Overview
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.
Eligibility
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
