Clinical trial NCT05672576: A Research Study to Evaluate the Efficacy and Safety of Cenerimod in Subjects Suffering From Systemic Lupus Erythematosus
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Lupus Erythematosus, Systemic
Keywords: Musculoskeletal and connective tissue disorders
Immune System Diseases
Autoimmune Diseases
Lead sponsor: Idorsia Pharmaceuticals Ltd.
Sponsor class: INDUSTRY
First posted: 2023-01-05
Enrollment: 420
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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:

  * 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.

Primary outcomes:
measure: Response on Systemic Lupus Erythematosus Responder Index 4 (SRI-4) at Month 12 compared to baseline
timeFrame: At Month 12 compared to Day 1 (pre-dose baseline)
Secondary outcomes:
measure: Response on BILAG-based Composite Lupus Assessment (BICLA) at Month 12 compared to baseline
timeFrame: At Month 12 compared to Day 1 (pre-dose baseline)
measure: Time to first confirmation of a 4-month sustained modified Systemic Lupus Erythematosus Disease Activity Index-2000 (mSLEDAI-2K) response
timeFrame: Day 1 (pre-dose baseline) to Month 12
measure: Time to first confirmation of a 4-month sustained response in mucocutaneous manifestations (i.e., rash, alopecia, mucosal ulcers)
timeFrame: Day 1 (pre-dose baseline) to Month 12
Other outcomes:
Locations:
city: Tucson
country: United States
facility: Tucson Clinical Research Institute, LLC
state: Arizona
city: La Jolla
country: United States
facility: UCSD Perlman Medical Offices
state: California
city: Northridge
country: United States
facility: Amicis Research Center
state: California
city: Poway
country: United States
facility: BioSolutions Clinical Research Center
state: California
city: Riverside
country: United States
facility: Arthritis Medical Clinic Osteoporosis Diagnostic Imaging and Treatment Center
state: California
city: Coral Gables
country: United States
facility: Hope Clinical Trials, Inc.
state: Florida
city: Hialeah
country: United States
facility: Vital Pharma Research
state: Florida
city: Hollywood
country: United States
facility: Tectum Medical Research
state: Florida
city: Kissimmee
country: United States
facility: Alloy Clinical Research, LLC
state: Florida
city: Miami Lakes
country: United States
facility: San Marcus Research Clinic, Inc.
state: Florida
city: Miami
country: United States
facility: D&H National Research Centers INC
state: Florida
city: Miami
country: United States
facility: Professional research Center INC
state: Florida
city: Miami
country: United States
facility: M&A Medical Research
state: Florida
city: Orlando
country: United States
facility: Integrity Trials LLC
state: Florida
city: Tamarac
country: United States
facility: D&H Tamarac Research Center
state: Florida
city: Orland Park
country: United States
facility: Advance Quality Medical Research
state: Illinois
city: Marrero
country: United States
facility: Tandem Clinical Research
state: Louisiana
city: Eagan
country: United States
facility: Saint Paul Rheumatology, P.A.
state: Minnesota
city: Las Vegas
country: United States
facility: IMA Clinical Research Las Vegas
state: Nevada
city: Las Vegas
country: United States
facility: RB Wellness Clinic
state: Nevada
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: Cary
country: United States
facility: Accellacare Research of Cary
state: North Carolina
city: Charlotte
country: United States
facility: Atrium Health South Park Rheumatology
state: North Carolina
city: Duncansville
country: United States
facility: Altoona Center for Clinical Research Department of Rheumatology
state: Pennsylvania
city: Colleyville
country: United States
facility: Precision Comprehensive Clinical Research Solutions
state: Texas
city: El Paso
country: United States
facility: Texas Arthritis Center
state: Texas
city: Houston
country: United States
facility: Northwest Houston Arthritis Center
state: Texas
city: Providencia
country: Chile
facility: Biomedica Research Group
city: Providencia
country: Chile
facility: PROSALUD
city: Providencia
country: Chile
facility: Sociedad Médica del Aparato Locomotor S. A.
city: Santiago
country: Chile
facility: Estudios G y C Ltda
city: Santiago
country: Chile
facility: Enroll SpA
city: Temuco
country: Chile
facility: Centro de Especialidades Medicas Vanguardia
city: Valdivia
country: Chile
facility: Clinical Research Chile SpA
city: Victoria
country: Chile
facility: Hospital San José de Victoria
city: Brno
country: Czechia
facility: iMedica s.r.o.
city: Praha 2
country: Czechia
facility: Institute of Rheumatology Prague
city: Batumi
country: Georgia
facility: LTD "New Plasma Clinic"
city: Tbilisi
country: Georgia
facility: Ltd "New Hospitals"
city: Tbilisi
country: Georgia
facility: Institute of Clinical Cardiology, Ltd
city: Tbilisi
country: Georgia
facility: LTD "Tbilisi Central Hospital"
city: Tbilisi
country: Georgia
facility: National Institute of Endocrinology Ltd.
city: Tbilisi
country: Georgia
facility: Tbilisi Heart and Vascular Clinic Ltd.
city: Tbilisi
country: Georgia
facility: Aversi Clinic LTD
city: Tbilisi
country: Georgia
facility: Medi Club Georgia Ltd.
city: Tbilisi
country: Georgia
facility: Tbilisi Institute of Medicine
city: Tbilisi
country: Georgia
facility: JSC Jerarsi Clinic
city: Tbilisi
country: Georgia
facility: Ltd. Mtskheta Street Clinic
city: Tbilisi
country: Georgia
facility: The First Medical Center Ltd.
city: Tbilisi
country: Georgia
facility: Caucasus Medical Centre
city: Tbilisi
country: Georgia
facility: LLC "Innova"
city: Tbilisi
country: Georgia
facility: LLC Raymann
city: Tbilisi
country: Georgia
facility: LTD "Tbilisi Heart Center"
city: Frankfurt am Main
country: Germany
facility: Fraunhofer-Institut für Translationale Medizin und Pharmakologie ITMP
city: Karlsruhe
country: Germany
facility: Städtisches Klinikum Karlsruhe gGmbH
city: Leipzig
country: Germany
facility: Universitätsklinikum Leipzig
city: Minden
country: Germany
facility: Johannes Wesling Klinikum Minden
city: Münster
country: Germany
facility: Universitätsklinikum Münster (UKM)
city: Iizuka City
country: Japan
facility: Iizuka Hospital
city: Nagasaki-shi
country: Japan
facility: Nagasaki University Hospital
city: Nagoya-shi
country: Japan
facility: Chukyo Hospital
city: Nagoya-shi
country: Japan
facility: Nagoya City University Hospital
city: Naha-shi
country: Japan
facility: Shinkenko Clinic
city: Tomakomai-shi
country: Japan
facility: Tomakomai City Hospital
city: Urayasu
country: Japan
facility: Juntendo University Urayasu Hospital
city: Batu Caves
country: Malaysia
facility: Hospital Selayang
city: Kangar
country: Malaysia
facility: Hospital Tuanku Fauziah, Kangar
city: Kuching
country: Malaysia
facility: Sarawak General Hospital
city: Sibu
country: Malaysia
facility: Hospital Sibu, Sarawak
city: Ciudad de México
country: Mexico
facility: Centro de Investigación Clínica GRAMEL, S.C.
city: Ciudad de México
country: Mexico
facility: Clinstile, S.A. de C.V.
city: Cuernavaca
country: Mexico
facility: Consultorio Particular Dr. Miguel Cortés Hernández
city: Guadalajara
country: Mexico
facility: Centro Integral en Reumatologia SA de CV (CIRSA)
city: León
country: Mexico
facility: Morales Vargas Centro de Investigación S.C.
city: Merida
country: Mexico
facility: Centro Multidisciplinario para el Desarrollo Especializado de la Investigacion Clinica en Yucatan S.C.P. (CEMDEICY S.C.P.)
city: Mexico City
country: Mexico
facility: Boca Clinical Trials Mexico, S.C.
city: Monterrey
country: Mexico
facility: Accelerium, S. de R.L. de C.V.
city: Monterrey
country: Mexico
facility: UBAM Unidad Biomédica Avanzada Monterrey
city: Oaxaca de Juárez
country: Mexico
facility: Oaxaca contra el Cáncer A.C
city: Querétaro
country: Mexico
facility: Centro de Estudios Clínicos de Querétaro S.C.
city: Tlanepantla de Baz
country: Mexico
facility: Clinical Research Institute S.C.
city: Toluca de Lerdo
country: Mexico
facility: PCR Toluca - Phylasis Clinical Research
city: Cayma
country: Peru
facility: Unidad de Investigación en Medicina Interna y Enfermedades Críticas / Hogar Clínica San Juan de Dios
city: Jesús María
country: Peru
facility: Centro de Investigacion Clinica Inmunoreumatologia / ACQ Medic SAC
city: Jesús María
country: Peru
facility: Centro de Investigación del Hospital Militar Central
city: Lima
country: Peru
facility: Alberto Sabogal Sologuren National Hospital
city: Lima
country: Peru
facility: Hospital Maria Auxiliadora
city: San Borja
country: Peru
facility: Unidad de Investigación de la Clinica International
city: San Isidro
country: Peru
facility: Instituto Peruano del Hueso y la Articulación S.A.C. (IPHAR)
city: San Isidro
country: Peru
facility: Clínica Anglo Americana
city: San Isidro
country: Peru
facility: Servicios Reumatológicos SOMA E.I.R.L. / Clinica El Golf
city: San Juan de Lurigancho
country: Peru
facility: Unidad de Investigación en Reumatología e Inmunología CSJB
city: San Martín de Porres
country: Peru
facility: Hospital Nacional Cayetano Heredia
city: Santiago De Surco
country: Peru
facility: Investigaciones Clinicas / Instituto de Ginecología y Reproducción, El Derby
city: Trujillo
country: Peru
facility: Centro de Investigación Clínica Trujillo EIRL / Clínica Peruano Americana S.A
city: Iloilo City
country: Philippines
facility: Iloilo Doctors Hospital
city: Makati City
country: Philippines
facility: Ospital ng Makati
city: Makati
country: Philippines
facility: Makati Medical Center
city: Manila
country: Philippines
facility: St Lukes Medical Center
city: Pampanga
country: Philippines
facility: The Medical City Clark
city: Sampaloc
country: Philippines
facility: St Luke's Medical Center Quezon City / University of Santo Tomas Hospital
city: Bydgoszcz
country: Poland
facility: Szpital Uniwersytecki nr 2 im. dr. Jana Biziela w Bydgoszczy
city: Poznań
country: Poland
facility: Medyczne Centrum Hetmańska
city: Poznań
country: Poland
facility: Twoja Przychodnia Poznańskie Centrum Medyczne
city: Szczecin
country: Poland
facility: Pomorski Uniwersytet Medyczny w Szczecinie
city: Warszawa
country: Poland
facility: MICS Centrum Medyczne Warszawa
city: Amadora
country: Portugal
facility: Hospital Prof. Doutor Fernando Fonseca
city: Faro
country: Portugal
facility: Centro Hospitalar Universitário do Algarve - Hospital de Faro
city: Guarda
country: Portugal
facility: ULS Guarda
city: Guimarães
country: Portugal
facility: Hospital Senhora Oliveira-Guimaraes
city: Lisbon
country: Portugal
facility: Instituto Portugues De Reumatologia
city: Lisbon
country: Portugal
facility: Unidade Local De Saude Lisboa Ocidental E.P.E.
city: Vila Nova de Gaia
country: Portugal
facility: Centro Hospitalar de Vila Nova de Gaia/Espinho, E.P.E.
city: Caguas
country: Puerto Rico
facility: Centro Reumatologico de Caguas
city: San Juan
country: Puerto Rico
facility: GCM Medical Group, PSC
city: Belgrade
country: Serbia
facility: Institute of Rheumatology, Belgrade (study site 1)
city: Belgrade
country: Serbia
facility: Institute of Rheumatology, Belgrade (study site 2)
city: Belgrade
country: Serbia
facility: Institute of Rheumatology, Belgrade (study site 3)
city: Belgrade
country: Serbia
facility: University Clinical Center of Serbia
city: Belgrade
country: Serbia
facility: Military Medical Academy
city: Kragujevac
country: Serbia
facility: Clinical Center Kragujevac
city: Novi Sad
country: Serbia
facility: Special Hospital for Rheumatic Diseases, Novi Sad
city: Zrenjanin
country: Serbia
facility: General Hospital "Djordje Joanovic"
city: Cape Town
country: South Africa
facility: Arthritis Clinical Research Trials
city: Cape Town
country: South Africa
facility: Panorama Medical Centre
city: Parktown
country: South Africa
facility: Charlotte Maxeke Johannesburg Academic Hospital
city: Pretoria
country: South Africa
facility: University of Pretoria
city: Somerset West
country: South Africa
facility: Winelands Medical Research
city: Alcobendas
country: Spain
facility: Accellacare
city: Barcelona
country: Spain
facility: Parc Tauli Sabadell University Hospital
city: Colmenar Viejo
country: Spain
facility: Hospital Universitari Vall d'Hebron
city: Colmenar Viejo
country: Spain
facility: Hospital Universitario Ramon y Cajal
city: Madrid
country: Spain
facility: Hospital Universitario Infanta Leonor
city: Madrid
country: Spain
facility: Hospital Clínico San Carlos
city: Santiago De Compostela
country: Spain
facility: Clinica Gaias Santiago
city: Sevilla
country: Spain
facility: Hospital QuironSalud Sagrado Corazon
city: Sevilla
country: Spain
facility: Hospital Universitario Nuestra Señora de Valme
city: Valencia
country: Spain
facility: Hospital Clinico Universitario de Valencia
city: Valencia
country: Spain
facility: Hospital Universitario Doctor Peset
city: Valladolid
country: Spain
facility: Hospital Universitario Río Hortega de Valladolid
city: Kyiv
country: Ukraine
facility: Medical Center "Universal Clinic "Oberih"" of Limited Liability Company "Capital"
city: Ternopil
country: Ukraine
facility: Ternopil Regional Clinical Hospital
city: Leicester
country: United Kingdom
facility: University Hospitals of Leicester Nhs Trust
city: London
country: United Kingdom
facility: Guy's and St. Thomas' NHS Foundation Trust - Guy's Hospital
Study officials:
affiliation: Idorsia Pharmaceuticals Ltd.
name: Clinical Trials
role: STUDY_DIRECTOR
References: