AI-guided personalized rituximab for membranous nephropathy

Study of Artificial Intelligence-based Personalized Rituximab Treatment Protocol in Membranous Nephropathy

This trial will test whether an AI-guided approach to dosing rituximab improves remission in adults with PLA2R1-positive nephrotic membranous nephropathy.

Quick facts

• Phase: PHASE3
• Study type: Interventional
• Enrollment: 120 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Centre Hospitalier Universitaire de Nice (other)
• Drugs / interventions: rituximab
• Locations: 13 sites (Besançon and 12 other locations)
• Trial ID: NCT06341205 on ClinicalTrials.gov

What this trial studies

This Phase 3 interventional trial uses an artificial intelligence model to personalize rituximab dosing for adults with PLA2R1-positive membranous nephropathy and nephrotic syndrome. Participants receive rituximab injections guided by the AI algorithm, with clinical and laboratory follow-up to monitor antibody levels, proteinuria, and kidney function. The trial tracks treatment response and safety over predefined time points to determine whether personalized dosing reduces nonresponse linked to urinary drug loss. The study is conducted at multiple French university hospitals.

Who should consider this trial

Good fit: Adults (≥18) with PLA2R1-associated membranous nephropathy, nephrotic-range proteinuria (>3.5 g/24h) with low serum albumin, eGFR >30 mL/min/1.73 m2, and on stable antiproteinuric therapy who are candidates for rituximab are ideal.

Not a fit: Patients with secondary membranous nephropathy, PLA2R1-negative disease, severe renal impairment (eGFR ≤30 mL/min/1.73 m2), or contraindications to rituximab are unlikely to benefit from this protocol.

Why it matters

Potential benefit: If successful, this approach could increase the number of patients achieving remission by improving rituximab exposure and reducing ineffective under-dosing.

How similar studies have performed: Rituximab is an established first-line therapy for PLA2R1-positive membranous nephropathy but up to 40% of patients do not respond to standard dosing, and AI-based personalization is a novel approach not yet validated in large trials.

Eligibility criteria

Inclusion Criteria:

* Age ≥ 18 years
* Ongoing episode of membranous nephropathy diagnosed by the presence of anti-PLA2R1 antibodies detected by ELISA (≥ 14 RU/ml, EUROIMMUN): the result must be validated by the Coordination team before randomization.
* Nephrotic syndrome defined by proteinuria \> 3.5 g/24h (or UPCR \> 3.5 g/g) and serum albumin \< 30 g/L at diagnosis
* Estimated Glomerular Filtration Rate (CKD-EPI formula) \> 30 mL/min/1,73 m2
* Indication for rituximab treatment according to the KDIGO and French guidelines
* Non-immunosuppressive antiproteinuric treatment at stable dose for 2 weeks according to French guidelines, including a renin angiotensin aldosterone system inhibitor, a diuretic and a low-salt diet at maximal tolerated dose (i.e., absence of orthostatic hypotension and no increase in creatinine \> 30%)

Exclusion Criteria:

* Secondary Membranous nephropathy related to cancer, infection, systemic lupus, drug
* Diagnosis of PLA2R1-associated Membranous nephropathy not confirmed by the Coordination team (validation mandatory for randomization)
* Pregnancy or breastfeeding
* Immunosuppressive treatment (including rituximab) in the 6 months preceding inclusion
* Presence of anti-rituximab antibodies detected by Central Lab
* Cancer under treatment
* Patients with active, severe infections
* Hypersensitivity to the active substance or excipients
* Patients severely immunocompromised
* Severe heart failure or severe, uncontrolled cardiac disease

Where this trial is running

Besançon and 12 other locations

• CHU de BESANCON — Besançon, France (RECRUITING)
• CHU de BORDEAUX - Hôpital Pellegrin — Bordeaux, France (RECRUITING)
• CHU de CAEN — Caen, France (RECRUITING)
• AP-HP - Hôpital H. Mondor — Créteil, France (RECRUITING)
• HCL - Hôpital E. Herriot — Lyon, France (RECRUITING)
• AP-HM - Hôpital de la Conception — Marseille, France (RECRUITING)
• CHU de NICE — Nice, France (RECRUITING)
• CHU de Nîmes - Hôpital CAREMEAU — Nîmes, France (RECRUITING)
• AP-HP - Hôpital Européen Georges Pompidou — Paris, France (NOT_YET_RECRUITING)
• AP-HP - Hôpital Necker — Paris, France (NOT_YET_RECRUITING)
• CHU de TOULOUSE - Hôpital Rangueil — Toulouse, France (RECRUITING)
• CHRU de TOURS - Hôpital Bretonneau — Tours, France (RECRUITING)
• CH de Valenciennes — Valenciennes, France (NOT_YET_RECRUITING)

Study contacts

• Study coordinator: Barbara SEITZ-POLSKI, MD, PhD

Conditions: Membranous Nephropathy