2023-508559-37-00招募中3 期
A randomized, double-blind, parallel group, placebo-controlled, multicenter phase 3 trial to evaluate the efficacy, safety and tolerability of ianalumab on top of standard-of-care therapy in participants with active lupus nephritis (SIRIUS-LN)
适应症
干预措施
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 105
- 试验地点
- 44
- 主要终点
- Incidence of stable CRR at Week 72; participants who discontinue treatment before Week 72 or use corticosteroids at a dose >7.5 mg/day after Week 60 will be considered non-responders
研究概览
简要总结
To demonstrate superiority of ianalumab, compared to placebo, in achieving stable complete renal response (CRR) at Week 72
入排标准
- 年龄范围
- 18 years 至 65+ years（65+ Years, 18-64 Years）
- 接受健康志愿者
- 是
入选标准
- •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 EULAR/ACR SLE classification criteria
- •Have a positive anti-nuclear antibody (ANA) test result defined as an ANA titer ≥1:80 (based on an indirect HEp-2 immunofluorescence assay or solid-phase ANA immunoassay with at least equivalent performance) at screening based on central laboratory results or a documented, positive historical result (ANA titer ≥1:80)
- •Presence of active LN at screening requiring induction therapy, 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/exclusion criteria. • UPCR ≥1.0 g/g on 24-hour urine collection at Screening • eGFR ≥25mL/min/1.73 m2
- •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 to randomization. Participants who cannot take the pulse i.v. corticosteroid therapy should directly start on 0.8-1.0 mg/kg/day (max 80 mg/day) oral predniso(lo)ne
- •Able to provide signed informed consent
排除标准
- •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
- •United States (and other countries, if locally required): sexually active male participants who do not agree to use barrier protection during intercourse with women of child-bearing potential while taking study treatment. As condom use alone has a reported failure rate exceeding 1% per year, it is recommended female partners of male study participants use a second method of birth control.
- •History of known intolerance/hypersensitivity to MPA, oral corticosteroids, or any component of the study drug(s) or its excipients or to drugs of similar chemical classes (e.g., mAb of IgG1 class) or to any of the constituents of the study drug
- •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
- •Any surgical, medical, psychiatric or additional physical condition that may jeopardize participation in this study
- •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 the following Traditional Chinese Medicines: Total glucoside of peony (TGP) or Tripterygium glycosides (TG) administered within 30 days prior to randomization.
- •Prior treatment with any of the following • Within 12 weeks prior to randomization o belimumab, telitacicept, abatacept, TNF-α mAb, immunoglobulins (i.v./s.c.) plasmapheresis o any other immuno-suppressants (e.g., i.v. or oral cyclophosphamide, calcineurin inhibitors, JAK inhibitors or other kinase inhibitors) o thalidomide treatment and/or methotrexate • 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 (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 • Platelet count <25 x 103/µL • Absolute neutrophil count (ANC) <0.8 x 103/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.
- •Chronic infection with hepatitis B (HBV) or hepatitis C (HCV). xxx
- •Evidence of active tuberculosis (TB) infection xxx.
- •Pregnant or nursing (lactating) women
研究组 & 干预措施
-
Auxiliary
Participants receiving -
干预措施: - (Drug)
结局指标
主要结局
Incidence of stable CRR at Week 72; participants who discontinue treatment before Week 72 or use corticosteroids at a dose >7.5 mg/day after Week 60 will be considered non-responders
Incidence of stable CRR at Week 72; participants who discontinue treatment before Week 72 or use corticosteroids at a dose >7.5 mg/day after Week 60 will be considered non-responders
次要结局
- Time to first occurrence of stable UPCR <0.5 g/g or ≥50% reduction from baseline up to Week 72
- Incidence of stable ORR at Week 48; participants who discontinue treatment before Week 48 or use corticosteroids at a dose >7.5 mg/day after Week 36 will be considered non-responders
- Incidence of stable CRR at Week 72 while maintaining daily corticosteroid dose ≤5mg/day between Week 24 and Week 72. Participants who discontinue treatment before Week 72 will be considered non-responders
- Incidence of renal flares related event or death through Week 72
- Change from baseline in BILAG-2004 at Week 72
- Change from baseline in FACIT-Fatigue at Week 72
- Ianalumab concentration in serum and calculated PK parameters
- Incidence and titer of anti-ianalumab antibodies in serum (ADA assay) over time
- Treatment-emergent Adverse Events (TEAEs)
- Serious Adverse Events (SAEs)
- Vital signs
- Clinical laboratory measurements
研究者
Novartis Pharma Arzneimittel GmbH
Scientific
Novartis Pharma AG
研究点 (44)
Loading locations...
相似试验
招募中
3 期
Phase 3 study to evaluate ianalumab on top of standard-of-care therapy in patients with systemic lupus erythematosus (SIRIUS-SLE 2)Systemic Lupus Erythematosus2023-508499-12-00Novartis Pharma AG67
进行中（未招募）
3 期
Ravulizumab 治疗 IgA 肾病的Ⅲ期研究CTR2024168880
招募中
2 期
Daratumumab in Combination with Carfilzomib, Pomalidomide and Dexamethasone in patients with myeloma induced acute renal failureMultiple myeloma2024-514702-31-00Medizinische Universitaet Innsbruck50
招募中
3 期
A study of efficacy and safety of ianalumab in previously treated patients with warm autoimmune haemolytic anaemia2024-510635-21-00Novartis Pharma AG32
招募中
3 期
Three-arm study of the clinical efficacy, safety and tolerability of ianalumab (VAY736) in patients with active Sjögren’s syndrome2024-511068-10-00Novartis Pharma AG150