Cutaneous Lupus Erythematosus, Systematic Lupus Erythematosus
Conditions
Keywords
Toll-like Receptor 7, Toll-like Receptor 8, Adults, SLE, CLE, Lupus, Discoid lupus erythematosus, Subacute cutaneous lupus erythematosus, M5049, Enpatoran, Cutaneous manifestations, Lupus erythematosus, Acute cutaneous lupus erythematosus, Systemic lupus erythematosus, Interferon gene signature
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.
Interventions
DRUGEnpatoran
Participants will receive a dose of Enpatoran orally twice daily from Day 1 to Day 168.
DRUGPlacebo
Participants will receive a single oral dose of a placebo matching Enpatoran tablet twice daily from Day 1 to Day 168.
DRUGStandard of care (SoC)
Participants will receive Investigator-recommended SoC.
Sponsors
EMD Serono Research & Development Institute, Inc.
Merck KGaA, Darmstadt, Germany
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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
Design outcomes
Primary
| 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
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With British Isles Lupus Assessment Group Based Composite Lupus Assessment (BICLA) Response | At Week 24 | 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). |
| 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-A less than and equal to (<=) 3 at Week 24 | 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. |
| 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 Clinically Meaningful Corticosteroid (CS) Reduction | Day 1 up to Week 12 and thereafter upto Week 24 | 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. |
| Change from Baseline in Worst Itch Numeric Rating Scale (NRS) Score at Week 24 | Baseline and 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). |
| Change from Baseline in CLASI-A Erythema at Week 24 | Baseline and 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. |
| Change from Baseline in CLASI-A Scale/Hypertrophy at Week 24 | Baseline and 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. |
| Change from Baseline in CLASI-A Alopecia at Week 24 | Baseline and 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. |
| 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 | 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. |
| Percentage of Participants with BILAG Moderate to Severe Flares | up to Week 24 | — |
| Time to First Moderate/Severe BILAG Flare | Day 1 through Week 24 | Median time to first moderate or severe BILAG Flare will be calculated. |
| Percentage of Participants with Corticosteroid (CS) reduction of Daily Prednisone Equivalent Dose | Day 1 up to 24 weeks | 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 |
Countries
Germany
Contacts
CONTACTUS Medical Information
CONTACTCommunication Center
STUDY_DIRECTORMedical Responsible
Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany
Outcome results
None listed