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)

Novartis Pharmaceuticals177 个研究点分布在 2 个国家目标入组 436 人2023年3月2日

适应症Systemic Lupus Erythematosus

干预措施Ianalumab Placebo

概览

阶段: 3 期
干预措施: Ianalumab
疾病 / 适应症: Systemic Lupus Erythematosus
发起方: Novartis Pharmaceuticals
入组人数: 436
试验地点: 177
主要终点: Proportion of participants on monthly ianalumab achieving Systemic Lupus Erythematosus Responder Index -4 (SRI-4)
状态: 进行中（未招募）
最后更新: 上个月

概览研究者入排标准研究组 & 干预措施结局指标研究点相似试验

概览

简要总结

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).

详细描述

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)

注册库

clinicaltrials.gov

开始日期

2023年3月2日

结束日期

2029年3月21日

最后更新

上个月

研究类型

Interventional

研究设计

Parallel

性别

All

研究者

发起方

Novartis Pharmaceuticals

责任方

Sponsor

入排标准

入选标准

•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

排除标准

•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)

研究组 & 干预措施

Ianalumab s.c. monthly

干预措施: Ianalumab

Ianalumab s.c. quarterly

干预措施: Ianalumab

Placebo s.c. monthly

placebo s.c. monthly

干预措施: Placebo

结局指标

主要结局

Proportion of participants on monthly ianalumab achieving Systemic Lupus Erythematosus Responder Index -4 (SRI-4)

时间窗: 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

次要结局

Proportion of participants on monthly or quarterly ianalumab achieving Short Form 36 (SF-36) Bodily Pain response(Week 60)
Proportion of participants on quarterly ianalumab achieving SRI-4(Week 60)
Proportion of participants on monthly or quarterly ianalumab with Adverse Events (AEs) and Serious Adverse Events (SAEs)(Baseline to Week 60)
Number of participants with adverse events(Baseline to Week 60)
Proportion of participants with anti-ianalumab antibodies in serum (ADA assay) over time(Baseline to Week 164)
Ianalumab concentration in serum during the treatment and follow-up(Baseline to week 164)
Proportion of participants on monthly or quarterly ianalumab achieving Lupus Low Disease Activity State (LLDAS)(Week 60)
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(Week 36 to Week 60)
Proportion of participants on monthly or quarterly ianalumab achieving BILAG-based Composite Lupus Assessment (BICLA)(Week 60)
Time to first occurrence of SRI-4 (participants on ianalumab monthly or quarterly)(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)
Proportion of participants on monthly or quarterly ianalumab with no moderate or severe British Isles Lupus Assessment Group (BILAG) flare(Baseline to Week 60)
Proportion of participants on monthly or quarterly ianalumab achieving SRI-6(Week 60)