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

Ki vehet részt

• 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; 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
• 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)
• Signature of informed consent
• French social security affiliation (beneficiary or legal)
• Time interval between kidney biopsy showing pure class V LN and baseline visit of no more than 12 months

Ki nem vehet részt

• Negativity for anti-nuclear antibodies (< 1/80) on immunofluorescence assay
• Patients with a previously documented kidney disease causing proteinuria (> 3 g/g or > 3 g/day) more than 1 year prior to the diagnosis of pure class V LN
• 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
• Contraindication to the use of obinutuzumab, its premedication drugs or hypersensitivity to its excipients
• 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 (<10 mg/day prednisone equivalent) for a prolonged period as part of the management of a previous and resolved flare are eligible for trial participation; Any biologic therapy (other than anti-CD20) such as, but not limited to, belimumab, ustekinumab, anifrolumab, secukinumab, or atacicept during the 2 months prior to screening or during screening; Oral inhibitors of Janus-associated kinase (JAK), Bruton's tyrosine kinase (BTK), or tyrosine kinase 2 (TYK2), including baricitinib, tofacitinib, upadacitinib, filgotinib, ibrutinib, or fenebrutinib or any investigational agent during the 2 months prior to screening or during screening; Any live vaccine during the 28 days prior to screening or during screening
• CKD stage 4 or 5, defined as eGFR <30 ml/min/1.73m2 according to CKD-EPI creatinine equation measured two times in an interval of 3 months (to be dissociated from acute kidney injury)
• Exclusion of primary membranous nephropathy, defined by positive anti-PLA2R antibodies on serum and/or glomerular PLA2R staining on kidney biopsy
• Ongoing treatment (induction or maintenance) for proliferative LN (class III-A or IV-A)
• Fewer than 10 non-sclerosed glomeruli analyzable on renal biopsy
• Ongoing pregnancy or breastfeeding women
• Obsolescence of more than 60% of glomeruli or tubulo-interstitial scarring of more than 60% on kidney biopsy
• Patients already included in an interventional study (RIPH1, clinical investigation or clinical trial)
• Patient under legal protection measure (tutorship or curatorship) and patient deprived of freedom