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

The goal of this clinical trial is to learn how different treatments affect immune cells in the kidney in people with active lupus nephritis (LN), a kidney manifestation of systemic lupus erythematosus (SLE). It will also investigate whether early changes in kidney tissue can predict long-term treatment response and whether blood or urine biomarkers can be used to monitor disease activity without the need for repeat kidney biopsies.

The main questions it aims to answer are:

• Does adding voclosporin to standard treatment with mycophenolate mofetil (MMF) and prednisolone result in greater early improvement of kidney inflammation compared with MMF and prednisolone alone?
• Are specific macrophage and monocyte populations associated with treatment response and long-term kidney outcomes?
• Can blood- or urine-based biomarkers be identified that reflect kidney inflammation and treatment response?

Researchers will compare MMF, prednisolone, and voclosporin (triple therapy) with MMF and prednisolone alone (dual therapy) to determine whether intensified treatment leads to faster and more complete immunological and histological remission.

Participants with newly diagnosed or relapsing proliferative lupus nephritis will:

• Be randomly assigned to receive either triple therapy (MMF, prednisolone, and voclosporin) or dual therapy (MMF and prednisolone).
• Undergo a kidney biopsy before treatment starts and a repeat kidney biopsy after 3 months of treatment.
• Provide blood and urine samples during follow-up for immune cell analyses and biomarker studies.
• Complete patient-reported outcomes questionnaires
• Attend regular study visits and clinical assessments for up to 2 years.

In addition, participants with SLE without lupus nephritis and healthy volunteers will provide blood samples to allow comparison of circulating immune cell populations between groups.