A Study of NKTR-358 (LY3471851) in Healthy Participants

Study Overview
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Brief Summary
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The main purpose of this study is to evaluate the safety and tolerability of a study drug known as LY3471851 in healthy participants. The study will last about 50 days for each participant.

Detailed Description
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LY3471851 is a potential first-in-class therapeutic that may address an underlying immune system imbalance in people with many autoimmune conditions. It targets the interleukin (IL-2) receptor complex in the body in order to stimulate proliferation of inhibitory immune cells known as regulatory T cells. By activating these cells, LY3471851 may act to bring the immune system back into balance.

Official Title
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A Phase 1, Double-Blind, Randomized, Placebo-Controlled Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Single Subcutaneous Dose of NKTR-358 in Healthy Volunteers

Conditions
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Healthy

Intervention / Treatment
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* Drug: LY3471851
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Overtly healthy males and females, as determined by medical history and physical examination Have a body mass index (BMI) of 18.0 to 32.0 kilograms per square meter (kg/m²) Exclusion Criteria: Previous or current autoimmune disease/disorder Current active bacterial, viral, or fungal infection Administration of an inactivated vaccine within two weeks of study drug administration or live attenuated vaccine within 90 days of dosing .

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 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: LY3471851<br>Healthy participants in each cohort will receive single subcutaneous (SC) doses of LY3471851. | Drug: LY3471851<br>* LY3471851 drug product is a sterile liquid for SC injection that may be diluted with sterile 0.9% sodium chloride solution for injection (USP) prior to administration.<br>* Other names: NKTR-358;|
| Placebo Comparator: Placebo<br>Healthy participants in each cohort will receive the placebo comparator. | Drug: Placebo<br>* The placebo dosing solution is 0.9% sodium chloride for injection (USP).<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 | Number of Participants with One or More SAEs Considered by the Investigator to be Related to Study Drug Administration | Baseline up to Day 50 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY3471851 | PK: Cmax of LY3471851 | Predose on Day 1 through Day 50 | 
| PK: Area Under the Concentration Versus Time Curve from Time Zero to Infinity (AUC[0-inf]) of LY3471851 | PK: (AUC[0-inf]) of LY3471851 | Predose on Day 1 through Day 50 | 
| Pharmacodynamics (PD): Mean Change from Baseline in Regulatory T cells (Tregs) | PD: Mean change from baseline in Tregs | Predose on Day 1 through Day 50 | 
| PD: Change from Baseline in Treg Activation Markers | PD: Treg activation markers include: Cytokine levels, conventional CD4+ and CD8+ Tcells, and natural killer (NK) cells | Predose on Day 1 through Day 50 |