A Study of Enpatoran in Participants With Cutaneous Manifestations of Lupus With or Without Systemic Disease (ELOWEN-2)

A Phase 3, Randomized, Double-Blind,Placebo-Controlled Parallel Study to Evaluate the Efficacy and Safety of Enpatoran in Participants With Active Cutaneous Manifestations of Lupus Erythematosus With or Without Systemic Disease Receiving Standard of Care (ELOWEN-2)

The purpose of this global, multicenter, Phase 3 study is to evaluate the efficacy and safety of enpatoran over 24 weeks in participants with active cutaneous manifestations of lupus erythematosus with or without systemic disease. Study details include:

Study Duration: Up to 35 weeks. Treatment Duration: 24 weeks. Visit Frequency: every 4 weeks, with the exception of the Week 2 televisit. Study Intervention Name: Enpatoran, Placebo.

Intervention Form: Film-coated tablet.

Study Overview

• Status: Not yet recruiting
• Conditions: Cutaneous Lupus Erythematosus; Systematic Lupus Erythematosus
• Intervention / Treatment: Drug: Enpatoran; Drug: Standard of care (SoC); Drug: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 202
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: US Medical Information; Phone Number: 888-275-7376; Email: eMediUSA@emdserono.com
• Study Contact Backup: Name: Communication Center; Phone Number: +49 6151 72 5200; Email: service@emdgroup.com

Study Locations

• Germany
  • Darmstadt, Germany
    • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria

• Vaccinations are up to date according to local guidelines/recommendations. Recombinant zoster vaccination is encouraged but not mandatory.
• Participants with diagnosis of Discoid Lupus Erythematosus (DLE) and/or Subacute Cutaneous Lupus Erythematosus (SCLE) documented in medical history, with or without Systemic Lupus Erythematosus (SLE).
• Participants with active Acute Cutaneous Lupus Erythematosus (ACLE) as sole cutaneous manifestations is allowed in the presence of SLE and should be present for at least 6 weeks prior to the Screening visit.
• Participants with diagnosis of SLE fulfilling the European Alliance of Associations for Rheumatology (EULAR)/American College of Rheumatology (ACR) 2019 classification criteria, must have active DLE and/or SCLE and/or ACLE.

For participants with SLE:

• Participants with diagnosis of SLE and fulfill EULAR/ACR 2019 classification criteria.
• Participants with disease duration (cutaneous disease and, where applicable, SLE) of >= 6 months from time of diagnosis to Screening.
• Participants with CLASI-A score >= 8 at Screening and Day 1 visits.
• Other protocol-defined inclusion criteria may apply.

Exclusion Criteria

• Participants with primary diagnosis of autoimmune rheumatic disease (e.g., systemic sclerosis, rheumatoid arthritis) other than Cutaneous Lupus Erythematosus (CLE) and SLE.
• Participants with any condition including dermatological diseases other than cutaneous manifestations of lupus (e.g. psoriasis), any uncontrolled disease (e.g. asthma, chronic obstructive pulmonary disease, interstitial lung disease, bronchiectasis, pulmonary arterial hypertension), or life-threatening manifestations of lupus (e.g. active systemic vasculitis) that in Investigator's or Sponsor/designee's opinion constitutes inappropriate risk or contraindication for participation.
• Participants with drug-induced lupus (SLE or CLE).
• Participants with active lupus nephritis on induction therapy, or induction therapy completed within 3 months of the Screening visit (stable maintenance therapy with either mycophenolate azathioprine or an oral calcineurin inhibitor is allowed).
• Participants with Urine Protein-to-Creatinine Ratio (UPCR) greater than (>) 339 milligrams per millimole (mg/mmol), and/or estimated Glomerular Filtration Rate (eGFR) less than 40 milliliters per minute per 1.73 square meters of body surface area (mL/min/1.73 m^2), as calculated by the Modification of Diet in Renal Disease (MDRD) equation.
• Participants with any active signs, symptoms, or diagnoses considered related to Central Nervous System (CNS) lupus within the past 3 months, or any history of uncontrolled seizures.
• Other protocol-defined exclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Standard of care (SoC); Participants will receive Investigator-recommended SoC.; Drug: Placebo; Participants will receive a single oral dose of a placebo matching Enpatoran tablet twice daily from Day 1 to Day 168.
Experimental: Enpatoran	Drug: Enpatoran; Participants will receive a dose of Enpatoran orally twice daily from Day 1 to Day 168.; Other Names: M5049; Drug: Standard of care (SoC); Participants will receive Investigator-recommended SoC.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Percentage of Participants With Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) 70 Response, Defined as >= 70 Percent (%) Decrease in CLASI-A Score From Baseline	At Week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With British Isles Lupus Assessment Group Based Composite Lupus Assessment (BICLA) Response	A BICLA response is defined as British Isles Lupus Assessment Group Disease Activity Index 2004 (BILAG 2004) -improvement without worsening (A scores at Baseline improved to B, C or D; B scores improved to C or D; no new A scores and less than or equal to [<=] 1 new B.); Here, score A ("Active"): Severely active disease; score B ("Beware"): Moderately active disease; score C ("Contentment"): Mild stable disease; score D ("Discount"): Inactive now but previously active; -no worsening in disease activity (no new BILAG 2004 A scores and <= 1 new B score); -no worsening of total Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score from Baseline; -no significant deterioration (less than [<] 10% worsening) in visual analog Physician's Global Assessment (PGA) and -no treatment failure i.e. protocol-prohibited medications as determined by Endpoint Adjudication Committee (EAC) or premature discontinuation from study treatment).	At Week 24
Number of Participants With Treatment Emergent adverse events (TEAEs), Serious Adverse Events (SAEs), and Adverse Events of Special Interest (AESI)		From Day 1 to Week 24
Number of Participants With Abnormal (greater than and equal to [>=] Grade 3) laboratory parameters		From Day 1 to Week 24
Percentage of Participants With CLASI-50 Response, Defined as >=50% Decrease in CLASI-A Score From Baseline		At Weeks 4 and 24
Percentage of Participants With CLASI-A less than and equal to (<=) 3 at Week 24	CLASI-A assesses the signs of CLE disease activity including erythema, scale, and hypertrophy, active alopecia, and mucous membrane disease, Scores range from 0 to 70 points for CLASI-A score. Mild, moderate, and severe disease corresponds with CLASI activity score ranges of 0 to 9, 10 to 20, and 21 to 70, respectively. Higher scores indicate more disease activity.	At Week 24
Change from Baseline in Worst Itch Numeric Rating Scale (NRS) Score at Week 24	The Worst Itch NRS is a self-rated single item scale designed for assessing worst itch in the past 7 days. The scale utilizes 11-point NRS, scored from of 0 (no itch) to 10 (worst imaginable itch).	Baseline and at Week 24
Change from Baseline in CLASI-A Erythema at Week 24	CLASI-A assesses the signs of CLE disease activity including erythema, scale, and hypertrophy, active alopecia, and mucous membrane disease, Scores range from 0 to 70 points for CLASI-A score. Mild, moderate, and severe disease corresponds with CLASI activity score ranges of 0 to 9, 10 to 20, and 21 to 70, respectively. Higher scores indicate more disease activity.	Baseline and at Week 24
Change from Baseline in CLASI-A Scale/Hypertrophy at Week 24	CLASI-A assesses the signs of CLE disease activity including erythema, scale, and hypertrophy, active alopecia, and mucous membrane disease, Scores range from 0 to 70 points for CLASI-A score. Mild, moderate, and severe disease corresponds with CLASI activity score ranges of 0 to 9, 10 to 20, and 21 to 70, respectively. Higher scores indicate more disease activity.	Baseline and at Week 24
Change from Baseline in CLASI-A Alopecia at Week 24	CLASI-A assesses the signs of CLE disease activity including erythema, scale, and hypertrophy, active alopecia, and mucous membrane disease, Scores range from 0 to 70 points for CLASI-A score. Mild, moderate, and severe disease corresponds with CLASI activity score ranges of 0 to 9, 10 to 20, and 21 to 70, respectively. Higher scores indicate more disease activity.	Baseline and at Week 24
Percentage of Participants With a Cutaneous Lupus Activity Investigator's Global Assessment-Revised (CLA-IGA-R OMC) Score of 0 or 1 and at Least a 1-Point Reduction at Week 24	The CLA-IGA-R is assessed by the investigator, who assigns rater to assign scores to 3 individual domains (e.g. erythema, other morphologic characteristics - OMC [scales, edema)/infiltration and secondary change (vesicles, erosion, crusting)] and follicular activity). Clinicians assess the severity of the first 2 domains of erythema and OMC from 0 (Clear) to 4 (Severe); they assess the severity of the third domain of follicular activity as "absent" or "present." Higher scores indicate more disease activity.	At Week 24
Percentage of Participants with BILAG Moderate to Severe Flares		up to Week 24
Percentage of Participants With Clinically Meaningful Corticosteroid (CS) Reduction	Clinically meaningful CS reduction, is defined as reduction of daily prednisone-equivalent dose from >= 10 milligrams (mg) at Day 1 to <= 5 mg by the Week 12 visit and sustained through Week 24.	Day 1 up to Week 12 and thereafter upto Week 24
Time to First Moderate/Severe BILAG Flare	Median time to first moderate or severe BILAG Flare will be calculated.	Day 1 through Week 24
Percentage of Participants with Corticosteroid (CS) reduction of Daily Prednisone Equivalent Dose	CS reduction is defined as of daily prednisone-equivalent dose from >= 10 milligrams per day (mg/day) at Day 1 to <= 5 mg/day and sustained for 12 weeks	Day 1 up to 24 weeks

Collaborators and Investigators

• Sponsor: EMD Serono Research & Development Institute, Inc.
• Collaborators: Merck KGaA, Darmstadt, Germany
• Investigators: Study Director: Medical Responsible, Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany

Publications and helpful links

Helpful Links

• US Medical Information website, Medical Resources
• Trial Awareness and Transparency website

Study record dates

Study Major Dates

• Study Start (Estimated): March 27, 2026
• Primary Completion (Estimated): May 25, 2029
• Study Completion (Estimated): May 25, 2029

Study Registration Dates

• First Submitted: March 10, 2026
• First Submitted That Met QC Criteria: March 10, 2026
• First Posted (Actual): March 13, 2026

Study Record Updates

• Last Update Posted (Actual): March 13, 2026
• Last Update Submitted That Met QC Criteria: March 10, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Lupus; Adults; SLE; Systemic lupus erythematosus; Toll-like Receptor 7; Toll-like Receptor 8; CLE; Discoid lupus erythematosus; Subacute cutaneous lupus erythematosus; M5049; Enpatoran; Lupus erythematosus; Cutaneous manifestations; Interferon gene signature; Acute cutaneous lupus erythematosus
• Additional Relevant MeSH Terms: Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Lupus Erythematosus, Systemic; Lupus Erythematosus, Cutaneous; Lupus Erythematosus, Discoid; Health Services Administration; Health Care Quality, Access, and Evaluation; Quality of Health Care; Quality Indicators, Health Care; Standard of Care
• Other Study ID Numbers: MS504908_0008; 169831 (Other Identifier: IND); 2025-524855-30-00 (Ctis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: We are committed to enhancing public health through responsible sharing of clinical trial data. Following approval of a new product or a new indication for an approved product in both the US and European Union, the study sponsor and/or its affiliated companies will share study protocols, anonymized patient data and study level data, and redacted clinical study reports with qualified scientific and medical researchers, upon request, as necessary for conducting legitimate research. Further information on how to request data can be found on our website bit.ly/IPD21.
• IPD Sharing Time Frame: Within six months after the approval of a new product or a new indication for an approved product in both the United States and the European Union.
• IPD Sharing Access Criteria: Qualified scientific and medical researchers can request the data. Such requests must be submitted in writing to the company's portal and will be internally reviewed regarding criteria for researchers' qualification and legitimacy of the research proposal.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No