Clinical trial NCT03720548: A Study of LY3372993 in Healthy Participants and Participants With Alzheimer's Disease (AD)
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Alzheimer Disease
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
First posted: 2018-10-25
Enrollment: 36
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

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

Eligibility criteria: 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

Primary outcomes:
measure: Number of Participants with One or More Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration
timeFrame: Baseline up to Day 562
Secondary outcomes:
measure: Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve of LY3372993 After a Single Dose
timeFrame: Predose up to Day 85
measure: PK: Maximum Observed Concentration (Cmax) of LY3372993 After a Single Dose
timeFrame: Predose up to Day 85
measure: PK: AUC of LY3372993 at Steady State after Multiple Doses
timeFrame: Week 14 through Week 18
measure: PK: Cmax of LY3372993 at Steady State After Multiple Doses
timeFrame: Week 14 through Week 18
measure: Pharmacodynamics (PD): Change from Baseline in Amyloid Load
timeFrame: Baseline, Week 28
Other outcomes:
Locations:
city: Long Beach
country: United States
facility: Collaborative Neuroscience Network - CNS
state: California
city: Daytona Beach
country: United States
facility: Covance Clinical Research Inc
state: Florida
city: DeLand
country: United States
facility: Avail Clinical Research LLC
state: Florida
city: Hallandale Beach
country: United States
facility: MD Clinical
state: Florida
city: Orlando
country: United States
facility: BioClinica Inc
state: Florida
city: Palmetto Bay
country: United States
facility: IMIC, Inc.
state: Florida
city: Port Orange
country: United States
facility: Progressive Medical Research
state: Florida
city: The Villages
country: United States
facility: BioClinica Inc
state: Florida
city: Atlanta
country: United States
facility: Atlanta Center of Medical Research
state: Georgia
city: Raleigh
country: United States
facility: Carolina Phase 1 Research (Wake M3)
state: North Carolina
city: Salt Lake City
country: United States
facility: PRA Health Sciences
state: Utah
Study officials:
affiliation: Eli Lilly and Company
name: 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)
role: STUDY_DIRECTOR
References: