A research study to evaluate the efficacy and safety of cenerimod in subjects suffering from Systemic Lupus Erythematosus

Phase 1

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

• Registration Number: EUCTR2022-002815-47-DE
• Lead Sponsor: Idorsia Pharmaceuticals Ltd

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2022-10-11
• Last Update Posted: 19 February 2024

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 420

Inclusion Criteria

Screening criteria:
• Signed Informed Consent Form (ICF) prior to any study-mandated procedure,
• Diagnosis of Systemic Lupus Erythematosus (SLE) made at least 6 months prior to Screening, according to 2019 European League Against Rheumatism / American College of Rheumatology Criteria.
• A modified Systemic Lupus Erythematosus Disease Activity Index-2000 (mSLEDAI-2K) score = 6 and clinical mSLEDAI-2K score = 4 with at least 2 points for musculoskeletal or mucocutaneous manifestations (i.e., myositis, arthritis, rash, alopecia, mucosal ulcers). The mSLEDAI-2K score does not include leukopenia.
• Currently treated with one or more of the following SLE background medications:
o Antimalarials (= 400 mg/day hydroxychloroquine, = 500 mg/day chloroquine, = 100 mg/day quinacrine).
o Mycophenolate mofetil (= 2 g/day) / mycophenolic acid (= 1.44 g/day).
o Azathioprine (= 2 mg/kg/day).
o Methotrexate (= 25 mg/week).
o Oral Corticosteroids (OCS):
- if OCS is the only SLE background medication: = 7.5 mg/day and = 30 mg/day prednisone or equivalent.
- if OCS is not the only SLE background medication: = 30 mg/day prednisone or equivalent.
o Belimumab (=10 mg/kg every 4 weeks intravenously, or 200 mg/week subcutaneously).
• Treatment with antimalarials, mycophenolate mofetil, mycophenolic acid, azathioprine, methotrexate or belimumab must have been started at least 90 days prior to Screening.
• Treatment with OCS must have been started at least 30 days prior to Screening.
• For women of childbearing potential (WoCBP):
o Negative serum pregnancy test at Screening.
o Agreement to undertake monthly urine pregnancy tests from Randomization up to 6 months after study treatment discontinuation.
o Agreement to use a highly effective method of contraception from Screening (Visit 1) up to 6 months after study treatment discontinuation.

Randomization criteria:
• A clinical mSLEDAI-2K score = 4 with at least 2 points for musculoskeletal or mucocutaneous manifestations (i.e., myositis, arthritis, rash, alopecia, mucosal ulcers).
• British Isles Lupus Assessment Group-2004 (BILAG) Grade B in 2 or more organ systems or a BILAG Grade A in 1 or more organ system.
• Physician's Global Assessment (PGA) score = 1.0 on a 0 to 3 visual analog scale.
• Presence of at least one of the following biomarkers of serological evidence of active SLE (in a Screening sample as measured by central laboratory):
o Anti-dsDNA antibodies elevated to above normal,
o Antinuclear antibodies with a titer of at least 1:160,
o Anti-Smith antibody elevated to above normal.
• Currently treated with one or more of the following SLE background medications that must be stable for at least 30 days prior to
Randomization (except OCS, which must be stable for at least 15 days prior to Randomization):
o Antimalarials (= 400 mg/day hydroxychloroquine, = 500 mg/day chloroquine, = 100 mg/day quinacrine);
o Mycophenolate mofetil (= 2 g/day) / mycophenolic acid (=1.44g/day);
o Azathioprine (= 2 mg/kg/day);
o Methotrexate (= 25 mg/week);
o OCS:
- if OCS is the only SLE background medication: = 7.5 mg/day and = 30 mg/day prednisone or equivalent.
- if OCS is not the only SLE background medication: = 30 mg/day prednisone or equivalent).
o Belimumab (= 10 mg/kg every 4 weeks intravenous (i.v.) or = 200 mg/ week s.c.).
• WoCBP must have a negative urine pregnancy test at Randomization.
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

Exclusion Criteria

• Pregnant, planning to be become pregnant up to Final Study Visit or lactating women.
• Severe active central nervous system lupus or active severe or unstable neuropsychiatric SLE including but not limited to: aseptic meningitis; cerebral vasculitis; myelopathy; demyelination syndromes (ascending, transverse, acute inflammatory demyelinating polyradiculopathy); acute confusional state; impaired level of consciousness; psychosis; acute stroke or stroke syndrome; cranial neuropathy; status epilepticus; cerebellar ataxia; or mononeuritis multiplex:
o That would make the subject unable to fully understand the ICF; OR
o Where, in the opinion of the investigator/delegate, protocol-specified standard of care is insufficient and the use of a more aggressive therapeutic approach, such as adding i.v. cyclophosphamide and/or high dose i.v. pulse corticosteroid (CS) therapy or other treatments not permitted in the protocol is indicated.
• 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 6 months prior to Screening.
• Resting Heart Rate < 50 bpm as measured by the 12-lead ECG at Screening or at Randomization.
• An elevated QT interval corrected according to Fridericia's formula (QTcF) interval of > 470 ms (females) / > 450 ms (males) at Screening or at Randomization.
• History or presence of severe respiratory disease or pulmonary fibrosis, based on medical history, lung function, and chest X-ray (or CT scan as per local guidelines), performed at Screening or within 6 months prior to Screening.
• History of clinically relevant bronchial asthma or chronic obstructive pulmonary disease that has required treatment with oral or parenteral CS for more than a total of 2 weeks within the last 6 months prior to Screening.
• History or presence of malignancy (except for surgically excised and non-recurrent cutaneous basal cell carcinoma, squamous cell carcinoma, or cervical carcinoma), lymphoproliferative disease, or history of total lymphoid irradiation within 10 years prior to Screening.
• Presence of macular edema or active uveitis detected by optical coherence tomography (OCT) during screening.
• History of chronic liver or biliary disease (other than Gilbert's Syndrome) or subjects with alanine aminotransferase or aspartate
aminotransferase > 3 × Upper Limit of Normal (ULN) or total bilirubin >1.5 ULN (unless in the context of known Gilbert's Syndrome).
• Significant hematology abnormality at screening assessment:
o lymphocyte count < 500 /µL (0.5 × 10^9/L);
o hemoglobin < 7 g/dL;
o white blood cell count < 2000/µL (2.0 × 10^9/L); or
o platelets < 25000/µL (25 × 10^9/L).
• Estimated glomerular filtration rate < 15 mL/min/1.73 m^2.
• Treatment with the following medications within 15 days or 5 half-lives of the medication (whichever is longer) prior to Randomization:
o ß-blockers, diltiazem, verapamil, digoxin, digitoxin, or any other antiarrhythmic or heart-rate -lowering systemic therapy.
o QT-prolonging drugs with known risk of torsade de pointes irrespective of indication.
• Treatment with the following medications within 30 days or 5 half-lives of the medicati

Study & Design

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

Primary Outcome Measures

Name	Time	Method
Main Objective: To evaluate the effectiveness of cenerimod 4 mg at reducing disease activity compared to placebo.;Secondary Objective: To evaluate the effect of cenerimod 4 mg to control the disease compared to placebo.;Primary end point(s): Response on Systemic Lupus Erythematosus Responder Index (SRI) at Month 12 compared to baseline, defined as meeting all of the following criteria:<br>• Reduction from baseline of at least 4 points in the mSLEDAI-2K, and<br>• No new British Isles Lupus Assessment Group-2004 (BILAG) A organ domain score and not more than one new BILAG B organ domain score compared to baseline, and<br>• No worsening from baseline in subjects' lupus disease activity, where worsening is defined as an increase = 0.30 points on a 3-point Physician's Global Assessment visual analog scale (PGA VAS), and<br>• No violation of specified medication rules detailed in the core protocol.;Timepoint(s) of evaluation of this end point: At Month 12 compared to Day 1 (pre-dose baseline)