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)
- Registration Number
- NCT05639114
- Lead Sponsor
- Novartis Pharmaceuticals
- 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)
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 406
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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 Ianalumab s.c. monthly Ianalumab Ianalumab s.c. monthly Ianalumab s.c. quarterly Ianalumab Ianalumab s.c. quarterly Placebo s.c. monthly Placebo placebo s.c. monthly
- Primary Outcome Measures
Name Time Method Proportion of participants on monthly ianalumab 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 on monthly or quarterly ianalumab achieving Short Form 36 (SF-36) Bodily Pain response Week 60 Achieving SF-36 Bodily Pain response
Proportion of participants on quarterly ianalumab achieving SRI-4 Week 60 SRI-4 response is defined as:
* SLEDAI-2K reduction from baseline of ≥ 4 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 on monthly or quarterly ianalumab with Adverse Events (AEs) and Serious Adverse Events (SAEs) Baseline to Week 60 To evaluate safety and tolerability of ianalumab s.c. monthly or quarterly
Number of participants with adverse events Baseline to Week 60 To evaluate safety and tolerability of ianalumab s.c. monthly or quarterly
Proportion of participants with anti-ianalumab antibodies in serum (ADA assay) over time Baseline to Week 164 Immunogenicity of ianalumab s.c. monthly or quarterly
Ianalumab concentration in serum during the treatment and follow-up Baseline to week 164 Ianalumab concentration in serum
Proportion of participants on monthly or quarterly ianalumab 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).
* 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 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 Week 36 to Week 60 Maintaining reduced CS dose from Week 36 to Week 60
Proportion of participants on monthly or quarterly ianalumab 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 scaleTime to first occurrence of SRI-4 (participants on ianalumab monthly or quarterly) Baseline to Week 60 Time to first occurrence of SRI-4 from baseline to Week 60
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 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 on monthly or quarterly ianalumab with no moderate or severe British Isles Lupus Assessment Group (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 on monthly or quarterly ianalumab 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 scale
Trial Locations
- Locations (30)
University of Colorado
🇺🇸Aurora, Colorado, United States
Providence Medical Center
🇺🇸Burbank, California, United States
University of California San Diego
🇺🇸La Jolla, California, United States
Keck School of Medicine
🇺🇸Los Angeles, California, United States
Millennium Clinical Trials
🇺🇸Westlake Village, California, United States
Yale University School Of Medicine
🇺🇸New Haven, Connecticut, United States
Stamford Hospital
🇺🇸Stamford, Connecticut, United States
Clinical Res Of W Florida
🇺🇸Clearwater, Florida, United States
GNP Research
🇺🇸Hollywood, Florida, United States
University Of Miami
🇺🇸Miami, Florida, United States
Clinical Research of West Florida Inc
🇺🇸Tampa, Florida, United States
Parris and Associates Rheumatology
🇺🇸Lawrenceville, Georgia, United States
Robert A Hozman MD SC
🇺🇸Skokie, Illinois, United States
Lake Cumberland Rheumatology and In
🇺🇸New Albany, Indiana, United States
Ochsner Clinic Foundation
🇺🇸Baton Rouge, Louisiana, United States
Henry Ford Health
🇺🇸Detroit, Michigan, United States
Univ of Nevada School of Med
🇺🇸Las Vegas, Nevada, United States
Innovative Health Research
🇺🇸Las Vegas, Nevada, United States
Sahni Rheumatology and Therapy
🇺🇸West Long Branch, New Jersey, United States
NYU Langone Health
🇺🇸Brooklyn, New York, United States
Medical Center Main Campus
🇺🇸Cleveland, Ohio, United States
STAT Research Inc
🇺🇸Dayton, Ohio, United States
Paramount Med Rsrch and Consult LLC
🇺🇸Middleburg Heights, Ohio, United States
University Of Pittsburgh
🇺🇸Pittsburgh, Pennsylvania, United States
Prisma Health
🇺🇸Columbia, South Carolina, United States
Shelby Research LLC
🇺🇸Memphis, Tennessee, United States
Accurate Clinical Research Research
🇺🇸Baytown, Texas, United States
Texas Arthritis Center
🇺🇸El Paso, Texas, United States
Epic Medical Research
🇺🇸Red Oak, Texas, United States
Novartis Investigative Site
🇹🇷Talas Kayseri, Turkey