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

Lupus Erythematosus, Systemic Clinical Trial

— OPUS-2  

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: NCT05672576
• Other study ID #: ID-064A302
• Secondary ID: 2022-002815-47
• Status: Recruiting
• Phase: Phase 3
• Start date: June 26, 2023
• 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 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.

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 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.

Related Conditions & MeSH terms

• Lupus Erythematosus, Systemic

Intervention

Drug:
• Cenerimod
Cenerimod will be supplied as 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
Chile	Biomedica Research Group	Providencia
Chile	PROSALUD	Providencia
Chile	Sociedad Médica del Aparato Locomotor S. A.	Providencia
Chile	Enroll SpA	Santiago
Chile	Clinical Research Chile SpA	Valdivia
Chile	Hospital San José de Victoria	Victoria
Czechia	iMedica s.r.o.	Brno
Czechia	Institute of Rheumatology Prague	Praha 2
Georgia	LTD "New Plasma Clinic"	Batumi
Georgia	Aversi Clinic LTD	Tbilisi
Georgia	Institute of Clinical Cardiology, Ltd	Tbilisi
Georgia	LLC "Innova"	Tbilisi
Georgia	LLC Raymann	Tbilisi
Georgia	LTD "Tbilisi Central Hospital"	Tbilisi
Georgia	LTD "Tbilisi Heart Center"	Tbilisi
Georgia	Ltd. Mtskheta Street Clinic	Tbilisi
Georgia	Medi Club Georgia Ltd.	Tbilisi
Georgia	National Institute of Endocrinology Ltd.	Tbilisi
Georgia	Tbilisi Heart and Vascular Clinic Ltd.	Tbilisi
Georgia	The First Medical Center Ltd.	Tbilisi
Germany	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
Japan	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
Mexico	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
Peru	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	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	Clínica Anglo Americana	San Isidro
Peru	Instituto Peruano del Hueso y la Articulación S.A.C. (IPHAR)	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
Philippines	Iloilo Doctors Hospital	Iloilo City
Philippines	Makati Medical Center	Makati
Philippines	St Lukes Medical Center	Manila
Philippines	St Luke's Medical Center Quezon City / University of Santo Tomas Hospital	Sampaloc
Poland	Szpital Uniwersytecki nr 2 im. dr. Jana Biziela w Bydgoszczy	Bydgoszcz
Poland	Medyczne Centrum Hetmanska	Poznan
Poland	Twoja Przychodnia Poznanskie Centrum Medyczne	Poznan
Poland	Pomorski Uniwersytet Medyczny w Szczecinie	Szczecin
Poland	MICS Centrum Medyczne Warszawa	Warszawa
Portugal	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	Centro Hospitalar de Vila Nova de Gaia/Espinho, E.P.E.	Vila Nova de Gaia
Puerto Rico	Centro Reumatologico de Caguas	Caguas
Puerto Rico	GCM Medical Group, PSC	San Juan
Serbia	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	Military Medical Academy	Belgrade
Serbia	University Clinical Center of Serbia	Belgrade
Serbia	Clinical Center Kragujevac	Kragujevac
Serbia	Special Hospital for Rheumatic Diseases, Novi Sad	Novi Sad
Serbia	General Hospital "Djordje Joanovic"	Zrenjanin
South Africa	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
Spain	Parc Tauli Sabadell University Hospital	Barcelona
Spain	Clinica Gaias Santiago	Santiago De Compostela
Spain	Hospital QuironSalud Sagrado Corazon	Sevilla
Spain	Hospital Clinico Universitario de Valencia	Valencia
Spain	Hospital Universitario Doctor Peset	Valencia
Spain	Hospital Universitario Río Hortega de Valladolid	Valladolid
United States	Accellacare Research of Cary	Cary	North Carolina
United States	Hope Clinical Trials, Inc.	Coral Gables	Florida
United States	Altoona Center for Clinical Research Department of Rheumatology	Duncansville	Pennsylvania
United States	Saint Paul Rheumatology, P.A.	Eagan	Minnesota
United States	Texas Arthritis Center	El Paso	Texas
United States	Vital Pharma Research	Hialeah	Florida
United States	Northwest Houston Arthritis Center	Houston	Texas
United States	UCSD Perlman Medical Offices	La Jolla	California
United States	IMA Clinical Research Las Vegas	Las Vegas	Nevada
United States	Tandem Clinical Research	Marrero	Louisiana
United States	D&H National Research Centers INC	Miami	Florida
United States	San Marcus Research Clinic, Inc.	Miami Lakes	Florida
United States	Columbia University Medical Center	New York	New York
United States	Integrity Trials LLC	Orlando	Florida
United States	Arthritis Medical Clinic Osteoporosis Diagnostic Imaging and Treatment Center	Riverside	California
United States	D&H Tamarac Research Center	Tamarac	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Idorsia Pharmaceuticals Ltd.

Countries where clinical trial is conducted

United States,  Chile,  Czechia,  Georgia,  Germany,  Japan,  Mexico,  Peru,  Philippines,  Poland,  Portugal,  Puerto Rico,  Serbia,  South Africa,  Spain, 

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