Macrophage and monocyte presence in lupus nephritis before and during treatment

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Amsterdam UMC Stichting

Participant type

Pediatric, Healthy volunteers, Patients

Age range

0-17 years, 18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

Trial duration

23 Apr 2026 → ongoing

Decision date (initial)

2025-12-15

Transition trial

No

Low-intervention

Yes

Rare-disease indication

Yes

Vulnerable population

No

Funding sources

Amsterdam UMC

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

Aim 1: Understanding early immunological changes in LN patients (class III/IV+/-V) on a cellular and histopathological level, comparing the CNI voclosporin on top of MMF and prednisolone (triple therapy) to MMF and prednisolone (dual therapy).
- Objective 1: determine differences in macrophage clusters in kidney tissue per treatment arm
- Objective 2: assess histological response of the addition of intensified treatment (addition of voclosporin)
compared to MMF+prednisolone
- Objective 3: assess if early histological response is associated with clinical remission after two years and
identify innovative early response determinants (including circulating monocyte phenotyping)

Secondary objectives 2

1. Assess phenotype of circulating monocytes in LN patients compared to SLE patients and healthy subjects, to be associated with clinical, biochemical parameters and scRNA-seq data - Objective 4: identify differences between LN, SLE and healthy subjects in peripheral monocyte phenotype, to be associated with scRNAseq data and clinical/biochemical/histological parameters
2. Identify potential biomarkers of disease activity in the scRNA-seq data to validate in urine and/or serum - Objective 5: attempt to render kidney biopsy in LN obsolete by identifying serum and/or urinary biomarkers

Conditions and MedDRA coding

Lupus Nephritis

Regulatory references

Plan to share IPD

Yes

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 3

1. Lupus nephritis patients: 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. eGFR as measured by cystatin C must be >20 mL/min.
2. SLE patients (disease control group): Diagnosis of SLE according to EULAR/ACR guidelines. Age 16-70.
3. Healthy subjects (control group): blank medical history. Age 16-70. A majority (75%) of female healthy subjects wil be sought.

Exclusion criteria 3

1. Lupus nephritis patients: LN class I, II or pure class V upon kidney biopsy (in the case of a class I, II or pure V, the patient will be asked consent for analysis of the scRNA-seq data from the kidney biopsy but the patient will not be randomized); eGFR as measured by cystatin C <20 mL/min; Histological chronicity score (NIH) of 8 or higher in the baseline 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; Pregnancy; 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 hypertension)*; Co-administration of voclosporin with strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, clarithromycin)
2. SLE patients (disease control group): Suspicion of LN; Signs of active infection
3. Healthy subjects (control group): signs of active infection

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Objective 1a: to determine scRNA-seq 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

Secondary endpoints 7

1. Objective 2a. numerically distinguish residential macrophages and monocyte-derived macrophages in kidney tissue with spatial scRNAseq, comparing arm 1 vs arm 2;
2. Objective 2b: to assess histological response of intensified treatment (arm 1) compared to SOC (arm 2);
3. Objective 3: to assess if early histological response is associated with clinical remission after two years and identify innovative early response determinants (including tissue monocyte/macrophage phenotyping)
4. Objective 4: to identify differences between LN, SLE and healthy subjects in peripheral monocyte phenotype by using bulk RNA sequencing and flowcytometric analyses, to be associated with scRNAseq data and clinical/biochemical parameters. 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
5. Objective 5: attempt to render (repeat) kidney biopsy in LN obsolete by identifying reliable serum and/or urinary biomarkers that reflect tissue damage and treatment response;
6. Objective 6: confirm scRNA-seq identified macrophage markers immunohistochemically, identify spatial distribution (glomerular vs interstitial) and assess their predictive and prognostic use.
7. Objective 1b: analyze rapid clinical remission of intensified treatment by proteinuria levels

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Amsterdam UMC Stichting

Sponsor organisation

Amsterdam UMC Stichting

Address

De Boelelaan 1117

City

Amsterdam

Postcode

1081 HV

Country

Netherlands

Scientific contact point

Organisation

Amsterdam UMC Stichting

Contact name

M.L. Hilhorst

Public contact point

Organisation

Amsterdam UMC Stichting

Contact name

M.L. Hilhorst

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 11 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications