Systemic lupus erythematosus (SLE) and cutaneous lupus erythematosus (CLE) MedDRA version: 21.1 Level: PT Classification code 10056509 Term: Cutaneous lupus erythematosus System Organ Class: 10040785 - Skin and subcutaneous tissue disorders MedDRA version: 21.1 Level: PT Classification code 10042945 Term: Systemic lupus erythematosus System Organ Class: 10028395 - Musculoskeletal and connective tissue disorders MedDRA version: 21.1 Level: PT Classification code 10057903 Term: Subacute cutaneo
Conditions
Interventions
Product Name: Enpatoran 25mg
Product Code: M5049
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Enpatoran
CAS Number: 2101938-42-3
Current Sponsor code: M5049
Concentration unit: mg mill
Sponsors
Merck Healthcare KGaA
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Age 1.Are = 18 to = 75 years of age at the time of signing the informed consent. If participants are enrolled in Japan, if a participant is < 20 years of age, the written informed consent from the participant’s parent or guardian will be required in addition to the participant’s written consent for this country. Vaccinations 2.Are up to date, according to local guidelines, with vaccination against Streptococcus pneumoniae and influenza virus (as seasonally required for influenza virus). Active SCLE and/or DLE (Cohort A) 3.Diagnosis of SCLE or DLE documented in medical history. Predominant findings of active lupus rash must be SCLE and/or DLE, but other skin manifestations of CLE will be allowed (e.g., lupus tumidus, Acute Cutaneous Lupus Erythematosus [ACLE], etc) on a case-by-case basis if their main diagnosis is active SCLE and/or DLE. Diagnosis must include one of the following options: a.Historical skin biopsy (i.e., pathology report; punch or shave biopsy) within 10 years prior to Screening visit and confirmation of current diagnosis by skin photography at Screening visit. OR b.Fresh punch skin biopsy at Screening visit. OR c.If target lesion is unsuitable for biopsy (e.g., malar rash, bridge of the nose, scalp), skin photography at Screening visit may be allowed on a case-by-case basis. 4.Disease duration of = 6 months from time of diagnosis to Screening. 5.CLASI-A = 8 at Screening Visit; this must be confirmed at Day 1 Visit. Active SLE 6.Diagnosis of SLE and fulfil Systemic Lupus International Collaborating Clinics (SLICC) classification criteria (Petri 2006), and/or = 4 ACR classification criteria (Hochberg 1997) and/or EULAR/ACR 2019 classification criteria (Aringer 2019). 7.Disease duration of = 6 months from when participant met 2012 SLICC, and/or 1997 ACR (Hochberg 1997), and/or 2019 EULAR/ACR classification criteria for SLE until Screening Visit. 8.Positive test results for ANA (human epithelial cell-2 ANA = 1:80) and/or anti dsDNA antibody (= 15 IU/mL) and/or anti-Smith antibody during Screening Period. 9.Presence of either Scenario 1 OR Scenario 2 (See Figure 1). please refer to Protocol Weight 10.Have a body mass index within the range 18.5 to 35.0 kg/m2 (inclusive). Sex 11.Are male or female at birth. 12.Contraceptive use by males or females will be consistent with local regulations on contraception methods for those participating in clinical studies. a.Female participant: •Is not breastfeeding. •Is not pregnant (i.e., has a negative serum pregnancy test, as required by local regulations, within 24 hours before the first dose of study intervention). Additional requirements for pregnancy testing during and after study intervention are in Section 8.3.4. •Not a Woman of childbearing potential (WOCBP). •If a WOCBP, use a highly effective contraceptive method (i.e., with a failure rate of <1% per year), preferably with low user dependency (two methods may be considered to achieve optimal results i.e. <1% failure rate per year), as described in Appendix 3 for the following time periods: •Before the first dose of the study intervention, if using hormonal contraception: -Has completed at least one 4-Week cycle of an oral contraception pill and either had or has begun her menses. OR -Has used a depot contraceptive or extended-cycle oral contraceptive for least 28 days and has a documented negative pregnancy test using a highly sensitive assay. AND -A barrier method, as described
Exclusion criteria
Exclusion criteria: Medical Conditions 1.Primary diagnosis of autoimmune or rheumatic disease other than SLE or CLE (discuss with Medical Monitor if overlap syndrome). Note: Secondary Sjögren’s syndrome or an autoimmune thyroiditis are not exclusionary. 2.Drug-induced lupus (SLE or CLE). 3.Any condition including dermatological diseases other than cutaneous manifestations of SLE or CLE (e.g., psoriasis), or any uncontrolled disease (e.g., asthma, interstitial lung disease, pulmonary arterial hypertension, morbid obesity), that in Investigator’s or Sponsor/designee’s opinion constitutes inappropriate risk or contraindication for participation. 4.Active lupus nephritis on induction therapy, or induction therapy completed within 3 months of Screening visit (stable maintenance therapy with mycophenolate or azathioprine allowed). 5.Urine protein: creatinine ratio (UPCR) > 4 mg/mg (> 339 mg/mmol), and/or estimated glomerular filtration rate (eGFR) < 45 mL/min/1.73 m2 as calculated by the Modification of Diet in Renal Disease equation by the central laboratory: eGFR = 175 × (serum creatinine in mg/dL)–1.154 × (age in years)–0.203 × 0.742 (if female) × 1.212 (if race is black). 6.Any active signs, symptoms or diagnoses considered related to central nervous system (CNS) lupus within past 3 months or any history of uncontrolled seizures. 7.Any other history of epilepsy, other neurological disorder with seizure propensity, or neuropsychiatric conditions that may interfere with study evaluations. 8.Significant cardiovascular events (e.g., acute myocardial infarction, unstable angina or peripheral vascular disease symptoms, hospitalization for congestive heart failure, uncontrolled or New York Heart Association Class 3 or 4 congestive heart failure, cardiac surgery, ischemic or hemorrhagic stroke, or transient ischemic attack), = 6 months before Screening Visit. 9.Active cardiac arrhythmia or clinically significant abnormality on ECG at Screening Visit or Day 1 that in the Investigator’s or Sponsor/designee’s opinion constitutes inappropriate risk or contraindication for study participation or could interfere with study objectives, conduct or evaluation (included but not limited to long QT syndrome, Wolff Parkinson White syndrome, or a malignant ventricular arrhythmia [e.g., ventricular fibrillation or tachycardia] unless treated). Note: any sinus bradycardia or tachycardia detected in the ECG will not be exclusionary unless other ECG abnormalities are identified. 10.Significant suicide risk in the last year (including suicidal ideation and/or suicidal behavior on the Columbia-Suicide Severity Rating Scale [C-SSRS] during Screening or Day 1). 11.History of or planned renal or solid organ transplant. Please refer to the Protocol for the full list.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the dose-response relationship of enpatoran in reducing disease activity based on Cutaneous Lupus Erythematosus Disease Area and Severity Index-A (CLASI-A) To evaluate the dose-response relationship of enpatoran in reducing disease activity based on BILAG-Based Composite Lupus Assessment (BICLA) response rate;Secondary Objective: To evaluate the safety and tolerability of enpatoran compared to placebo To evaluate the efficacy in disease control of enpatoran compared to placebo in lupus participants with active lupus rash To demonstrate the effect of enpatoran compared with placebo on achieving both BICLA response and clinically meaningful CS reduction in SLE participants on prednisone = 10 mg at Day 1 To evaluate the efficacy in disease control of enpatoran compared to placebo in lupus participants with predominantly active lupus rash To evaluate the efficacy in disease control of enpatoran compared to placebo in participants with active SLE To evaluate the efficacy of enpatoran compared to placebo in patient-reported symptoms and functional status, in lupus participants with active lupus rash To evaluate the efficacy of enpatoran compared to placebo in patient-reported symptoms, in participants with active SLE;Primary end point(s): Percent change from baseline in CLASI-A at Week 16 BICLA response at Week 24;Timepoint(s) of evaluation of this end point: Week 16 and Week 24 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): From Day 1 to the end of Safety Follow-up period •Occurrence of TEAEs, SAEs and AESI •Occurrence of abnormalities (Grade 3) in laboratory parameters •Occurrence of Clinically Important increases in QT Interval Corrected Using Fridericia's Formula (QTcF) •Change from baseline in Cutaneous Lupus Activity Investigator’s Global Assessment (CLA-IGA) at Week 16 and Week 24 •Change from baseline in Physician’s Global Assessment of Cutaneous Lupus Disease Activity at Week 16 and 24 •BICLA response and clinically meaningful CS reduction, defined as reduction of daily prednisone-equivalent dose from = 10 mg at Day 1 to = 5 mg by the Week 12 visit and sustained through Week 24 •Clinically meaningful CS reduction, defined as reduction of daily prednisone-equivalent dose from = 10 mg at Day 1 to = 5 mg by the Week 12 visit and sustained through Week 24 •Occurrence of CLA-IGA 0 or 1 at Week 16 and Week 24 •Systemic lupus erythematosus Responder Index-4 (SRI-4) response at Week 24 •Lupus Low Disease Activity State (LLDAS) attainment at Week 24 •Remission attainment at Week 24 •Clinically meaningful CS reduction, defined as reduction of daily prednisone-equivalent dose from = 10 mg at Day 1 to < 5 mg by the Week 12 visit and sustained through Week 24 •Change in the number of joints which are tender and swollen in 28 joint count from baseline at Week 24 •Change from baseline in Physician’s Global Assessment at Week 24 •Time to first moderate/severe British Isles Lupus Assessment Group (BILAG) flare from Day 1 through Week 24 •Time to first SFI severe flare from Day 1 through Week 24 •Change from Baseline in the Skindex 29+3 Symptom domain score at Week 24 •Change from Baseline in the Skindex 29+3 Functioning and Emotion domain scores at Week 24 •Change from Baseline in the Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue scores at Week 24 •Change from Baseline in the Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue sco | — |
Countries
Argentina, Australia, Brazil, Bulgaria, Chile, China, Colombia, Greece, Hungary, Japan, Mauritius, Mexico, Moldova, Republic of, Philippines, Poland, Romania, Russian Federation, Serbia, South Africa, Spain, Ukraine, United States
Contacts
Public ContactCommunication Center
Merck Healthcare KGaA
Outcome results
None listed