Change From Baseline to End Time Point in Clinical Dementia Rating Scale - Sum of Boxes (CDR-SB) | Change From Baseline to End Time Point in CDR-SB | Baseline, 76 to 124 Weeks | 
| Change from Baseline to End Time Point in Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog13) | Change from Baseline to End Time Point in ADAS-Cog13 | Baseline, 76 to 124 Weeks | 
| Change from Baseline to End Time Point in Alzheimer's Disease Cooperative Study Instrumental Activities of Daily Living Inventory (ADCS-iADL) | Change from Baseline to End Time Point in ADCS-iADL | Baseline, 76 to 124 Weeks | 
| Change from Baseline to End Time Point in Mini Mental State Examination (MMSE) | Change from Baseline to End Time Point in MMSE | Baseline, 76 to 124 Weeks | 
| Change from Baseline to End Time Point in Brain Tau Deposition as Measured by Flortaucipir F18 PET scan | Change from Baseline to End Time Point in Brain Tau Deposition as Measured by Flortaucipir F18 PET scan | Baseline, 76 to 124 Weeks | 
| Change from Baseline to End Time Point in Volumetric Magnetic Resonance Imaging (vMRI) Measures | Change from Baseline to End Time Point in Volumetric MRI Measures | Baseline, 76 to 124 Weeks | 
| Pharmacokinetics (PK) Plasma Concentration of LY3372689 | PK Plasma Concentration of LY3372689 | Up to 124 Weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Dementia, Mild Cognitive Impairment, Prodromal Alzheimer's Disease, Tauopathy, Tau, OGA Inhibitor