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NCT Number: NCT07760480

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.

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Key information

Conditions

Lupus Nephritis Autoimmune Diseases Connective Tissue Diseases Female Urogenital Diseases Female Urogenital Diseases and Pregnancy Complications Glomerulonephritis Immune System Diseases Kidney Diseases Lupus Erythematosus, Systemic Male Urogenital Diseases Nephritis Skin and Connective Tissue Diseases Systemic Lupus Erythematosus (SLE) Urogenital Diseases Urologic Diseases

Age range

16 year–70 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 4

Primary location

Amsterdam University Medical Center

Amsterdam, Netherlands

Location status: Recruiting

Location contact

Marc L Hilhorst, MD, PhD

PRINCIPAL_INVESTIGATOR

Marc L Hilhorst, Principal Investigator

CONTACT

[email protected]

+31205669111

Suryanti D Crum, MD

SUB_INVESTIGATOR

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Lupus nephritis patients

Inclusion criteria

  • 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

Exclusion criteria

  • 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
  • A single elevated blood pressure measurement will not lead to immediate exclusion from the trial. Antihypertensive therapy may be initiated as appropriate. Dose adjustments of voclosporin should be made in accordance with Section 11.3.2 of the protocol

SLE patients without LN (disease control group) Inclusion criteria

  • Diagnosis of SLE according to EULAR/ACR guidelines
  • Age 16-70

Exclusion criteria

  • Suspicion of LN
  • Signs of active infection

Healthy subjects (control group) Inclusion criteria

  • Blank medical history
  • Age 16-70
  • A majority (75%) of female healthy subjects will be sought

Exclusion criteria

  • Signs of active infection

Treatment and study plan

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.

Voclosporin (LUPKYNIS)

Drug

Arm 1 will receive triple therapy (addition of 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.

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.

Mycophenolate Mofetil (MMF) Treatment

Drug

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

Prednisolone

Drug

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

Primary outcomes

  1. Determining single cell RNA sequencing differences within the full macrophage spectrum between arm 1 vs arm 2

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

    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.

Secondary outcomes

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

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

    Clinical remission achievement will be related to transcriptomic tissue signature

  2. Assess differences in macrophage subtypes within kidney tissue

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

    Numerically distinguish residential macrophages and monocyte derived macrophages in kidney tissue with spatial scRNAseq, comparing arm 1 vs arm 2.

  3. Assess histological response of both treatment arms

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

    Assessment of histological response of intensified treatment (arm 1) compared to dual therapy (arm 2)

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

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

    Phenotype of circulating monocytes of LN patients will be associated with kidney tissue signature and compared to circulating monocyte phenotype of SLE patients without clinical kidney involvement and healthy participants.

  5. To identify potential non-invasive urinary biomarkers

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

    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

  6. Confirm scRNA-seq identified macrophage markers immunohistochemically, identify spatial distribution (glomerular vs interstitial) and assess their predictive and prognostic use.

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

Sponsors and collaborators

Lead sponsor

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

Other

Registry information

Official study title

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

Acronym: MAPLE

Important dates

Study start
2026
Primary completion
2028
Study completion
2030
First posted
Aug 12, 2026
Registry last updated
Aug 12, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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