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临床试验/NCT05126277
NCT05126277进行中（未招募）3 期

A Randomized, Double-blind, Parallel Group, Placebo-controlled, Multicenter Phase 3 Trial to Evaluate Efficacy, Safety and Tolerability of Ianalumab on Top of Standard-of-care Therapy in Participants With Active Lupus Nephritis (SIRIUS-LN).

Novartis Pharmaceuticals206 个研究点 分布在 2 个国家目标入组 452 人开始时间: 2022年7月14日最近更新:
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适应症
干预措施
相关药物

试验速览

阶段
3 期
状态
进行中（未招募）
入组人数
452
试验地点
206
主要终点
Frequency and percentage of participants achieving stable Complete Renal Response (CRR)
研究概览研究设计入排标准研究组 & 干预措施结局指标研究者研究点记录与标识符相似试验

研究概览

简要总结

This trial will evaluate efficacy, safety, and tolerability of subcutaneous (s.c.) ianalumab given every 4 weeks (q4w) or every 12 weeks (q12w) compared to placebo, in combination with SoC, in adult participants with active LN

详细描述

This trial will evaluate the efficacy, safety, and tolerability of subcutaneous (s.c.) ianalumab given every 4 weeks (q4w) or ianalumab given every 12 weeks (q12w) compared to placebo, in combination with SoC, in adult participants with active LN (ISN/RPS class III, IV active glomerulonephritis with or without co-existing class V features, or pure class V membranous). using the 2003 International Society for Nephrology (ISN)/Renal Pathology Society (RPS) criteria).

研究设计

研究类型
Interventional
分配方式
Randomized
干预模型
Parallel
主要目的
Treatment
盲法
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

盲法说明

Double-blind

入排标准

年龄范围
18 Years 至 100 Years（Adult, Older Adult）
性别
All
接受健康志愿者
否

入选标准

  • •Participants eligible for inclusion in this study must meet all of the following criteria:
  • •Adult male and female participants aged 18 years or older at the time of screening
  • •Weigh at least 35 kg at screening
  • •Have a confirmed clinical diagnosis of SLE according to European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) Systemic Lupus Erythematosus (SLE) classification criteria
  • •Have a positive anti-nuclear antibody (ANA) test result; ANA titer ≥ 1:80 at screening visit based on central or local laboratory result
  • •Active LN at screening, as defined by meeting the 3 following criteria:
  • •Renal biopsy within 6 months prior to screening period indicating ISN/RPS class III or IV active glomerulonephritis with or without co-existing class V features, or pure class V membranous LN. If no biopsy was performed within 6 months prior to screening period, a biopsy will need to be performed during the screening period after having met all other inclusion/

排除标准

  • •UPCR ≥ 1.0 g/g on 24h urine collection at Screening
  • •eGFR ≥ 25mL/min/1.73 m
  • •Participants with eGFR < 30 mL/min/1.73 m2 require renal biopsy during the screening period showing sclerosis in ≤ 50% of glomeruli
  • •Newly diagnosed participants as well as pre-treated LN participants (including refractory cases) can be included, as long as they are currently on, or willing to initiate SoC induction therapy for LN using MPA
  • •Induction therapy, as defined by treatment including both high dose corticosteroids and MPA, should be initiated prior to or on day of randomization
  • •Anti-malarial treatment at stable dosing prior to randomization is strongly recommended, in the absence of contraindications
  • •Participants on azathioprine treatment at Screening must be switched to MPA prior to randomization
  • •Receipt of at least one dose of pulse methylprednisolone i.v. (250 - 1000 mg per day up to 3000 mg cumulative dose) or equivalent for treatment of current episode of active LN within 60 days prior randomization. Participant who cannot take the pulse i.v. corticosteroid therapy should directly start on 0.8-1.0 mg/day (max 80mg/day) oral predniso(lo)ne.
  • •Able to communicate well with the Investigator to understand and comply with the requirements of the study
  • •Exclusion Criteria:
  • •Participants meeting any of the following criteria are not eligible for inclusion in this study:
  • •Severe renal impairment as defined by i.) presence of oliguria (defined as a documented urine volume <400 mL/24 hrs) or ii.) End-Stage Renal Disease (ESRD) requiring dialysis or transplantation
  • •Sclerosis in > 50% of glomeruli on renal biopsy
  • •Use of other investigational drugs within 5 half-lives of enrollment, or within 30 days or until the expected pharmacodynamic effect has returned to baseline. Use of certain Traditional Chinese Medicines
  • •Prior use of ianalumab (ever); or prior use other B cell depleting therapy within 36 weeks prior to randomization or if therapy was administered < 36 weeks prior to randomization, B cell count less than the lower limit of normal or patient's own baseline value prior to having received an earlier B cell-depleting therapy
  • •Prior treatment with any of the following within 12 weeks prior to randomization
  • •Belimumab, telitacicept, abatacept, TNF-α mAb, immunoglobulins (i.v./s.c.) plasmapheresis
  • •Any other immuno-suppressants (i.v. or oral cyclophosphamide, calcineurin inhibitors, JAK inhibitors or other kinase inhibitors)
  • •Thalidomide treatment and/or methotrexate
  • •Combination of DMARDs
  • •Imidazole derivative (e.g., azathioprine, mizoribine) must be discontinued prior to starting treatment with MPA
  • •Receipt of more than 3000 mg i.v. pulse methylprednisolone (cumulative dose) within 12 weeks prior to randomization
  • •History of major organ transplant or hematopoietic stem cell/bone marrow transplant or are due to receive transplantation
  • •Any one of the following laboratory values at screening:
  • •Hemoglobin levels < 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
  • •Platelet count < 25 x 1000/µL
  • •Absolute neutrophil count (ANC) < 0.8 x 1000/µL
  • •Active viral, bacterial or other infections requiring intravenous or intramuscular treatment for clinically significant infection or history of recurrent clinically significant infection which in the opinion of the investigator will place the participant at risk for participation.
  • •History of known intolerance/hypersensitivity to MPA, oral corticosteroids, or any component of the study drug(s) or its excipients
  • •Receipt of live/attenuated vaccine within a 4-week period prior to randomization
  • •History of primary or secondary immunodeficiency, including a positive HIV test result
  • •History of malignancy of any organ system (other than localized basal cell carcinoma or squamous cell carcinoma of the skin or or in-situ cervical cancer), treated or untreated, within the past 5 years, regardless of whether there is evidence of local recurrence or metastases
  • •Any surgical, medical (e.g., uncontrolled hypertension, heart failure or diabetes), psychiatric or additional physical condition that the Investigator feels may jeopardize the participants in case of participation in this study
  • •Chronic infection with hepatitis B (HBV) or hepatitis C (HCV). Positive serology for hepatitis B surface antigen (HBsAg) excludes the participant
  • •Evidence of active tuberculosis (TB) infection (after anti-TB treatment, participants with history of TB may become eligible according to national local guidelines)
  • •Pregnant or nursing (lactating) women
  • •Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception during dosing and for 6 months after stopping of investigational medication
  • •Sexually active male participants, who do not agree to use barrier protection during intercourse with women of child-bearing potential while taking study treatment
  • •Other protocol -defined Inclusion/Exclusion may apply.

研究组 & 干预措施

Arm 2 - ianalumab s.c. q12w

Experimental

ianalumab s.c. q12w in addition to SoC

干预措施: ianalumab s.c. q12w (Drug)

Arm 3 - placebo s.c. q4w

Placebo Comparator

Placebo s.c. q4w in addition to SoC

干预措施: placebo s.c. (Drug)

Arm 1 - ianalumab s.c. q4w

Experimental

ianalumab s.c. q4w in addition to standard of care (SoC)

干预措施: ianalumab s.c. q4w (Drug)

结局指标

主要结局

Frequency and percentage of participants achieving stable Complete Renal Response (CRR)

时间窗: Week 72

The primary objective is to demonstrate superiority of ianalumab compared to placebo, in achieving stable CRR (defined as estimated glomerular filtration rate (eGFR) ≥90 ml/min/1.73 m2 or no less than 85% of baseline, AND, 24-hour UPCR \<0.5 g/g) at Week 72 in active lupus nephritis (ISN/RPS class III, IV active glomerulonephritis with or without co-existing class V features, or pure class V membranous) participants on background SoC therapy.

次要结局

  • Time to first occurrence of stable urine protein-to-creatinine ratio (UPCR) <0.5 g/g or ≥50% reduction from baseline(Week 72)
  • Percentage of participants achieving stable Overall Renal Response (ORR), defined as achievement as either Complete Renal Response (CRR) or Partial Renal Response (PRR)(Week 48)
  • Number of participants with treatment-emergent Adverse Events (AEs)(Week 72)
  • Ianalumab concentration in serum(Week 72)
  • Incidence of stable Complete Renal Response (CRR) while maintaining daily corticosteroid dose ≤5 mg/day(Week 72)
  • Incidence of renal-related event or death(Week 72)
  • Change in British Isles Lupus Activity Group (BILAG) score(Week 72)
  • Change in Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue score(Week 72)
  • Incidence and titer of anti-ianalumab antibodies in serum (ADA assay) over time(Week 72)

研究者

申办方类型
Industry
责任方
Sponsor

研究点 (206)

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