Voclosporin for Lupus nephritis|Systemic lupus erythematosus

Inclusion criteria

• {"criterion_text":"- 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 16-70. eGFR as measured by cystatin C must be >20 mL/min.\n- SLE patients (disease control group): Diagnosis of SLE according to EULAR/ACR guidelines. Age 16-70.\n- Healthy subjects (control group): blank medical history. Age 16-70. A majority (75%) of female healthy subjects wil be sought."}

Exclusion criteria

• {"criterion_text":"- 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)\n- SLE patients (disease control group): Suspicion of LN; Signs of active infection\n- Healthy subjects (control group): signs of active infection"}

Primary endpoints

• {"endpoint_text":"- 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","definition_or_measurement_approach":"Comparison of single-cell RNA sequencing (scRNA-seq) profiles of macrophage populations between baseline kidney biopsy and 3-month kidney biopsy, comparing arm 1 versus arm 2."}

Secondary endpoints

• {"endpoint_text":"- Objective 2a. numerically distinguish residential macrophages and monocyte-derived macrophages in kidney tissue with spatial scRNAseq, comparing arm 1 vs arm 2;","definition_or_measurement_approach":"Spatial scRNA-seq to quantitatively distinguish tissue-resident macrophages versus monocyte-derived macrophages in kidney tissue between arms."}
• {"endpoint_text":"- Objective 2b: to assess histological response of intensified treatment (arm 1) compared to SOC (arm 2);","definition_or_measurement_approach":"Assessment of histological response on kidney biopsy comparing intensified treatment (voclosporin + MMF + prednisolone) versus standard of care (MMF + prednisolone)."}
• {"endpoint_text":"- 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)","definition_or_measurement_approach":"Correlation of early histological responses with clinical remission status at two years and identification of early response determinants including tissue monocyte/macrophage phenotyping."}
• {"endpoint_text":"- 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","definition_or_measurement_approach":"Bulk RNA sequencing and flow cytometry of peripheral monocytes to compare LN, SLE and healthy subjects; identify candidate urinary/serum biomarkers from scRNA-seq data and test them in stored urine/serum samples."}
• {"endpoint_text":"- 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;","definition_or_measurement_approach":"Validation of serum and/or urinary biomarkers identified from scRNA-seq data in sequentially stored patient specimens to assess their reflection of tissue damage and treatment response."}
• {"endpoint_text":"- Objective 6: confirm scRNA-seq identified macrophage markers immunohistochemically, identify spatial distribution (glomerular vs interstitial) and assess their predictive and prognostic use.","definition_or_measurement_approach":"Immunohistochemical confirmation of scRNA-seq macrophage markers, mapping spatial distribution (glomerular vs interstitial) and evaluating predictive/prognostic performance."}
• {"endpoint_text":"- Objective 1b: analyze rapid clinical remission of intensified treatment by proteinuria levels","definition_or_measurement_approach":"Analysis of proteinuria levels to assess rapid clinical remission following intensified treatment."}

Netherlands

Earliest CTIS Part Ii Submission Date

04-11-2025

Latest Decision Or Authorization Date

17-03-2026

Processing Time Days

133

Number Of Sites

1

Number Of Participants

55

Primary sponsor

Full Name

Amsterdam UMC Stichting

Organisation Type

Patient organisation/association

Country Of Registered Address

Netherlands