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

Inclusion Criteria: 1. Diagnosis of SLE fulfilling the 2019 EULAR/ACR classification criteria (score \> 10) 2. Age from 18 to 75 years old included 3. 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 * Uncontrolled proteinuria after at least 3 months of well-conducted anti-proteinuric therapy \[UPCR\> 1 g/g despite maximal or maximally tolerated dose of ACEi or ARB + SGLT2i therapy +/- diuretic therapy\] and up to 12 months after pure class V lupus nephritis diagnosis. 4. For women of childbearing age, agreement to remain abstinent (refrain from heterosexual intercourse) or willingness to use appropriate and effective contraception, as recommended when using obinutuzumab (18 months after last infusion) 5. Signature of informed consent 6. French social security affiliation (beneficiary or legal) 7. Time interval between kidney biopsy showing pure class V LN and baseline visit of no more than 12 months Exclusion Criteria: 1. Ongoing treatment (induction or maintenance) for proliferative LN (class III-A or IV-A) 2. Negativity for anti-nuclear antibodies (\< 1/80) on immunofluorescence assay 3. 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. 4. Receipt of any of the following excluded therapies: * 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 * Cyclophosphamide, tacrolimus, ciclosporin, mycophenolate mofetil, pulse methylprednisolone or voclosporin during the 2 months prior to screening or during screening. Patients maintained on low-dose corticosteroids (\