Phase 3 Study to Evaluate Ianalumab on Top of Standard-of-care Therapy in Patients With Systemic Lupus Erythematosus (SIRIUS-SLE 2)
- Registration Number
- NCT05624749
- Lead Sponsor
- Novartis Pharmaceuticals
- 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)
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 280
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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.
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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.
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Elevated serum titers at screening of anti-nuclear antibodies ≥ 1:80 as determined by a central laboratory with a SLE-typical fluorescence pattern.
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Currently receiving CS and/or anti-malarial treatment and/or another disease-modifying antirheumatic drug (DMARD) as specified in the protocol.
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SLEDAI-2K criteria at screening: SLEDAI-2K score ≥ 6 points, excluding points attributed to "fever", "lupus headache", "alopecia", and "organic brain syndrome"
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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
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Weigh at least 35 kg at screening
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Prior treatment with ianalumab
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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
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Active viral, bacterial or other infections requiring intravenous or intramuscular treatment for clinically significant infection
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Chronic infection with hepatitis B virus (HBV) or hepatitis C virus (HCV)
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Evidence of active tuberculosis infection
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History of primary or secondary immunodeficiency, including a positive human immunodeficiency virus (HIV) test result at screening
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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)
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Severe organ dysfunction or life-threatening disease at screening
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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
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Receipt of live/attenuated vaccine within a 4-week period before first dosing
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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
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Non-lupus conditions such as asthma, gout or urticaria, requiring intermittent or chronic treatment with systemic CS
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History of malignancy of any organ system other than localized basal cell carcinoma of the skin or in situ cervical cancer
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Pregnant or nursing (lactating) women.
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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.
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Any surgical, medical, psychiatric or additional physical condition that may jeopardize participation in this study
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description placebo s.c. monthly placebo placebo s.c. monthly ianalumab s.c. monthly ianalumab ianalumab s.c. monthly
- Primary Outcome Measures
Name Time Method Proportion of participants achieving Systemic Lupus Erythematosus Responder Index -4 (SRI-4) Week 60 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
- Secondary Outcome Measures
Name Time Method Proportion of participants with no moderate or severe BILAG flare Baseline to Week 60 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
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 Week 36 to Week 60 Maintaining reduced CS dose from Week 36 to Week 60
Proportion of participants achieving BILAG-based Composite Lupus Assessment (BICLA) Week 60 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 scaleProportion 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 Week 36 to Week 60 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
Proportion of participants achieving Lupus Low Disease Activity State (LLDAS) Week 60 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 agentsProportion of participants achieving SRI-6 Week 60 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 scaleProportion of participants achieving SF-36 Bodily Pain response Week 60 Achieving Short Form 36 (SF-36) Bodily Pain response
Time to first occurrence of SRI-4 Baseline to Week 60 Time to first occurrence of SRI-4 from baseline to Week 60
Proportion of participants with Adverse Events (AEs) Baseline to Week 60 To evaluate safety and tolerability of ianalumab s.c. monthly
Ianalumab concentration in serum during the treatment and follow-up Baseline to Week 164 Concentration of Ianalumab in serum
Incidence and titer of anti-drug (ianalumab) antibodies (ADAs) in serum over time Baseline to Week 164 To evaluate immunogenicity of ianalumab s.c. monthly
Trial Locations
- Locations (18)
Pinnacle Research Group LLC
🇺🇸Anniston, Alabama, United States
University of Calif Irvine Med Cntr
🇺🇸Irvine, California, United States
Advanced Medical Research
🇺🇸La Palma, California, United States
University of California LA
🇺🇸Los Angeles, California, United States
Homestead Assoc In Research Inc
🇺🇸Homestead, Florida, United States
IRIS Research and Development
🇺🇸Plantation, Florida, United States
Emory University
🇺🇸Atlanta, Georgia, United States
Willow Rheumatology Wellness
🇺🇸Willowbrook, Illinois, United States
Bluegrass Community Research Inc
🇺🇸Lexington, Kentucky, United States
Accurate Clinical Research
🇺🇸Lake Charles, Louisiana, United States
UMC New Orleans
🇺🇸New Orleans, Louisiana, United States
University Of Maryland
🇺🇸Baltimore, Maryland, United States
Ahmed Arif Medical Research Center
🇺🇸Grand Blanc, Michigan, United States
Washington Univ School Of Medicine
🇺🇸Saint Louis, Missouri, United States
Thomas Jefferson University
🇺🇸Philadelphia, Pennsylvania, United States
West Tennessee Research Institute
🇺🇸Jackson, Tennessee, United States
Novel Research LLC
🇺🇸Bellaire, Texas, United States
Novartis Investigative Site
🇬🇧London, United Kingdom