Clinical trial NCT03742037: Efficacy and Safety of Four Doses of Cenerimod Compared to Placebo in Adult Subjects With Active Systemic Lupus Erythematosus
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Systemic Lupus Erythematosus
Keywords: Musculoskeletal and connective tissue disorders
Lead sponsor: Idorsia Pharmaceuticals Ltd.
Sponsor class: INDUSTRY
First posted: 2018-11-15
Enrollment: 427
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Participants randomized to the 4 mg arm who are still on treatment at month 6 will be re-randomized in a 1:1 ratio to placebo or cenerimod 2 mg to enter Treatment Period 2 and will continue study treatment for a total maximum of 12 months.
Primary purpose: TREATMENT

Brief 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).

Detailed 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).

Eligibility criteria: 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

Primary outcomes:
measure: Change From Baseline to Month 6 in the Modified Systemic Lupus Erythematosus Activity Index 2000 (mSLEDAI-2K) Score
timeFrame: Baseline (Day 1) and Month 6
Secondary outcomes:
measure: Response on Systemic Lupus Erythematosus Responder Index 4 (SRI-4) at Month 6 as Compared to Baseline
timeFrame: Baseline (Day 1) and Month 6
measure: British Isles Lupus Assessment Group-2004 (BILAG) Disease Activity Index Response at Month 6
timeFrame: Baseline (Day 1) and Month 6
Other outcomes:
Locations:
city: Anniston
country: United States
facility: Pinnacle Research Group
state: Alabama
city: La Jolla
country: United States
facility: University of California San Diego
state: California
city: Los Alamitos
country: United States
facility: Valerius Medical Group and Research Center
state: California
city: Aurora
country: United States
facility: University of Colorado School of Medicine
state: Colorado
city: Clearwater
country: United States
facility: Robert W Levin MD PA
state: Florida
city: Fort Lauderdale
country: United States
facility: Center for Rheumatology Immunology and Arthritis
state: Florida
city: Margate
country: United States
facility: Life Clinical Trials
state: Florida
city: Miami Lakes
country: United States
facility: San Marcus Research Clinic
state: Florida
city: Miami
country: United States
facility: D&H National Research Centers INC
state: Florida
city: Ormond Beach
country: United States
facility: Millennium Research
state: Florida
city: Plantation
country: United States
facility: Integral Rheumatology & Immunology Specialists
state: Florida
city: Saint Petersburg
country: United States
facility: Advanced Research Institute Inc Allergy & Rheumatology
state: Florida
city: Tampa
country: United States
facility: Axiom Clinical Research of Florida
state: Florida
city: Lawrenceville
country: United States
facility: North Georgia Rheumatology Group - Duluth
state: Georgia
city: Idaho Falls
country: United States
facility: Institute of Arthritis Research
state: Idaho
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Las Vegas
country: United States
facility: Innovative Health Research
state: Nevada
city: New York
country: United States
facility: New York Presbyterian Columbia University Medical Center
state: New York
city: Syracuse
country: United States
facility: State University of New York Upstate Medical University
state: New York
city: Charlotte
country: United States
facility: Joint Muscle Medical Care and Research Institute - Lilington Office
state: North Carolina
city: Charlotte
country: United States
facility: DJL Clinical Research
state: North Carolina
city: Middleburg Heights
country: United States
facility: Paramount Medical Research and Consulting
state: Ohio
city: Duncansville
country: United States
facility: Altoona Center for Clinical Research
state: Pennsylvania
city: Memphis
country: United States
facility: Office of Ramesh C. Gupta, MD
state: Tennessee
city: Amarillo
country: United States
facility: Amarillo Center for Clinical Research
state: Texas
city: Houston
country: United States
facility: Accurate Clinical Research
state: Texas
city: Mesquite
country: United States
facility: Southwest Rheumatology Research, LLC
state: Texas
city: San Antonio
country: United States
facility: Sun Research Institute
state: Texas
city: Stafford
country: United States
facility: Accurate Clinical Management
state: Texas
city: Plovdiv
country: Bulgaria
facility: Multiprofile Hospital For Active Treatment Trimontium
state: Plodiv
city: Plovdiv
country: Bulgaria
facility: University Multiprofile Hospital for Active Treatment Pulmed
city: Sofia
country: Bulgaria
facility: Diagnostic and Consulting Center "Aleksandrovska" EOOD
city: Sofia
country: Bulgaria
facility: Diagnostic Consulting Center Fokus-5
city: Santiago
country: Chile
facility: Enroll SpA
city: Santiago
country: Chile
facility: Biomedica Research Group
city: Santiago
country: Chile
facility: Meditek Ltda.
city: Santiago
country: Chile
facility: Prosalud
city: Valdivia
country: Chile
facility: Clinical Research Chile SpA
city: Pardubice
country: Czechia
facility: CCR Pardubice
state: Vychodocesky KRAJ
city: Brest
country: France
facility: Centre Hospitalier Regional Universitaire Brest Hôpital de la Cavale Blanche à Brest
state: Bretagne
city: Pessac
country: France
facility: Hôpital Haut-Lévêque
city: Batumi
country: Georgia
facility: LTD "New Plasma Clinic"
city: Tbilisi
country: Georgia
facility: Aversi Clinic LTD
city: Tbilisi
country: Georgia
facility: Medi Club Georgia Ltd.
city: Tbilisi
country: Georgia
facility: Ltd. Mtskheta Street Clinic
city: Tbilisi
country: Georgia
facility: The First Medical Center Ltd.
city: Tbilisi
country: Georgia
facility: LLC "Innova"
city: Tbilisi
country: Georgia
facility: LLC Raymann
city: Tbilisi
country: Georgia
facility: LTD "Tbilisi Heart Center"
city: Tbilisi
country: Georgia
facility: Medicore
city: Tbilisi
country: Georgia
facility: Multiprofile Clinic Consilium Medulla
city: Karlsruhe
country: Germany
facility: Städtisches Klinikum Karlsruhe gGmbH
city: Goudí
country: Greece
facility: General Hospital of Athens "Laiko"
city: Budapest
country: Hungary
facility: Egyesitett Szent Istvan es Szent Laszlo Korhaz Rendelointezet
city: Haifa
country: Israel
facility: Rambam Healthcare Campus
city: Haifa
country: Israel
facility: Bnai Zion Medical Center
city: Nahariya
country: Israel
facility: Galilee Medical Center
city: Ramat-Gan
country: Israel
facility: The Chaim Sheba Medical Center
city: Genova
country: Italy
facility: LUPUS CLINIC c/o DIMI
city: Milano
country: Italy
facility: Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico
city: Milano
country: Italy
facility: Ospedale San Raffaele
city: Roma
country: Italy
facility: Azienda Ospedaliera San Camillo Forlanini
city: Roma
country: Italy
facility: Fondazione Policlinico Universitario A. Gemelli
city: Torino
country: Italy
facility: A.O. Mauriziano Umberto I di Torino
city: Tomakomai-shi
country: Japan
facility: Tomakomai City Hospital
city: Ciudad de México
country: Mexico
facility: Karla Adriana Espinosa Bautista
city: Cuernavaca
country: Mexico
facility: Consultorio Particular Dr. Miguel Cortés Hernández
city: Guadalajara
country: Mexico
facility: Centro Integral en Reumatología S.A. de C.V.
city: Guadalajara
country: Mexico
facility: Icle S.C.
city: Guadalajara
country: Mexico
facility: Consultorio Privado de Especialidad del Dr. José Javier Orozco Alcalá
city: Guadalajara
country: Mexico
facility: Consultorio Médico del Dr. Federico Galván Villegas
city: León
country: Mexico
facility: Morales Vargas Centro de Investigación S.C.
city: Mexico City
country: Mexico
facility: Centro de Investigación Clínica GRAMEL, S.C.
city: Mexico City
country: Mexico
facility: Biológicos Especializados S.A. de C.V.
city: Monterrey
country: Mexico
facility: Accelerium, S. de R.L. de C.V.
city: Monterrey
country: Mexico
facility: UBAM Unidad Biomédica Avanzada Monterrey
city: Mérida
country: Mexico
facility: Unidad de Atención Médica e Investigación en Salud
city: Mérida
country: Mexico
facility: Kohler & Milstein Research S.A. de C.V.
city: Queretaro
country: Mexico
facility: SMIQ, S. de R.L. de C.V.
city: Saltillo
country: Mexico
facility: Hospital Universitario "Dr. Gonzalo Valdés Valdés"
city: San Luis Potosí
country: Mexico
facility: Unidad de Investigaciones Reumatológicas A.C.
city: San Luis Potosí
country: Mexico
facility: Centro de Atención e Investigación Cardiovascular del Potosí, S.C.
city: Zapopan
country: Mexico
facility: Investigacion Biomedica para el Desarrollo de Farmacos S.A. de C.V.
city: Lipa City
country: Philippines
facility: Lipa Medix Medical Center
state: Batangas
city: Angeles City
country: Philippines
facility: Angeles University Foundation Medical Center
city: Davao City
country: Philippines
facility: Davao Doctors Hospital
city: Iloilo City
country: Philippines
facility: Iloilo Doctors Hospital
city: Makati City
country: Philippines
facility: Makati Medical Center
city: Manila
country: Philippines
facility: University of the Philippines Manila - Philippine General Hospital
city: Manila
country: Philippines
facility: Jose R. Reyes Memorial Medical Center
city: Manila
country: Philippines
facility: University of Santo Tomas Hospital
city: Quezon City
country: Philippines
facility: St. Luke's Medical Center
city: Quezon City
country: Philippines
facility: Far Eastern University - Nicanor Reyes Medical Foundation
city: Bydgoszcz
country: Poland
facility: Szpital Uniwersytecki Number 2 im. dr. Jana Biziela w Bydgoszczy
city: Koscian
country: Poland
facility: Intermedius Uslugi Medyczne
city: Krakow
country: Poland
facility: Szpital Specjalistyczny im. J. Dietla w Krakowie
city: Kraków
country: Poland
facility: Centrum Medyczne Plejady
city: Poznań
country: Poland
facility: Twoja Przychodnia Poznańskie Centrum Medyczne
city: Ustroń
country: Poland
facility: Śląskie Centrum Reumatologii, Rehabilitacji i Zapobiegania Niepełnosprawności im gen. Jerzego Zi
city: Caguas
country: Puerto Rico
facility: Centro Reumatologico de Caguas
city: Brasov
country: Romania
facility: Centrul Medical de Diagnostic si Tratament Ambulatoriu Neomed
city: Bucharest
country: Romania
facility: Spitalul Clinic "Sf. Maria"
city: Bucuresti
country: Romania
facility: SC Sana Monitoring SRL
city: Cluj-Napoca
country: Romania
facility: Spitalul Clinic Judetean de Urgenta Cluj-Napoca
city: Chelyabinsk
country: Russian Federation
facility: Chelyabinsk Regional Clinical Hospital
city: Ekaterinburg
country: Russian Federation
facility: JSC "Center of Family Medicine"
city: Moscow
country: Russian Federation
facility: City Clinical Hospital #15 named after O.M. Filatova
city: Moscow
country: Russian Federation
facility: Federal State Budget Scientific Research Institution "Scientific Research Institute of Rheumatology n.a. V.A. Nasonova"
city: Moscow
country: Russian Federation
facility: Non-governmental private healthcare organization, Scientific Clinical Centre of JSC Russian Railways
city: Novosibirsk
country: Russian Federation
facility: Medical Center "Zdorovaya Semiya", LLC
city: Orenburg
country: Russian Federation
facility: Orenburg State Medical University
city: Saint Petersburg
country: Russian Federation
facility: Clinical Rheumatological Hospital Number 25
city: Saint Petersburg
country: Russian Federation
facility: Polyclinic of Private Security and Detectives
city: Saint Petersburg
country: Russian Federation
facility: Medical Research Institute, LLC
city: Saint Petersburg
country: Russian Federation
facility: Medical Center Maksimum Zdorovia
city: Saint-Petersburg
country: Russian Federation
facility: Military Medical Academy S.M. Kirov
city: Saratov
country: Russian Federation
facility: Saratov Regional Clinical Hospital
city: Yaroslavl
country: Russian Federation
facility: State Institution of Health Protection "Clinical Hospital #8"
city: Málaga
country: Spain
facility: Hospital Universitario Regional de Málaga
state: Malaga
city: Barcelona
country: Spain
facility: Hospital Clinic i Provincial de Barcelona
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Sevilla
country: Spain
facility: Hospital Quirónsalud Infanta Luisa
city: Valencia
country: Spain
facility: Hospital Universitario Doctor Peset
city: Kaohsiung
country: Taiwan
facility: Kaohsiung Medical University Hospital
city: Kaohsiung
country: Taiwan
facility: Kaohsiung Veterans General Hospital
city: Bangkok
country: Thailand
facility: Rajavithi Hospital
city: Songkhla
country: Thailand
facility: Songklanagarind Hospital
city: Istanbul
country: Turkey
facility: Istanbul Universitesi Istanbul Tip Fakultesi
city: Konya
country: Turkey
facility: Necmettin Erbakan Üniversitesi Meram Tıp Fakültesi
city: Kyiv
country: Ukraine
facility: Kyiv City Clinical Hospital №3
city: Kyiv
country: Ukraine
facility: Clinic of State Institution "National Scientific Centre "Acad. Strazhesko Institute of Cardiology"
city: Kyiv
country: Ukraine
facility: Medical Centre "Consilium medical"
city: Kyiv
country: Ukraine
facility: Municipal Institution Kyiv Regional Council "Kyiv Regional Clinical Hospital"
city: Lviv
country: Ukraine
facility: Municipal Nonprofit Institution of Lviv Regional Council "Lviv Regional Clinical Hospital"
city: Lviv
country: Ukraine
facility: Municipal Nonprofit Institution of Lviv Regional Council
city: Lviv
country: Ukraine
facility: Lviv Regional Clinical Hospital
city: Poltava
country: Ukraine
facility: Poltava Regional Clinical Hospital named after M.V. Sklifossovsky
city: Ternopil
country: Ukraine
facility: Ternopil University Clinic - Rheumatology department
city: Uzhgorod
country: Ukraine
facility: Zakarpattya Regional Clinical Hospital n.a. A.Novak - Rheumatology Department
city: Vinnytsia
country: Ukraine
facility: Private Small Scale Medical Center "Pulse"
city: Vinnytsia
country: Ukraine
facility: Medical Center "Health Clinic", LLC
city: Vinnytsia
country: Ukraine
facility: Municipal Nonprofit Institution "Vinnytsia City Clinical Hospital №1"
city: Vinnytsia
country: Ukraine
facility: Scientific and Research Institute of Invalid Rehabilitation (EST Complex) of Vinnytsia M.I.Pyrogov NMU MOHU,
city: Vinnytsya
country: Ukraine
facility: Vinnytsya Regional Clinical Hospital - Rheumatology Department
city: Zaporizhzhya
country: Ukraine
facility: Municipal Institution "Zaporizhzhya Regional Clinical Hospital"
city: Zhytomyr
country: Ukraine
facility: Municipal institution "Regional Clinical Hospital n.a. O.F. Herbachevskoho"
city: Cambridge
country: United Kingdom
facility: Cambridge University Hospitals NHS Foundation Trust
city: London
country: United Kingdom
facility: Guy's and Saint Thomas' NHS Foundation Trust
Study officials:
affiliation: Idorsia Pharmaceuticals
name: ClinicalTrials
role: STUDY_DIRECTOR
References: