A research study to evaluate the effects of a new oral drug called cenerimod in adults with Systemic Lupus Erythematosus disease

Phase 1

• Conditions: Moderate to severe systemic lupus erythematosus; Therapeutic area: Diseases [C] - Immune System Diseases [C20]; MedDRA version: 21.1Level: PTClassification code 10042945Term: Systemic lupus erythematosusSystem Organ Class: 10028395 - Musculoskeletal and connective tissue disorders

• Registration Number: EUCTR2018-001808-11-BG
• Lead Sponsor: Idorsia Pharmaceuticals Ltd

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2018-12-06
• Study Completion: 2022-08-25
• Last Update Posted: 11 September 2023

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 427

Inclusion Criteria

- Signed ICF 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). The mSLEDAI-2K score does not take into account leukopenia”
- 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 [i.v.], or 200
mg/week subcutaneously [s.c.]).
- Presence of at least one of the following autoantibodies measured by
central laboratory defined as follows: (a) Positive antinuclear antibody
(ANA) test measured by immunofluorescence assay (IFA) with titre =
1:80; or (b) positive anti-double stranded deoxyribonucleic acid (antidsDNA)
antibodies with titre =30 IU/mL.
- Women of childbearing potential (WOCBP):
- 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 (WOCBP):
• 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 4 months after taking the last dose of study treatment

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 310
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 15

Exclusion Criteria

- Active lupus nephritis or a renal biopsy demonstrating immune
complex-mediated glomerulonephritis compatible with lupus nephritis
within 90 days prior to Screening.
- Severe active central nervous system (CNS) lupus requiring therapeutic
intervention (including aseptic meningitis, seizures, psychosis,
cerebritis, cerebrovascular accident [CVA], organic brain syndrome, CNS
vasculitis) and severe forms of vasculitis requiring systemic
immunosuppressive treatment (including retinal vasculitis, coronary
vasculitis, pulmonary vasculitis, mesenteric vasculitis) within 90 days
prior to Screening.
- 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 on the basis of Fridericia’s formula interval of > 470 ms (females) / > 450 ms (males).
- History of clinically relevant bronchial asthma or chronic obstructive
pulmonary disease that has required treatment with oral or parenteral
corticosteroids for more than 2 weeks within the last 6 months prior to
Screening.
- 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 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 receptor modulators or any of the cenerimod formulation excipients

Study & Design

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

Primary Outcome Measures

Name	Time	Method
Main Objective: To assess the efficacy of 6 months cenerimod treatment given at 4 different dose levels (0.5, 1, 2, and 4 mg once daily) on disease activity in adult subjects with moderate to severe SLE concurrently receiving background therapy;Secondary Objective: To evaluate over 6 months in adult subjects with moderate to severe SLE concurrently receiving background therapy:<br>• the safety and tolerability of cenerimod treatment<br>• the effect of cenerimod treatment on quality of life and fatigue using relevant patient reported outcome (PRO) instruments<br>• the effect of cenerimod treatment on SLE biomarkers<br>;Primary end point(s): Change from baseline to Month 6 in the mSLEDAI-2K score;Timepoint(s) of evaluation of this end point: From Baseline (Baseline is defined as the last available measurement<br>before the start of randomized) to Month 6 (Day 180).

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): 1. Response on Systemic Lupus Erythematosus Responder Index (SRI-4)<br>at Month 6 as compared to baseline, defined as follows:<br>- Reduction from baseline of at least 4 points in the mSLEDAI-2K<br>AND<br>- No new British Isles Lupus Assessment Group (BILAG) A organ domain<br>score and no more than one new BILAG B organ domain score compared<br>with baseline<br>AND<br>- No increase of more than 0.3 points on the Physician's Global<br>Assessment (PGA) since baseline.<br>2. Response (no worsening) at Month 6 on BILAG-2004 disease activity<br>index defined as no new BILAG A organ domain score and no more than<br>one new BILAG B organ domain score compared with baseline.;Timepoint(s) of evaluation of this end point: 1. Response on Systemic Lupus Erythematosus Responder Index (SRI-4)<br>at Month 6 (Day 180) after start of treatment.<br>2. Response on BILAG-2004 disease activity index at Month 6 (Day 180)<br>after start of treatment.