Active Cutaneous Manifestations of Lupus Erythematosus With or Without Systemic Disease
Conditions
Interventions
Enpatoran or Placebo
Placebo
Sponsors
Merck Healthcare KGaA
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: = 18 to = 75 years of age at the time of signing the informed consent. Are up to date according to local guidelines/recommendations. Recombinant zoster vaccination is encouraged but not mandatory. Cutaneous manifestation criteria: • Diagnosis of DLE and/or SCLE documented in medical history, with or without SLE. • Active ACLE as sole cutaneous manifestations is allowed in the presence of SLE (meeting criterion 4) and should be present for at least 6 weeks prior to the Screening visit. • Other skin manifestations will be allowed (e.g. lupus tumidus, lupus profundus, Chilblain lupus, etc.) on a case-by-case basis if the main diagnosis is active DLE, SCLE, and/or ACLE, as described above. Confirmation of diagnosis must include 1 of the following options: a. Pathology report from punch or shave biopsy within 10 years prior to Screening visit and confirmation of current diagnosis by mandatory skin photography at Screening visit. OR b. Fresh punch skin biopsy and confirmation of current diagnosis by mandatory skin photography, both performed at/during Screening. OR c. On a case-by-case basis (e.g. the target lesion is unsuitable for biopsy), mandatory skin photography may be used for diagnosis in lieu of a skin biopsy, if feasible, after discussion with the medical monitor. The Sponsor/SET may provide expert opinion for disease diagnosis based on the required photographs submitted at Screening. For participants with SLE: a. Diagnosis of SLE and fulfill EULAR/ACR 2019 classification criteria (Aringer 2019). b. Positive ANA (IFA titer = 1:80) and/or dsDNA and/or a-Sm autoantibody at Screening. Note: All participants, regardless of initial diagnosis, will be reviewed at Screening for meeting SLE classification criteria. BILAG will be performed in all SLE participants at Screening to confirm level of disease activity. Disease duration (both cutaneous disease and SLE, where applicable) of = 6 months from time of diagnosis to Screening. CLASI-A = 8 at Screening and Day 1 Visits
Exclusion criteria
Exclusion criteria: Primary diagnosis of autoimmune rheumatic disease (e.g. systemic sclerosis, rheumatoid arthritis) other than CLE and SLE. Note: Secondary Sjögren’s syndrome is not exclusionary. 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. Drug-induced lupus (SLE or CLE). Active lupus nephritis on induction therapy, or induction therapy completed within 3 months of Screening visit (stable maintenance therapy with either mycophenolate, azathioprine or an oral calcineurin inhibitor is allowed). UPCR > 339 mg/mmol, and/or eGFR < 40 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) Any active signs, symptoms or diagnoses considered related to CNS lupus within the past 3 months or any history of uncontrolled seizures. Any other history of epilepsy or other neurological disorder with seizure propensity which requires ongoing pharmacological treatment, or neuropsychiatric conditions that may interfere with study evaluations. Significant thrombotic (e.g. catastrophic antiphospholipid syndrome, pulmonary embolism) or 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. Any clinically significant ECG abnormality (e.g. acute myocardial infarction, WPW, etc.) that in the Investigator’s or Sponsor/designee’s opinion constitutes inappropriate risk or contraindication for study participation. Suicide risk in the last 6 months (including suicidal ideation and/or suicidal behavior on the C-SSRS during Screening or Day 1). History of or planned solid organ transplant. Ongoing or active clinically significant viral (including SARS CoV 2), parasitic, bacterial (including active or untreated latent TB, see Exclusion Criterion 14) or fungal infection: • Requiring hospitalization or, • Treatment with parenteral anti-infectives = 4 weeks prior to or during Screening Period, or • Completion of oral anti-infectives = 2 weeks prior to Day 1 Visit. • Investigators should follow their local guidelines for SARS CoV 2 testing during the Screening period (e.g. testing regardless of symptoms, or potential exposure may be required before entering a research study, symptomatic, or exposure-based testing at Screening only, etc.). • Vaginal candidiasis, onychomycosis, and genital, or oral herpes simplex virus considered to be sufficiently controlled will not be exclusionary. Any of the following: a. A positive HIV test. b. Positive HCV Ab and detectable HCV RNA NAAT performed reflexively at Screening, or history of treated HCV with detectable HCV RNA NAAT performed reflexively at Screening. c. Positive HBV surface antigen, or positive HBV core Ab with negative HBV surface Ab and
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To demonstrate the efficacy of enpatoran in reducing cutaneous disease activity by achieving at least 70% reduction from Baseline in CLASI-A total score (CLASI 70) at Week 24 | — |
Secondary
| Measure | Time frame |
|---|---|
| To demonstrate the efficacy of enpatoran in reducing overall disease activity by achieving BICLA response at Week 24;To evaluate safety and tolerability of enpatoran;To demonstrate the fast onset of action of enpatoran in reducing cutaneous disease by achieving at least 50% reduction from Baseline in CLASI-A total score (CLASI 50) at Week 4;To demonstrate the efficacy of enpatoran in the achievement of low cutaneous disease activity/remission at Week 24 ;To evaluate the efficacy of enpatoran on reduction of cutaneous disease activity;To demonstrate the efficacy of enpatoran in reducing systemic disease activity and CS use;To evaluate the effect of enpatoran on itch | — |
Countries
South Africa
Contacts
Public ContactDeidre Marais
Start up Specialist
Outcome results
None listed