A Study of LY3454738 in Healthy Participants and Participants With Atopic Dermatitis

Study Overview
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Brief Summary
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The main purpose of this study is to investigate the safety, tolerability, and efficacy of the study drug known as LY3454738 in healthy participants and participants with atopic dermatitis. The study has three parts. Each participant will enroll in one part. The study will last 12 to 24 weeks, depending on part.

Official Title
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Phase 1, Multicenter, Randomized, Placebo-Controlled, Triple-Blind, Single-Ascending Dose and Repeat-Dose Trial in Healthy Participants and Participants With Atopic Dermatitis

Conditions
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Dermatitis, Atopic

Intervention / Treatment
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* Drug: LY3454738
* Drug: LY3454738
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: All: Must have a body mass index of 18.0 to 32.0 kilograms per square meter (kg/m²), inclusive, for Parts A and B, and 18.0 to 45.0 kg/m², inclusive, for Part C and a minimum body weight of 50 kilograms For PART A and B only, regarding the inclusion of healthy Japanese participants: Minimum age is 20 years and the participant's biological parents and all of the participant's biological grandparents must be of exclusive Japanese descent and must have been born in Japan AD: Must have a diagnosis of AD for at least 12 months with either poor response to topical treatments or inability to use topical treatments Must agree to use moisturizer daily throughout the treatment period Exclusion Criteria: All: must not have previously completed a clinical trial with a molecule targeting interleukin-33 (IL-33) or its receptor AD: Must not have received certain topical medications for AD within 2 weeks prior to randomization Must not have received certain oral medications for AD or received phototherapy within 4 weeks prior to randomization Must not have received any antibody-based biologic agents (marketed or investigational) within 5 half lives (t1/2) of the drug prior to randomization Must not have received intravenous, intramuscular, or intra-articular steroids in the past 6 weeks prior to randomization

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LY3454738 - Part A<br>Escalating doses of LY3454738 administered intravenously (IV) or subcutaneously (SC) to healthy participants | Drug: LY3454738<br>* Administered IV<br>Drug: LY3454738<br>* Administered SC<br>|
| Placebo Comparator: Placebo - Part A<br>Placebo administered IV to healthy participants | Drug: Placebo<br>* Administered IV<br>|
| Experimental: LY3454738 - Part B<br>LY3454738 administered IV to healthy participants | Drug: LY3454738<br>* Administered IV<br>|
| Placebo Comparator: Placebo - Part B<br>Placebo administered IV to healthy participants | Drug: Placebo<br>* Administered IV<br>|
| Experimental: LY3454738 - Part C<br>LY3454738 administered IV to participants with atopic dermatitis (AD) | Drug: LY3454738<br>* Administered IV<br>|
| Placebo Comparator: Placebo - Part C<br>Placebo administered IV to participants with AD | 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 Week 24 | 
| Number of Participants Achieving a Validated Investigator's Global Assessment for Atopic Dermatitis (vIGA-AD) Score of 0 or 1 with a ≥ 2-point Improvement from Baseline | The vIGA-AD measures the investigator's global assessment of the participant's overall severity of their AD, based on a static, numeric 5-point scale from 0 (clear skin) to 4 (severe disease). The score is based on an overall assessment of the degree of erythema, papulation/induration, oozing/crusting, and lichenification | Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Observed Drug Concentration (Cmax) of LY3454738 | Cmax of LY3454738 | Day 1 through Day 85 (Day 99 for Part C) | 
| Area Under the Concentration-Versus-Time Curve (AUC) of LY3454738 | AUC of LY3454738 | Day 1 through Day 85 (Day 99 for Part C) |