A Study of LY3372993 in Healthy Participants and Participants With Alzheimer's Disease (AD)

Study Overview
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Brief Summary
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The main purpose of this study is to evaluate the safety and tolerability of LY3372993 in healthy participants and participants with AD. The study will also investigate how much LY3372993 gets into the bloodstream and test the effects of LY3372993 in participants with AD. The study has two parts: Part A - Healthy participants will receive LY3372993 or placebo. Part A will last up to 17 weeks; Part B - Participants with AD will receive LY3372993 or placebo. Part B will last about 317 days.

Detailed Description
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In April, 2019, Eli Lilly and Company made a business decision to terminate Part B. No participants were enrolled.

Official Title
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A Single-Dose and Multiple-Dose, Dose-Escalation Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of LY3372993 in Healthy Subjects and Patients With Alzheimer's Disease

Conditions
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Alzheimer Disease

Intervention / Treatment
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* Drug: LY3372993
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria : Part A: Overtly healthy males or females as determined by medical history and physical examination Are between 18 to 45 years old, inclusive Male participants agree to use a reliable method of birth control during the study and 3 months following the last dose of the investigational product Female participants not of child-bearing potential Have a body mass index of 18.0 to 32 kilograms per square meter (kg/m²) inclusive Part B: Present with mild cognitive impairment (MCI) due to Alzheimer's disease (AD) or mild-to-moderate AD Positive florbetapir scan Men or nonfertile women, at least 55 years of age. Nonfertile is defined as hysterectomy and/or bilateral oophorectomy, or amenorrhea for at least 1 year Have up to 2 study partners who can provide health information related to the study about the participant. Study partner(s) will provide a separate written informed consent to participate Exclusion Criteria: Have significant abnormalities in brain magnetic resonance imaging (MRI); or have contraindications for MRI Have significant allergic reactions to LY3372993, or related compounds, or have significant allergies to humanized monoclonal antibodies, diphenhydramine, epinephrine, or methylprednisolone Have clinically significant neurological or psychological illness, or other illnesses that could affect the study results Part A: Have family history of early onset Alzheimer's Disease (AD) Have impaired cognitive function Part B: History of intracranial hemorrhage, cerebrovascular aneurysm or arteriovenous malformation, or carotid artery occlusion, or stroke or epilepsy Previously dosed in any other study investigating active immunization against amyloid beta (Aβ) Previously dosed in any other study investigating passive immunization against Aβ within the last 6 months Have current serious or unstable illnesses

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LY3372993 (Part A)<br>LY3372993 administered intravenously (IV) to healthy participants. | Drug: LY3372993<br>* Administered IV.<br>|
| Placebo Comparator: Placebo (Part A)<br>Placebo administered IV to healthy participants. | Drug: Placebo<br>* Administered IV.<br>|
| Experimental: LY3372993 (Part B)<br>LY3372993 administered IV to participants with AD. Part B was terminated before any participants received treatment. | Drug: LY3372993<br>* Administered IV.<br>|
| Placebo Comparator: Placebo (Part B)<br>Placebo administered IV to participants with AD. Part B was terminated before any participants received treatment. | Drug: Placebo<br>* Administered IV.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants with One or More Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration | A summary of SAEs and other non-serious adverse events (AEs), regardless of causality, will be reported in the Reported Adverse Events module | Baseline up to Day 562 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve of LY3372993 After a Single Dose | PK: AUC of LY3372993 After a Single Dose | Predose up to Day 85 | 
| PK: Maximum Observed Concentration (Cmax) of LY3372993 After a Single Dose | PK: Cmax of LY3372993 After a Single Dose | Predose up to Day 85 | 
| PK: AUC of LY3372993 at Steady State after Multiple Doses | PK: AUC of LY3372993 at Steady State after Multiple Doses | Week 14 through Week 18 | 
| PK: Cmax of LY3372993 at Steady State After Multiple Doses | PK: Cmax of LY3372993 at Steady State After Multiple Doses | Week 14 through Week 18 | 
| Pharmacodynamics (PD): Change from Baseline in Amyloid Load | Amyloid load measured by florbetapir F18 positron emission tomography (PET) scan | Baseline, Week 28 |