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

Condition(s) studied

Investigational drug(s) / intervention(s)

Obinutuzumab 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.

Administration 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.

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

Study 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

Primary outcome measure(s)

• Complete renal response (CR) — at week 52
  CR at week 52 without receiving corticosteroids above a prespecified dose. CR at week 52 is defined as: * Urine PCR (protein to creatinine ratio) \< 0.5 g/g in a spot urine AND: * eGFR (estimated glomerular filtration rate using CKD-epi) ≥ 60 ml/min, or if \< 60 ml/min at screening, no decline \>20% compared to screening/randomisation (whichever worse) * AND: * In the obinutuzumab arm: with no steroids or without receiving oral corticosteroids \> 10 mg/day within the first 6 month, and then, without receiving oral corticosteroids \> 7.5 mg/day between 6 and 9 months and \> 5 mg/day between 9 and 12 months for SLE indication (according to the French PNDS for SLE after 6 months). * In the steroid arm: without receiving corticosteroids above the prescribed taper (according to the French PNDS for SLE, see Appendix A), including without receiving oral corticosteroids \> 7.5 mg/day between 6 and 9 months and \> 5 mg/day between 9 and 12 months for SLE indication (according to the French
• Proteinuria measurement — at baseline
  Proteinuria measurement: the proteinuria/creatinuria ratio will be assessed on a 24-hour urine collection.
• Proteinuria measurement — at week 52
  Proteinuria measurement: the proteinuria/creatinuria ratio will be assessed on a 24-hour urine collection.

Trial sites (1)

More Assistance Publique - Hôpitaux de Paris trials in France

Other trials for the same condition