Efficacy and Safety of Four Doses of Cenerimod Compared to Placebo in Adult Subjects With Active Systemic Lupus Erythematosus

Systemic Lupus Erythematosus Clinical Trial

Official title:

A Phase 2b, Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel Group Study to Evaluate the Efficacy, Safety, and Tolerability of Cenerimod in Subjects With Moderate to Severe Systemic Lupus Erythematosus (SLE)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03742037
• Other study ID #: ID-064A202
• Secondary ID: 2018-001808-11
• Status: Completed
• Phase: Phase 2
• Start date: December 21, 2018
• Est. completion date: August 25, 2022

Study information

• Verified date: September 2023
• Source: Idorsia Pharmaceuticals Ltd.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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 information / eligibility

• Status: Completed
• Enrollment: 427
• Est. completion date: August 25, 2022
• Est. primary completion date: August 31, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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

Related Conditions & MeSH terms

• Lupus Erythematosus, Systemic
• Systemic Lupus Erythematosus

Intervention

Drug:
• Cenerimod 0.5 mg
Cenerimod will be supplied as a film-coated tablets at the dose of 0.5 mg
• Cenerimod 1 mg
Cenerimod will be supplied as a film-coated tablets at the dose of 1 mg
• Cenerimod 2 mg
Cenerimod will be supplied as a film-coated tablets at the dose of 2 mg
• Cenerimod 4 mg
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
• cenerimod 2 mg (ex-4 mg)
Cenerimod will be supplied as a film-coated tablets at the dose of 2 mg

Locations

Country	Name	City	State
Bulgaria	Multiprofile Hospital For Active Treatment Trimontium	Plovdiv	Plodiv
Bulgaria	University Multiprofile Hospital for Active Treatment Pulmed	Plovdiv
Bulgaria	Diagnostic and Consulting Center "Aleksandrovska" EOOD	Sofia
Bulgaria	Diagnostic Consulting Center Fokus-5	Sofia
Chile	Biomedica Research Group	Santiago
Chile	Enroll SpA	Santiago
Chile	Meditek Ltda.	Santiago
Chile	Prosalud	Santiago
Chile	Clinical Research Chile SpA	Valdivia
Czechia	CCR Pardubice	Pardubice	Vychodocesky KRAJ
France	Centre Hospitalier Regional Universitaire Brest Hôpital de la Cavale Blanche à Brest	Brest	Bretagne
France	Hôpital Haut-Lévêque	Pessac
Georgia	LTD "New Plasma Clinic"	Batumi
Georgia	Aversi Clinic LTD	Tbilisi
Georgia	LLC "Innova"	Tbilisi
Georgia	LLC Raymann	Tbilisi
Georgia	LTD "Tbilisi Heart Center"	Tbilisi
Georgia	Ltd. Mtskheta Street Clinic	Tbilisi
Georgia	Medi Club Georgia Ltd.	Tbilisi
Georgia	Medicore	Tbilisi
Georgia	Multiprofile Clinic Consilium Medulla	Tbilisi
Georgia	The First Medical Center Ltd.	Tbilisi
Germany	Städtisches Klinikum Karlsruhe gGmbH	Karlsruhe
Greece	General Hospital of Athens "Laiko"	Goudí
Hungary	Egyesitett Szent Istvan es Szent Laszlo Korhaz Rendelointezet	Budapest
Israel	Bnai Zion Medical Center	Haifa
Israel	Rambam Healthcare Campus	Haifa
Israel	Galilee Medical Center	Nahariya
Israel	The Chaim Sheba Medical Center	Ramat-Gan
Italy	LUPUS CLINIC c/o DIMI	Genova
Italy	Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico	Milano
Italy	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
Japan	Tomakomai City Hospital	Tomakomai-shi
Mexico	Karla Adriana Espinosa Bautista	Ciudad de México
Mexico	Consultorio Particular Dr. Miguel Cortés Hernández	Cuernavaca
Mexico	Centro Integral en Reumatología S.A. de C.V.	Guadalajara
Mexico	Consultorio Médico del Dr. Federico Galván Villegas	Guadalajara
Mexico	Consultorio Privado de Especialidad del Dr. José Javier Orozco Alcalá	Guadalajara
Mexico	Icle S.C.	Guadalajara
Mexico	Morales Vargas Centro de Investigación S.C.	León
Mexico	Kohler & Milstein Research S.A. de C.V.	Mérida
Mexico	Unidad de Atención Médica e Investigación en Salud	Mérida
Mexico	Biológicos Especializados S.A. de C.V.	Mexico City
Mexico	Centro de Investigación Clínica GRAMEL, S.C.	Mexico City
Mexico	Accelerium, S. de R.L. de C.V.	Monterrey
Mexico	UBAM Unidad Biomédica Avanzada Monterrey	Monterrey
Mexico	SMIQ, S. de R.L. de C.V.	Queretaro
Mexico	Hospital Universitario "Dr. Gonzalo Valdés Valdés"	Saltillo
Mexico	Centro de Atención e Investigación Cardiovascular del Potosí, S.C.	San Luis Potosí
Mexico	Unidad de Investigaciones Reumatológicas A.C.	San Luis Potosí
Mexico	Investigacion Biomedica para el Desarrollo de Farmacos S.A. de C.V.	Zapopan
Philippines	Angeles University Foundation Medical Center	Angeles City
Philippines	Davao Doctors Hospital	Davao City
Philippines	Iloilo Doctors Hospital	Iloilo City
Philippines	Lipa Medix Medical Center	Lipa City	Batangas
Philippines	Makati Medical Center	Makati City
Philippines	Jose R. Reyes Memorial Medical Center	Manila
Philippines	University of Santo Tomas Hospital	Manila
Philippines	University of the Philippines Manila - Philippine General Hospital	Manila
Philippines	Far Eastern University - Nicanor Reyes Medical Foundation	Quezon City
Philippines	St. Luke's Medical Center	Quezon City
Poland	Szpital Uniwersytecki Number 2 im. dr. Jana Biziela w Bydgoszczy	Bydgoszcz
Poland	Intermedius Uslugi Medyczne	Koscian
Poland	Szpital Specjalistyczny im. J. Dietla w Krakowie	Krakow
Poland	Centrum Medyczne Plejady	Kraków
Poland	Twoja Przychodnia Poznanskie Centrum Medyczne	Poznan
Poland	Slaskie Centrum Reumatologii, Rehabilitacji i Zapobiegania Niepelnosprawnosci im gen. Jerzego Zi	Ustron
Puerto Rico	Centro Reumatologico de Caguas	Caguas
Romania	Centrul Medical de Diagnostic si Tratament Ambulatoriu Neomed	Brasov
Romania	Spitalul Clinic "Sf. Maria"	Bucharest
Romania	SC Sana Monitoring SRL	Bucuresti
Romania	Spitalul Clinic Judetean de Urgenta Cluj-Napoca	Cluj-Napoca
Russian Federation	Chelyabinsk Regional Clinical Hospital	Chelyabinsk
Russian Federation	JSC "Center of Family Medicine"	Ekaterinburg
Russian Federation	City Clinical Hospital #15 named after O.M. Filatova	Moscow
Russian Federation	Federal State Budget Scientific Research Institution "Scientific Research Institute of Rheumatology n.a. V.A. Nasonova"	Moscow
Russian Federation	Non-governmental private healthcare organization, Scientific Clinical Centre of JSC Russian Railways	Moscow
Russian Federation	Medical Center "Zdorovaya Semiya", LLC	Novosibirsk
Russian Federation	Orenburg State Medical University	Orenburg
Russian Federation	Clinical Rheumatological Hospital Number 25	Saint Petersburg
Russian Federation	Medical Center Maksimum Zdorovia	Saint Petersburg
Russian Federation	Medical Research Institute, LLC	Saint Petersburg
Russian Federation	Polyclinic of Private Security and Detectives	Saint Petersburg
Russian Federation	Military Medical Academy S.M. Kirov	Saint-Petersburg
Russian Federation	Saratov Regional Clinical Hospital	Saratov
Russian Federation	State Institution of Health Protection "Clinical Hospital #8"	Yaroslavl
Spain	Hospital Clinic i Provincial de Barcelona	Barcelona
Spain	Hospital Universitario 12 de Octubre	Madrid
Spain	Hospital Universitario Regional de Málaga	Málaga	Malaga
Spain	Hospital Quirónsalud Infanta Luisa	Sevilla
Spain	Hospital Universitario Doctor Peset	Valencia
Taiwan	Kaohsiung Medical University Hospital	Kaohsiung
Taiwan	Kaohsiung Veterans General Hospital	Kaohsiung
Thailand	Rajavithi Hospital	Bangkok
Thailand	Songklanagarind Hospital	Songkhla
Turkey	Istanbul Universitesi Istanbul Tip Fakultesi	Istanbul
Turkey	Necmettin Erbakan Üniversitesi Meram Tip Fakültesi	Konya
Ukraine	Clinic of State Institution "National Scientific Centre "Acad. Strazhesko Institute of Cardiology"	Kyiv
Ukraine	Kyiv City Clinical Hospital ?3	Kyiv
Ukraine	Medical Centre "Consilium medical"	Kyiv
Ukraine	Municipal Institution Kyiv Regional Council "Kyiv Regional Clinical Hospital"	Kyiv
Ukraine	Lviv Regional Clinical Hospital	Lviv
Ukraine	Municipal Nonprofit Institution of Lviv Regional Council	Lviv
Ukraine	Municipal Nonprofit Institution of Lviv Regional Council "Lviv Regional Clinical Hospital"	Lviv
Ukraine	Poltava Regional Clinical Hospital named after M.V. Sklifossovsky	Poltava
Ukraine	Ternopil University Clinic - Rheumatology department	Ternopil
Ukraine	Zakarpattya Regional Clinical Hospital n.a. A.Novak - Rheumatology Department	Uzhgorod
Ukraine	Medical Center "Health Clinic", LLC	Vinnytsia
Ukraine	Municipal Nonprofit Institution "Vinnytsia City Clinical Hospital ?1"	Vinnytsia
Ukraine	Private Small Scale Medical Center "Pulse"	Vinnytsia
Ukraine	Scientific and Research Institute of Invalid Rehabilitation (EST Complex) of Vinnytsia M.I.Pyrogov NMU MOHU,	Vinnytsia
Ukraine	Vinnytsya Regional Clinical Hospital - Rheumatology Department	Vinnytsya
Ukraine	Municipal Institution "Zaporizhzhya Regional Clinical Hospital"	Zaporizhzhya
Ukraine	Municipal institution "Regional Clinical Hospital n.a. O.F. Herbachevskoho"	Zhytomyr
United Kingdom	Cambridge University Hospitals NHS Foundation Trust	Cambridge
United Kingdom	Guy's and Saint Thomas' NHS Foundation Trust	London
United States	Amarillo Center for Clinical Research	Amarillo	Texas
United States	Pinnacle Research Group	Anniston	Alabama
United States	University of Colorado School of Medicine	Aurora	Colorado
United States	DJL Clinical Research	Charlotte	North Carolina
United States	Joint Muscle Medical Care and Research Institute - Lilington Office	Charlotte	North Carolina
United States	Robert W Levin MD PA	Clearwater	Florida
United States	Altoona Center for Clinical Research	Duncansville	Pennsylvania
United States	Center for Rheumatology Immunology and Arthritis	Fort Lauderdale	Florida
United States	Accurate Clinical Research	Houston	Texas
United States	Institute of Arthritis Research	Idaho Falls	Idaho
United States	University of California San Diego	La Jolla	California
United States	Innovative Health Research	Las Vegas	Nevada
United States	North Georgia Rheumatology Group - Duluth	Lawrenceville	Georgia
United States	Valerius Medical Group and Research Center	Los Alamitos	California
United States	Life Clinical Trials	Margate	Florida
United States	Office of Ramesh C. Gupta, MD	Memphis	Tennessee
United States	Southwest Rheumatology Research, LLC	Mesquite	Texas
United States	D&H National Research Centers INC	Miami	Florida
United States	San Marcus Research Clinic	Miami Lakes	Florida
United States	Paramount Medical Research and Consulting	Middleburg Heights	Ohio
United States	New York Presbyterian Columbia University Medical Center	New York	New York
United States	Millennium Research	Ormond Beach	Florida
United States	Integral Rheumatology & Immunology Specialists	Plantation	Florida
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	Advanced Research Institute Inc Allergy & Rheumatology	Saint Petersburg	Florida
United States	Sun Research Institute	San Antonio	Texas
United States	Accurate Clinical Management	Stafford	Texas
United States	State University of New York Upstate Medical University	Syracuse	New York
United States	Axiom Clinical Research of Florida	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Idorsia Pharmaceuticals Ltd.

Countries where clinical trial is conducted

United States,  Bulgaria,  Chile,  Czechia,  France,  Georgia,  Germany,  Greece,  Hungary,  Israel,  Italy,  Japan,  Mexico,  Philippines,  Poland,  Puerto Rico,  Romania,  Russian Federation,  Spain,  Taiwan,  Thailand,  Turkey,  Ukraine,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline to Month 6 in the Modified Systemic Lupus Erythematosus Activity Index 2000 (mSLEDAI-2K) Score	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.	Baseline (Day 1) and Month 6
Secondary	Response on Systemic Lupus Erythematosus Responder Index 4 (SRI-4) at Month 6 as Compared to Baseline	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.	Baseline (Day 1) and Month 6
Secondary	British Isles Lupus Assessment Group-2004 (BILAG) Disease Activity Index Response at 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.	Baseline (Day 1) and Month 6