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

Summary

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.

Conditions

• Lupus Nephritis
• Systemic Lupus Erythematosus (SLE)

Interventions

PROCEDURE

Kidney Biopsy

At 3 months after the start of treatment, participants will undergo a repeat renal biopsy for assessment of early histological response and for single-cell RNA sequencing.

DRUG

Voclosporin (LUPKYNIS)

Arm 1 will receive triple therapy (addition of voclosporin)

DIAGNOSTIC_TEST

Blood, feces and urine sample collection

Blood, feces and urine samples will be collected at multiple timepoints during study follow-up period.

OTHER

LupusPRO questionnaire

The lupusPRO v1.7 questionnaire (20) is a 43-question patient reported outcome survey tool to follow the impact of lupus or its treatment on the patient's quality of life. The questionnaire takes 7-8 minutes to complete and is validated and available in multiple languages. Participants will be asked to either fill in the questionnaire at home (and bring it on their next outpatient clinic visit) or while visiting the hospital during follow-up time. The questionnaires are filled in on paper.

DRUG

Mycophenolate Mofetil (MMF) Treatment

MMF 1000 mg twice daily (or 500 mg four times daily)

DRUG

Prednisolone

Following intravenous methylprednisolone induction (500mg, 3 days), oral prednisolone 1 mg/kg/day tapered to ≤5 mg/day within 3 months.

Sponsors & Collaborators

• Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

  lead OTHER

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

16 Years

Max Age

70 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2026-04-23

Primary Completion

2028-04-30

Completion

2030-04-30

Countries

• Netherlands

Study Locations