Study of Edecesertib in Participants With Cutaneous Lupus Erythematosus (CLE)

Study Overview
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Brief Summary
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The goal of this clinical study is to test how edecesertib (formerly known as GS-5718) can be useful in treating Cutaneous Lupus Erythematosus (CLE) in participants with CLE. Information on what is happening in the body relating to CLE, how the body processes, is affected by and responds to the study drug, and any study drug side effects will also be collected in this study.

Official Title
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A Randomized, Blinded, Placebo-Controlled, Phase 2a, Proof-of-Concept Study to Evaluate Efficacy, Safety, and Tolerability of GS-5718 in Participants With Cutaneous Lupus Erythematosus (CLE)

Conditions
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Cutaneous Lupus Erythematosus (CLE)

Intervention / Treatment
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* Drug: Edecesertib
* Drug: Edecesertib Placebo


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Either fulfill European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) 2019 classification criteria for systemic lupus erythematosus (SLE) and/or have biopsy confirmed Cutaneous Lupus Erythematosus (CLE) at any time. Must have active CLE at screening and Day 1. Individuals with acute CLE (ACLE) must have involvement of 2 distinct body areas. Cutaneous Lupus Erythematosus Disease Area and Severity Index activity - A (CLASI-A) score (excluding alopecia) of ≥ 8 and CLASI-A erythema score of ≥ 4 during screening and on Day 1. Individuals with SLE must have Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score of ≥ 4 at screening. Presence of at least 1 representative lupus skin lesion amenable to punch biopsy and individual willingness to undergo skin punch biopsy at 2 time points. Must have documented prior intolerance or inadequate response at any time (per investigator judgement) to protocol-specified treatments. Topical corticosteroids or topical calcineurin inhibitors. Oral corticosteroids. Any other nonbiologic standard-of-care therapy, including, but not limited to: chloroquine, quinacrine, hydroxychloroquine, azathioprine, mycophenolate mofetil (MMF), leflunomide, dapsone, or methotrexate (MTX). Individuals willing to comply with all study visits and assessments. Key Exclusion Criteria: Individuals with only chilblains lupus, lupus panniculitis, lupus tumidus and/or localized acute CLE involving only 1 distinct body area at screening and Day 1. Have highly active SLE (including but not limited to lupus nephritis, neuropsychiatric SLE, and/or vasculitis). Presence of active skin conditions other than cutaneous lupus that may interfere with assessing lupus-specific skin lesion(s) (eg, psoriasis, and/or drug-induced lupus). Meet protocol-specified infection or lab criteria. Any active infection that is clinically significant (per investigator judgment). Any history of clinically significant liver disease. Significant cardiovascular disease. Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: Edecesertib<br>Participants will receive edecesertib 30 mg, once daily starting on Day 1 for up to 12 weeks. | Drug: Edecesertib<br>* Tablets administered orally<br>* Other names: GS-5718;|
| Placebo Comparator: Edecesertib Placebo<br>Participants will receive edecesertib placebo, once daily starting on Day 1 for up to 12 weeks. | Drug: Edecesertib Placebo<br>* Tablets administered orally<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change From Baseline in Cutaneous Lupus Erythematosus Disease Area and Severity Index Activity (CLASI-A) Score at Week 12 | The CLASI is a standardized, validated measure of cutaneous lupus disease activity and damage, widely used in clinical trials. CLASI consists of CLASI - activity (A) and - damage (D) measurements. CLASI-A scores range from 0 to 70, with higher scores indicating more severe disease activity. | Baseline, Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of Participants With Cutaneous Lupus Activity Investigator Global Assessment (CLA-IGA) Score of 0 or 1 at Week 12 | The CLA-IGA is a measure of cutaneous lupus erythematosus (CLE) activity and will be recorded on a scale of 0 to 4, with 0 indicating clear and 4 indicating severe. | Week 12 | 
| Percentage of Participants Experiencing Treatment-emergent Adverse Events (TEAEs) |  | First dose date up to 12 weeks plus 30 days | 
| Percentage of Participants Experiencing Serious Treatment-emergent Adverse Events (TESAEs) |  | First dose date up to 12 weeks plus 30 days | 
| Percentage of Participants Experiencing Laboratory Abnormalities |  | First dose date up to 12 weeks plus 30 days | 
| Plasma Concentration of Edecesertib |  | Postdose at Week 2, Predose at Week 4 and 12, and Week 8 (anytime of the day) |