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

A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of LY3372993 in Participants With Alzheimer's Disease and Healthy Participants

The main purpose of this study is to evaluate the safety and tolerability of LY3372993 in participants with AD, non-Japanese, and Japanese healthy participants who are of first-generation Japanese origin. The study will also investigate how much LY3372993 gets into the bloodstream and will test the effects of LY3372993. The study will be conducted in two parts. The part A includes participants with AD and part B includes healthy participants. Participation could last up to about 61 weeks and may include up to 31 visits to the study center.

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 139
• Phase: Phase 1

Contacts and Locations

Study Locations

• Japan
  • Oita
    • Yufu, Oita, Japan, 879-5503
      • Oita University Hospital
  • Tokyo
    • Bunkyo-ku, Tokyo, Japan, 113-8655
      • The University of Tokyo Hospital
    • Shinjuku-ku, Tokyo, Japan, 162-0053
      • Clinical Research Hospital Tokyo
• United States
  • California
    • Cypress, California, United States, 90630
      • Altasciences Clinical Los Angeles, Inc
    • Long Beach, California, United States, 90806
      • Collaborative Neuroscience Research, LLC
  • Florida
    • DeLand, Florida, United States, 32720
      • Accel Research Sites- Clinical Research Unit
    • Hallandale Beach, Florida, United States, 33009
      • MD Clinical
    • Miami, Florida, United States, 33176
      • IMIC, Inc.
    • Orlando, Florida, United States, 32806-1041
      • Ppd Development
    • Port Orange, Florida, United States, 32127
      • Progressive Medical Research
    • The Villages, Florida, United States, 32162
      • Synexus Clinical Research US, Inc.
    • The Villages, Florida, United States, 32162
      • Charter Research
  • Texas
    • Dallas, Texas, United States, 75247
      • Covance Dallas

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

(Part A)

• Gradual and progressive changes in memory function reported by participants or their partners for greater than or equal to (≥) 6 months at screening, and a clinical diagnosis of mild cognitive impairment due to AD, or AD dementia, as determined by the investigator or based upon medical history
• Mini-Mental State Examination score ≥16
• Have clinical laboratory test results within normal reference range or results with acceptable deviations that are judged to be not clinically significant by the investigator
• 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 study visits or be available through telephone at designated times

(Part B)

• overtly healthy males or females
• have a body mass index of 18.0 to 32.0 kg/m2, inclusive
• To qualify as a participant of the first-generation Japanese origin, the participant, the participant's biological parents, and all of the participant's biological grandparents must be of exclusive Japanese descent and born in Japan.

Exclusion Criteria:

(Part A)

• Have history or presence of uncontrolled asthma, significant autoimmune disease, hereditary angioedema, or known history of common variable immune deficiency
• Contraindication to positron emission tomography (PET)
• Have a history or presence of serious or unstable illnesses including cardiovascular, hepatic, renal, gastrointestinal, respiratory, endocrine, psychiatric, immunologic, or hematologic disease and other conditions that, in the investigator's opinion, could interfere with the analyses in this study, or increase risk for study intervention administration, or result in a participant's life expectancy of less than (<)24 months
• Have received treatment with biologic agents (such as monoclonal antibodies, including marketed drugs) within 3 months or 5 half-lives (whichever is longer) prior to dosing
• Have had significant medical history of dizziness, syncope, or vasovagal attacks within the past 3 years
• Contraindication to magnetic resonance imaging (MRI), including claustrophobia that cannot be managed with low-dose sedatives or the presence of contraindicated metal (ferromagnetic) implants/cardiac pacemaker

(Part B)

• have a family history of early onset AD (AD diagnosed prior to 65 years of age)
• have used or intend to use over-the-counter or prescription medication including herbal medications within 14 days prior to dosing.
• have a history or presence of significant psychiatric disorders
• have an abnormal blood pressure and/or pulse rate as determined by the investigator, or a pre-existing history of hypertension
• any clinically significant ECG or brain MRI abnormalities

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: LY3372993 (Part A); LY3372993 administered as multiple doses either intravenously (IV) or subcutaneously (SC).	Drug: LY3372993; Administered IV or SC.
Experimental: LY3372993 (Part B); LY3372993 administered as single dose IV or SC.	Drug: LY3372993; Administered IV or SC.
Placebo Comparator: Placebo (Part A); Placebo administered as multiple doses IV or SC.	Drug: Placebo; Administered IV or SC.
Placebo Comparator: Placebo (Part B); Placebo administered as single dose IV or SC.	Drug: Placebo; Administered IV or SC.

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 through Week 61 (part A) and Week 13 (Part B)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY3372993	PK: Cmax of LY3372993	Day 1 Predose through Week 61 (part A) and Week 13 (Part B)
PK: Area Under the Concentration Versus Time Curve (AUC) of LY3372993	PK: AUC of LY3372993	Day 1 Predose through Week 61 (part A) and Week 13 (Part B)
Pharmacodynamics (PD): Change from Baseline in Cerebral Amyloid Plaque Level (Part A only)	PD: Cerebral amyloid plaque level measured using florbetapir positron emission tomography	Baseline and Week 61 (part A)

Collaborators and Investigators

• Sponsor: Eli Lilly and Company
• Investigators: Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST), Eli Lilly and Company

Publications and helpful links

Helpful Links

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

Study record dates

Study Major Dates

• Study Start (Actual): July 7, 2020
• Primary Completion (Actual): November 18, 2024
• Study Completion (Actual): November 18, 2024

Study Registration Dates

• First Submitted: June 26, 2020
• First Submitted That Met QC Criteria: June 26, 2020
• First Posted (Actual): June 30, 2020

Study Record Updates

• Last Update Posted (Actual): March 28, 2025
• Last Update Submitted That Met QC Criteria: March 27, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Mental Disorders; Neurocognitive Disorders; Dementia; Tauopathies; Neurodegenerative Diseases; Alzheimer Disease
• Other Study ID Numbers: 17755; J1G-MC-LAKB (Other Identifier: 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