About this trial

Lupus nephritis (LN) is a frequent and severe complication of systemic lupus erythematosus, with important mortality and morbidity. International 2024 guidelines recommend immunosuppressive therapy (MMF, cyclophosphamide, calcineurin inhibitors, rituximab, azathioprine) in patients with heavy or uncontrolled proteinuria, but none of these therapies has been evaluated in robust multicenter prospective. Therefore, no treatment has regulatory approval for pure class V LN.

Obinutuzumab, a 2nd-generation B-cell targeting therapy, is more efficient than rituximab in inducing B-cell depletion and complete renal response in patient with class III or IV lupus nephritis.

This study aims to assess the efficacy and safety of an obinutuzumab monotherapy in patients with pure class V LN. The primary endpoint is complete renal response at week 52 according to 2024 KDIGO criteria (UPCR \< 0.5 g/g, eGFR ≥ 85% of baseline, and no intercurrent event: treatment failure, rescue therapy, long-term dialysis, renal transplantation, death or early trial withdrawal)

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Diagnosis of SLE fulfilling the 2019 EULAR/ACR classification criteria (score > 10)

Age from 18 to 75 years old included

Pure class V lupus nephritis, defined on a renal biopsy sample following the ISN/RPS 2003 criteria AND

Nephrotic range proteinuria (UPCr or UACr > 3 g/g) at screening visit OR

Disqualifiers

Ongoing treatment (induction or maintenance) for proliferative LN (class III-A or IV-A)

Negativity for anti-nuclear antibodies (< 1/80) on immunofluorescence assay

Severe extra-renal (i.e but not limited to : cardiac, central nervous system, pulmonary, enteric) lupus flare requiring high dose (> 1 mg/kg/day) corticosteroids.

Any anti-CD20 therapy such as rituximab, ocrelizumab, or ofatumumab less than 6 months prior to screening or during screening. If an anti-CD20 therapy has been received between 6 and 12 months prior to screening, the peripheral CD19+ B-cell count by flow cytometry must be > 25 cells/µL

Trial design

Design model

Single group

Treatments tested in this trial

Obinutuzumab
Drug
Obinutuzumab, 1000 mg, solution for dilution for infusion, 2 infusions spaced 15 days apart (day 1, day 15) +/- two additional 1000 mg infusions at week 24 and week 26 in patients with no kidney response at week 24, slow intravenous infusion, maximum 4 injections in 7 months

Treatment groups

65 Participants

are divided into 1 treatment group

Group A: pure class V lupus nephritis in adult patientsExperimental treatment 1 intervention

Trial outcomes

Primary outcomes

1

To assess, in patients with pure class V lupus nephritis, the efficacy of obinutuzumab to reach complete renal response as defined by 2024 international KDIGO guidelines, 52 weeks after the first obinutuzumab infusion.

The primary endpoint is therapeutic success at Week 52 (W52) after the first obinutuzumab infusion, defined as: Complete Renal Response (CRR) of pure class V LN, as defined by the international KDIGO 2024 guidelines, as follows: * Urine Protein-to-Creatinine Ratio (UPCR) \< 0.5 g/g measured from a 24-hour urine collection AND * An eGFR ≥ 85% of the baseline value (assessed using the 2021 CKD-EPI creatinine equation), with baseline defined as the last non-missing value prior to receipt of the first obinutuzumab infusion. AND o No intercurrent event, including: * Use of rescue therapy (i.e., another immunosuppressive agent used to achieve remission, including: mycophenolate mofetil, cyclophosphamide, tacrolimus, cyclosporine, or azathioprine) or high-dose corticosteroids (\> 1 mg/kg/day of prednisone equivalent) OR * Occurrence of end-stage renal disease (CKD-EPI 2021 eGFR \< 15 mL/min/1.73 m², long-term dialysis, or pre-emptive kidney transplantation) OR * Death from any cause

Time frame

week 52 (week 48 to week 56) after the first infusion of obinutuzumab.

Secondary outcomes

1

To assess the safety of obinutuzumab in patients with pure class V lupus nephritis by quantifying adverse events, serious adverse events, and adverse events of special interest between the first obinutuzumab infusion and W52

collection, analysis and quantification of adverse events according to the CTCAE v5.0

Time frame

first obinutuzumab infusion to week 52 (week 48 to week 56)

2

To assess the overall efficacy of obinutuzumab on pure class V lupus nephritis by quantifying the proportion of patient with no-kidney response, partial response (PRR), complete response (CRR) and renal relapses without any intercurrent event

* Proportion of patients with complete renal response (urinary protein creatinine ratio \< 0.5 g/g on 24-hour urine collection, eGFR ≥ 85% of baseline, and absence of intercurrent events * Proportion of patients with partial renal response (decrease of UPCR \> 50% and an UPCR of \< 3 g/g measured from a 24-h urine collection * Proportion of patient with no kidney response (reaching none of the above response) * Renal relapses definition * After reaching PRR or CRR * Increase of urine protein/creatinine ratio (UPCR) \> 50% and increase of \> 1 g/g measured from a 24-h urine collection * On two consecutive urine samples spaced by an interval of at least 1 month * Identified at any time 3 months after the first obinutuzumab infusion onward and before primary endpoint assessment

Time frame

first obinutuzumab infusion to week 52 (week 48 to week 56)

3

To assess the efficacy of obinutuzumab on overall SLE activity by quantifying the proportion of patients reaching immunologic remission (normalization C3 and C4 levels and negativation of anti-dsDNA) and the number of renal and extrarenal flares during f

Proportion of patients with negativation of anti-dsDNA and normalization of complement C3 and C4 according to local laboratory limits. o Unit: Percentage of participants (%)

Time frame

First obinutuzumab infusion to week 52 (week 48 to week 56)

4

To assess the efficacy of obinutuzumab on overall SLE activity by quantifying the proportion of patients reaching immunologic remission (normalization C3 and C4 levels and negativation of anti-dsDNA) and the number of renal and extrarenal flares during f

Disease activity assessed using the Safety of Estrogens in Lupus National Assessment-Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) * Unit: Score * Range: 0 to 105 * Interpretation: Higher scores indicate worse disease activity

Time frame

first obinutuzumab infusion to week 52 (week 48 to week 56)

Obinutuzumab for Systemic Lupus Erythematosus Pure Membranous Nephropathy: a Phase II Trial

About this trial

Eligibility criteria

Qualifiers

Disqualifiers

Trial design

Treatments tested in this trial

Treatment groups

Trial outcomes

Primary outcomes

Secondary outcomes

Other outcomes

Sponsors and contacts