The Willow LTE Study With M5049 in Participants With SCLE, DLE and/or SLE (WILLOW LTE)

Study Overview
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Brief Summary
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The purpose of the study is to evaluate the long term safety and efficacy of orally administered M5049 in participants with subacute cutaneous lupus erythematosus (SCLE), discoid lupus erythematosus (DLE) and/or systemic lupus erythematosus (SLE) who have completed the 24 week treatment period of Willow study (MS200569_0003 [NCT05162586]).

Official Title
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A Phase II, Double-blind, Dose-Ranging, Parallel, Long-term Extension Study to Evaluate the Safety and Efficacy of Enpatoran in Participants With Subacute Cutaneous Lupus Erythematosus, Discoid Lupus Erythematosus and/or Systemic Lupus Erythematosus Having Completed the WILLOW (MS200569_0003) Study Treatment (WILLOW LTE)

Conditions
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Systemic Lupus Erythematosus

Intervention / Treatment
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* Drug: M5049 low dose
* Drug: M5049 medium dose
* Drug: M5049 high dose
* Drug: Placebo
* Drug: M5049 very high dose


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Are active SCLE, DLE and/or SLE that have completed the 24 week Treatment of the Willow Study Have a Body Mass Index (BMI) within the >= 40 kilograms per meter square (inclusive) at Screening Other protocol defined inclusion criteria could apply Exclusion Criteria: Participants who experienced serious event(s) related to the study intervention during the WILLOW study Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with Long Term Extension (LTE) study participation Ongoing or active clinically significant viral (including Severe acute respiratory syndrome coronavirus 2 [(SARS-CoV-2)], bacterial or fungal infection, or any major episode of infection requiring hospitalization Received LTE prohibited medication during the WILLOW study or after the WILLOW study Week 24 Participation in any other investigational drug study after the WILLOW study Week 24 Other protocol defined exclusion criteria could apply

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 76 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: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: M5049 low dose + Placebo<br>Participants with CLE (active SCLE and/or DLE) or SLE who received low dose of M5049 in WILLOW study will continue to receive M5049 low dose and matching placebo. | Drug: M5049 low dose<br>* Participants will receive film-coated tablets of M5049 at a low dose orally, twice a day (BID) for up to 48 weeks.<br>* Other names: Enpatoran;Drug: Placebo<br>* Participants will receive M5049 matching placebo orally, BID for up to 48 weeks.<br>|
| Experimental: M5049 medium dose+ Placebo<br>Participants with CLE (active SCLE and/or DLE) or SLE who received medium dose of M5049 in WILLOW study will continue to receive M5049 medium dose and matching placebo. | Drug: M5049 medium dose<br>* Participants will receive film-coated tablets of M5049 at a medium dose orally, BID for up to 48 weeks.<br>* Other names: Enpatoran;Drug: Placebo<br>* Participants will receive M5049 matching placebo orally, BID for up to 48 weeks.<br>|
| Experimental: M5049 high dose + Placebo<br>Participants with CLE (active SCLE and/or DLE) or SLE who received M5049 matched placebo or high dose of M5049 in WILLOW study will receive M5049 high dose . | Drug: M5049 high dose<br>* Participants will receive film-coated tablets of M5049 at a high dose orally, BID for up to 48 weeks.<br>* Other names: Enpatoran;Drug: Placebo<br>* Participants will receive M5049 matching placebo orally, BID for up to 48 weeks.<br>|
| Experimental: M5049 very high dose + Placebo<br>Participants with CLE (active SCLE and/or DLE) or SLE who received M5049 matched placebo or very high dose of M5049 in WILLOW study will receive M5049 very high dose. | Drug: Placebo<br>* Participants will receive M5049 matching placebo orally, BID for up to 48 weeks.<br>Drug: M5049 very high dose<br>* Participants will receive film-coated tablets of M5049 at a very high dose orally, BID for up to 48 weeks.<br>* Other names: Enpatoran;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety Profile as Assessed by Incidence of Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Adverse Event of Special Interest (AESIs) |  | Baseline up to Week 50 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants with Abnormalities in Laboratory Parameters and QT Interval Corrected |  | Baseline up to Week 50 | 
| Percent Change from WILLOW Study Baseline in Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI-A) at Weeks 0, 2, 4, 12, 24, 36 and 48 |  | Baseline (WILLOW study), Weeks 0, 2, 4, 12, 24, 36 and 48 | 
| Change from WILLOW Study Baseline in Cutaneous Lupus Activity Investigator's Global Assessment (CLA-IGA) at Weeks 0, 2, 4, 12, 24, 36 and 48 |  | Baseline (WILLOW study), Weeks 0, 2, 4, 12, 24, 36 and 48 | 
| Number of Participants With Based Composite Lupus Assessment (BICLA) Response |  | At Weeks 24 and 48 | 
| Number of Participants With Systemic lupus Erythematosus Responder Index-4 (SRI-4) Response |  | At Weeks 24 and 48 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Toll-like Receptor 7, Toll-like Receptor 8, WILLOW, Adults, SLE, CLE, Lupus, Discoid lupus erythematosus, Subacute cutaneous lupus erythematosus, M5049, Enpatoran, LTE