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

NCT07760480 | Recruiting Phase 4

• 1 other identifier: 2025-522187-32-01
• Study Type: interventional
• Target: 55
• Locations: 1 country
• Sites: 1

Brief 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)

Keywords

Lupus Nephritis; LN; SLE; Systemic lupus erythematosus; volcosporin; mmf; cellcept; prednisolone; kidney biopsy

Outcome Measures

Primary Outcomes (1)

• Determining single cell RNA sequencing 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. Differences in celltype proportions, gene expression and spatial organization will be assessed using spatial single cell RNA sequencing techniques.

  From enrollment to the repeat kidney biopsy at 3 months after starting treatment

Secondary Outcomes (6)

• Analyze rapid clinical remission of intensified treatment by proteinuria levels for relation to tissue changes

  From enrollment to the end of follow-up at 24 months

• Assess differences in macrophage subtypes within kidney tissue

  From enrollment to the repeat kidney biopsy at 3 months after starting treatment

• Assess histological response of both treatment arms

  From enrollment to the repeat kidney biopsy at 3 months after starting treatment

• To assess phenotype of circulating monocytes in LN patients compared to SLE patients without clinical kidney involvement and healthy participants

  From enrollment to the end of follow-up at 24 months

• To identify potential non-invasive urinary biomarkers

  From enrollment to the end of follow-up at 24 months

Study Arms (4)

Triple Therapy (MMF + Prednisolone + Voclosporin)

ACTIVE COMPARATOR

Participants receive induction corticosteroid therapy consisting of intravenous methylprednisolone 500 mg daily for 3 days, followed by oral prednisolone 1 mg/kg/day with tapering to ≤5 mg/day within 3 months, mycophenolate mofetil (MMF) 1000 mg twice daily (or 500 mg four times daily), and voclosporin 23.7 mg twice daily.

Procedure: Kidney Biopsy; Drug: Voclosporin (LUPKYNIS); Diagnostic Test: Blood, feces and urine sample collection; Other: LupusPRO questionnaire; Drug: Mycophenolate Mofetil (MMF) Treatment; Drug: Prednisolone

Dual Therapy (MMF + Prednisolone)

ACTIVE COMPARATOR

Participants receive induction corticosteroid therapy consisting of intravenous methylprednisolone 500 mg daily for 3 days, followed by oral prednisolone 1 mg/kg/day with tapering to ≤5 mg/day within 3 months, and mycophenolate mofetil (MMF) 1000 mg twice daily (or 500 mg four times daily).

Procedure: Kidney Biopsy; Diagnostic Test: Blood, feces and urine sample collection; Other: LupusPRO questionnaire; Drug: Mycophenolate Mofetil (MMF) Treatment; Drug: Prednisolone

SLE without LN control

NO INTERVENTION

From the SLE without LN patients (disease control), blood and urine samples are collected at two timepoints, with an interval of (min) 3 and (max) 6 months between collection. Participants in this arm are not randomized and do not undergo treatment or kidney biopsy.

Healthy control

NO INTERVENTION

Healthy participants (healthy control) blood and urine samples are collected at two timepoints, with an interval of (min) 3 and (max) 6 months between collection. Participants in this arm are not randomized and do not undergo treatment or kidney biopsy.

Interventions

Kidney Biopsy PROCEDURE

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.

Dual Therapy (MMF + Prednisolone); Triple Therapy (MMF + Prednisolone + Voclosporin)

Voclosporin (LUPKYNIS) DRUG

Arm 1 will receive triple therapy (addition of voclosporin)

Triple Therapy (MMF + Prednisolone + Voclosporin)

Blood, feces and urine sample collection DIAGNOSTIC_TEST

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

Dual Therapy (MMF + Prednisolone); Triple Therapy (MMF + Prednisolone + Voclosporin)

LupusPRO questionnaire OTHER

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.

Dual Therapy (MMF + Prednisolone); Triple Therapy (MMF + Prednisolone + Voclosporin)

Mycophenolate Mofetil (MMF) Treatment DRUG

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

Dual Therapy (MMF + Prednisolone); Triple Therapy (MMF + Prednisolone + Voclosporin)

Prednisolone DRUG

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

Dual Therapy (MMF + Prednisolone); Triple Therapy (MMF + Prednisolone + Voclosporin)

Eligibility Criteria

• Age: 16 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 years
• eGFR as measured by cystatin C \>20 mL/min

You may not qualify if:

• LN class I, II or pure class V upon kidney biopsy
• eGFR as measured by cystatin C \<20 mL/min
• Histological chronicity score (NIH) of 8 or higher in the 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
• 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 hyperten sion)\*
• Co-administration of voclosporin with strong CYP3A4 inhibitors (e.g., ke toconazole, itraconazole, clarithromycin)
• Pregnancy
• Diagnosis of SLE according to EULAR/ACR guidelines
• Age 16-70
• Suspicion of LN

Sponsors & Collaborators

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

Study Sites (1)

Amsterdam University Medical Center

Amsterdam, Netherlands

RECRUITING

MeSH Terms

Conditions

Lupus Nephritis; Lupus Erythematosus, Systemic

Interventions

voclosporin; Blood Specimen Collection; Defecation; Mycophenolic Acid; Therapeutics; Prednisolone

Condition Hierarchy (Ancestors)

Glomerulonephritis; Nephritis; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques; Digestive System Physiological Phenomena; Digestive System and Oral Physiological Phenomena; Caproates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Fatty Acids; Lipids; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, PhD

Study Record Dates

• First Submitted: July 7, 2026
• First Posted: August 12, 2026
• Study Start: April 23, 2026
• Primary Completion (Estimated): April 1, 2028
• Study Completion (Estimated): April 1, 2030
• Last Updated: August 12, 2026

Record last verified: 2026-08

Locations

NL (1)