Clinical trial NCT05639114: Phase 3 Study to Evaluate Two Regimens of Ianalumab on Top of Standard-of-care Therapy in Patients With Systemic Lupus Erythematosus (SIRIUS-SLE 1)
Official title: A Randomized, Double-blind, Parallel Group, Placebo-controlled Multicenter Phase 3 Study to Evaluate Efficacy, Safety and Tolerability of Two Regimens of Ianalumab on Top of Standard-of-care Therapy in Patients With Systemic Lupus Erythematosus (SIRIUS-SLE 1)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Systemic Lupus Erythematosus
Keywords: Systemic Lupus Erythematosus
SLE
B cell depletion
SLEDAI-2K
BILAG-2004
SRI
ANA
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2022-12-06
Enrollment: 406
Sex: ALL
Minimum age (years): 12
Maximum age (years): 100
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: The trial is designed to evaluate efficacy, safety and tolerability of two regimens of ianalumab compared to placebo, given as monthly or quarterly subcutaneous (s.c.) injection on top of standard-of-care (SoC) treatment in participants with active systemic lupus erythematosus (SLE).
Primary purpose: TREATMENT

Brief summary: The trial will evaluate efficacy, safety and tolerability of two regimens of ianalumab compared to placebo, given as monthly or quarterly subcutaneous (s.c.) injection on top of standard-of-care (SoC) treatment in participants with active systemic lupus erythematosus (SLE).

Detailed description: A randomized, double-blind, parallel group, placebo-controlled multicenter phase 3 study to evaluate efficacy, safety and tolerability of two regimens of ianalumab on top of standard-of-care therapy in patients with systemic lupus erythematosus (SIRIUS-SLE 1)

Eligibility criteria: Inclusion Criteria:

* Male and female participants aged 12 years or older at the time of screening, or limited to 18 years or older in European Economic Area countries and other countries where inclusion of participants below 18 years is not allowed.
* Diagnosis of systemic lupus erythematosus meeting the 2019 European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) SLE classification criteria at least 6 months prior to screening.
* Elevated serum titers at screening of anti-nuclear antibodies ≥ 1:80 as determined by a central laboratory with a SLE-typical fluorescence pattern.
* Currently receiving CS and/or anti-malarial treatment and/or another disease-modifying antirheumatic drug (DMARD) as specified in the protocol.
* SLEDAI-2K criteria at screening: SLEDAI-2K score ≥ 6 points, excluding points attributed to "fever", "lupus headache", "alopecia", and "organic brain syndrome"
* BILAG-2004 disease activity level at screening of at least 1 of the following:

  * BILAG-2004 level 'A' disease in ≥ 1 organ system, Or
  * BILAG-2004 level 'B' disease in ≥ 2 organ systems
* Weigh at least 35 kg at screening

Exclusion Criteria:

* Prior treatment with ianalumab
* History of receiving following treatment: I) high dose CS, calcineurin inhibitors, JAK or other kinase inhibitors or other DMARD (except as listed in inclusion criteria) administered within 12 weeks prior to screening. II) cyclophosphamide or biologics such as immunoglobulins (intravenous or s.c.), plasmapheresis, anti-type I interferon receptor biologic agents, anti-CD40 agents, CTLA4-Fc Ig or B-cell activating factor (BAFF)-targeting agents administered within 24 weeks prior to screening; belimumab administered within 12 weeks prior to screening. III) any B cell-depleting therapies, other than ianalumab administered within 36 weeks prior to randomization or as long as B cell count is less than the lower limit of normal or baseline value prior to receipt of B cell-depleting therapy (whichever is lower). IV) Traditional Chinese medicines administered within 30 days prior to randomization.
* Active viral, bacterial or other infections requiring intravenous or intramuscular treatment for clinically significant infection
* Chronic infection with hepatitis B virus (HBV) or hepatitis C virus (HCV)
* Evidence of active tuberculosis infection
* History of primary or secondary immunodeficiency, including a positive human immunodeficiency virus (HIV) test result at screening
* Any one of the following abnormal laboratory values prior to randomization

  * Platelets \< 25000/mm\^3 (\< 25 x 10\^3/μL)
  * Hemoglobin (Hgb) \< 8.0 g/dL (\< 5 mmol/L), or \< 7.0 g/dL (\< 4.3 mmol/L) if related to participant's SLE such as in active hemolytic anaemia
  * Absolute neutrophil count (ANC) (\< 0.8 x 10\^3/ μL)
* Severe organ dysfunction or life-threatening disease at screening
* Presence of severe lupus kidney disease as defined by proteinuria above 2 g/day or equivalent using spot urine protein creatinine ratio, or serum creatinine greater than 2.0 mg/dL (176.84 µmol/L), or requiring immune-suppressive induction or maintenance treatment at screening
* Receipt of live/attenuated vaccine within a 4-week period before first dosing
* Any uncontrolled, co-existing serious disease, which in the opinion of the investigator will place the participant at risk for participation or interfere with evaluation for SLE-related symptoms
* Non-lupus conditions such as asthma, gout or urticaria, requiring intermittent or chronic treatment with systemic CS
* History of malignancy of any organ system other than localized basal cell carcinoma of the skin or in situ cervical cancer
* Pregnant or nursing (lactating) women.
* Women of child-bearing potential (WOCBP), defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception while on study treatment and for 6 months after stopping of investigational drug.
* Any surgical, medical, psychiatric or additional physical condition that may jeopardize participation in this study

Primary outcomes:
measure: Proportion of participants on monthly ianalumab achieving Systemic Lupus Erythematosus Responder Index -4 (SRI-4)
timeFrame: Week 60
Secondary outcomes:
measure: Proportion of participants on monthly or quarterly ianalumab with no moderate or severe British Isles Lupus Assessment Group (BILAG) flare
timeFrame: Baseline to Week 60
measure: Proportion of participants on monthly or quarterly ianalumab maintaining between Week 36 and Week 60 a reduced corticosteroid (CS) dose of predniso(lo)ne ≤ 5 mg/day or ≤ baseline dose, whichever is lower
timeFrame: Week 36 to Week 60
measure: Proportion of participants on monthly or quarterly ianalumab achieving BILAG-based Composite Lupus Assessment (BICLA)
timeFrame: Week 60
measure: Proportion of participants on monthly or quarterly ianalumab achieving Lupus Low Disease Activity State (LLDAS)
timeFrame: Week 60
measure: Time to first occurrence of SRI-4 (participants on ianalumab monthly or quarterly)
timeFrame: Baseline to Week 60
measure: Proportion of participants on monthly or quarterly ianalumab achieving SRI-4 at Week 60 while maintaining between Week 36 and Week 60 a reduced corticosteroid dose of predniso(lo)ne ≤ 5 mg/day or ≤ baseline dose, whichever is lower
timeFrame: Week 36 to Week 60
measure: Proportion of participants on monthly or quarterly ianalumab achieving SRI-6
timeFrame: Week 60
measure: Proportion of participants on monthly or quarterly ianalumab achieving Short Form 36 (SF-36) Bodily Pain response
timeFrame: Week 60
measure: Proportion of participants on quarterly ianalumab achieving SRI-4
timeFrame: Week 60
measure: Proportion of participants on monthly or quarterly ianalumab with Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: Baseline to Week 60
measure: Number of participants with adverse events
timeFrame: Baseline to Week 60
measure: Proportion of participants with anti-ianalumab antibodies in serum (ADA assay) over time
timeFrame: Baseline to Week 164
measure: Ianalumab concentration in serum during the treatment and follow-up
timeFrame: Baseline to week 164
Other outcomes:
Locations:
city: Burbank
country: United States
facility: Providence Medical Center
state: California
city: La Jolla
country: United States
facility: University of California San Diego
state: California
city: Los Angeles
country: United States
facility: Keck School of Medicine
state: California
city: Westlake Village
country: United States
facility: Millennium Clinical Trials
state: California
city: Aurora
country: United States
facility: University of Colorado
state: Colorado
city: New Haven
country: United States
facility: Yale University School Of Medicine
state: Connecticut
city: Stamford
country: United States
facility: Stamford Hospital
state: Connecticut
city: Clearwater
country: United States
facility: Clinical Res Of W Florida
state: Florida
city: Hollywood
country: United States
facility: GNP Research
state: Florida
city: Miami
country: United States
facility: University Of Miami
state: Florida
city: Tampa
country: United States
facility: Clinical Research of West Florida Inc
state: Florida
city: Lawrenceville
country: United States
facility: Parris and Associates Rheumatology
state: Georgia
city: Skokie
country: United States
facility: Robert A Hozman MD SC
state: Illinois
city: New Albany
country: United States
facility: Lake Cumberland Rheumatology and In
state: Indiana
city: Baton Rouge
country: United States
facility: Ochsner Clinic Foundation
state: Louisiana
city: Detroit
country: United States
facility: Henry Ford Health
state: Michigan
city: Las Vegas
country: United States
facility: Univ of Nevada School of Med
state: Nevada
city: Las Vegas
country: United States
facility: Innovative Health Research
state: Nevada
city: West Long Branch
country: United States
facility: Sahni Rheumatology and Therapy
state: New Jersey
city: Brooklyn
country: United States
facility: NYU Langone Health
state: New York
city: Cleveland
country: United States
facility: Medical Center Main Campus
state: Ohio
city: Dayton
country: United States
facility: STAT Research Inc
state: Ohio
city: Middleburg Heights
country: United States
facility: Paramount Med Rsrch and Consult LLC
state: Ohio
city: Pittsburgh
country: United States
facility: University Of Pittsburgh
state: Pennsylvania
city: Columbia
country: United States
facility: Prisma Health
state: South Carolina
city: Memphis
country: United States
facility: Shelby Research LLC
state: Tennessee
city: Baytown
country: United States
facility: Accurate Clinical Research Research
state: Texas
city: El Paso
country: United States
facility: Texas Arthritis Center
state: Texas
city: Red Oak
country: United States
facility: Epic Medical Research
state: Texas
city: Salvador
country: Brazil
facility: Novartis Investigative Site
state: BA
city: Brasilia
country: Brazil
facility: Novartis Investigative Site
state: DF
city: Vitoria
country: Brazil
facility: Novartis Investigative Site
state: ES
city: Belo Horizonte
country: Brazil
facility: Novartis Investigative Site
state: MG
city: Curitiba
country: Brazil
facility: Novartis Investigative Site
state: PR
city: Niteroi
country: Brazil
facility: Novartis Investigative Site
state: RJ
city: Rio de Janeiro
country: Brazil
facility: Novartis Investigative Site
state: RJ
city: Barretos
country: Brazil
facility: Novartis Investigative Site
state: Sao Paulo
city: Sao Paulo
country: Brazil
facility: Novartis Investigative Site
state: SP
city: Sao Paulo
country: Brazil
facility: Novartis Investigative Site
state: SP
city: Salvador
country: Brazil
facility: Novartis Investigative Site
city: Plovdiv
country: Bulgaria
facility: Novartis Investigative Site
city: Ruse
country: Bulgaria
facility: Novartis Investigative Site
city: Sofia
country: Bulgaria
facility: Novartis Investigative Site
city: Calgary
country: Canada
facility: Novartis Investigative Site
state: Alberta
city: Edmonton
country: Canada
facility: Novartis Investigative Site
state: Alberta
city: Vancouver
country: Canada
facility: Novartis Investigative Site
state: British Columbia
city: Hamilton
country: Canada
facility: Novartis Investigative Site
state: Ontario
city: Toronto
country: Canada
facility: Novartis Investigative Site
state: Ontario
city: Rimouski
country: Canada
facility: Novartis Investigative Site
state: Quebec
city: Guangzhou
country: China
facility: Novartis Investigative Site
state: Guangdong
city: Guangzhou
country: China
facility: Novartis Investigative Site
state: Guangdong
city: Shantou
country: China
facility: Novartis Investigative Site
state: Guangdong
city: Haikou
country: China
facility: Novartis Investigative Site
state: Hainan
city: Zhuzhou
country: China
facility: Novartis Investigative Site
state: Hunan
city: Baotou
country: China
facility: Novartis Investigative Site
state: Inner Mongolia
city: Nanjing
country: China
facility: Novartis Investigative Site
state: Jiangsu
city: Suzhou
country: China
facility: Novartis Investigative Site
state: Jiangsu
city: Nanchang
country: China
facility: Novartis Investigative Site
state: Jiangxi
city: Pingxiang
country: China
facility: Novartis Investigative Site
state: Jiangxi
city: Chang Chun
country: China
facility: Novartis Investigative Site
state: Jilin
city: Linyi
country: China
facility: Novartis Investigative Site
state: Shandong
city: Chengdu
country: China
facility: Novartis Investigative Site
state: Sichuan
city: Urumqi
country: China
facility: Novartis Investigative Site
state: Xinjiang
city: Wenzhou
country: China
facility: Novartis Investigative Site
state: Zhejiang
city: Beijing
country: China
facility: Novartis Investigative Site
city: Beijing
country: China
facility: Novartis Investigative Site
city: Shanghai
country: China
facility: Novartis Investigative Site
city: Shanghai
country: China
facility: Novartis Investigative Site
city: Wuhan
country: China
facility: Novartis Investigative Site
city: Xinxiang
country: China
facility: Novartis Investigative Site
city: Zhejiang
country: China
facility: Novartis Investigative Site
city: Brno
country: Czechia
facility: Novartis Investigative Site
city: Praha 2
country: Czechia
facility: Novartis Investigative Site
city: Uherske Hradiste
country: Czechia
facility: Novartis Investigative Site
city: Guatemala City
country: Guatemala
facility: Novartis Investigative Site
city: Guatemala City
country: Guatemala
facility: Novartis Investigative Site
city: Guatemala
country: Guatemala
facility: Novartis Investigative Site
city: Szekesfehervar
country: Hungary
facility: Novartis Investigative Site
state: Fejer
city: Budapest
country: Hungary
facility: Novartis Investigative Site
city: Budapest
country: Hungary
facility: Novartis Investigative Site
city: Gyula
country: Hungary
facility: Novartis Investigative Site
city: Zalaegerszeg
country: Hungary
facility: Novartis Investigative Site
city: Haifa
country: Israel
facility: Novartis Investigative Site
city: Ramat Gan
country: Israel
facility: Novartis Investigative Site
city: Nagoya
country: Japan
facility: Novartis Investigative Site
state: Aichi
city: Nagoya
country: Japan
facility: Novartis Investigative Site
state: Aichi
city: Ichikawa
country: Japan
facility: Novartis Investigative Site
state: Chiba
city: Fukuoka city
country: Japan
facility: Novartis Investigative Site
state: Fukuoka
city: Kitakyushu
country: Japan
facility: Novartis Investigative Site
state: Fukuoka
city: Sapporo city
country: Japan
facility: Novartis Investigative Site
state: Hokkaido
city: Ono
country: Japan
facility: Novartis Investigative Site
state: Hyogo
city: Kawasaki
country: Japan
facility: Novartis Investigative Site
state: Kanagawa
city: Yokohama-city
country: Japan
facility: Novartis Investigative Site
state: Kanagawa
city: Yokohama
country: Japan
facility: Novartis Investigative Site
state: Kanagawa
city: Sendai city
country: Japan
facility: Novartis Investigative Site
state: Miyagi
city: Kurashiki
country: Japan
facility: Novartis Investigative Site
state: Okayama
city: Suita
country: Japan
facility: Novartis Investigative Site
state: Osaka
city: Iruma-gun
country: Japan
facility: Novartis Investigative Site
state: Saitama
city: Bunkyo ku
country: Japan
facility: Novartis Investigative Site
state: Tokyo
city: Bunkyo ku
country: Japan
facility: Novartis Investigative Site
state: Tokyo
city: Bunkyo-ku
country: Japan
facility: Novartis Investigative Site
state: Tokyo
city: Chuo ku
country: Japan
facility: Novartis Investigative Site
state: Tokyo
city: Fuchu-city
country: Japan
facility: Novartis Investigative Site
state: Tokyo
city: Fuchu
country: Japan
facility: Novartis Investigative Site
state: Tokyo
city: Itabashi-ku
country: Japan
facility: Novartis Investigative Site
state: Tokyo
city: Meguro
country: Japan
facility: Novartis Investigative Site
state: Tokyo
city: Shinjuku-ku
country: Japan
facility: Novartis Investigative Site
state: Tokyo
city: Chiba
country: Japan
facility: Novartis Investigative Site
city: Fukuoka
country: Japan
facility: Novartis Investigative Site
city: Gifu
country: Japan
facility: Novartis Investigative Site
city: Miyazaki
country: Japan
facility: Novartis Investigative Site
city: Osaka
country: Japan
facility: Novartis Investigative Site
city: Wroclaw
country: Poland
facility: Novartis Investigative Site
state: Dolnoslaskie
city: Bydgoszcz
country: Poland
facility: Novartis Investigative Site
city: Bydgoszcz
country: Poland
facility: Novartis Investigative Site
city: Bytom
country: Poland
facility: Novartis Investigative Site
city: Lodz
country: Poland
facility: Novartis Investigative Site
city: Rzeszow
country: Poland
facility: Novartis Investigative Site
city: Warszawa
country: Poland
facility: Novartis Investigative Site
city: Warszawa
country: Poland
facility: Novartis Investigative Site
city: Braga
country: Portugal
facility: Novartis Investigative Site
city: Leiria
country: Portugal
facility: Novartis Investigative Site
city: Lisboa
country: Portugal
facility: Novartis Investigative Site
city: Lisboa
country: Portugal
facility: Novartis Investigative Site
city: Lisboa
country: Portugal
facility: Novartis Investigative Site
city: Vila Nova De Gaia
country: Portugal
facility: Novartis Investigative Site
city: Singapore
country: Singapore
facility: Novartis Investigative Site
city: Singapore
country: Singapore
facility: Novartis Investigative Site
city: Singapore
country: Singapore
facility: Novartis Investigative Site
city: Bratislava
country: Slovakia
facility: Novartis Investigative Site
city: Bratislava
country: Slovakia
facility: Novartis Investigative Site
city: Bratislava
country: Slovakia
facility: Novartis Investigative Site
city: Kosice
country: Slovakia
facility: Novartis Investigative Site
city: Kosice
country: Slovakia
facility: Novartis Investigative Site
city: Piestany
country: Slovakia
facility: Novartis Investigative Site
city: Zvolen
country: Slovakia
facility: Novartis Investigative Site
city: Cape Town
country: South Africa
facility: Novartis Investigative Site
city: Panorama
country: South Africa
facility: Novartis Investigative Site
city: Pretoria
country: South Africa
facility: Novartis Investigative Site
city: Stellenbosch
country: South Africa
facility: Novartis Investigative Site
city: Umhlanga
country: South Africa
facility: Novartis Investigative Site
city: Elche
country: Spain
facility: Novartis Investigative Site
state: Alicante
city: Santander
country: Spain
facility: Novartis Investigative Site
state: Cantabria
city: Valladolid
country: Spain
facility: Novartis Investigative Site
state: Castilla Y Leon
city: Badalona
country: Spain
facility: Novartis Investigative Site
state: Catalunya
city: Barcelona
country: Spain
facility: Novartis Investigative Site
state: Catalunya
city: Barcelona
country: Spain
facility: Novartis Investigative Site
state: Catalunya
city: Valencia
country: Spain
facility: Novartis Investigative Site
state: Comunidad Valenciana
city: Badajoz
country: Spain
facility: Novartis Investigative Site
state: Extremadura
city: Merida
country: Spain
facility: Novartis Investigative Site
state: Extremadura
city: Santiago De Compostela
country: Spain
facility: Novartis Investigative Site
state: Galicia
city: San Sebastian de los Reyes
country: Spain
facility: Novartis Investigative Site
state: Madrid
city: El Palmar
country: Spain
facility: Novartis Investigative Site
state: Murcia
city: Pamplona
country: Spain
facility: Novartis Investigative Site
state: Navarra
city: Vitoria Gasteiz
country: Spain
facility: Novartis Investigative Site
state: Pais Vasco
city: Vigo
country: Spain
facility: Novartis Investigative Site
state: Pontevedra
city: La Laguna
country: Spain
facility: Novartis Investigative Site
state: Santa Cruz De Tenerife
city: Madrid
country: Spain
facility: Novartis Investigative Site
city: Songkhla
country: Thailand
facility: Novartis Investigative Site
state: Hat Yai
city: Bangkok
country: Thailand
facility: Novartis Investigative Site
city: Bangkok
country: Thailand
facility: Novartis Investigative Site
city: Chiang Mai
country: Thailand
facility: Novartis Investigative Site
city: Muang
country: Thailand
facility: Novartis Investigative Site
city: Ankara
country: Turkey
facility: Novartis Investigative Site
city: Ankara
country: Turkey
facility: Novartis Investigative Site
city: Ankara
country: Turkey
facility: Novartis Investigative Site
city: Aydin
country: Turkey
facility: Novartis Investigative Site
city: Etlik Ankara
country: Turkey
facility: Novartis Investigative Site
city: Istanbul
country: Turkey
facility: Novartis Investigative Site
city: Istanbul
country: Turkey
facility: Novartis Investigative Site
city: Istanbul
country: Turkey
facility: Novartis Investigative Site
city: Izmir
country: Turkey
facility: Novartis Investigative Site
city: Konya
country: Turkey
facility: Novartis Investigative Site
city: Talas Kayseri
country: Turkey
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: