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

NCT ID: NCT03742037

Last Updated: 2025-10-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 427 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-12-21
• Study Completion Date: 2022-08-25

Brief 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).

Detailed Description

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).

Conditions

Systemic Lupus Erythematosus

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Cenerimod 0.5 mg

Participants will receive cenerimod 0.5 mg once daily in addition to background SLE therapy. Treatment Period 1 is 6 months long. It will start with the administration of the first dose of study treatment, after randomization, and end at the Month 6 visit. All randomized participants need to complete Treatment Period 1 before continuing in Treatment Period 2. In Treatment Period 2 participants will continue with cenerimod 0.5 mg for a further 6 months and end study treatment at the Month 12 visit.

Group Type: EXPERIMENTAL

Cenerimod 0.5 mg

Intervention Type: DRUG

Cenerimod will be supplied as a film-coated tablets at the dose of 0.5 mg

Cenerimod 1 mg

Participants will receive cenerimod 1 mg once daily in addition to background SLE therapy. Treatment Period 1 is 6 months long. It will start with the administration of the first dose of study treatment, after randomization, and end at the Month 6 visit. All randomized participants need to complete Treatment Period 1 before continuing in Treatment Period 2. In Treatment Period 2 participants will continue with cenerimod 1 mg for a further 6 months and end study treatment at the Month 12 visit.

Group Type: EXPERIMENTAL

Cenerimod 1 mg

Intervention Type: DRUG

Cenerimod will be supplied as a film-coated tablets at the dose of 1 mg

Cenerimod 2 mg

Participants will receive cenerimod 2 mg once daily in addition to background SLE therapy. Treatment Period 1 is 6 months long. It will start with the administration of the first dose of study treatment, after randomization, and end at the Month 6 visit. All randomized participants need to complete Treatment Period 1 before continuing in Treatment Period 2. In Treatment Period 2 participants will continue with cenerimod 2 mg for a further 6 months and end study treatment at the Month 12 visit.

Group Type: EXPERIMENTAL

Cenerimod 2 mg

Intervention Type: DRUG

Cenerimod will be supplied as a film-coated tablets at the dose of 2 mg

Cenerimod 2 mg (Ex-4mg)

Half the participants that complete treatment with cenerimod 4 mg in Treatment Period 1 will be re-randomized to cenerimod 2 mg once daily in addition to background SLE therapy during Treatment Period 2. Participants will receive cenerimod 2 mg for 6 months and end study treatment at the Month 12 visit.

Group Type: EXPERIMENTAL

cenerimod 2 mg (ex-4 mg)

Intervention Type: DRUG

Cenerimod will be supplied as a film-coated tablets at the dose of 2 mg

Placebo (Ex-4mg)

Half the participants that complete treatment with cenerimod 4 mg in Treatment Period 1 will be re-randomized to placebo (matching cenerimod) once daily in addition to background SLE therapy during Treatment Period 2. Participants will receive cenerimod 2 mg for 6 months and end study treatment at the Month 12 visit.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Matching placebo will be supplied as identical film-coated tablets formulated with the same excipients but without the active ingredient, cenerimod

Cenerimod 4 mg

Participants will received cenerimod 4 mg once daily in addition to background SLE therapy for up to 6 months in Treatment Period 1. The participants randomized to the 4 mg treatment who were still on treatment at Month 6 were re-randomized in a 1:1 ratio to placebo or cenerimod 2 mg to enter Treatment Period 2. The participants who did not complete 6 months of cenerimod 4 mg treatment will be analyzed in the "Non Re-randomized (Ex-4mg)" treatment group.

Group Type: EXPERIMENTAL

Cenerimod 4 mg

Intervention Type: DRUG

Cenerimod will be supplied as a film-coated tablets at the dose of 4 mg

Placebo

Participants will receive placebo (matching cenerimod) once daily in addition to background SLE therapy. Treatment Period 1 is 6 months long. It will start with the administration of the first dose of study treatment, after randomization, and end at the Month 6 visit. All randomized participants need to complete Treatment Period 1 before continuing in Treatment Period 2. In Treatment Period 2 participants will continue with placebo (matching cenerimod) for a further 6 months and end study treatment at the Month 12 visit.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Matching placebo will be supplied as identical film-coated tablets formulated with the same excipients but without the active ingredient, cenerimod

Interventions

Cenerimod 0.5 mg

Cenerimod will be supplied as a film-coated tablets at the dose of 0.5 mg

Intervention Type: DRUG

Cenerimod 1 mg

Cenerimod will be supplied as a film-coated tablets at the dose of 1 mg

Intervention Type: DRUG

Cenerimod 2 mg

Cenerimod will be supplied as a film-coated tablets at the dose of 2 mg

Intervention Type: DRUG

Cenerimod 4 mg

Cenerimod will be supplied as a film-coated tablets at the dose of 4 mg

Intervention Type: DRUG

Placebo

Matching placebo will be supplied as identical film-coated tablets formulated with the same excipients but without the active ingredient, cenerimod

Intervention Type: DRUG

cenerimod 2 mg (ex-4 mg)

Cenerimod will be supplied as a film-coated tablets at the dose of 2 mg

Intervention Type: DRUG

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Viatris Innovation GmbH

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Trials

Role: STUDY_DIRECTOR

Viatris Innovation GmbH

Locations

Pinnacle Research Group

Anniston, Alabama, United States

University of California San Diego

La Jolla, California, United States

Valerius Medical Group and Research Center

Los Alamitos, California, United States

University of Colorado School of Medicine

Aurora, Colorado, United States

Robert W Levin MD PA

Clearwater, Florida, United States

Center for Rheumatology Immunology and Arthritis

Fort Lauderdale, Florida, United States

Life Clinical Trials

Margate, Florida, United States

D&H National Research Centers INC

Miami, Florida, United States

San Marcus Research Clinic

Miami Lakes, Florida, United States

Millennium Research

Ormond Beach, Florida, United States

Integral Rheumatology & Immunology Specialists

Plantation, Florida, United States

Advanced Research Institute Inc Allergy & Rheumatology

St. Petersburg, Florida, United States

Axiom Clinical Research of Florida

Tampa, Florida, United States

North Georgia Rheumatology Group - Duluth

Lawrenceville, Georgia, United States

Institute of Arthritis Research

Idaho Falls, Idaho, United States

Washington University School of Medicine

St Louis, Missouri, United States

Innovative Health Research

Las Vegas, Nevada, United States

New York Presbyterian Columbia University Medical Center

New York, New York, United States

State University of New York Upstate Medical University

Syracuse, New York, United States

Joint Muscle Medical Care and Research Institute - Lilington Office

Charlotte, North Carolina, United States

DJL Clinical Research

Charlotte, North Carolina, United States

Paramount Medical Research and Consulting

Middleburg Heights, Ohio, United States

Altoona Center for Clinical Research

Duncansville, Pennsylvania, United States

Office of Ramesh C. Gupta, MD

Memphis, Tennessee, United States

Amarillo Center for Clinical Research

Amarillo, Texas, United States

Accurate Clinical Research

Houston, Texas, United States

Southwest Rheumatology Research, LLC

Mesquite, Texas, United States

Sun Research Institute

San Antonio, Texas, United States

Accurate Clinical Management

Stafford, Texas, United States

Multiprofile Hospital For Active Treatment Trimontium

Plovdiv, Plodiv, Bulgaria

University Multiprofile Hospital for Active Treatment Pulmed

Plovdiv, , Bulgaria

Diagnostic and Consulting Center "Aleksandrovska" EOOD

Sofia, , Bulgaria

Diagnostic Consulting Center Fokus-5

Sofia, , Bulgaria

Enroll SpA

Santiago, , Chile

Biomedica Research Group

Santiago, , Chile

Meditek Ltda.

Santiago, , Chile

Prosalud

Santiago, , Chile

Clinical Research Chile SpA

Valdivia, , Chile

CCR Pardubice

Pardubice, Vychodocesky KRAJ, Czechia

Centre Hospitalier Regional Universitaire Brest Hôpital de la Cavale Blanche à Brest

Brest, Brittany Region, France

Hôpital Haut-Lévêque

Pessac, , France

LTD "New Plasma Clinic"

Batumi, , Georgia

Aversi Clinic LTD

Tbilisi, , Georgia

Medi Club Georgia Ltd.

Tbilisi, , Georgia

Ltd. Mtskheta Street Clinic

Tbilisi, , Georgia

The First Medical Center Ltd.

Tbilisi, , Georgia

LLC "Innova"

Tbilisi, , Georgia

LLC Raymann

Tbilisi, , Georgia

LTD "Tbilisi Heart Center"

Tbilisi, , Georgia

Medicore

Tbilisi, , Georgia

Multiprofile Clinic Consilium Medulla

Tbilisi, , Georgia

Städtisches Klinikum Karlsruhe gGmbH

Karlsruhe, , Germany

General Hospital of Athens "Laiko"

Goudi, , Greece

Egyesitett Szent Istvan es Szent Laszlo Korhaz Rendelointezet

Budapest, , Hungary

Rambam Healthcare Campus

Haifa, , Israel

Bnai Zion Medical Center

Haifa, , Israel

Galilee Medical Center

Nahariya, , Israel

The Chaim Sheba Medical Center

Ramat Gan, , Israel

LUPUS CLINIC c/o DIMI

Genova, , Italy

Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico

Milan, , Italy

Ospedale San Raffaele

Milan, , Italy

Azienda Ospedaliera San Camillo Forlanini

Roma, , Italy

Fondazione Policlinico Universitario A. Gemelli

Roma, , Italy

A.O. Mauriziano Umberto I di Torino

Torino, , Italy

Tomakomai City Hospital

Tomakomai-shi, , Japan

Consultorio Particular Dr. Miguel Cortés Hernández

Cuernavaca, , Mexico

Centro Integral en Reumatología S.A. de C.V.

Guadalajara, , Mexico

Icle S.C.

Guadalajara, , Mexico

Consultorio Privado de Especialidad del Dr. José Javier Orozco Alcalá

Guadalajara, , Mexico

Consultorio Médico del Dr. Federico Galván Villegas

Guadalajara, , Mexico

Morales Vargas Centro de Investigación S.C.

León, , Mexico

Karla Adriana Espinosa Bautista

Mexico City, , Mexico

Centro de Investigación Clínica GRAMEL, S.C.

Mexico City, , Mexico

Biológicos Especializados S.A. de C.V.

Mexico City, , Mexico

Unidad de Atención Médica e Investigación en Salud

Mérida, , Mexico

Kohler & Milstein Research S.A. de C.V.

Mérida, , Mexico

Accelerium, S. de R.L. de C.V.

Monterrey, , Mexico

UBAM Unidad Biomédica Avanzada Monterrey

Monterrey, , Mexico

SMIQ, S. de R.L. de C.V.

Querétaro, , Mexico

Hospital Universitario "Dr. Gonzalo Valdés Valdés"

Saltillo, , Mexico

Unidad de Investigaciones Reumatológicas A.C.

San Luis Potosí City, , Mexico

Centro de Atención e Investigación Cardiovascular del Potosí, S.C.

San Luis Potosí City, , Mexico

Investigacion Biomedica para el Desarrollo de Farmacos S.A. de C.V.

Zapopan, , Mexico

Lipa Medix Medical Center

Lipa City, Batangas, Philippines

Angeles University Foundation Medical Center

Angeles City, , Philippines

Davao Doctors Hospital

Davao City, , Philippines

Iloilo Doctors Hospital

Iloilo City, , Philippines

Makati Medical Center

Makati City, , Philippines

University of the Philippines Manila - Philippine General Hospital

Manila, , Philippines

Jose R. Reyes Memorial Medical Center

Manila, , Philippines

University of Santo Tomas Hospital

Manila, , Philippines

St. Luke's Medical Center

Quezon City, , Philippines

Far Eastern University - Nicanor Reyes Medical Foundation

Quezon City, , Philippines

Szpital Uniwersytecki Number 2 im. dr. Jana Biziela w Bydgoszczy

Bydgoszcz, , Poland

Intermedius Uslugi Medyczne

Kościan, , Poland

Szpital Specjalistyczny im. J. Dietla w Krakowie

Krakow, , Poland

Centrum Medyczne Plejady

Krakow, , Poland

Twoja Przychodnia Poznańskie Centrum Medyczne

Poznan, , Poland

Śląskie Centrum Reumatologii, Rehabilitacji i Zapobiegania Niepełnosprawności im gen. Jerzego Zi

Ustroń, , Poland

Centro Reumatologico de Caguas

Caguas, , Puerto Rico

Centrul Medical de Diagnostic si Tratament Ambulatoriu Neomed

Brasov, , Romania

SC Sana Monitoring SRL

Bucharest, , Romania

Spitalul Clinic "Sf. Maria"

Bucharest, , Romania

Spitalul Clinic Judetean de Urgenta Cluj-Napoca

Cluj-Napoca, , Romania

Chelyabinsk Regional Clinical Hospital

Chelyabinsk, , Russia

City Clinical Hospital #15 named after O.M. Filatova

Moscow, , Russia

Federal State Budget Scientific Research Institution "Scientific Research Institute of Rheumatology n.a. V.A. Nasonova"

Moscow, , Russia

Non-governmental private healthcare organization, Scientific Clinical Centre of JSC Russian Railways

Moscow, , Russia

Medical Center "Zdorovaya Semiya", LLC

Novosibirsk, , Russia

Orenburg State Medical University

Orenburg, , Russia

Clinical Rheumatological Hospital Number 25

Saint Petersburg, , Russia

Military Medical Academy S.M. Kirov

Saint Petersburg, , Russia

Polyclinic of Private Security and Detectives

Saint Petersburg, , Russia

Medical Research Institute, LLC

Saint Petersburg, , Russia

Medical Center Maksimum Zdorovia

Saint Petersburg, , Russia

Saratov Regional Clinical Hospital

Saratov, , Russia

State Institution of Health Protection "Clinical Hospital #8"

Yaroslavl, , Russia

JSC "Center of Family Medicine"

Yekaterinburg, , Russia

Hospital Universitario Regional de Málaga

Málaga, Malaga, Spain

Hospital Clinic i Provincial de Barcelona

Barcelona, , Spain

Hospital Universitario 12 de Octubre

Madrid, , Spain

Hospital Quirónsalud Infanta Luisa

Seville, , Spain

Hospital Universitario Doctor Peset

Valencia, , Spain

Kaohsiung Medical University Hospital

Kaohsiung City, , Taiwan

Kaohsiung Veterans General Hospital

Kaohsiung City, , Taiwan

Rajavithi Hospital

Bangkok, , Thailand

Songklanagarind Hospital

Songkhla, , Thailand

Istanbul Universitesi Istanbul Tip Fakultesi

Istanbul, , Turkey (Türkiye)

Necmettin Erbakan Üniversitesi Meram Tıp Fakültesi

Konya, , Turkey (Türkiye)

Kyiv City Clinical Hospital №3

Kyiv, , Ukraine

Clinic of State Institution "National Scientific Centre "Acad. Strazhesko Institute of Cardiology"

Kyiv, , Ukraine

Medical Centre "Consilium medical"

Kyiv, , Ukraine

Municipal Institution Kyiv Regional Council "Kyiv Regional Clinical Hospital"

Kyiv, , Ukraine

Municipal Nonprofit Institution of Lviv Regional Council "Lviv Regional Clinical Hospital"

Lviv, , Ukraine

Municipal Nonprofit Institution of Lviv Regional Council

Lviv, , Ukraine

Lviv Regional Clinical Hospital

Lviv, , Ukraine

Poltava Regional Clinical Hospital named after M.V. Sklifossovsky

Poltava, , Ukraine

Ternopil University Clinic - Rheumatology department

Ternopil, , Ukraine

Zakarpattya Regional Clinical Hospital n.a. A.Novak - Rheumatology Department

Uzhhorod, , Ukraine

Private Small Scale Medical Center "Pulse"

Vinnytsia, , Ukraine

Medical Center "Health Clinic", LLC

Vinnytsia, , Ukraine

Municipal Nonprofit Institution "Vinnytsia City Clinical Hospital №1"

Vinnytsia, , Ukraine

Vinnytsya Regional Clinical Hospital - Rheumatology Department

Vinnytsia, , Ukraine

Scientific and Research Institute of Invalid Rehabilitation (EST Complex) of Vinnytsia M.I.Pyrogov NMU MOHU,

Vinnytsia, , Ukraine

Municipal Institution "Zaporizhzhya Regional Clinical Hospital"

Zaporizhzhya, , Ukraine

Municipal institution "Regional Clinical Hospital n.a. O.F. Herbachevskoho"

Zhytomyr, , Ukraine

Cambridge University Hospitals NHS Foundation Trust

Cambridge, , United Kingdom

Guy's and Saint Thomas' NHS Foundation Trust

London, , United Kingdom

Countries

United States; Bulgaria; Chile; Czechia; France; Georgia; Germany; Greece; Hungary; Israel; Italy; Japan; Mexico; Philippines; Poland; Puerto Rico; Romania; Russia; Spain; Taiwan; Thailand; Turkey (Türkiye); Ukraine; United Kingdom

References

Suffiotti M, Brazauskas P, Keller MP, Berkani O, Seifer G, Cornelisse P, Murphy MJ, Strasser DS. Pharmacodynamics of the S1P1 receptor modulator cenerimod in a phase 2b randomised clinical trial in patients with moderate to severe SLE. Ann Rheum Dis. 2025 Feb;84(2):284-293. doi: 10.1136/ard-2024-226547. Epub 2025 Jan 16.

Reference Type: DERIVED

PMID: 39919901 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 39586304 (View on PubMed)

Provided Documents

Document Type: Study Protocol: Protocol

View Document

Document Type: Study Protocol: COVID-19 addendum to protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2018-001808-11

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

ID-064A202

Identifier Type: -

Identifier Source: org_study_id