Phase 3 Study to Evaluate Ianalumab on Top of Standard-of-care Therapy in Patients With Systemic Lupus Erythematosus (SIRIUS-SLE 2) (SIRIUS-SLE 2)

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)

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).

Study Overview

• Status: Active, not recruiting
• Conditions: Systemic Lupus Erythematosus
• Intervention / Treatment: Drug: ianalumab; Drug: placebo

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)

• Study Type: Interventional
• Enrollment (Actual): 288
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Caba, Argentina, C1015ABO
    • Novartis Investigative Site
  • Caba, Argentina, C1427CCL
    • Novartis Investigative Site
  • San Miguel de Tucumán, Argentina, 4000
    • Novartis Investigative Site
  • Buenos Aires
    • La Plata, Buenos Aires, Argentina, B1900AWT
      • Novartis Investigative Site
    • Quilmes, Buenos Aires, Argentina, 1878
      • Novartis Investigative Site
    • San Miguel, Buenos Aires, Argentina, B1663GKT
      • Novartis Investigative Site
  • Tucumán Province
    • San Miguel, Tucumán Province, Argentina, T4000CBC
      • Novartis Investigative Site
• Australia
  • St Leonards, Australia, 2065
    • Novartis Investigative Site
  • Queensland
    • Maroochydore, Queensland, Australia, 4558
      • Novartis Investigative Site
• Chile
  • Biobio
    • Concepción, Biobio, Chile, 4070280
      • Novartis Investigative Site
  • Los Ríos Region
    • Valdivia, Los Ríos Region, Chile, 5110683
      • Novartis Investigative Site
  • RM
    • Santiago, RM, Chile, 7500588
      • Novartis Investigative Site
  • Santiago Metropolitan
    • Santiago, Santiago Metropolitan, Chile, 7500710
      • Novartis Investigative Site
• Colombia
  • Bogotá, Colombia, 111211
    • Novartis Investigative Site
  • Antioquia
    • Medellín, Antioquia, Colombia, 050001
      • Novartis Investigative Site
  • Atlántico
    • Barranquilla, Atlántico, Colombia, 080002
      • Novartis Investigative Site
    • Barranquilla, Atlántico, Colombia, 080020
      • Novartis Investigative Site
  • Cundinamarca
    • Chía, Cundinamarca, Colombia, 250001
      • Novartis Investigative Site
  • Santander Department
    • Bucaramanga, Santander Department, Colombia, 680003
      • Novartis Investigative Site
  • Valle del Cauca Department
    • Cali, Valle del Cauca Department, Colombia, 760046
      • Novartis Investigative Site
• France
  • Grenoble, France, 38043
    • Novartis Investigative Site
  • Montpellier, France, 34295
    • Novartis Investigative Site
  • Paris, France, 75014
    • Novartis Investigative Site
  • Paris, France, 75013
    • Novartis Investigative Site
  • Paris, France, 75018
    • Novartis Investigative Site
  • Toulouse, France, 31059
    • Novartis Investigative Site
  • Toulouse, France, 31054
    • Novartis Investigative Site
  • Tours, France, 37044
    • Novartis Investigative Site
• Germany
  • Herne, Germany, 44649
    • Novartis Investigative Site
  • Mainz, Germany, 55131
    • Novartis Investigative Site
  • Baden-Wurttemberg
    • Freiburg im Breisgau, Baden-Wurttemberg, Germany, 79106
      • Novartis Investigative Site
  • North Rhine-Westphalia
    • Cologne, North Rhine-Westphalia, Germany, 50937
      • Novartis Investigative Site
  • Saxony
    • Leipzig, Saxony, Germany, 04103
      • Novartis Investigative Site
• India
  • New Delhi, India, 110029
    • Novartis Investigative Site
  • New Delhi, India, 110075
    • Novartis Investigative Site
  • Gujarat
    • Ahmedabad, Gujarat, India, 380006
      • Novartis Investigative Site
    • Ahmedabad, Gujarat, India, 380015
      • Novartis Investigative Site
  • Kerala
    • Kozhikode, Kerala, India, 673008
      • Novartis Investigative Site
  • Maharashtra
    • Kolhāpur, Maharashtra, India, 416001
      • Novartis Investigative Site
    • Nagpur, Maharashtra, India, 441108
      • Novartis Investigative Site
    • Nashik, Maharashtra, India, 422101
      • Novartis Investigative Site
    • Pune, Maharashtra, India, 411007
      • Novartis Investigative Site
    • Pune, Maharashtra, India, 411001
      • Novartis Investigative Site
  • National Capital Territory of Delhi
    • New Delhi, National Capital Territory of Delhi, India, 110060
      • Novartis Investigative Site
  • Uttarakhand
    • Dehradun, Uttarakhand, India, 248001
      • Novartis Investigative Site
• Italy
  • AN
    • Ancona, AN, Italy, 60126
      • Novartis Investigative Site
  • FE
    • Cona, FE, Italy, 44124
      • Novartis Investigative Site
  • PD
    • Padova, PD, Italy, 35128
      • Novartis Investigative Site
  • PI
    • Pisa, PI, Italy, 56126
      • Novartis Investigative Site
  • RM
    • Roma, RM, Italy, 00152
      • Novartis Investigative Site
  • TO
    • Torino, TO, Italy, 10128
      • Novartis Investigative Site
• Malaysia
  • Kuala Lumpur, Malaysia, 59100
    • Novartis Investigative Site
  • Selangor Darul Ehsan, Malaysia, 68100
    • Novartis Investigative Site
  • Negeri Sembilan
    • Seremban, Negeri Sembilan, Malaysia, 70300
      • Novartis Investigative Site
  • Perak
    • Ipoh, Perak, Malaysia, 30450
      • Novartis Investigative Site
• Mexico
  • México, Mexico, 07760
    • Novartis Investigative Site
  • Guanajuato
    • León, Guanajuato, Mexico, 37160
      • Novartis Investigative Site
  • Jalisco
    • Guadalajara, Jalisco, Mexico, 44160
      • Novartis Investigative Site
  • Mexico City
    • Mexico City, Mexico City, Mexico, 06700
      • Novartis Investigative Site
  • Michoacán
    • Morelia, Michoacán, Mexico, 58000
      • Novartis Investigative Site
  • Yucatán
    • Mérida, Yucatán, Mexico, 97070
      • Novartis Investigative Site
    • Mérida, Yucatán, Mexico, 97000
      • Novartis Investigative Site
• Romania
  • Brasov, Romania, 500283
    • Novartis Investigative Site
  • Bucharest, Romania, 011172
    • Novartis Investigative Site
  • Cluj
    • Cluj-Napoca, Cluj, Romania, 400006
      • Novartis Investigative Site
  • Ilfov
    • Afumaţi, Ilfov, Romania, 077010
      • Novartis Investigative Site
• South Korea
  • Seoul, South Korea, 04763
    • Novartis Investigative Site
  • Seoul, South Korea, 06591
    • Novartis Investigative Site
  • Gwangju
    • Gwangju Gwangyeoksi, Gwangju, South Korea, 61748
      • Novartis Investigative Site
• Taiwan
  • Kaohsiung City, Taiwan, 83301
    • Novartis Investigative Site
  • Taichung, Taiwan, 40447
    • Novartis Investigative Site
  • Taichung, Taiwan, 407219
    • Novartis Investigative Site
  • Taipei, Taiwan, 10002
    • Novartis Investigative Site
  • Taipei, Taiwan, 11217
    • Novartis Investigative Site
  • Taoyuan, Taiwan, 33305
    • Novartis Investigative Site
• United Kingdom
  • Doncaster, United Kingdom, DN2 5LT
    • Novartis Investigative Site
  • West Yorkshire
    • Leeds, West Yorkshire, United Kingdom, LS7 4SA
      • Novartis Investigative Site
• United States
  • Alabama
    • Anniston, Alabama, United States, 36207-5710
      • Pinnacle Research Group Llc
  • California
    • La Palma, California, United States, 90623
      • Advanced Medical Research
    • Los Angeles, California, United States, 90095
      • University of California LA
  • Florida
    • Homestead, Florida, United States, 33033
      • Homestead Assoc In Research Inc
    • Plantation, Florida, United States, 33324
      • IRIS Research and Development
  • Georgia
    • Atlanta, Georgia, United States, 30307
      • Emory University
  • Illinois
    • Willowbrook, Illinois, United States, 60527
      • Willow Rheumatology Wellness
  • Kentucky
    • Lexington, Kentucky, United States, 40504
      • Bluegrass Community Research Inc
  • Louisiana
    • Lake Charles, Louisiana, United States, 70601
      • Accurate Clinical Research
    • New Orleans, Louisiana, United States, 70112
      • UMC New Orleans
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • University of Maryland
  • Michigan
    • Grand Blanc, Michigan, United States, 48439
      • Ahmed Arif Medical Research Center
  • Missouri
    • St Louis, Missouri, United States, 63110
      • Washington Univ School Of Medicine
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Thomas Jefferson University
  • Tennessee
    • Jackson, Tennessee, United States, 38305
      • West Tennessee Research Institute
  • Texas
    • Bellaire, Texas, United States, 77401
      • Novel Research LLC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ianalumab s.c. monthly	Drug: ianalumab; ianalumab s.c. monthly; Other Names: VAY736
Placebo Comparator: placebo s.c. monthly	Drug: placebo; placebo s.c. monthly

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of participants achieving Systemic Lupus Erythematosus Responder Index -4 (SRI-4)	SRI-4 response is defined as: Systemic Lupus Erythematosus Disease Activity Index - 2000 (SLEDAI-2K) reduction from baseline of ≥ 4 points; No British Isles Lupus Assessment Group-2004 (BILAG-2004) worsening, defined as ≥ 1 new A or ≥ 2 new B items compared to baseline; No worsening in Physician Global Assessment of Disease Activity (PhGA), defined as an increase of ≥ 0.3 from baseline on a 0 to 3 visual analog scale	Week 60

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of participants with no moderate or severe BILAG flare	Moderate BILAG flare is defined as 2 or more new BILAG-2004 B items compared to the previous visit; severe BILAG flare is defined as 1 or more new BILAG-2004 A items compared to the previous visit	Baseline to Week 60
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	Maintaining reduced CS dose from Week 36 to Week 60	Week 36 to Week 60
Proportion of participants achieving BILAG-based Composite Lupus Assessment (BICLA)	BICLA response is defined as: Reduction of all baseline BILAG-2004 A to B/C/D and baseline B to C/D and no worsening in other organ systems defined as ≥ 1 new A or ≥ 2 new B items compared to baseline; No worsening from baseline in SLEDAI-2K defined as an increase from baseline of > 0 points; No worsening in PhGA defined as an increase of ≥ 0.3 from baseline on a 0 to 3 PhGA visual analog scale	Week 60
Proportion of participants achieving Lupus Low Disease Activity State (LLDAS)	LLDAS response is defined as: SLEDAI-2K ≤ 4, with no activity in major organ systems (renal, central nervous system (CNS), cardiopulmonary, vasculitis, fever) (Golder et al 2019); No new lupus disease activity compared with the previous assessment, defined as any new SLEDAI-2K component that was not present at the previous assessment; PhGA (scale 0-3) ≤ 1; Current predniso(lo)ne (or equivalent) dose ≤ 7.5 mg daily; Well tolerated standard maintenance doses of immunosuppressive drugs and approved biological agents	Week 60
Time to first occurrence of SRI-4	Time to first occurrence of SRI-4 from baseline to Week 60	Baseline to Week 60
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	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	Week 36 to Week 60
Proportion of participants achieving SRI-6	SRI-6 response is defined as: SLEDAI-2K reduction from baseline of ≥ 6 points; No BILAG-2004 worsening, defined as ≥ 1 new A or ≥ 2 new B items compared to baseline; No worsening in PhGA, defined as an increase of ≥ 0.3 from baseline on a 0 to 3 visual analog scale	Week 60
Incidence and titer of anti-drug (ianalumab) antibodies (ADAs) in serum over time	To evaluate immunogenicity of ianalumab s.c. monthly	Baseline to Week 164
Ianalumab concentration in serum during the treatment and follow-up	Concentration of Ianalumab in serum	Baseline to Week 164
Proportion of participants with Adverse Events (AEs)	To evaluate safety and tolerability of ianalumab s.c. monthly	Baseline to Week 60
Proportion of participants achieving SF-36 Bodily Pain response	Achieving Short Form 36 (SF-36) Bodily Pain response	Week 60

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals
• Investigators: Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): April 21, 2023
• Primary Completion (Estimated): April 12, 2027
• Study Completion (Estimated): April 9, 2029

Study Registration Dates

• First Submitted: November 7, 2022
• First Submitted That Met QC Criteria: November 21, 2022
• First Posted (Actual): November 22, 2022

Study Record Updates

• Last Update Posted (Actual): June 3, 2026
• Last Update Submitted That Met QC Criteria: June 2, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: Systemic Lupus Erythematosus, SLE, B cell depletion, SLEDAI-2K, BILAG-2004, SRI, ANA
• Additional Relevant MeSH Terms: Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Skin and Connective Tissue Diseases; Lupus Erythematosus, Systemic; ianalumab
• Other Study ID Numbers: CVAY736F12302; 2022-002690-29 (EudraCT Number); 2023-508499-12-00 (Other Identifier: EU CT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No