A Research Study to Evaluate the Effects of a New Oral Medicine Called Cenerimod in Adults With Systemic Lupus Erythematosus

Lupus Erythematosus, Systemic Clinical Trial

— OPUS-1  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05648500
• Other study ID #: ID-064A301
• Secondary ID: 2022-002814-17
• Status: Recruiting
• Phase: Phase 3
• Start date: December 13, 2022
• Est. completion date: May 1, 2027

Study information

• Verified date: June 2024
• Source: Idorsia Pharmaceuticals Ltd.
• Contact: Idorsia Clinical Trial Information USA
• Phone: +1 856 661 3721
• Email: idorsiaclinicaltrials[@]idorsia.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The goal of this clinical trial is to see how well cenerimod reduces symptoms of Systemic Lupus Erythematosus 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 420
• Est. completion date: May 1, 2027
• Est. primary completion date: October 31, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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 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:

• ß-blockers, diltiazem, verapamil, digoxin, digitoxin, or any other anti-arrhythmic 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.

Related Conditions & MeSH terms

• Lupus Erythematosus, Systemic

Intervention

Drug:
• Cenerimod
Cenerimod will be supplied as a film-coated tablets at the dose of 4 mg.
• Placebo
Matching placebo will be supplied as identical film-coated tablets formulated with the same excipients but without the active ingredient, cenerimod.

Locations

Country	Name	City	State
Argentina	Instituto Medico CER	Buenos Aires
Argentina	Aprillus Asistencia e Investigacion	Ciudad Autónoma de Buenos Aires
Argentina	Arsema Clinica Adventista Belgrano	Ciudad Autónoma de Buenos Aires
Argentina	Fundación Respirar	Ciudad Autónoma de Buenos Aires
Argentina	Hospital Ramos Mejia	Ciudad Autónoma de Buenos Aires
Argentina	IR Medical Center /Hospital de Día/ Instituto de Reumatología y Traumatología	Mendoza
Argentina	Instituto CAICI SRL	Rosario
Argentina	Centro Integral de Reumatología	San Miguel de Tucumán
Argentina	ICT (Investigaciones Clínicas Tucumán)	San Miguel De Tucumán
Argentina	Centro de investigaciones medicas Tucuman	Tucuman
Brazil	Santa Casa de Belo Horizonte	Belo Horizonte
Brazil	Hospital Brasília	Brasilia
Brazil	Centro Mineiro de Pesquisas	Juiz De Fora
Brazil	Instituto Méderi de Pesquisa e Saúde	Passo Fundo
Brazil	Centro Multidisciplinar de Pesquisa Clínica (Irmandade da Santa Casa de Misericórdia de Porto Alegre	Porto Alegre
Brazil	LMK Servicos Medico S/S	Porto Alegre
Brazil	IMPAR SERVICOS HOSPITALARES S/A ; Hospital São Lucas	Rio de Janeiro
Brazil	SER - Serviços Especializados em Reumatologia da Bahia	Salvador
Brazil	Hospital de Clínicas de Porto Alegre	Santa Cecília
Brazil	Centro Multidiciplinar de Estudos Clínicos- CEMEC	São Bernardo do Campo
Brazil	Fundação Faculdade Regional de Medicina de São José do Rio Preto	São José do Rio Preto
Brazil	CPClin - Centro de Pesquisas Clínicas	São Paulo
Brazil	Ebserh Hospital de Clínicas da Universidade Federal de Uberlândia-HC-UFU	Uberlandia
Bulgaria	Medical Center ArtMed OOD	Plovdiv
Bulgaria	Outpatient Clinic for Specialized Outpatient Medical Care - Medical Center Kyuchuk Parizh Ltd.	Plovdiv
Bulgaria	University Multi-profile Hospital for Active Treatment - Plovdiv AD	Plovdiv
Bulgaria	DCC 1 Ruse	Ruse
Bulgaria	Acibadem City Clinic Diagnostic-Consultative Center" EOOD, 127 Okolovrasten pat, Mladost	Sofia
Bulgaria	DCC Equita EOOD	Varna
Colombia	Clínica de la costa Ltda.	Barranquilla
Colombia	IDEARG (Instituto de Enfermedades Autoinmunes Renato Guzmán)	Bogota
Colombia	Bluecare salud SAS	Bogotá
Colombia	SERVIMED S.A.S Bucaramanga	Bucaramanga
Colombia	Centro de Estudios de Reumatología y Dermatología	Cali
Colombia	Fundación Valle de Lili	Cali
Colombia	Preventive Care SAS	Chía
Colombia	Hospital Pablo Tobón Uribe	Medellín
Colombia	Fundación Centro De Excelencia En Enfermedades Crónicas No Transmisibles-FUNCENTRA	Monteria
Colombia	Healthy Medical Center SAS	Zipaquira
France	Hôpital Pitié-Salpêtrière	Paris
France	CHU Félix Guyon Site Nord	Saint-Denis
France	CHU de Purpan	Toulouse
Greece	General Hospital of Athens "Laiko"	Athen
Greece	General Hospital of Athens "Hippokration"	Athens
Greece	Naval Hospital of Athens	Athens
Greece	University General Hospital "Attikon"	Athens
Greece	General University Hospital of Larissa	Larissa
Greece	General University Hospital of Patras	Patras
Greece	424 General Military Hospital	Thessaloniki
Greece	General Hospital of Thessaloniki "Hippokration"	Thessaloniki
Greece	Euromedica - Kyanos Stavros	Thessaloníki
Korea, Republic of	Pusan National University Hospital	Busan
Korea, Republic of	Catholic University of Daegu (Daegu Catholic University Medical Center)	Daegu
Korea, Republic of	Seoul National University Hospital	Junggu
Korea, Republic of	Ewha University Mokdong Hospital, Yangcheon-gu	Seoul
Korea, Republic of	Hanyang University Hospital, Seongdong-gu	Seoul
Korea, Republic of	KonKuk University Medical Center, Gwangjin-gu	Seoul
Korea, Republic of	Seoul Saint Mary's Hospital of the Catholic University of Korea, Seocho-gu	Seoul
Mexico	Biológicos Especializados S.A. de C.V.	Ciudad de México
Mexico	CITER, Centro de Investigación y Tratamiento de las Enfermedades Reumáticas S.A. de C.V.	Ciudad de México
Mexico	Panamerican Clinical Research Mexico S.A. de C.V.	Cuernavaca
Mexico	Centro de Estudios de Investigación Básica y Clínica, S.C.	Guadalajara
Mexico	Consultorio Privado de Especialidad	Guadalajara
Mexico	Consultorio Médico de Reumatología - Hospital Aranda de la Parra	León
Mexico	Unidad de Atención Médica e Investigación en Salud	Mérida
Mexico	Centro de Investigación Clínica Chapultepec S. A. de C. V.	Morelia
Mexico	SMIQ, S. de R.L. de C.V.	Querétaro
Mexico	Unidad de Investigaciones Reumatológicas A.C	San Luis Potosi
Mexico	Centro de Atención e Investigación Cardiovascular del Potosí, S.C.	San Luis Potosí
Mexico	Investigación Biomédica para el Desarrollo de Fármacos S.A. de C.V.	Zapopan
Philippines	Chong-Hua Hospital	Cebu City
Philippines	Mary Mediatrix Medical Center	Lipa
Philippines	Makati Medical Center	Makati
Philippines	Far Eastern University - Nicanor Reyes Medical Foundation	Quezon City
Philippines	Jose R. Reyes Memorial Medical Center	Santa Cruz
Poland	Centrum Medyczne Pratia Czestochowa	Czestochowa
Poland	Centrum Medyczne Angelius Provita	Katowice
Poland	Vita Longa Sp. z o.o.	Katowice
Poland	Centrum Medyczne Plejady	Kraków
Poland	Malopolskie Badania Kliniczne	Kraków
Poland	Zespól Poradni Specjalistycznych REUMED	Lublin
Poland	Malwa-Med Iwona Chlebicka	Wroclaw
Romania	Neomed Brasov	Brasov
Romania	Spitalul Clinic Dr. Ion Cantacuzino	Bucharest
Romania	Delta Health Care SRL	Bucuresti
Romania	SC Sana Monitoring SRL	Bucuresti
Romania	Spitalul Clinic Judetean de Urgentã Craiova	Craiova
Romania	SC Medaudio-Optica SRL	Râmnicu Vâlcea
Taiwan	Kaohsiung Medical University Hospital	Kaohsiung
Taiwan	Far Eastern Memorial Hospital	New Taipei City
Taiwan	China Medical University Hospital	Taichung
Taiwan	Chi Mei Medical Center	Tainan City
Taiwan	National Taiwan University Hospital	Taipei
Taiwan	Cheng Hsin General Hospital	Taipei City
Taiwan	Taipei Medical University Hospital	Taipei City
Taiwan	Taipei Veterans General Hospital	Taipei City
Taiwan	TRI-Service General Hospital	Taipei City
Taiwan	Linkou Chang Gung Memorial Hospital	Taoyuan City
United States	Allen Arthritis	Allen	Texas
United States	Augusta University	Augusta	Georgia
United States	University of Colorado Denver	Aurora	Colorado
United States	Accurate Clinical Research Inc.	Baytown	Texas
United States	Rheumatology Care Center, PLLC	Bellaire	Texas
United States	RASF-Clinical Research Inc.	Boca Raton	Florida
United States	DJL Clinical Research, PLLC	Charlotte	North Carolina
United States	Clinical Research of West Florida, Inc.	Clearwater	Florida
United States	Metroplex Clinical Research Center	Dallas	Texas
United States	Omega Research MetroWest, LLC	DeBary	Florida
United States	Providence Medical Foundation	Fullerton	California
United States	Klein & Associates, M.D., P.A.	Hagerstown	Maryland
United States	Accurate Clinical Research Inc.	Houston	Texas
United States	Accurate Clinical Research Inc. - Lake Charles	Lake Charles	Louisiana
United States	June DO, PC	Lansing	Michigan
United States	Shelby Research, LLC	Memphis	Tennessee
United States	SouthCoast Research Center, Inc.	Miami	Florida
United States	IRIS Research and Development, LLC	Plantation	Florida
United States	Sun Research Institute	San Antonio	Texas
United States	Renew Health Clinical Research LLC	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Idorsia Pharmaceuticals Ltd.

Countries where clinical trial is conducted

United States,  Argentina,  Brazil,  Bulgaria,  Colombia,  France,  Greece,  Korea, Republic of,  Mexico,  Philippines,  Poland,  Romania,  Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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)
Secondary	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
Secondary	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