A Research Study to Evaluate the Efficacy and Safety of Cenerimod in Subjects Suffering From Systemic Lupus Erythematosus (OPUS-2)

A Phase 3, Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel-group Study to Evaluate the Efficacy, Safety, and Tolerability of Cenerimod in Adult Subjects With Moderate-to-severe Systemic Lupus Erythematosus (SLE) on Top of Background Therapy

The goal of this clinical trial is to see how well cenerimod reduces symptoms of Systemic Lupus Erythematous in adult patients with moderate to severe symptoms. The main questions it aims to answer are:

• How well cenerimod works on top of the treatment already being administered.
• How safe cenerimod is for adult patients with Systemic Lupus Erythematosus.

Researchers will compare one dose of cenerimod and a placebo to see how well cenerimod works when it is added to the treatment already being administered.

In this research study approximately 210 participants will receive cenerimod and approximately 210 participants will receive placebo for 12 months.

Study Overview

• Status: Active, not recruiting
• Conditions: Lupus Erythematosus, Systemic
• Intervention / Treatment: Drug: Placebo; Drug: Cenerimod

• Study Type: Interventional
• Enrollment (Actual): 451
• Phase: Phase 3

Contacts and Locations

Study Locations

• Chile
  • Providencia, Chile, 7500710
    • Biomedica Research Group
  • Providencia, Chile, 7510186
    • Sociedad Médica del Aparato Locomotor S. A.
  • Santiago, Chile, 7500587
    • Enroll Spa
  • Santiago, Chile, 7500504
    • Estudios G y C Ltda
  • Temuco, Chile, 4810345
    • Centro de especialidades médicas Vanguardia
  • Valdivia, Chile, 5110683
    • Clinical Research Chile SpA
  • Victoria, Chile, 4720001
    • Hospital San Jose de Victoria
• Czechia
  • Brno, Czechia, 60200
    • iMedica s.r.o.
  • Prague, Czechia, 12800
    • Institute of Rheumatology Prague
• Georgia
  • Batumi, Georgia, 6010
    • LTD "New Plasma Clinic"
  • Tbilisi, Georgia, 0160
    • Aversi Clinic Ltd
  • Tbilisi, Georgia, 0160
    • Medi Club Georgia Ltd.
  • Tbilisi, Georgia, 0179
    • Ltd. Mtskheta Street Clinic
  • Tbilisi, Georgia, 0180
    • The First Medical Center Ltd.
  • Tbilisi, Georgia, 0186
    • LLC "Innova"
  • Tbilisi, Georgia, 0186
    • LLC Raymann
  • Tbilisi, Georgia, 0186
    • LTD "Tbilisi Heart Center"
  • Tbilisi, Georgia, 0160
    • Tbilisi Institute of Medicine
  • Tbilisi, Georgia, 0159
    • Institute of Clinical Cardiology, Ltd
  • Tbilisi, Georgia, 0159
    • LTD "Tbilisi Central Hospital"
  • Tbilisi, Georgia, 0159
    • National Institute of Endocrinology Ltd.
  • Tbilisi, Georgia, 0159
    • Tbilisi Heart and Vascular Clinic Ltd.
  • Tbilisi, Georgia, 0186
    • Caucasus Medical Centre
  • Tbilisi, Georgia, 0167
    • JSC Jerarsi Clinic
• Germany
  • Frankfurt am Main, Germany, 60596
    • Fraunhofer-Institut für Translationale Medizin und Pharmakologie ITMP
  • Leipzig, Germany, 4103
    • Universitätsklinikum Leipzig
  • Minden, Germany, 32429
    • Johannes Wesling Klinikum Minden
  • Münster, Germany, 48149
    • Universitätsklinikum Münster (UKM)
• India
  • Ahmedabad, India, 380015
    • Shalby Hospitals
  • Chennai, India, 600004
    • Chennai Meenakshi Multispeciality Hospital Pvt. Ltd.
  • Hyderabad, India, 500038
    • ESIC Medical College and Hospital
  • Kolkata, India, 700020
    • IPGME&R and SSKM Hospital
  • Nagpur, India, 440012
    • Jasleen Hospital
  • Nashik, India, 422005
    • Chopda Medicare & Research Centre
  • New Delhi, India, 110029
    • AIIMS New Delhi
  • Pune, India, 411001
    • Center for Rheumatic Diseases
  • Secunderabad, India, 500003
    • Yashoda Hospital
  • Surat, India, 395002
    • Nirmal Hospital Private Limited
• Malaysia
  • Batu Caves, Malaysia, 68100
    • Hospital Selayang
  • Cheras, Malaysia, 56000
    • Universiti Kebangsaan Malaysia - Medical Centre
  • Kangar, Malaysia, 01000
    • Hospital Tuanku Fauziah, Kangar
  • Kuala Lumpur, Malaysia, 59100
    • University of Malaya Medical Centre
  • Kuching, Malaysia, 93586
    • Sarawak General Hospital
  • Sibu, Malaysia, 96000
    • Hospital Sibu, Sarawak
• Mexico
  • Cuernavaca, Mexico, 62448
    • Consultorio Particular Dr. Miguel Cortés Hernández
  • Guadalajara, Mexico, 44160
    • Centro Integral en Reumatologia SA de CV (CIRSA)
  • León, Mexico, 37000
    • Morales Vargas Centro de Investigación S.C.
  • Mexico City, Mexico, 03720
    • Centro de Investigación Clínica GRAMEL, S.C.
  • Mexico City, Mexico, 06700
    • Clinstile, S.A. de C.V.
  • Mexico City, Mexico, 01120
    • Boca Clinical Trials Mexico, S.C.
  • Monterrey, Mexico, 64460
    • UBAM Unidad Biomedica Avanzada Monterrey
  • Monterrey, Mexico, 64000
    • Accelerium, S. de R.L. de C.V.
  • Mérida, Mexico, 97130
    • Centro Multidisciplinario Para El Desarrollo Especializado De La Investigación Clínica En Yucatán S.C.P. (CEMDEICY S.C.P.)
  • Oaxaca City, Mexico, 68000
    • Oaxaca contra el Cáncer A.C
  • Querétaro, Mexico, 76000
    • Centro de Estudios Clínicos de Querétaro S.C.
  • Tlalnepantla, Mexico, 54055
    • Clinical Research Institute S.C.
  • Toluca, Mexico, 50090
    • PCR Toluca - Phylasis Clinical Research
• Peru
  • Cayma, Peru, 04017
    • Unidad de Investigación en Medicina Interna y Enfermedades Críticas / Hogar Clínica San Juan de Dios
  • Jesús María, Peru, 15076
    • Centro de Investigacion Clinica Inmunoreumatologia / ACQ Medic SAC
  • Jesús María, Peru, 15076
    • Centro de Investigación del Hospital Militar Central
  • Lima, Peru, 07011
    • Alberto Sabogal Sologuren National Hospital
  • Lima, Peru, 15828
    • Hospital Maria Auxiliadora
  • San Borja, Peru, 15036
    • Unidad de Investigación de la Clinica International
  • San Isidro, Peru, 15046
    • Instituto Peruano del Hueso y la Articulación S.A.C. (IPHAR)
  • San Isidro, Peru, 15073
    • Clínica Anglo Americana
  • San Isidro, Peru, 15076
    • Servicios Reumatológicos SOMA E.I.R.L. / Clinica El Golf
  • San Juan de Lurigancho, Peru, 15431
    • Unidad de Investigación en Reumatología e Inmunología CSJB
  • San Martín de Porres, Peru, 15102
    • Hospital Nacional Cayetano Heredia
  • Santiago de Surco, Peru, 15023
    • Investigaciones Clinicas / Instituto de Ginecología y Reproducción, El Derby
  • Trujillo, Peru, 13011
    • Centro de Investigación Clínica Trujillo EIRL / Clínica Peruano Americana S.A
• Philippines
  • Iloilo City, Philippines, 5000
    • Iloilo Doctors Hospital
  • Makati, Philippines, 1229
    • Makati Medical Center
  • Makati City, Philippines, 1218
    • Ospital ng Makati
  • Manila, Philippines, 1102
    • St Lukes Medical Center
  • Pampanga, Philippines, 2023
    • The Medical City Clark
  • Sampaloc, Philippines, 1015
    • St Luke's Medical Center Quezon City / University of Santo Tomas Hospital
• Poland
  • Bydgoszcz, Poland, 85-168
    • Szpital Uniwersytecki nr 2 im. dr. Jana Biziela w Bydgoszczy
  • Lodz, Poland, 90-302
    • Santa Sp. z o.o.
  • Poznan, Poland, 60-218
    • Medyczne Centrum Hetmańska
  • Poznan, Poland, 61-293
    • Twoja Przychodnia Poznańskie Centrum Medyczne
  • Szczecin, Poland, 71-252
    • Pomorski Uniwersytet Medyczny w Szczecinie
  • Warsaw, Poland, 00-874
    • MICS Centrum Medyczne Warszawa
• Portugal
  • Amadora, Portugal, 2720-276
    • Hospital Prof. Doutor Fernando Fonseca
  • Faro, Portugal, 8000-386
    • Centro Hospitalar Universitário do Algarve - Hospital de Faro
  • Guarda, Portugal, 6300-749
    • ULS Guarda
  • Guimarães, Portugal, 4835-044
    • Hospital Senhora Oliveira-Guimaraes
  • Lisbon, Portugal, 1050-034
    • Instituto Portugues de Reumatologia
  • Lisbon, Portugal, 1349-019
    • Unidade Local De Saude Lisboa Ocidental E.P.E.
  • Vila Nova de Gaia, Portugal, 4434-502
    • Centro Hospitalar de Vila Nova de Gaia/Espinho, E.P.E.
• Puerto Rico
  • Caguas, Puerto Rico, 00725
    • Centro Reumatologico de Caguas
  • San Juan, Puerto Rico, 917
    • GCM Medical Group, PSC
• Serbia
  • Belgrade, Serbia, 11000
    • University Clinical Center of Serbia
  • Belgrade, Serbia, 11040
    • Military Medical Academy
  • Belgrade, Serbia, 11000
    • Institute of Rheumatology, Belgrade (study site 1)
  • Belgrade, Serbia, 11000
    • Institute of Rheumatology, Belgrade (study site 2)
  • Belgrade, Serbia, 11000
    • Institute of Rheumatology, Belgrade (study site 3)
  • Kragujevac, Serbia, 34000
    • Clinical Center Kragujevac
  • Novi Sad, Serbia, 21000
    • Special Hospital for Rheumatic Diseases, Novi Sad
  • Zrenjanin, Serbia, 23000
    • General Hospital "Djordje Joanovic"
• South Africa
  • Cape Town, South Africa, 7405
    • Arthritis Clinical Research Trials
  • Cape Town, South Africa, 7500
    • Panorama Medical Centre
  • Parktown, South Africa, 2193
    • Charlotte Maxeke Johannesburg Academic Hospital
  • Pretoria, South Africa, 0002
    • University of Pretoria
  • Somerset West, South Africa, 7130
    • Winelands Medical Research
• Spain
  • Alcobendas, Spain, 28100
    • Accellacare
  • Barcelona, Spain, 08208
    • Parc Taulí Sabadell University Hospital
  • Colmenar Viejo, Spain, 08035
    • Hospital Universitari Vall d'Hebron
  • Colmenar Viejo, Spain, 28770
    • Hospital Universitario Ramon y Cajal
  • Madrid, Spain, 28040
    • Hospital Clinico San Carlos
  • Madrid, Spain, 28031
    • Hospital Universitario Infanta Leonor
  • Santiago de Compostela, Spain, 15702
    • Clínica Gaias Santiago
  • Seville, Spain, 41014
    • Hospital Universitario Nuestra Señora de Valme
  • Seville, Spain, 41013
    • Hospital Quirónsalud Sagrado Corazón
  • Valencia, Spain, 46010
    • Hospital Clinico Universitario de Valencia
  • Valencia, Spain, 46017
    • Hospital Universitario Doctor Peset
  • Valladolid, Spain, 47012
    • Hospital Universitario Río Hortega de Valladolid
• Ukraine
  • Chernihiv, Ukraine, 14029
    • Communal Non-profit Enterprise "Chernihiv Regional Hospital" of the Chernihiv Regional Council, Rheumatology Department
  • Ivano-Frankivsk, Ukraine, 76019
    • St. Luke's Treatment and Diagnostic Center
  • Kyiv, Ukraine, 01135
    • Medical Center "Harmoniia krasy", LLC
  • Kyiv, Ukraine, 02002
    • Medical Center of the Limited Liability Company "Edelweiss Medics", Treatment and Prevention Department
  • Kyiv, Ukraine, 02091
    • Med Center "Ok!Clinic+" of Ltd Liability Com "Inter Ins of Clin Rsrch", Inpatient dprt, Unit of Ther, Rheuma and Cardio
  • Kyiv, Ukraine, 03037
    • "Medbud-Clinic" LLC, Treatment and Prevention Department of the Medical Center
  • Kyiv, Ukraine, 03057
    • Medical Center "Universal Clinic "Oberih"" of Limited Liability Company "Capital"
  • Kyiv, Ukraine, 04050
    • Limited Liability Company "Medical Centre 'Consilium Medical'", Clinical and Consultation Department
  • Kyiv, Ukraine, 04210
    • Medical Center "Center of Family Medicine Plus" LLC, Treatment and Prevention Department
  • Ternopil, Ukraine, 46002
    • Ternopil Regional Clinical Hospital
  • Vinnytsia, Ukraine, 21009
    • "Medical Center Health Clinic" LLC, Medical Clinical Investigational Center, Department of Cardiology and Rheumatology
  • Vinnytsia, Ukraine, 21029
    • Communal Non-Com Entr Vinnytsia City Clin Hpt 1, Clin Therapy Dprt 2, Vinnytsia Nat Pirogov Memo Med Uni, Dprt of Internal Med 3
• United Kingdom
  • Leicester, United Kingdom, LE5 4PW
    • University Hospitals of Leicester NHS Trust
  • London, United Kingdom, SE1 9RT
    • Guy's and St. Thomas' NHS Foundation Trust - Guy's Hospital
• United States
  • Arizona
    • Tucson, Arizona, United States, 85712
      • Tucson Clinical Research Institute, LLC
  • California
    • La Jolla, California, United States, 92037-0943
      • UCSD Perlman Medical Offices
    • Northridge, California, United States, 91234
      • Amicis Research Center
  • Florida
    • Coral Gables, Florida, United States, 33134
      • Hope Clinical Trials, Inc.
    • Hialeah, Florida, United States, 33016
      • Vital Pharma Research
    • Hollywood, Florida, United States, 33024
      • Tectum Medical Research
    • Kissimmee, Florida, United States, 34741
      • Alloy Clinical Research, LLC
    • Miami, Florida, United States, 33155
      • Allied Biomedical Research Institute
    • Miami, Florida, United States, 33155
      • D&H National Research Centers INC
    • Miami, Florida, United States, 33172
      • Professional Research Center Inc
    • Miami Lakes, Florida, United States, 33014
      • San Marcus Research Clinic, Inc.
  • Louisiana
    • Marrero, Louisiana, United States, 70072
      • Tandem Clinical Research
  • Nevada
    • Las Vegas, Nevada, United States, 89102
      • RB Wellness Clinic
  • New York
    • New York, New York, United States, 10032
      • Columbia University Medical Center
  • Texas
    • Colleyville, Texas, United States, 76034
      • Precision Comprehensive Clinical Research Solutions
    • El Paso, Texas, United States, 79902
      • Texas Arthritis Center
    • Houston, Texas, United States, 77090
      • Northwest Houston Arthritis Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

Inclusion criteria at screening:

• 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".
• British Isles Lupus Assessment Group-2004 (BILAG) Grade B in ≥ 2 organ systems or a BILAG Grade A in ≥ 1 organ system.
• Physician's Global Assessment (PGA) score ≥ 1.0 on a 0 to 3 visual analog scale.

• Currently treated with one or more of the following SLE background medications:

  • Anti-malarials (≤ 400 mg/day hydroxychloroquine, ≤ 500 mg/day chloroquine, ≤ 100 mg/day quinacrine).
  • Mycophenolate mofetil (≤ 2 g/day) / mycophenolic acid (≤1.44 g/day).
  • Azathioprine (≤ 2 mg/kg/day).
  • Methotrexate (≤ 25 mg/week).

  • 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.
  • Belimumab (≤10 mg/kg every 4 weeks intravenously [i.v.], or 200 mg/week subcutaneously [s.c.]).

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):

• Negative serum pregnancy test at Screening.
• Agreement to undertake monthly urine pregnancy tests from Randomization up to 6 months after study treatment discontinuation.
• Agreement to use a highly effective method of contraception from Screening (Visit 1) up to 6 months after study treatment discontinuation.

Inclusion criteria at randomization:

• A clinical mSLEDAI-2K score ≥ 4 with at least 2 points for musculoskeletal or mucocutaneous manifestations (i.e., myositis, arthritis, rash, alopecia, mucosal ulcers).
• BILAG Grade B in 2 or more organ systems or a BILAG Grade A in 1 or more organ system.
• 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):

  • Anti-dsDNA antibodies elevated above normal,
  • Antinuclear antibodies with a titer of at least 1:160,
  • Anti-Smith antibody elevated 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):

  • Antimalarials (≤ 400 mg/day hydroxychloroquine, ≤ 500 mg/day chloroquine, ≤ 100 mg/day quinacrine);
  • Mycophenolate mofetil (≤ 2 g/day) / mycophenolic acid (≤ 1.44g/day);
  • Azathioprine (≤ 2 mg/kg/day);
  • Methotrexate (≤ 25 mg/week);

  • 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.
  • Belimumab (≤ 10 mg/kg every 4 weeks i.v. or ≤ 200 mg/week s.c.).
• WoCBP must have a negative urine pregnancy test at Randomization.

Main 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:

  • That would make the subject unable to fully understand the ICF; OR
  • 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.
• A diagnosis of mixed connective tissue disease or any history of overlap syndromes of SLE with psoriasis, rheumatoid arthritis, erosive arthritis, scleroderma, autoimmune hepatitis or uncontrolled autoimmune thyroid disease.
• 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 any of the following abnormalities detected during the ophthalmological evaluation and/or by optical coherence tomography (OCT) during screening:

  • Macular edema of any cause: diabetic, cystoid, tractional.
  • Foveal degeneration, macular hole, macular pseudohole, hereditary or degenerative maculopathies.
  • Active uveitis, papilledema.
  • Retinal neovascularization of any cause and in any location.
• 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:

  • lymphocyte count < 500 /μL (0.5 × 10^9/L);
  • hemoglobin < 7 g/dL;
  • white blood cell count < 2000/μL (2.0 × 10^9/L); or
  • 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:

  • β-blockers, diltiazem, verapamil, digoxin, digitoxin, or any other antiarrhythmic or heart-rate -lowering systemic therapy.
  • 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 medication (whichever is longer) prior to Randomization:

  • Cyclophosphamide, cyclosporine, voclosporin, tacrolimus, sirolimus, etc.
  • Pulse methylprednisolone.
  • Vaccination with live vaccines (including live vaccines for COVID-19).
• Intra-articular, intramuscular or i.v. CS within 6 weeks prior to Randomization.

• Treatment with the following medications within 90 days or 5 half-lives of the medication (whichever is longer) prior to Randomization:

  • Leflunomide.
  • i.v. immunoglobulins.
• Treatment with any investigational agent within 90 days or 5 half-lives of the drug (whichever is longer) prior to Randomization.
• Treatment with B cell-depleting biological agents (e.g., rituximab or ocrelizumab) or biological immunosuppressive agents (e.g., anti-tumor necrosis factor [TNF], anti-interleukin [IL]-1, anti-IL6 therapies), within 12 months prior to Randomization.
• Treatment with anifrolumab within 6 months prior to Randomization.

• Treatment with any of the following medications any time prior to Screening:

  • Alemtuzumab,
  • Sphingosine-1-phosphate receptor modulators (e.g., fingolimod),
  • Subjects previously randomized to cenerimod or placebo in any trial involving cenerimod.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cenerimod 4 mg; Participants will receive cenerimod once daily in addition to background SLE therapy.	Drug: Cenerimod; Cenerimod will be supplied as film-coated tablets at the dose of 4 mg.; Other Names: ACT-334441
Placebo Comparator: Placebo; Participants will receive matching placebo once daily in addition to background SLE therapy.	Drug: Placebo; Matching placebo will be supplied as identical film-coated tablets formulated with the same excipients but without the active ingredient, cenerimod.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Response on Systemic Lupus Erythematosus Responder Index 4 (SRI-4) at Month 12 compared to baseline	Response on SRI-4 is defined as: Reduction from baseline of at least 4 points in the modified Systemic Lupus Erythematosus Disease Activity Index-2000 score (mSLEDAI-2K [SLEDAI-2K modified to exclude leukopenia, thus mSLEDAI-2K]), and; 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; 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; No violation of specified medication rules detailed in the core protocol.	At Month 12 compared to Day 1 (pre-dose baseline)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to first confirmation of a 4-month sustained modified Systemic Lupus Erythematosus Disease Activity Index-2000 (mSLEDAI-2K) response	A response is defined as a reduction of at least 4 points from baseline.	Day 1 (pre-dose baseline) to Month 12
Response on BILAG-based Composite Lupus Assessment (BICLA) at Month 12 compared to baseline	Response on BICLA is defined as: Improvement from baseline in disease activity as measured by BILAG. Improvement is defined as a reduction of all baseline BILAG A to B/C/D and baseline BILAG B to C/D and no BILAG worsening in other organ systems, where worsening is defined as ≥ 1 new BILAG A or ≥ 2 new BILAG B, and; No worsening from baseline in mSLEDAI-2K, where worsening is defined as an increase from baseline of > 0 points in mSLEDAI-2K, and; No worsening from baseline in the patient's lupus disease activity, where worsening is defined as an increase of ≥ 0.30 points on a 3-point PGA VAS, and; No discontinuation of investigational product, and; No violation of specified medication rules detailed in the core protocol.	At Month 12 compared to Day 1 (pre-dose baseline)
Time to first confirmation of a 4-month sustained response in mucocutaneous manifestations (i.e., rash, alopecia, mucosal ulcers)	Response is defined as: No increase in the overall mSLEDAI-2K score excluding mucocutaneous manifestations, and; Remission (score of zero) from baseline in the mSLEDAI-2K score of mucocutaneous manifestations.	Day 1 (pre-dose baseline) to Month 12

Collaborators and Investigators

• Sponsor: Viatris Innovation GmbH
• Investigators: Study Director: Clinical Trials, Viatris Innovation GmbH

Publications and helpful links

General Publications

• Askanase AD, D'Cruz D, Kalunian K, Merrill JT, Navarra SV, Cahuzac C, Cornelisse P, Murphy MJ, Strasser DS, Trokan L, Berkani O. Cenerimod, a sphingosine-1-phosphate receptor modulator, versus placebo in patients with moderate-to-severe systemic lupus erythematosus (CARE): an international, double-blind, randomised, placebo-controlled, phase 2 trial. Lancet Rheumatol. 2025 Jan;7(1):e21-e32. doi: 10.1016/S2665-9913(24)00246-7. Epub 2024 Nov 22.

Study record dates

Study Major Dates

• Study Start (Actual): June 26, 2023
• Primary Completion (Estimated): October 31, 2026
• Study Completion (Estimated): May 1, 2027

Study Registration Dates

• First Submitted: January 3, 2023
• First Submitted That Met QC Criteria: January 3, 2023
• First Posted (Actual): January 5, 2023

Study Record Updates

• Last Update Posted (Actual): April 2, 2026
• Last Update Submitted That Met QC Criteria: March 27, 2026
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Keywords: Immune System Diseases; Autoimmune Diseases; Musculoskeletal and connective tissue disorders
• Additional Relevant MeSH Terms: Skin and Connective Tissue Diseases; Lupus Erythematosus, Systemic; Autoimmune Diseases; Immune System Diseases; Connective Tissue Diseases; cenerimod
• Other Study ID Numbers: ID-064A302; 2022-002815-47 (EudraCT Number); 2024-515871-37-00 (Ctis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No