Comparing treatments for lupus nephritis without added oral steroids

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

This study is testing whether a treatment for lupus nephritis using obinutuzumab and mycophenolate mofetil without steroids can work just as well as a treatment that includes steroids.

Quick facts

• Phase: Phase 3
• Study type: Interventional
• Enrollment: 196 (estimated)
• Ages: 14 Years and up
• Sex: All
• Sponsor: Assistance Publique - Hôpitaux de Paris (Academic / other)
• Drugs / interventions: obinutuzumab, belimumab, prednisone
• Locations: 1 site (Paris)
• Trial ID: NCT04702256 on ClinicalTrials.gov

What this trial studies

This phase III trial aims to compare the effectiveness of a treatment regimen for lupus nephritis that uses obinutuzumab and mycophenolate mofetil (MMF) without additional oral corticosteroids against a regimen that includes oral corticosteroids and MMF. The primary goal is to demonstrate that the steroid-free regimen is non-inferior in achieving complete renal response at 52 weeks. Secondary objectives include assessing partial renal responses, proteinuria levels, extrarenal flares, and safety outcomes related to corticosteroid use. The study will involve randomization of eligible patients across multiple centers, with assessments conducted at regular intervals over the course of the trial.

Who should consider this trial

Good fit: Ideal candidates include children aged 14-17 and adults with active lupus nephritis as confirmed by recent kidney biopsy.

Not a fit: Patients experiencing severe SLE flares or those unable to tolerate any corticosteroids may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could provide a safer treatment option for lupus nephritis patients by reducing reliance on corticosteroids.

How similar studies have performed: Preliminary data suggest that similar approaches using anti-CD20 monoclonal antibodies may be effective, but this specific regimen's efficacy needs confirmation.

Eligibility criteria

Inclusion Criteria:

* 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 Criteria:

* 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.

Where this trial is running

Paris

• Internal medicine, Cochin hospital, APHP — Paris, France (Recruiting)

Study contacts

• Principal investigator: Nathalie COSTEDOAT-CHALUMEAU, MD, PhD — Centre de référence maladies auto-immunes et systémiques rares, Internal medicine, Cochin hospital, APHP
• Study coordinator: Nathalie COSTEDOAT-CHALUMEAU, MD, PhD

Conditions Lupus Nephritis; Systemic Lupus Erythematosus; lupus nephritis; obinutuzumab; corticosteroids; non-inferiority