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

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.

Conditions

• Lupus Nephritis
• Systemic Lupus Erythematosus (SLE)

Interventions

DRUG

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.

DRUG

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.

DRUG

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.

Sponsors & Collaborators

• Roche Pharma AG

  collaborator INDUSTRY

• Assistance Publique - Hôpitaux de Paris

  lead OTHER

Principal Investigators

• Nathalie COSTEDOAT-CHALUMEAU, MD, PhD · Centre de référence maladies auto-immunes et systémiques rares, Internal medicine, Cochin hospital, APHP

• Eric DAUGAS, MD, PhD · Nephrology department, Bichat Hospital, APHP, Paris

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

14 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2021-12-09

Primary Completion

2031-12-31

Completion

2031-12-31

Countries

• France

Study Locations