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

Sponsor
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Study ID
NCT07760480
Phase
PHASE4
Status
Recruiting
Apply to this trial

Conditions

Eligibility Criteria

Sex
ALL
Age
16 Years - 70 Years
Healthy Volunteers
Accepted

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.
  • 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.

Study Details

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.

Key Dates

First listed
Aug 12, 2026
Start date
Apr 23, 2026
Status verified
Aug 2026
Primary completion
Apr 30, 2028
Completion
Apr 30, 2030

Study Design

Enrollment
55 participants (estimated)
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT

Arms

  • Active Comparator: Triple Therapy (MMF + Prednisolone + Voclosporin)
    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.
  • Active Comparator: Dual Therapy (MMF + Prednisolone)
    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).
  • No Intervention: SLE without LN control
    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.
  • No Intervention: Healthy control
    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.

Primary Outcome Measure

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 ]

Find similar trials

Nationwide
Lupus (SLE) trialsRheumatology trialsAutoimmune disease trials

Related Studies