2025-522187-32-01招募中4 期
Assessing residual inflammation and macrophage presence in lupus nephritis after 3 months of intensified treatment with prednisolone, mycofenolate mofetil and voclosporin as compared to mycofenolate mofetil and prednisolone: an open label randomized controlled trial (MAPLE study)
适应症
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 入组人数
- 55
- 试验地点
- 1
- 主要终点
- Objective 1a: to determine scRNA-seq differences within the full macrophage spectrum between arm 1 vs arm 2; the macrophage spectrum will be compared between baseline kidney biopsy and kidney biopsy at 3 months treatment
研究概览
简要总结
Aim 1: establish that rapidly induced immunological remission on a cellular and histopathological level of LN patients (class III/IV+/-V) with addition of the CNI voclosporin on top of MMF+prednisolone, compared to MMF+prednisolone alone is attainable
- Objective 1: determine differences in macrophage clusters in kidney tissue per treatment arm
- Objective 2: assess histological response of the addition of intensified treatment (addition of voclosporin) compared to MMF+prednisolone
- Objective 3: assess if early histological response is associated with clinical remission after two years and identify innovative early response determinants (including circulating monocyte phenotyping)
入排标准
- 年龄范围
- 0 years 至 65+ years（18-64 Years, 0-17 Years, 65+ Years）
- 接受健康志愿者
- 是
入选标准
- •Lupus nephritis patients: Patients with de novo or flaring SLE according to the EULAR/ACR criteria and a suspicion of class III or IV LN with a clinical indication to perform a kidney biopsy. Age 16-
- •eGFR as measured by cystatin C must be >20 mL/min.
- •SLE patients (disease control group): Diagnosis of SLE according to EULAR/ACR guidelines. Age 16-
- •Healthy subjects (control group): blank medical history. Age 16-
- •A majority (75%) of female healthy subjects wil be sought.
排除标准
- •Lupus nephritis patients: LN class I, II or pure class V upon kidney biopsy (in the case of a class I, II or pure V, the patient will be asked consent for analysis of the scRNA-seq data from the kidney biopsy but the patient will not be randomized); eGFR as measured by cystatin C <20 mL/min; Histological chronicity score (NIH) of 8 or higher in the baseline kidney biopsy; Active infection of any kind as evidenced by cultures (blood, urine or otherwise); History of hepatitis B, hepatitis C, tuberculosis and/or HIV; Treatment with any of the following agents within one month before screening: tacrolimus, belimumab, anifrolumab; Treatment with any of the following agents within 6 months before screening: rituximab, daratumumab, eculizumab; Pregnancy; Prolongation of QT-interval (QTc >470ms) and/or bradycardia (resting heart rate <50bpm) measured on two separate occasions; Hyperkalaemia (serum potassium >6.0 mmol/L); Hypertension (blood pressure > 165/105 mmHg, with symptoms of hypertension)*; Co-administration of voclosporin with strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, clarithromycin)
- •SLE patients (disease control group): Suspicion of LN; Signs of active infection
- •Healthy subjects (control group): signs of active infection
结局指标
主要结局
Objective 1a: to determine scRNA-seq differences within the full macrophage spectrum between arm 1 vs arm 2; the macrophage spectrum will be compared between baseline kidney biopsy and kidney biopsy at 3 months treatment
Objective 1a: to determine scRNA-seq differences within the full macrophage spectrum between arm 1 vs arm 2; the macrophage spectrum will be compared between baseline kidney biopsy and kidney biopsy at 3 months treatment
次要结局
- Objective 2a. numerically distinguish residential macrophages and monocyte-derived macrophages in kidney tissue with spatial scRNAseq, comparing arm 1 vs arm 2;
- Objective 2b: to assess histological response of intensified treatment (arm 1) compared to SOC (arm 2);
- Objective 3: to assess if early histological response is associated with clinical remission after two years and identify innovative early response determinants (including tissue monocyte/macrophage phenotyping)
- Objective 4: to identify differences between LN, SLE and healthy subjects in peripheral monocyte phenotype by using bulk RNA sequencing and flowcytometric analyses, to be associated with scRNAseq data and clinical/biochemical parameters. To identify potential non-invasive urinary biomarkers of disease activity in the scRNA-seq data, to be tested in sequentially stored urine and/or serum from patients
- Objective 5: attempt to render (repeat) kidney biopsy in LN obsolete by identifying reliable serum and/or urinary biomarkers that reflect tissue damage and treatment response;
- Objective 6: confirm scRNA-seq identified macrophage markers immunohistochemically, identify spatial distribution (glomerular vs interstitial) and assess their predictive and prognostic use.
- Objective 1b: analyze rapid clinical remission of intensified treatment by proteinuria levels
研究者
M.L. Hilhorst
Scientific
Amsterdam UMC Stichting
研究点 (1)
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