Enpatoran for cutaneous 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)

This 24-week study will test whether enpatoran tablets can improve active skin symptoms in adults with cutaneous lupus, with or without systemic lupus.

Quick facts

• Phase: PHASE3
• Study type: Interventional
• Enrollment: 202 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: EMD Serono (industry)
• Locations: 4 sites (Upland, California and 3 other locations)
• Trial ID: NCT07355218 on ClinicalTrials.gov

What this trial studies

This global, multicenter Phase 3 trial compares oral enpatoran to placebo alongside standard-of-care in adults with active cutaneous lupus manifestations. Participants take film-coated enpatoran tablets or matching placebo for 24 weeks, attend clinic visits every four weeks with a Week 2 televisit, and are followed for up to 35 weeks in total. Eligible participants have documented discoid, subacute, or acute cutaneous lupus (ACLE allowed if present ≥6 weeks and, when applicable, in the setting of SLE) and meet local vaccination guidance. Safety data and measures of skin response will be collected throughout treatment to determine whether enpatoran provides superior benefit to placebo.

Who should consider this trial

Good fit: Adults with documented DLE, SCLE, or ACLE (ACLE present at least 6 weeks) who have active cutaneous disease — including those with SLE meeting EULAR/ACR 2019 criteria — are the intended participants.

Not a fit: People without active cutaneous lesions or those whose lupus presentations are not included in the eligibility criteria (for example isolated systemic disease without active skin involvement) are unlikely to benefit from this study.

Why it matters

Potential benefit: If effective, enpatoran could reduce skin lesions and symptoms, improving patients' skin-related quality of life and providing a new oral treatment option.

How similar studies have performed: Targeting Toll-like receptor 7/8 is a relatively new approach with promising signals from early-phase studies of enpatoran and related agents, but confirmatory phase 3 evidence is limited.

Eligibility criteria

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.

Where this trial is running

Upland, California and 3 other locations

• Inland Rheumatology Clinical Trials, Inc. — Upland, California, United States (RECRUITING)
• Omega Research Debary, LLC — DeBary, Florida, United States (RECRUITING)
• Bolanos Clinical Research — Pembroke Pines, Florida, United States (RECRUITING)
• Dawes Fretzin Clinical Research Group, LLC — Indianapolis, Indiana, United States (RECRUITING)

Study contacts

• Study coordinator: US Medical Information

Conditions: Systematic Lupus Erythematosus, Cutaneous Lupus Erythematosus, Toll-like Receptor 7, Toll-like Receptor 8, Adults, SLE, CLE, Lupus