Efficacy and Safety of Four Doses of Cenerimod Compared to Placebo in Adult Subjects With Active Systemic Lupus Erythematosus
- Conditions
- Systemic Lupus Erythematosus
- Interventions
- Registration Number
- NCT03742037
- Lead Sponsor
- Idorsia Pharmaceuticals Ltd.
- 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).
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 427
-
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.
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Cenerimod 0.5 mg 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. Cenerimod 1 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. Placebo 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. Cenerimod 2 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. Cenerimod 4 mg 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. Cenerimod 2 mg (Ex-4mg) cenerimod 2 mg (ex-4 mg) 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. Placebo (Ex-4mg) Placebo 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.
- Primary Outcome Measures
Name Time Method Change From Baseline to Month 6 in the Modified Systemic Lupus Erythematosus Activity Index 2000 (mSLEDAI-2K) Score Baseline (Day 1) and Month 6 The primary endpoint is the absolute change from baseline in the modified Systemic Lupus Erythematosus Activity Index 2000 (mSLEDAI-2K) score. The SLEDAI-2K is a cumulative index of lupus disease activity scored by the physician. It is calculated from 24 individual descriptors across 9 organ systems, with weighted scores of 2-8, and measures disease activity within the last 10 days. 0 points indicates inactive disease, and 105 points is the maximum possible score. In this study the SLEDAI-2K was modified, to exclude leucopenia (minus 1 point), due to the mechanism of action of cenerimod. Improvement in systemic lupus erythematosus disease activity is defined as a reduction in SLEDAI-2K score of greater than or equal to 4. A decreased score, i.e., a negative change, indicates an improvement in systemic lupus erythematosus disease activity from baseline to Month 6.
- Secondary Outcome Measures
Name Time Method British Isles Lupus Assessment Group-2004 (BILAG) Disease Activity Index Response at Month 6 Baseline (Day 1) and Month 6 The British Isles Lupus Assessment Group-2004 (BILAG) is a comprehensive tool used by the physician to assess disease activity and is sensitive to small changes over time.
Response (no worsening) at Month 6 on BILAG-2004 disease activity index was defined as no new BILAG A organ domain score and no more than one new BILAG B organ domain score compared with baseline.
No analysis is reported because the model did not meet the convergence criteria.Response on Systemic Lupus Erythematosus Responder Index 4 (SRI-4) at Month 6 as Compared to Baseline Baseline (Day 1) and Month 6 A responder could only be assessed if the full information of all body systems was available. A participant was defined as a responder based on the Systemic Lupus Erythematosus Responder Index 4 (SRI-4) was a composite, binary endpoint based on three variables:
* mSLEDAI-2K score had to have a reduction from baseline greater than or equal to 4,
* Physician Global Assessment (PGA) had to have an increase from baseline less than or equal to 0.3. The PGA is a 100 mm visual analog scale used by the physician to assess disease activity ranging for 0 to 3. The scale is anchored with values from 0 = "none" and 3 = "severe"), and
* BILAG-2004 (no new BILAG A organ domain score and at most one new BILAG B organ domain score) compared with baseline.
If one of the SRI-4 mSLEDAI-2K, PGA and BILAG variables were not met the subject was scored a non-responder. Participants that did not fit at least one of the above criteria were assigned to the missing group.
Trial Locations
- Locations (148)
North Georgia Rheumatology Group - Duluth
🇺🇸Lawrenceville, Georgia, United States
Pinnacle Research Group
🇺🇸Anniston, Alabama, United States
Hôpital Haut-Lévêque
🇫🇷Pessac, France
Valerius Medical Group and Research Center
🇺🇸Los Alamitos, California, United States
The First Medical Center Ltd.
🇬🇪Tbilisi, Georgia
Life Clinical Trials
🇺🇸Margate, Florida, United States
Prosalud
🇨🇱Santiago, Chile
Altoona Center for Clinical Research
🇺🇸Duncansville, Pennsylvania, United States
CCR Pardubice
🇨🇿Pardubice, Vychodocesky KRAJ, Czechia
LUPUS CLINIC c/o DIMI
🇮🇹Genova, Italy
LLC "Innova"
🇬🇪Tbilisi, Georgia
Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico
🇮🇹Milano, Italy
Städtisches Klinikum Karlsruhe gGmbH
🇩🇪Karlsruhe, Germany
Hospital Universitario Doctor Peset
🇪🇸Valencia, Spain
Hospital Clinic i Provincial de Barcelona
🇪🇸Barcelona, Spain
Galilee Medical Center
🇮🇱Nahariya, Israel
Cambridge University Hospitals NHS Foundation Trust
🇬🇧Cambridge, United Kingdom
Hospital Universitario 12 de Octubre
🇪🇸Madrid, Spain
Municipal Nonprofit Institution of Lviv Regional Council
🇺🇦Lviv, Ukraine
Hospital Quirónsalud Infanta Luisa
🇪🇸Sevilla, Spain
Guy's and Saint Thomas' NHS Foundation Trust
🇬🇧London, United Kingdom
Robert W Levin MD PA
🇺🇸Clearwater, Florida, United States
Center for Rheumatology Immunology and Arthritis
🇺🇸Fort Lauderdale, Florida, United States
San Marcus Research Clinic
🇺🇸Miami Lakes, Florida, United States
State University of New York Upstate Medical University
🇺🇸Syracuse, New York, United States
DJL Clinical Research
🇺🇸Charlotte, North Carolina, United States
Joint Muscle Medical Care and Research Institute - Lilington Office
🇺🇸Charlotte, North Carolina, United States
University Multiprofile Hospital for Active Treatment Pulmed
🇧🇬Plovdiv, Bulgaria
Diagnostic Consulting Center Fokus-5
🇧🇬Sofia, Bulgaria
General Hospital of Athens "Laiko"
🇬🇷Goudí, Greece
Egyesitett Szent Istvan es Szent Laszlo Korhaz Rendelointezet
🇭🇺Budapest, Hungary
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
Centro de Investigación Clínica GRAMEL, S.C.
🇲🇽Mexico City, Mexico
Morales Vargas Centro de Investigación S.C.
🇲🇽León, Mexico
Biológicos Especializados S.A. de C.V.
🇲🇽Mexico City, Mexico
Accelerium, S. de R.L. de C.V.
🇲🇽Monterrey, Mexico
Davao Doctors Hospital
🇵🇭Davao City, Philippines
Lipa Medix Medical Center
🇵🇭Lipa City, Batangas, Philippines
Jose R. Reyes Memorial Medical Center
🇵🇭Manila, Philippines
Federal State Budget Scientific Research Institution "Scientific Research Institute of Rheumatology n.a. V.A. Nasonova"
🇷🇺Moscow, Russian Federation
Hospital Universitario Regional de Málaga
🇪🇸Málaga, Malaga, Spain
Songklanagarind Hospital
🇹🇭Songkhla, Thailand
Necmettin Erbakan Üniversitesi Meram Tıp Fakültesi
🇹🇷Konya, Turkey
Medical Centre "Consilium medical"
🇺🇦Kyiv, Ukraine
Municipal Institution "Zaporizhzhya Regional Clinical Hospital"
🇺🇦Zaporizhzhya, Ukraine
Scientific and Research Institute of Invalid Rehabilitation (EST Complex) of Vinnytsia M.I.Pyrogov NMU MOHU,
🇺🇦Vinnytsia, Ukraine
Ospedale San Raffaele
🇮🇹Milano, Italy
Azienda Ospedaliera San Camillo Forlanini
🇮🇹Roma, Italy
Fondazione Policlinico Universitario A. Gemelli
🇮🇹Roma, Italy
A.O. Mauriziano Umberto I di Torino
🇮🇹Torino, Italy
Biomedica Research Group
🇨🇱Santiago, Chile
Ltd. Mtskheta Street Clinic
🇬🇪Tbilisi, Georgia
LTD "Tbilisi Heart Center"
🇬🇪Tbilisi, Georgia
Tomakomai City Hospital
🇯🇵Tomakomai-shi, Japan
Consultorio Médico del Dr. Federico Galván Villegas
🇲🇽Guadalajara, Mexico
Hospital Universitario "Dr. Gonzalo Valdés Valdés"
🇲🇽Saltillo, Mexico
University of Santo Tomas Hospital
🇵🇭Manila, Philippines
Far Eastern University - Nicanor Reyes Medical Foundation
🇵🇭Quezon City, Philippines
Diagnostic and Consulting Center "Aleksandrovska" EOOD
🇧🇬Sofia, Bulgaria
LTD "New Plasma Clinic"
🇬🇪Batumi, Georgia
The Chaim Sheba Medical Center
🇮🇱Ramat-Gan, Israel
Institute of Arthritis Research
🇺🇸Idaho Falls, Idaho, United States
Unidad de Atención Médica e Investigación en Salud
🇲🇽Mérida, Mexico
Kohler & Milstein Research S.A. de C.V.
🇲🇽Mérida, Mexico
Aversi Clinic LTD
🇬🇪Tbilisi, Georgia
Rambam Healthcare Campus
🇮🇱Haifa, Israel
Bnai Zion Medical Center
🇮🇱Haifa, Israel
Consultorio Particular Dr. Miguel Cortés Hernández
🇲🇽Cuernavaca, Mexico
Office of Ramesh C. Gupta, MD
🇺🇸Memphis, Tennessee, United States
Washington University School of Medicine
🇺🇸Saint Louis, Missouri, United States
University of California San Diego
🇺🇸La Jolla, California, United States
Multiprofile Hospital For Active Treatment Trimontium
🇧🇬Plovdiv, Plodiv, Bulgaria
Medi Club Georgia Ltd.
🇬🇪Tbilisi, Georgia
LLC Raymann
🇬🇪Tbilisi, Georgia
Enroll SpA
🇨🇱Santiago, Chile
Meditek Ltda.
🇨🇱Santiago, Chile
Clinical Research Chile SpA
🇨🇱Valdivia, Chile
Medicore
🇬🇪Tbilisi, Georgia
Multiprofile Clinic Consilium Medulla
🇬🇪Tbilisi, Georgia
Karla Adriana Espinosa Bautista
🇲🇽Ciudad de México, Mexico
Investigacion Biomedica para el Desarrollo de Farmacos S.A. de C.V.
🇲🇽Zapopan, Mexico
Makati Medical Center
🇵🇭Makati City, Philippines
University of the Philippines Manila - Philippine General Hospital
🇵🇭Manila, Philippines
St. Luke's Medical Center
🇵🇭Quezon City, Philippines
Szpital Specjalistyczny im. J. Dietla w Krakowie
🇵🇱Krakow, Poland
JSC "Center of Family Medicine"
🇷🇺Ekaterinburg, Russian Federation
Clinical Rheumatological Hospital Number 25
🇷🇺Saint Petersburg, Russian Federation
Polyclinic of Private Security and Detectives
🇷🇺Saint Petersburg, Russian Federation
Municipal Institution Kyiv Regional Council "Kyiv Regional Clinical Hospital"
🇺🇦Kyiv, Ukraine
UBAM Unidad Biomédica Avanzada Monterrey
🇲🇽Monterrey, Mexico
SMIQ, S. de R.L. de C.V.
🇲🇽Queretaro, Mexico
Unidad de Investigaciones Reumatológicas A.C.
🇲🇽San Luis Potosí, Mexico
Iloilo Doctors Hospital
🇵🇭Iloilo City, Philippines
Szpital Uniwersytecki Number 2 im. dr. Jana Biziela w Bydgoszczy
🇵🇱Bydgoszcz, Poland
Śląskie Centrum Reumatologii, Rehabilitacji i Zapobiegania Niepełnosprawności im gen. Jerzego Zi
🇵🇱Ustroń, Poland
SC Sana Monitoring SRL
🇷🇴Bucuresti, Romania
Medical Research Institute, LLC
🇷🇺Saint Petersburg, Russian Federation
Military Medical Academy S.M. Kirov
🇷🇺Saint-Petersburg, Russian Federation
Kaohsiung Veterans General Hospital
🇨🇳Kaohsiung, Taiwan
Rajavithi Hospital
🇹🇭Bangkok, Thailand
Poltava Regional Clinical Hospital named after M.V. Sklifossovsky
🇺🇦Poltava, Ukraine
Centro de Atención e Investigación Cardiovascular del Potosí, S.C.
🇲🇽San Luis Potosí, Mexico
Centrum Medyczne Plejady
🇵🇱Kraków, Poland
Centrul Medical de Diagnostic si Tratament Ambulatoriu Neomed
🇷🇴Brasov, Romania
Spitalul Clinic Judetean de Urgenta Cluj-Napoca
🇷🇴Cluj-Napoca, Romania
Chelyabinsk Regional Clinical Hospital
🇷🇺Chelyabinsk, Russian Federation
Medical Center "Zdorovaya Semiya", LLC
🇷🇺Novosibirsk, Russian Federation
Kyiv City Clinical Hospital №3
🇺🇦Kyiv, Ukraine
Lviv Regional Clinical Hospital
🇺🇦Lviv, Ukraine
City Clinical Hospital #15 named after O.M. Filatova
🇷🇺Moscow, Russian Federation
Angeles University Foundation Medical Center
🇵🇭Angeles City, Philippines
Intermedius Uslugi Medyczne
🇵🇱Koscian, Poland
Twoja Przychodnia Poznańskie Centrum Medyczne
🇵🇱Poznań, Poland
Centro Reumatologico de Caguas
🇵🇷Caguas, Puerto Rico
Spitalul Clinic "Sf. Maria"
🇷🇴Bucharest, Romania
Orenburg State Medical University
🇷🇺Orenburg, Russian Federation
Saratov Regional Clinical Hospital
🇷🇺Saratov, Russian Federation
Kaohsiung Medical University Hospital
🇨🇳Kaohsiung, Taiwan
Vinnytsya Regional Clinical Hospital - Rheumatology Department
🇺🇦Vinnytsya, Ukraine
Medical Center Maksimum Zdorovia
🇷🇺Saint Petersburg, Russian Federation
State Institution of Health Protection "Clinical Hospital #8"
🇷🇺Yaroslavl, Russian Federation
Istanbul Universitesi Istanbul Tip Fakultesi
🇹🇷Istanbul, Turkey
Clinic of State Institution "National Scientific Centre "Acad. Strazhesko Institute of Cardiology"
🇺🇦Kyiv, Ukraine
Municipal Nonprofit Institution of Lviv Regional Council "Lviv Regional Clinical Hospital"
🇺🇦Lviv, Ukraine
Municipal Nonprofit Institution "Vinnytsia City Clinical Hospital №1"
🇺🇦Vinnytsia, Ukraine
Municipal institution "Regional Clinical Hospital n.a. O.F. Herbachevskoho"
🇺🇦Zhytomyr, Ukraine
Ternopil University Clinic - Rheumatology department
🇺🇦Ternopil, Ukraine
Zakarpattya Regional Clinical Hospital n.a. A.Novak - Rheumatology Department
🇺🇦Uzhgorod, Ukraine
Private Small Scale Medical Center "Pulse"
🇺🇦Vinnytsia, Ukraine
Medical Center "Health Clinic", LLC
🇺🇦Vinnytsia, Ukraine
University of Colorado School of Medicine
🇺🇸Aurora, Colorado, United States
Innovative Health Research
🇺🇸Las Vegas, Nevada, United States
Sun Research Institute
🇺🇸San Antonio, Texas, United States
Integral Rheumatology & Immunology Specialists
🇺🇸Plantation, Florida, United States
D&H National Research Centers INC
🇺🇸Miami, Florida, United States
Advanced Research Institute Inc Allergy & Rheumatology
🇺🇸Saint Petersburg, Florida, United States
Axiom Clinical Research of Florida
🇺🇸Tampa, Florida, United States
New York Presbyterian Columbia University Medical Center
🇺🇸New York, New York, United States
Paramount Medical Research and Consulting
🇺🇸Middleburg Heights, Ohio, 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
Accurate Clinical Management
🇺🇸Stafford, Texas, United States
Millennium Research
🇺🇸Ormond Beach, Florida, United States
Non-governmental private healthcare organization, Scientific Clinical Centre of JSC Russian Railways
🇷🇺Moscow, Russian Federation
Centre Hospitalier Regional Universitaire Brest Hôpital de la Cavale Blanche à Brest
🇫🇷Brest, Bretagne, France
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