A Phase 2 interventional study of Obinutuzumab in Lupus Nephritis and Membranous Nephropathy, sponsored by Assistance Publique - Hôpitaux de Paris. Not yet recruiting at 1 site in France. Open to participants aged 18 Years to 75 Years. Per ClinicalTrials.gov, last updated 2026-07-23.
Sponsored by Assistance Publique - Hôpitaux de Paris · Phase 2, Interventional, and Treatment
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)
Lupus nephritis (LN) is a frequent manifestation of systemic lupus erythematosus and conveys important risk of morbidity and mortality in affected patients. Pure class V LN, also referred to as lupus membranous nephropathy, remains difficult to manage despite available therapy. Current immunosuppressive options proposed in the 2024 international recommendations include mycophenolate mofetil, cyclophosphamide, calcineurin inhibitors, rituximab or azathioprine in situations of uncontrolled or nephrotic proteinuria. However, none of these drugs has been validated through prospective multicenter protocol-based trials specifically dedicated to assess their efficacy and safety in pure class V LN. Therefore no therapy holds specific approval for this condition.
Observational data from multiple French centers highlight the heterogeneous therapeutic choices and variable response rates obtained with treatments. Although efficacy appears broadly similar across these strategies, concerns persist regarding infertility, teratogenicity, myelotoxicity and corticosteroid exposure, reinforcing the need for alternatives with improved tolerance. Rituximab is increasingly used to treat pure lupus membranous nephropathy but is less efficient than obinutuzumab in inducing complete renal response in class III or IV lupus nephritis.
Obinutuzumab is a second-generation therapy targeting B cells, developed to enhance activity compared with rituximab. Clinical studies conducted in follicular lymphoma and chronic lymphocytic leukemia demonstrated superior outcomes and supported its approval. In LN, evaluations combining obinutuzumab with standard-of-care therapy in proliferative classes (NOBILITY and REGENCY trials) reported higher complete renal response than placebo with acceptable safety, although events such as infections, serious adverse events, neutropenia and infusion-related reactions were documented. In contrast, a study using rituximab with standard-of-care therapy (LUNAR) did not show improvement in complete renal response.
Based on these findings, this phase 2 study evaluates obinutuzumab monotherapy in adults with pure class V LN. The main endpoint is complete renal response at week 52 after first infusion, defined by urinary protein creatinine ratio \< 0.5 g/g on 24-hour urine collection, eGFR ≥ 85% of baseline, and absence of intercurrent events including treatment failure, need for rescue therapy, high-dose corticosteroids, long-term dialysis, renal transplantation, death or premature withdrawal.
Secondary objectives include: assessment of safety by recording adverse events, serious adverse events and events of interest (neutropenia, infection, infusion-related events, new cancer) from first infusion to week 52; evaluation of renal outcomes documenting no kidney response, partial renal response, complete renal response and renal relapses free of intercurrent event; monitoring of systemic lupus erythematosus activity based on immunologic remission defined by C3 and C4 normalization and anti-dsDNA negativation, as well as renal and extrarenal flares; estimation of participants without corticosteroids at week 52; and evaluation of quality of life at week 52.
The trial uses a single-arm, open, non-comparative A'Hern phase II design (Category 2, Phase 2). This protocol aims to generate prospective data on the activity and safety of obinutuzumab monotherapy in pure class V LN, with precise definitions of renal response, systematic follow-up of adverse events and detailed assessment of systemic and renal outcomes over a 52-week period.
Pure class V lupus nephritis, defined on a renal biopsy sample following the ISN/RPS 2003 criteria AND
Exclusion Criteria:
Receipt of any of the following excluded therapies:
Drug: Obinutuzumab
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
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.
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)
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)
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)
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)
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
Assessed using the SELENA Flare Index (SFI) o Unit: Number of flares / categorical severity
Time frame: 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
Total cumulative number of SLE flares at Week 52 o Unit: Number of flares
Time frame: first obinutuzumab infusion to week 52 (week 48 to week 56)
To assess the proportion of patients that are free from corticosteroids at W52 with respect to corticosteroids indication (to treat lupus or another disease).
proportion of patient without any steroid prescription to treat SLE at week 52.
Time frame: week 52 (week 48 to week 56) after the first infusion of obinutuzumab.
To assess the quality of life of patients at W52
Health-related quality of life assessed using the EQ-5D-5L descriptive system. Utility index calculated using the French value set (Andrade et al., 2020). Range: -0.530 to 1.000; higher scores indicate better health-related quality of life. Unit: utility index score
Time frame: first obinutuzumab infusion to week 52 (week 48 to week 56)
To assess the quality of life of patients at W52
Self-rated overall health status assessed using the EQ-5D-5L Visual Analogue Scale. Range: 0 to 100; higher scores indicate better self-rated health. Unit: score on a scale (0-100)
Time frame: first obinutuzumab infusion to week 52 (week 48 to week 56)
To assess the quality of life of patients at W52
Quality of life assessed using the Lupus Quality of Life (LupusQoL) questionnaire (French version). * Unit of Measure : Score * Range: 0 to 100 * Interpretation: Higher scores indicate better quality of life
Time frame: first obinutuzumab infusion to week 52 (week 48 to week 56)
Plan to share: Undecided
No publications or documents are linked to this record.
This study is not yet recruiting, as verified in Jul 2026. You cannot join it, but the record below documents what was studied.
Get an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
Assistance Publique - Hôpitaux de Paris