A Study of LY3471851 in Adults With Systemic Lupus Erythematosus (SLE)

Study Overview
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Brief Summary
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The reason for this study is to see if the study drug LY3471851 (NKTR-358) is safe and effective in adults with systemic lupus erythematosus (SLE).

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 Randomized, Double-Blind, Placebo-Controlled, Phase 2 Study of LY3471851 (NKTR-358) in Adults With Systemic Lupus Erythematosus

Conditions
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Systemic Lupus Erythematosus

Intervention / Treatment
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* Drug: LY3471851
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Have a clinical diagnosis of SLE at least 24 weeks prior to screening. Have documentation of having met at least 4 of 11 Revised Criteria for Classification of Systemic Lupus Erythematosus according to the 1997 Update of the 1982 American College of Rheumatology (ACR) criteria for classification of SLE prior to randomization. Have a positive antinuclear antibody (ANA) (titer ≥1:80) and/or a positive anti-double-stranded deoxyribonucleic acid (dsDNA), and/or a positive anti-Smith (anti-Sm) as assessed by a central laboratory during screening. Have a total Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score ≥6 during screening. Have a clinical SLEDAI-2K score ≥4 at randomization. Have active arthritis and/or active rash. Exclusion Criteria: Have severe active lupus nephritis. Have active central nervous system (CNS) lupus. Have a history or presence of cardiovascular, respiratory, hepatic, gastrointestinal, endocrine, hematological, neurological, or neuropsychiatric disorders or any other serious and/or unstable illness that, in the opinion of the investigator, could constitute an unacceptable risk when taking investigational product or interfere with the interpretation of data. Have a current or recent clinically serious viral, bacterial, fungal, or parasitic infection.

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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No

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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LY3471851 High Dose<br>LY3471851 administered subcutaneously (SC). | Drug: LY3471851<br>* Administered SC<br>* Other names: NKTR-358;|
| Experimental: LY3471851 Mid Dose<br>LY3471851 administered SC. | Drug: LY3471851<br>* Administered SC<br>* Other names: NKTR-358;|
| Experimental: LY3471851 Low Dose<br>LY3471851 administered SC | Drug: LY3471851<br>* Administered SC<br>* Other names: NKTR-358;|
| Placebo Comparator: Placebo<br>Placebo administered SC. | Drug: Placebo<br>* Administered SC<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants who Achieve a ≥4 Point Reduction in Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) 2000 (2K) Score | Percentage of Participants who Achieve a ≥4 Point Reduction in SLEDAI-2K Score | Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants who Achieve British Isles Lupus Assessment Group (BILAG) Based Composite Lupus Assessment (BICLA) Response | Percentage of Participants who Achieve BICLA Response | Week 24 | 
| Percentage of Participants who Achieve Systemic Lupus Erythematosus Responder Index 4 (SRI-4) Response | Percentage of Participants who Achieve SRI-4 Response | Week 24 | 
| Percentage of Participants who Achieve Lupus Low Disease Activity State (LLDAS) | Percentage of Participants who Achieve LLDAS | Week 24 | 
| Pharmacokinetics (PK): Trough Concentrations (Ctrough) of LY3471851 | PK: Ctrough of LY3471851 | Week 24 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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T regulatory cells (Tregs), Interleukin 2, Interleukin-2