A Study of Enpatoran in Participants With Cutaneous Manifestations of Lupus With or Without Systemic Disease

NCT07332481 | Recruiting Phase 3 FDA Drug

• 3 other identifiers: MS504908_00011698312025-523871-44-00
• Study Type: interventional
• Target: 202
• Locations: 1 country
• Sites: 3

Brief Summary

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.

Conditions

Systemic Lupus Erythematosus (SLE); Cutaneous Lupus Erythematosus (CLE)

Keywords

Toll-like Receptor 7; Toll-like Receptor 8; Adults; SLE; CLE; Lupus; Discoid lupus erythematosus (DLE); Subacute Cutaneous Lupus Erythematosus (SCLE); M5049; Enpatoran; Cutaneous manifestations; Lupus erythematosus; Acute cutaneous lupus erythematosus (ACLE); Interferon gene signature

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (14)

• Percentage of Participants With British Isles Lupus Assessment Group Based Composite Lupus Assessment (BICLA) Response

  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

  At Week 24

Study Arms (2)

Enpatoran

EXPERIMENTAL

Drug: Enpatoran; Drug: Standard of care (SoC)

Placebo

PLACEBO COMPARATOR

Drug: Placebo; Drug: Standard of care (SoC)

Interventions

Enpatoran DRUG

Participants will receive a dose of Enpatoran orally twice daily from Day 1 to Day 168.

Also known as: M5049

Enpatoran

Placebo DRUG

Participants will receive a single oral dose of a placebo matching Enpatoran tablet twice daily from Day 1 to Day 168.

Placebo

Standard of care (SoC) DRUG

Participants will receive Investigator-recommended SoC.

Enpatoran; Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• EMD Serono Research & Development Institute, Inc.: lead
• Merck KGaA, Darmstadt, Germany: collaborator

Study Sites (3)

Dermatology Research Associates - 300204025

Los Angeles, California, 90045, United States

RECRUITING

Revival Research Institute, LLC

Troy, Michigan, 48084, United States

RECRUITING

Arthritis and Rheumatology Research Institute PLLC

Allen, Texas, 75013, United States

RECRUITING

Related Links

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

MeSH Terms

Conditions

Lupus Erythematosus, Systemic; Lupus Erythematosus, Cutaneous; Lupus Erythematosus, Discoid

Interventions

Standard of Care

Condition Hierarchy (Ancestors)

Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Skin Diseases

Intervention Hierarchy (Ancestors)

Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Study Officials

• Medical Responsible

  Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany

  STUDY DIRECTOR

Central Study Contacts

Communication Center

CONTACT

+49 6151 72 5200; service@emdgroup.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 9, 2026
• First Posted: January 12, 2026
• Study Start: March 10, 2026
• Primary Completion (Estimated): May 24, 2029
• Study Completion (Estimated): May 24, 2029
• Last Updated: April 27, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• 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.
• 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.

Locations

US (3)