2024-510718-34-00招募中4 期
Study of Artificial Intelligence-based Personalized Rituximab Treatment Protocol in Membranous nephropathy
适应症
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 入组人数
- 130
- 试验地点
- 14
- 主要终点
- Clinical remission (complete or partial) according to KDIGO or French guidelines: - Complete: urine protein/creatinine ratio (UPCR) <0.3 g/g and serum albumin>30 g/L - Partial: UPCR <3.5 g/g with a decrease >50% from baseline (i.e., at first rituximab infusion) and serum albumin improvement or normalization
研究概览
简要总结
To compare, in nephrotic rituximab-treated membranous nephropathy, the efficacy of a standard-of-care treatment versus a personalized treatment driven by the recommendation of the algorithm that predicts the risk of drug underexposure at month-3, in inducing clinical remission 6 months after rituximab treatment initiation.
研究设计
- 分配方式
- Randomized
- 主要目的
- Treatment period
- 盲法
- None
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
- 否
入选标准
- •Age ≥ 18 years
- •Ongoing episode of membranous nephropathy diagnosed either by: the presence of anti-PLA2R1 or anti-THSD7A antibodies, or renal biopsy
- •Nephrotic syndrome defined by proteinuria > 3.5 g/24h (or UPCR > 3.5 g/g) and serum albumin < 30 g/L at screening
- •Indication for rituximab treatment according to the KDIGO or French guidelines
- •Non-immunosuppressive antiproteinuric treatment at stable dose for 2 weeks according to French guidelines, including a renin angiotensin aldosterone system inhibitor, a diuretic and a low-salt diet
- •Estimated Glomerular Filtration Rate CKD-EPI > 30 mL/min/1,73 m²
排除标准
- •Secondary membranous nephropathy related to cancer, infection, systemic lupus, drug
- •Patient refusing to follow the algorithm recommendation approved by their referring nephrologist
- •Patient who, in the opinion of the investigator, cannot receive the treatment recommended by the iRITUX algorithm (safety or compliance reasons)
- •Pregnancy or breastfeeding
- •Immunosuppressive treatment (including rituximab) in the 6 months preceding inclusion
- •Presence of anti-rituximab antibodies detected by Central Lab
- •Cancer under treatment
- •Patients with active, severe infections
- •Hypersensitivity to the active substance or excipients
- •Patients severely immunocompromised who, in the opinion of the investigator, cannot receive more than two 1-gram doses of rituximab
- •Severe heart failure or severe, uncontrolled cardiac disease
结局指标
主要结局
Clinical remission (complete or partial) according to KDIGO or French guidelines: - Complete: urine protein/creatinine ratio (UPCR) <0.3 g/g and serum albumin>30 g/L - Partial: UPCR <3.5 g/g with a decrease >50% from baseline (i.e., at first rituximab infusion) and serum albumin improvement or normalization
Clinical remission (complete or partial) according to KDIGO or French guidelines: - Complete: urine protein/creatinine ratio (UPCR) <0.3 g/g and serum albumin>30 g/L - Partial: UPCR <3.5 g/g with a decrease >50% from baseline (i.e., at first rituximab infusion) and serum albumin improvement or normalization
次要结局
- Complete clinical remission at month-12 according to KDIGO or French guidelines
- Partial clinical remission at month-12 according to KDIGO or French guidelines
- Immunological remission: If membranous nephropathy anti-PLA2R1 associated: anti-PLA2R1 depletion (i.e., PLA2R1 titer < 14 RU/mL by ELISA EUROIMMUN kit) at month-3, month-6, month-12 ✓ If membranous nephropathy anti-THSD7A associated: anti-THSD7A depletion (i.e., positive or negative immunofluorescence)
- Percentage of change in urine protein/creatinine ratio (UPCR) (g/g) and urine albumin/creatinine ratio (mg/g) from day-0 to month-3, month-6, month-9, month-12
- Percentage of change in serum creatinine (μmol/L) and Glomerular Filtration Rate estimated by CKD-EPI formula (mL/min/1.73m²) from day-0 to month-3, month-6, month-9, month-12
- Percentage of change in anti-PLA2R1 titer (RU/mL) by ELISA (EUROIMMUN Kit) from day-0 to month-3, month-6, month-9, month-12 (membranous nephropathy anti-PLA2R1 associated only)
- Serum anti-rituximab antibodies (ng/mL) at month-3, month-6, month-9, month-12
- Percentage of patients with serum rituximab (μg/mL) >2 μg/mL 3 months after the last infusion
- Serious adverse events
- Modification of non-immunosuppressive anti-proteinuric treatment during study follow-up
- Pharmacokinetics in all patients with serum creatinine and serum albumin levels, weight, anti- PLA2R1 and rituximab level at day-0, day-15, day-30, day-45, month-3, month-6
- Clinicians' satisfaction with the iRITUX algorithm and its value in helping them decide on the dose of rituximab to use to treat their patients will be assessed with a close-ended question.
- Predictive rate (%) of the algorithm for rituximab underdosing (i.e. serum level <2 mg/ml at month-3) in the control group (i.e. patients treated according to the standard-of-care strategy).
- Cytokine levels in pg/mL (IFN-γ, IFN-α, IL-12p70, IL-17A, IL-4, IL-5, IL-10, IL-1, IL-6) at day- 0 and month-6.
研究者
Fernandez Céline
Scientific
Centre Hospitalier Universitaire De Nice
研究点 (14)
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