Clinical trial NCT05624749: Phase 3 Study to Evaluate Ianalumab on Top of Standard-of-care Therapy in Patients With Systemic Lupus Erythematosus (SIRIUS-SLE 2)
Official title: A Randomized, Double-blind, Placebo-controlled Multicenter Phase 3 Study to Evaluate Efficacy, Safety and Tolerability of Ianalumab on Top of Standard-of-care Therapy in Patients With Systemic Lupus Erythematosus (SIRIUS-SLE 2)
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: 2022-11-22
Enrollment: 280
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
Primary purpose: TREATMENT

Brief summary: The trial will evaluate efficacy, safety and tolerability of ianalumab compared to placebo, given as monthly 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, placebo-controlled multicenter phase 3 study to evaluate efficacy, safety and tolerability of ianalumab on top of standard-of-care therapy in patients with systemic lupus erythematosus (SIRIUS-SLE 2)

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 achieving Systemic Lupus Erythematosus Responder Index -4 (SRI-4)
timeFrame: Week 60
Secondary outcomes:
measure: Proportion of participants with no moderate or severe BILAG flare
timeFrame: Baseline to Week 60
measure: Proportion of participants 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 achieving BILAG-based Composite Lupus Assessment (BICLA)
timeFrame: Week 60
measure: Proportion of participants achieving Lupus Low Disease Activity State (LLDAS)
timeFrame: Week 60
measure: Time to first occurrence of SRI-4
timeFrame: Baseline to Week 60
measure: Proportion of participants achieving SRI-4 at Week 60 while maintaining between Week 36 and Week 60 a reduced 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 achieving SRI-6
timeFrame: Week 60
measure: Proportion of participants achieving SF-36 Bodily Pain response
timeFrame: Week 60
measure: Proportion of participants with Adverse Events (AEs)
timeFrame: Baseline to Week 60
measure: Incidence and titer of anti-drug (ianalumab) antibodies (ADAs) in serum 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: Anniston
country: United States
facility: Pinnacle Research Group LLC
state: Alabama
city: Irvine
country: United States
facility: University of Calif Irvine Med Cntr
state: California
city: La Palma
country: United States
facility: Advanced Medical Research
state: California
city: Los Angeles
country: United States
facility: University of California LA
state: California
city: Homestead
country: United States
facility: Homestead Assoc In Research Inc
state: Florida
city: Plantation
country: United States
facility: IRIS Research and Development
state: Florida
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Willowbrook
country: United States
facility: Willow Rheumatology Wellness
state: Illinois
city: Lexington
country: United States
facility: Bluegrass Community Research Inc
state: Kentucky
city: Lake Charles
country: United States
facility: Accurate Clinical Research
state: Louisiana
city: New Orleans
country: United States
facility: UMC New Orleans
state: Louisiana
city: Baltimore
country: United States
facility: University Of Maryland
state: Maryland
city: Grand Blanc
country: United States
facility: Ahmed Arif Medical Research Center
state: Michigan
city: Saint Louis
country: United States
facility: Washington Univ School Of Medicine
state: Missouri
city: Philadelphia
country: United States
facility: Thomas Jefferson University
state: Pennsylvania
city: Jackson
country: United States
facility: West Tennessee Research Institute
state: Tennessee
city: Bellaire
country: United States
facility: Novel Research LLC
state: Texas
city: Ciudad Autonoma de Bs As
country: Argentina
facility: Novartis Investigative Site
state: Buenos Aires
city: La Plata
country: Argentina
facility: Novartis Investigative Site
state: Buenos Aires
city: Quilmes
country: Argentina
facility: Novartis Investigative Site
state: Buenos Aires
city: San Miguel
country: Argentina
facility: Novartis Investigative Site
state: Buenos Aires
city: San Miguel de Tucuman
country: Argentina
facility: Novartis Investigative Site
state: Tucuman
city: Caba
country: Argentina
facility: Novartis Investigative Site
city: Tucuman
country: Argentina
facility: Novartis Investigative Site
city: Maroochydore
country: Australia
facility: Novartis Investigative Site
state: Queensland
city: Victoria Park
country: Australia
facility: Novartis Investigative Site
state: Western Australia
city: St Leonards
country: Australia
facility: Novartis Investigative Site
city: Valdivia
country: Chile
facility: Novartis Investigative Site
state: Los Rios
city: Santiago
country: Chile
facility: Novartis Investigative Site
state: RM
city: Concepcion
country: Chile
facility: Novartis Investigative Site
city: Santiago
country: Chile
facility: Novartis Investigative Site
city: Medellin
country: Colombia
facility: Novartis Investigative Site
state: Antioquia
city: Barranquilla
country: Colombia
facility: Novartis Investigative Site
state: Atlantico
city: Chia
country: Colombia
facility: Novartis Investigative Site
state: Cundinamarca
city: Bucaramanga
country: Colombia
facility: Novartis Investigative Site
state: Santander
city: Cali
country: Colombia
facility: Novartis Investigative Site
state: Valle Del Cauca
city: Barranquilla
country: Colombia
facility: Novartis Investigative Site
city: Bogota
country: Colombia
facility: Novartis Investigative Site
city: Angers Cedex 9
country: France
facility: Novartis Investigative Site
city: Grenoble
country: France
facility: Novartis Investigative Site
city: Montpellier 5
country: France
facility: Novartis Investigative Site
city: Paris
country: France
facility: Novartis Investigative Site
city: Paris
country: France
facility: Novartis Investigative Site
city: Paris
country: France
facility: Novartis Investigative Site
city: Toulouse 4
country: France
facility: Novartis Investigative Site
city: Toulouse
country: France
facility: Novartis Investigative Site
city: Tours
country: France
facility: Novartis Investigative Site
city: Leipzig
country: Germany
facility: Novartis Investigative Site
state: Sachsen
city: Aachen
country: Germany
facility: Novartis Investigative Site
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Erlangen
country: Germany
facility: Novartis Investigative Site
city: Freiburg
country: Germany
facility: Novartis Investigative Site
city: Herne
country: Germany
facility: Novartis Investigative Site
city: Koeln
country: Germany
facility: Novartis Investigative Site
city: Mainz
country: Germany
facility: Novartis Investigative Site
city: Muenchen
country: Germany
facility: Novartis Investigative Site
city: Ahmedabad
country: India
facility: Novartis Investigative Site
state: Gujarat
city: Ahmedabad
country: India
facility: Novartis Investigative Site
state: Gujarat
city: Kozhikode
country: India
facility: Novartis Investigative Site
state: Kerala
city: Kolhapur
country: India
facility: Novartis Investigative Site
state: Maharashtra
city: Nagpur
country: India
facility: Novartis Investigative Site
state: Maharashtra
city: Nashik
country: India
facility: Novartis Investigative Site
state: Maharashtra
city: Pune
country: India
facility: Novartis Investigative Site
state: Maharashtra
city: Pune
country: India
facility: Novartis Investigative Site
state: Maharashtra
city: Secunderabad
country: India
facility: Novartis Investigative Site
state: Telangana
city: New Delhi
country: India
facility: Novartis Investigative Site
city: New Delhi
country: India
facility: Novartis Investigative Site
city: Puducherry
country: India
facility: Novartis Investigative Site
city: Visakhapatnam
country: India
facility: Novartis Investigative Site
city: Ancona
country: Italy
facility: Novartis Investigative Site
state: AN
city: Caserta
country: Italy
facility: Novartis Investigative Site
state: CE
city: Cona
country: Italy
facility: Novartis Investigative Site
state: FE
city: Padova
country: Italy
facility: Novartis Investigative Site
state: PD
city: Pisa
country: Italy
facility: Novartis Investigative Site
state: PI
city: Roma
country: Italy
facility: Novartis Investigative Site
state: RM
city: Torino
country: Italy
facility: Novartis Investigative Site
state: TO
city: Milano
country: Italy
facility: Novartis Investigative Site
city: Daejeon
country: Korea, Republic of
facility: Novartis Investigative Site
state: Korea
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
state: Seocho Gu
city: Gwangju Gwangyeoksi
country: Korea, Republic of
facility: Novartis Investigative Site
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
city: Seremban
country: Malaysia
facility: Novartis Investigative Site
state: Negeri Sembilan
city: Ipoh
country: Malaysia
facility: Novartis Investigative Site
state: Perak
city: Kuching
country: Malaysia
facility: Novartis Investigative Site
state: Sarawak
city: Petaling Jaya
country: Malaysia
facility: Novartis Investigative Site
state: Selangor Darul Ehsan
city: Kuala Lumpur
country: Malaysia
facility: Novartis Investigative Site
city: Selangor Darul Ehsan
country: Malaysia
facility: Novartis Investigative Site
city: Ciudad de Mexico
country: Mexico
facility: Novartis Investigative Site
state: Distrito Federal
city: Leon
country: Mexico
facility: Novartis Investigative Site
state: Guanajuato
city: Guadalajara
country: Mexico
facility: Novartis Investigative Site
state: Jalisco
city: Morelia
country: Mexico
facility: Novartis Investigative Site
state: Michoacan
city: Merida
country: Mexico
facility: Novartis Investigative Site
state: Yucatan
city: Mexico
country: Mexico
facility: Novartis Investigative Site
city: Afumati
country: Romania
facility: Novartis Investigative Site
state: Ilfov
city: Brasov
country: Romania
facility: Novartis Investigative Site
city: Bucuresti
country: Romania
facility: Novartis Investigative Site
city: Cluj Napoca
country: Romania
facility: Novartis Investigative Site
city: Kaohsiung
country: Taiwan
facility: Novartis Investigative Site
city: Taichung
country: Taiwan
facility: Novartis Investigative Site
city: Taichung
country: Taiwan
facility: Novartis Investigative Site
city: Taipei
country: Taiwan
facility: Novartis Investigative Site
city: Taipei
country: Taiwan
facility: Novartis Investigative Site
city: Taoyuan
country: Taiwan
facility: Novartis Investigative Site
city: Birmingham
country: United Kingdom
facility: Novartis Investigative Site
city: Leicester
country: United Kingdom
facility: Novartis Investigative Site
city: London
country: United Kingdom
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: