Efficacy and Safety of Four Doses of Cenerimod Compared to Placebo in Adult Subjects With Active Systemic Lupus Erythematosus

This is a Phase 2b, multicenter, multinational, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of 4 doses of cenerimod versus placebo in adult subjects with moderately to severely active, autoantibody-positive systemic lupus erythematosus (SLE).

Inclusion criteria

• Signed Informed Consent Form prior to any study-mandated procedure
• Diagnosis of SLE made at least 6 months prior to Screening, by fulfilling at least 4 of the 11 criteria for SLE as defined by the American College of Rheumatology (ACR) criteria
• A mSLEDAI-2K score ≥ 6 of at least 2 points for musculoskeletal or mucocutaneous manifestations (i.e., myositis, arthritis, rash, alopecia, mucosal ulcers).
• Currently treated with stable doses of one or more of the following background medications:

• NSAIDs
• Anti-malarials (≤ 400 mg/day hydroxychloroquine, ≤ 500 mg/day chloroquine, ≤ 100 mg/day quinacrine)
• Mycophenolate mofetil (≤ 2 g/day)
• Mycophenolic acid (≤ 1440 mg/day)
• Azathioprine (≤ 2 mg/kg/day)
• Methotrexate (≤ 20 mg/week)
• Corticosteroids (≤ 40 mg/day prednisone or equivalent)
• Belimumab (≤10 mg/kg every 4 weeks intravenously, or 200 mg/week subcutaneously).
• History or presence of positive autoantibodies measured by central laboratory defined as follows: (a) Positive antinuclear antibody (ANA) test measured by immunofluorescence assay (IFA) with titre ≥1:80; AND/OR (b) positive anti-double stranded deoxyribonucleic acid (anti-dsDNA) antibodies with titre ≥30 IU/mL
• Women of childbearing potential:

• Must have a negative serum pregnancy test at Screening
• Must agree to undertake monthly urine pregnancy tests during the study
• Must use highly effective methods of contraception from the screening visit until 6 months after taking the last dose of study treatment.

Exclusion criteria

• Active lupus nephritis or a renal biopsy demonstrating immune complex mediated glomerulonephritis compatible with lupus nephritis.
• CNS (Central Nervous System) lupus and severe forms of vasculitis requiring systemic immunosuppressive treatment
• A diagnosis of mixed connective tissue disease or any history of overlap syndromes of SLE with rheumatoid arthritis, erosive arthritis, scleroderma or autoimmune hepatitis
• History or presence of Mobitz type II or third-degree atrioventricular block, sick sinus syndrome, symptomatic bradycardia or syncope associated with cardiac disorders
• Subjects who experienced myocardial infarction, unstable angina pectoris, stroke, transient ischemic attack, vascular thrombosis, decompensated heart failure requiring hospitalization, or heart failure defined by the New York Heart Association Class III/IV within six months prior to Screening
• An elevated QT corrected for HR (Heart Rate) on the basis of Fridericia's formula interval of > 470 ms (females) / > 450 ms (males)
• History or presence of severe respiratory disease or pulmonary fibrosis
• Active or latent tuberculosis
• Ongoing bacterial, viral or fungal infection that is of clinical concern in the judgment of the investigator or history of any serious infection
• Subjects who have congenital or acquired severe immunodeficiency or known HIV infection or positive HIV testing
• Presence of macular edema or active uveitis
• Type 1 or 2 diabetes that is poorly controlled according to investigator judgment, or diabetes complicated with organ involvement such as diabetic nephropathy or retinopathy
• Significant hematology abnormality: Lymphocyte count < 800 /μL (0.8 × 10e9/L); hemoglobin < 9 g/dL; WBC (White Blood Cell) count < 2500/μL (2.5 × 10e9/L) or platelets < 75000/μL (75 × 10e9/L)
• Estimated glomerular filtration rate < 60 mL/min/1.73 m2
• Known allergy to S1P (sphingosine-1-phosphate) receptor modulators or any of the cenerimod formulation excipients