A Research Study to Evaluate the Efficacy and Safety of Cenerimod in Subjects Suffering From Systemic Lupus Erythematosus

Phase 3

Recruiting

• Conditions: Lupus Erythematosus, Systemic
• Interventions: Drug: Cenerimod; Drug: Placebo

• Registration Number: NCT05672576
• Lead Sponsor: Idorsia Pharmaceuticals Ltd.

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2023-01-03
• Study First Submitted QC: 2023-01-03
• Study First Posted: 2023-01-05
• Study Start: 2023-06-26
• Status Verified: 2024-07
• Last Update Submitted: 2024-12-19
• Last Update Posted: 2024-12-24
• Primary Completion: 2026-10-31
• Study Completion: 2027-05-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 420

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

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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 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:

  • 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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Cenerimod 4 mg	Cenerimod	Participants will receive cenerimod once daily in addition to background SLE therapy.
Placebo	Placebo	Participants will receive matching placebo once daily in addition to background SLE therapy.

Primary Outcome Measures

Name	Time	Method
Response on Systemic Lupus Erythematosus Responder Index 4 (SRI-4) at Month 12 compared to baseline	At Month 12 compared to Day 1 (pre-dose 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.

Secondary Outcome Measures

Name	Time	Method
Response on BILAG-based Composite Lupus Assessment (BICLA) at Month 12 compared to baseline	At Month 12 compared to Day 1 (pre-dose 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.
Time to first confirmation of a 4-month sustained response in mucocutaneous manifestations (i.e., rash, alopecia, mucosal ulcers)	Day 1 (pre-dose baseline) to Month 12	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.
Time to first confirmation of a 4-month sustained modified Systemic Lupus Erythematosus Disease Activity Index-2000 (mSLEDAI-2K) response	Day 1 (pre-dose baseline) to Month 12	A response is defined as a reduction of at least 4 points from baseline.

Trial Locations

Locations (132)

Centro de Investigación del Hospital Militar Central; 🇵🇪 Jesús María, Peru

Alberto Sabogal Sologuren National Hospital; 🇵🇪 Lima, Peru

Hospital Maria Auxiliadora; 🇵🇪 Lima, Peru

Unidad de Investigación de la Clinica International; 🇵🇪 San Borja, Peru

Instituto Peruano del Hueso y la Articulación S.A.C. (IPHAR); 🇵🇪 San Isidro, Peru

Clínica Anglo Americana; 🇵🇪 San Isidro, Peru

Servicios Reumatológicos SOMA E.I.R.L. / Clinica El Golf; 🇵🇪 San Isidro, Peru

Unidad de Investigación en Reumatología e Inmunología CSJB; 🇵🇪 San Juan de Lurigancho, Peru

Hospital Nacional Cayetano Heredia; 🇵🇪 San Martín de Porres, Peru

Investigaciones Clinicas / Instituto de Ginecología y Reproducción, El Derby; 🇵🇪 Santiago De Surco, Peru

Centro de Investigación Clínica Trujillo EIRL / Clínica Peruano Americana S.A; 🇵🇪 Trujillo, Peru

Iloilo Doctors Hospital; 🇵🇭 Iloilo City, Philippines

Ospital ng Makati; 🇵🇭 Makati City, Philippines

Makati Medical Center; 🇵🇭 Makati, Philippines

St Lukes Medical Center; 🇵🇭 Manila, Philippines

The Medical City Clark; 🇵🇭 Pampanga, Philippines

St Luke's Medical Center Quezon City / University of Santo Tomas Hospital; 🇵🇭 Sampaloc, Philippines

Szpital Uniwersytecki nr 2 im. dr. Jana Biziela w Bydgoszczy; 🇵🇱 Bydgoszcz, Poland

Medyczne Centrum Hetmańska; 🇵🇱 Poznań, Poland

Twoja Przychodnia Poznańskie Centrum Medyczne; 🇵🇱 Poznań, Poland

Pomorski Uniwersytet Medyczny w Szczecinie; 🇵🇱 Szczecin, Poland

MICS Centrum Medyczne Warszawa; 🇵🇱 Warszawa, Poland

Hospital Prof. Doutor Fernando Fonseca; 🇵🇹 Amadora, Portugal

Centro Hospitalar Universitário do Algarve - Hospital de Faro; 🇵🇹 Faro, Portugal

ULS Guarda; 🇵🇹 Guarda, Portugal

Hospital Senhora Oliveira-Guimaraes; 🇵🇹 Guimarães, Portugal

Instituto Portugues De Reumatologia; 🇵🇹 Lisbon, Portugal

Unidade Local De Saude Lisboa Ocidental E.P.E.; 🇵🇹 Lisbon, Portugal

Centro Hospitalar de Vila Nova de Gaia/Espinho, E.P.E.; 🇵🇹 Vila Nova de Gaia, Portugal

Centro Reumatologico de Caguas; 🇵🇷 Caguas, Puerto Rico

GCM Medical Group, PSC; 🇵🇷 San Juan, Puerto Rico

Institute of Rheumatology, Belgrade (study site 1); 🇷🇸 Belgrade, Serbia

Institute of Rheumatology, Belgrade (study site 2); 🇷🇸 Belgrade, Serbia

Institute of Rheumatology, Belgrade (study site 3); 🇷🇸 Belgrade, Serbia

University Clinical Center of Serbia; 🇷🇸 Belgrade, Serbia

Military Medical Academy; 🇷🇸 Belgrade, Serbia

Clinical Center Kragujevac; 🇷🇸 Kragujevac, Serbia

Special Hospital for Rheumatic Diseases, Novi Sad; 🇷🇸 Novi Sad, Serbia

General Hospital "Djordje Joanovic"; 🇷🇸 Zrenjanin, Serbia

Arthritis Clinical Research Trials; 🇿🇦 Cape Town, South Africa

Panorama Medical Centre; 🇿🇦 Cape Town, South Africa

Charlotte Maxeke Johannesburg Academic Hospital; 🇿🇦 Parktown, South Africa

University of Pretoria; 🇿🇦 Pretoria, South Africa

Winelands Medical Research; 🇿🇦 Somerset West, South Africa

Accellacare; 🇪🇸 Alcobendas, Spain

Parc Tauli Sabadell University Hospital; 🇪🇸 Barcelona, Spain

Hospital Universitari Vall d'Hebron; 🇪🇸 Colmenar Viejo, Spain

Hospital Universitario Ramon y Cajal; 🇪🇸 Colmenar Viejo, Spain

Hospital Universitario Infanta Leonor; 🇪🇸 Madrid, Spain

Hospital Clínico San Carlos; 🇪🇸 Madrid, Spain

Clinica Gaias Santiago; 🇪🇸 Santiago De Compostela, Spain

Hospital QuironSalud Sagrado Corazon; 🇪🇸 Sevilla, Spain

Hospital Universitario Nuestra Señora de Valme; 🇪🇸 Sevilla, Spain

Hospital Clinico Universitario de Valencia; 🇪🇸 Valencia, Spain

Hospital Universitario Doctor Peset; 🇪🇸 Valencia, Spain

Hospital Universitario Río Hortega de Valladolid; 🇪🇸 Valladolid, Spain

Ternopil Regional Clinical Hospital; 🇺🇦 Ternopil, Ukraine

University Hospitals of Leicester Nhs Trust; 🇬🇧 Leicester, United Kingdom

Guy's and St. Thomas' NHS Foundation Trust - Guy's Hospital; 🇬🇧 London, United Kingdom

LTD "Tbilisi Heart Center"; 🇬🇪 Tbilisi, Georgia

Tucson Clinical Research Institute, LLC; 🇺🇸 Tucson, Arizona, United States

UCSD Perlman Medical Offices; 🇺🇸 La Jolla, California, United States

Amicis Research Center; 🇺🇸 Northridge, California, United States

BioSolutions Clinical Research Center; 🇺🇸 Poway, California, United States

Arthritis Medical Clinic Osteoporosis Diagnostic Imaging and Treatment Center; 🇺🇸 Riverside, California, United States

Hope Clinical Trials, Inc.; 🇺🇸 Coral Gables, Florida, United States

Vital Pharma Research; 🇺🇸 Hialeah, Florida, United States

Tectum Medical Research; 🇺🇸 Hollywood, Florida, United States

Alloy Clinical Research, LLC; 🇺🇸 Kissimmee, Florida, United States

San Marcus Research Clinic, Inc.; 🇺🇸 Miami Lakes, Florida, United States

D&H National Research Centers INC; 🇺🇸 Miami, Florida, United States

Professional research Center INC; 🇺🇸 Miami, Florida, United States

M&A Medical Research; 🇺🇸 Miami, Florida, United States

Integrity Trials LLC; 🇺🇸 Orlando, Florida, United States

D&H Tamarac Research Center; 🇺🇸 Tamarac, Florida, United States

Tandem Clinical Research; 🇺🇸 Marrero, Louisiana, United States

Saint Paul Rheumatology, P.A.; 🇺🇸 Eagan, Minnesota, United States

IMA Clinical Research Las Vegas; 🇺🇸 Las Vegas, Nevada, United States

RB Wellness Clinic; 🇺🇸 Las Vegas, Nevada, United States

Columbia University Medical Center; 🇺🇸 New York, New York, United States

Accellacare Research of Cary; 🇺🇸 Cary, North Carolina, United States

Atrium Health South Park Rheumatology; 🇺🇸 Charlotte, North Carolina, United States

Altoona Center for Clinical Research Department of Rheumatology; 🇺🇸 Duncansville, Pennsylvania, United States

Texas Arthritis Center; 🇺🇸 El Paso, Texas, United States

Northwest Houston Arthritis Center; 🇺🇸 Houston, Texas, United States

Biomedica Research Group; 🇨🇱 Providencia, Chile

PROSALUD; 🇨🇱 Providencia, Chile

Sociedad Médica del Aparato Locomotor S. A.; 🇨🇱 Providencia, Chile

Enroll SpA; 🇨🇱 Santiago, Chile

Centro de Especialidades Medicas Vanguardia; 🇨🇱 Temuco, Chile

Clinical Research Chile SpA; 🇨🇱 Valdivia, Chile

Hospital San José de Victoria; 🇨🇱 Victoria, Chile

iMedica s.r.o.; 🇨🇿 Brno, Czechia

Institute of Rheumatology Prague; 🇨🇿 Praha 2, Czechia

LTD "New Plasma Clinic"; 🇬🇪 Batumi, Georgia

Institute of Clinical Cardiology, Ltd; 🇬🇪 Tbilisi, Georgia

LTD "Tbilisi Central Hospital"; 🇬🇪 Tbilisi, Georgia

National Institute of Endocrinology Ltd.; 🇬🇪 Tbilisi, Georgia

Tbilisi Heart and Vascular Clinic Ltd.; 🇬🇪 Tbilisi, 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

Fraunhofer-Institut für Translationale Medizin und Pharmakologie ITMP; 🇩🇪 Frankfurt am Main, Germany

Städtisches Klinikum Karlsruhe gGmbH; 🇩🇪 Karlsruhe, Germany

Universitätsklinikum Leipzig; 🇩🇪 Leipzig, Germany

Johannes Wesling Klinikum Minden; 🇩🇪 Minden, Germany

Universitätsklinikum Münster (UKM); 🇩🇪 Münster, Germany

Iizuka Hospital; 🇯🇵 Iizuka City, Japan

Nagasaki University Hospital; 🇯🇵 Nagasaki-shi, Japan

Chukyo Hospital; 🇯🇵 Nagoya-shi, Japan

Nagoya City University Hospital; 🇯🇵 Nagoya-shi, Japan

Shinkenko Clinic; 🇯🇵 Naha-shi, Japan

Tomakomai City Hospital; 🇯🇵 Tomakomai-shi, Japan

Juntendo University Urayasu Hospital; 🇯🇵 Urayasu, Japan

Centro de Investigación Clínica GRAMEL, S.C.; 🇲🇽 Ciudad de México, Mexico

Clinstile, S.A. de C.V.; 🇲🇽 Ciudad de México, Mexico

Consultorio Particular Dr. Miguel Cortés Hernández; 🇲🇽 Cuernavaca, Mexico

Centro Integral en Reumatologia SA de CV (CIRSA); 🇲🇽 Guadalajara, Mexico

Morales Vargas Centro de Investigación S.C.; 🇲🇽 León, Mexico

Centro Multidisciplinario para el Desarrollo Especializado de la Investigacion Clinica en Yucatan S.C.P. (CEMDEICY S.C.P.); 🇲🇽 Merida, Mexico

Boca Clinical Trials Mexico, S.C.; 🇲🇽 Mexico City, Mexico

Accelerium, S. de R.L. de C.V.; 🇲🇽 Monterrey, Mexico

UBAM Unidad Biomédica Avanzada Monterrey; 🇲🇽 Monterrey, Mexico

Oaxaca contra el Cáncer A.C; 🇲🇽 Oaxaca de Juárez, Mexico

Centro de Estudios Clínicos de Querétaro S.C.; 🇲🇽 Querétaro, Mexico

Clinical Research Institute S.C.; 🇲🇽 Tlanepantla de Baz, Mexico

PCR Toluca - Phylasis Clinical Research; 🇲🇽 Toluca de Lerdo, Mexico

Unidad de Investigación en Medicina Interna y Enfermedades Críticas / Hogar Clínica San Juan de Dios; 🇵🇪 Cayma, Peru

Centro de Investigacion Clinica Inmunoreumatologia / ACQ Medic SAC; 🇵🇪 Jesús María, Peru