A Study of Enpatoran in Patients With Systemic Lupus Erythematosus andCutaneous Lupus Erythematosus

Phase 1

• Conditions: Systemic lupus erythematosus (SLE) and cutaneous lupus erythematosus (CLE); MedDRA version: 21.1Level: PTClassification code 10056509Term: Cutaneous lupus erythematosusSystem Organ Class: 10040785 - Skin and subcutaneous tissue disorders; MedDRA version: 21.1Level: PTClassification code 10042945Term: Systemic lupus erythematosusSystem Organ Class: 10028395 - Musculoskeletal and connective tissue disorders; MedDRA version: 21.1Level: PTClassification code 10057903Term: Subacute cutaneous lupus erythematosusSystem Organ Class: 10040785 - Skin and subcutaneous tissue disorders; Therapeutic area: Diseases [C] - Immune System Diseases [C20]

• Registration Number: EUCTR2021-004648-27-ES
• Lead Sponsor: Merck Healthcare KGaA

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2021-11-19
• Last Update Posted: 28 March 2022

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 440

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

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.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified