RecruitingPhase 3NCT04702256

Induction Therapy for Lupus Nephritis With no Added Oral Steroids: A Trial Comparing Oral Corticosteroids Plus Mycophenolate Mofetil (MMF) Versus Obinutuzumab and MMF

Induction Therapy for Lupus Nephritis With no Added Oral Steroids: An Open Label Randomised Multicentre Controlled Trial Comparing Oral Corticosteroids Plus Mycophenolate Mofetil (MMF) Versus Obinutuzumab and MMF

Sponsor

Assistance Publique - Hôpitaux de Paris

Enrollment

196 participants

Start Date

Dec 9, 2021

Study Type

INTERVENTIONAL

Conditions

Systemic Lupus Erythematosus (SLE)Lupus Nephritis

Summary

This is a randomised, open label, controlled non-inferiority phase III multicentre trial. As primary objective, the study aims to demonstrate that a regimen free of additional oral corticosteroids but with obinutuzumab (and MMF) is non-inferior to a regimen based on oral corticosteroids and MMF in achieving the primary outcome of complete renal response at week 52 without receiving corticosteroids above a prespecified dose. As secondary objectives, the study aims: * To compare the efficacy of the treatments in both arms in terms of: * partial plus complete renal response at week 52; * proteinuria \< 0.8g/g at week 52; * extrarenal flares; * response as defined by a \>4 points reduction in SELENA-SLEDAI score at week 52. * To compare the safety of the treatments in both arms in terms of occurrence of: * toxicity of corticosteroids; * serious Adverse Events; * serious Infectious Episodes; * new damage. * To compare the number of patients with non-adherence to treatment in both arms. * To estimate the efficiency of obinutuzumab in this indication. The ancillary studies will allow: * To implement a biobank (serum, plasma, DNA, cells and urine) and a bank of renal biopsies for studies that will be part of separate research funding bids (patients will be informed that their samples and data may be used for subsequent studies and offered to consent or not). * To identify which target therapeutic levels of MMF best predicts response with least toxicity (ancillary study). * To have long term data on renal function and damage.

Eligibility

Min Age: 14 Years

Inclusion Criteria6

Children aged 14-17 years old and adults;
Active lupus nephritis, as defined by kidney biopsy within the preceding 8 weeks, assessed by the International Society of Nephrology/Renal Pathology Society (ISN/RPS) classification: class III or IV (A or A/C) ± V with active lesions in at least 10% of the viable glomeruli;
Urine protein-to-creatinine ratio (uPCR) ≥ 0.5 g/g at any time in the 14 days before inclusion;
No contraindications to the use of IV methylprednisolone, MMF, oral corticosteroids or obinutuzumab;
Ability to provide informed consent;
Willingness to use appropriate contraception, as recommended when using MMF.

Exclusion Criteria9

Severe "critical" SLE flare defined as any SLE manifestation requiring more immunosuppression than allowed in the protocol, in the physician's opinion;
Patients who cannot be prescribed 10 mg prednisone corticosteroids "only", after inclusion according to the physician's opinion;
Pregnant and breastfeeding woman;
Prior use within 6 months of inclusion of therapeutic monoclonal antibody and/or B- or T cell modulating 'biologic' except belimumab that can be used up to 7 days before inclusion;
Obsolescence of >60% of the glomeruli or tubulointerstitial scarring of >60%;
CKD stage 4 or stage 5 defined as eGFR <30 ml/min/1.73 m2 according to CKD-EPI (to be differentiated from acute renal injury);
Active infections, including but not limited to human immunodeficiency virus (HIV), hepatitis B in the absence of a specific therapy, hepatitis C or tuberculosis;
Receipt of a live-attenuated vaccine in the 4 weeks prior to study enrolment;
History of cervical dysplasia CIN Grade III, cervical high-risk human papillomavirus or abnormal cervical cytology other than abnormal squamous cells of undetermined significance (ASCUS) in the past 3 years in female patients. However, the patient will be eligible in the following conditions: follow-up HPV test is negative or cervical abnormality was effectively treated >1 year ago.

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Interventions

DRUGObinutuzumab administration

Obinutuzumab administration by intravenous infusion (IV), IV of methylprednisolone, oral mycophenolate mofetil, no prednisone (or if required for extrarenal manifestation(s): less than 10mg/day at any time, less than 7.5mg/day after 6 months and less than 5mg/day after 9 months). Hydroxychloroquine will be strongly recommended for all the patients.

DRUGAdministration of Methylprednisolone + Prednisone + Mycophenolate mofetil

IV of methylprednisolone, oral prednisone (according to the PNDS), and oral mycophenolate mofetil. Hydroxychloroquine will be strongly recommended for all the patients.

DRUGAdministration of methylprednisolone, paracetamol and dexchlorpheniramine

Prior to infusion of obinutuzumab, patients receiving obinutuzumab will receive premedication including 100 mg of methylprednisolone, paracetamol and dexchlorpheniramine.