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

NCT07721363 | Not Yet Recruiting Phase 2 DMC

• 2 other identifiers: APHP2409372024-519985-35-00
• Study Type: interventional
• Target: 65
• Locations: 1 country
• Sites: 1

Brief Summary

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)

Conditions

Lupus Nephritis; Membranous Nephropathy

Keywords

Class V lupus nephritis; Pure lupus membranous nephropathy; Systemic lupus erythematosus; Membranous nephropathy; Obinutuzumab; B-cell targeted therapy

Outcome Measures

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

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

Secondary Outcomes (10)

• 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

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

• 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

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

• 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

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

• 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

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

• 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

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

Study Arms (1)

pure class V lupus nephritis in adult patients

EXPERIMENTAL

Drug: Obinutuzumab

Interventions

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

Also known as: GAZYVARO

pure class V lupus nephritis in adult patients

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.
• 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
• Contraindication to the use of obinutuzumab, its premedication drugs or hypersensitivity to its excipients.
• Fewer than 10 non-sclerosed glomeruli analyzable on renal biopsy
• Ongoing pregnancy or breastfeeding women
• 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).
• 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)

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead
• Roche-Genentech: collaborator

Study Sites (1)

Sorbonne University - Nephrology Départment - Tenon APHP

Paris, France, 75012, France

Location

MeSH Terms

Conditions

Lupus Nephritis; Glomerulonephritis, Membranous; Lupus Erythematosus, Systemic

Interventions

obinutuzumab

Condition Hierarchy (Ancestors)

Glomerulonephritis; Nephritis; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Study Officials

• Romain Brousse, Dr

  Assistance Publique - Hôpitaux de Paris

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Romain Brousse, Dr

CONTACT

+33 1 56 01 70 43; romain.brousse@aphp.fr

Jean-Jacques BOFFA, Pr

CONTACT

+33 1 56 01 69 99; jean-jacques.boffa@aphp.fr

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 10, 2026
• First Posted: July 23, 2026
• Study Start (Estimated): September 2, 2026
• Primary Completion (Estimated): September 2, 2029
• Study Completion (Estimated): September 2, 2029
• Last Updated: July 23, 2026

Record last verified: 2026-07

Locations

FR (1)