Efficacy and Safety of Four Doses of Cenerimod Compared to Placebo in Adult Subjects With Active Systemic Lupus Erythematosus
Condition: Systemic Lupus Erythematosus
MeSH terms: Lupus Erythematosus, Systemic
Intervention: Cenerimod 0.5 mg; Cenerimod 1 mg; Cenerimod 2 mg; Cenerimod 4 mg; Placebo; cenerimod 2 mg (ex-4 mg)
Intervention description: Cenerimod will be supplied as a film-coated tablets at the dose of 0.5 mg; Cenerimod will be supplied as a film-coated tablets at the dose of 1 mg; Cenerimod will be supplied as a film-coated tablets at the dose of 2 mg; Cenerimod will be supplied as a film-coated tablets at the dose of 4 mg; Matching placebo will be supplied as identical film-coated tablets formulated with the same excipients but without the active ingredient, cenerimod; Cenerimod will be supplied as a film-coated tablets at the dose of 2 mg
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Participants randomized to the 4 mg arm who are still on treatment at month 6 will be re-randomized in a 1:1 ratio to placebo or cenerimod 2 mg to enter Treatment Period 2 and will continue study treatment for a total maximum of 12 months.
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 427.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: No
Keywords: Musculoskeletal and connective tissue disorders

Summary:

      The purpose of the study is to assess the efficacy and safety of 4 doses of cenerimod versus
      placebo in adult subjects with systemic lupus erythematosus (SLE).
    

Eligibility criteria:

        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