A Study of LY3002813 in Participants With Alzheimer's Disease

Study Overview
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Brief Summary
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The study will evaluate the safety of LY3002813 by looking at adverse events. The study will also look at the effect the body has on LY3002813. Study participants will be healthy or will have mild cognitive impairment (MCI) due to Alzheimer's disease (AD) or mild to moderate AD. There will be seven groups of study participants. Five groups will receive a single dose of LY3002813 or placebo (no drug), followed by up to 4 multiple doses of LY3002813 or placebo given as an injection into a vein. Approximately 12 weeks will pass between the single dose and the first multiple dose. One group of participants will receive a single dose of LY3002813 given as an injection under the skin. One group of participants will receive a single dose of LY3002813 given as an injection into a vein.

Official Title
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A Single-Dose and Multiple-Dose, Dose-Escalation Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of LY3002813 in Patients With Mild Cognitive Impairment Due to Alzheimer's Disease or Mild to Moderate Alzheimer's Disease

Conditions
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Alzheimer Disease

Intervention / Treatment
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* Biological: LY3002813-IV
* Biological: LY3002183-SC
* Drug: Placebo-IV


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy Participants: Overtly healthy males, as determined by medical history and physical examination, willing to use a reliable method of birth control and will not donate sperm during the study Between 18 to 40 years old. Body Mass Index (BMI) of between 18.0 and 30.0 kilogram per meter square (kg/m^2), inclusive Participants with Mild Cognitive Impairment Due to Alzheimer's Disease (AD) or AD: Present with mild cognitive impairment (MCI) due to AD or mild-to-moderate AD Men or nonfertile women, at least 50 years of age. Nonfertile is defined as hysterectomy and/or bilateral oophorectomy, or amenorrhea for at least 1 year Have a caregiver/study informant who provides a separate written informed consent to participate Have adequate vision and hearing for neuropsychological testing in the opinion of the investigator Positive florbetapir scan Exclusion Criteria: -Healthy Participants: Have a history or presence of cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematological, immunological, or neurological disorders capable of significantly altering the absorption,metabolism, or elimination of drugs; of constituting a risk when taking the study medication; or of interfering with the interpretation of data Participants with Mild Cognitive Impairment Due to AD or AD: Do not have a reliable caregiver/study informant who is in frequent contact with the participant, who will accompany the participant to the office and/or be available by telephone at designated times, and will monitor administration of prescribed medications Are being monitored for radiation due to occupational exposure to ionized radiation, or exposure to ionizing radiation within last 12 months from an investigational study History within the past 5 years of a primary or recurrent malignant disease with the exception of resected cutaneous squamous cell carcinoma in situ, basal cell carcinoma, cervical carcinoma in situ, or in situ prostate cancer with a normal prostate-specific antigen post resection All Participants: History of intracranial hemorrhage, cerebrovascular aneurysm or arteriovenous malformation, or carotid artery occlusion, or stroke or epilepsy Have any contraindications for magnetic resonance imaging (MRI) studies, including claustrophobia, the presence of contraindicated metal (ferromagnetic) implants, cardiac pacemaker Have allergies to humanized monoclonal antibodies, including proteins and diphenhydramine, epinephrine, and methylprednisolone Have gamma globulin therapy within the last year 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

Ages Eligible for Study
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Minimum Age: 18 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: LY3002813-Single 0.1 mg/kg then multiple 0.3 mg/kg<br>0.1 milligram per kilogram (mg/kg) single dose then 0.3 mg/kg LY3002813 given every 4 weeks for up to 16 weeks intravenously (IV) | Biological: LY3002813-IV<br>* Administered IV<br>|
| Experimental: LY3002813-Single then multiple 0.3 mg/kg<br>0.3 mg/kg single dose then 0.3 mg/kg LY3002813 given every 4 weeks for up to 16 weeks IV | Biological: LY3002813-IV<br>* Administered IV<br>|
| Experimental: LY3002813-Single then multiple 1 mg/kg<br>1 mg/kg single dose then 1 mg/kg LY3002813 given every 4 weeks for up to 16 weeks IV | Biological: LY3002813-IV<br>* Administered IV<br>|
| Experimental: LY3002813-Single then multiple 3 mg/kg<br>3 mg/kg single dose then 3 mg/kg LY3002813 given every 4 weeks for up to 16 weeks IV | Biological: LY3002813-IV<br>* Administered IV<br>|
| Experimental: LY3002813-Single then multiple 10 mg/kg<br>10 mg/kg single dose then 10 mg/kg LY3002813 given every 4 weeks for up to 16 weeks IV | Biological: LY3002813-IV<br>* Administered IV<br>|
| Placebo Comparator: Placebo-Single then multiple<br>Placebo given once, then every 4 weeks for up to 16 weeks IV | Drug: Placebo-IV<br>* Administered IV<br>|
| Experimental: LY3002813-SC<br>Up to 3 mg/kg LY3002813 given once subcutaneously (SC) | Biological: LY3002183-SC<br>* Administered SC<br>|
| Experimental: LY3002813-IV<br>Up to 3mg/kg LY3002813 given once intravenously (IV) | Biological: LY3002813-IV<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 Events (SAEs) Considered by the Investigator to be Related to Study Drug Administration |  | Day 1 up to Day 253 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics: Maximum Concentration (Cmax) of LY3002813 |  | Predose up to Day 253 | 
| Pharmacokinetics: Area Under the Concentration Curve (AUC) of LY3002813 |  | Predose up to Day 253 |