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

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

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.

Study Overview

• Status: Completed
• Conditions: Alzheimer Disease
• Intervention / Treatment: Drug: Placebo; Drug: LY3372993

Detailed Description

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

• Study Type: Interventional
• Enrollment (Actual): 36
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Long Beach, California, United States, 90806
      • Collaborative Neuroscience Network - CNS
  • Florida
    • Daytona Beach, Florida, United States, 32117
      • Covance Clinical Research Inc
    • DeLand, Florida, United States, 32720
      • Avail Clinical Research LLC
    • Hallandale Beach, Florida, United States, 33009
      • MD Clinical
    • Orlando, Florida, United States, 32806
      • BioClinica Inc
    • Palmetto Bay, Florida, United States, 33157
      • IMIC, Inc.
    • Port Orange, Florida, United States, 32127
      • Progressive Medical Research
    • The Villages, Florida, United States, 32162
      • BioClinica Inc
  • Georgia
    • Atlanta, Georgia, United States, 30331
      • Atlanta Center of Medical Research
  • North Carolina
    • Raleigh, North Carolina, United States, 27612
      • Carolina Phase 1 Research (Wake M3)
  • Utah
    • Salt Lake City, Utah, United States, 84124
      • PRA Health Sciences

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: BASIC_SCIENCE
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: LY3372993 (Part A); LY3372993 administered intravenously (IV) to healthy participants.	Drug: LY3372993; Administered IV.
PLACEBO_COMPARATOR: Placebo (Part A); Placebo administered IV to healthy participants.	Drug: Placebo; Administered IV.
EXPERIMENTAL: LY3372993 (Part B); LY3372993 administered IV to participants with AD. Part B was terminated before any participants received treatment.	Drug: LY3372993; Administered IV.
PLACEBO_COMPARATOR: Placebo (Part B); Placebo administered IV to participants with AD. Part B was terminated before any participants received treatment.	Drug: Placebo; Administered IV.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Eli Lilly and Company

Study record dates

Study Major Dates

• Study Start (ACTUAL): November 5, 2018
• Primary Completion (ACTUAL): May 14, 2019
• Study Completion (ACTUAL): May 14, 2019

Study Registration Dates

• First Submitted: October 24, 2018
• First Submitted That Met QC Criteria: October 24, 2018
• First Posted (ACTUAL): October 25, 2018

Study Record Updates

• Last Update Posted (ACTUAL): June 5, 2019
• Last Update Submitted That Met QC Criteria: June 4, 2019
• Last Verified: June 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Neurodegenerative Diseases; Dementia; Tauopathies; Alzheimer Disease
• Other Study ID Numbers: 17019; J1G-MC-LAKA (OTHER: Eli Lilly and Company)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No