• Personalized Medicine for Membranous Nephropathy

  NCT03804359

  CompletedInterventionalPhase 2Updated Jul 25, 2025
• Evaluate Rituximab Treatment for Idiopathic Membranous Nephropathy

  NCT01508468

  CompletedInterventionalPhase 3Updated Oct 26, 2021
• Rituximab Versus Steroids and Cyclophosphamide in the Treatment of Idiopathic Membranous Nephropathy

  NCT03018535

  Unknown statusInterventionalPhase 3Updated May 20, 2019
• Rituximab in Membranous Nephropathy

  NCT00425217

  CompletedInterventionalPhase 2Phase 3Updated Feb 25, 2011
• Rituximab in the Treatment of Idiopathic Membranous Nephropathy

  NCT00405340

  CompletedInterventionalEarly Phase 1Updated Oct 27, 2015
• Circulating B-cell, Drug and Anti-drug Antibodies Monitoring in Patients Treated With Rituximab for Autoimmune Disorders

  NCT07037732

  RecruitingObservationalUpdated Jun 25, 2025

ClinicalTrials.gov ID

NCT06341205

Lead Sponsor

Centre Hospitalier Universitaire de NiceOTHER

Overall Status

Recruiting

Study Type

Interventional

Phase

Phase 3

Enrollment

120Estimated

Last Update Posted

Jun 22, 2026Actual

Start Date

Feb 4, 2025Actual

Primary Completion Date

Aug 31, 2031Estimated

Completion Date

Sep 30, 2031Estimated

Official Title

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

Brief Summary

Membranous nephropathy is an autoimmune disease affecting the kidney, and the most common cause of nephrotic syndrome in non-diabetic Caucasian adults. The course of this disease is highly variable from one individual to another, ranging from spontaneous remission to progressive chronic kidney disease.

The identification of autoantibodies - e.g., the phospholipase A2 receptor type 1 (PLA2R1) - has promoted the use of immunosuppressive drugs such as rituximab which is now a safe and effective first-line treatment for the management of membranous nephropathy. However, up to 40% of patients do not respond to a first course of rituximab treatment. In nephrotic patients, due to urinary drug loss, rituximab blood level is lower than in other autoimmune diseases treated with rituximab without proteinuria. This high urinary drug loss decreases the drug exposure, potentially explaining why rituximab regimen with low dose infusions (375 mg/m2) did not demonstrate efficacy after month-6 compared to a non-immunosuppressive antiproteinuric treatment in a previous study. In contrast, a regimen of two 1-g infusions two weeks apart was associated with a significantly greater remission rate after 6 months.

Recently, the investigators have shown that after two 1-g rituximab infusions, the rituximab blood level 3 months after the first rituximab infusion, was correlated with the likelihood of remission after 6 and 12 months of the rituximab treatment. Patients with positive rituximab blood level 3 months after treatment had a higher chance of remission at month-6 and at month-12 than patients with an undetectable rituximab level at month-3.

Nowadays, machine learning algorithms are increasingly used in medicine, especially in pharmacology, to predict the exposure to a drug, the initial dose to administer or the interval between two infusions.

The objective of this study is to use a machine learning algorithm predicting the risk of having an undetectable residual level of rituximab 3 months after treatment, in order to propose a personalized treatment management with early additional doses of rituximab for the patients at risk.

• Membranous Nephropathy

• RiTUXimab Injection

Ages Eligible for Study

Adult (18-64)Older Adult (65+)

Sexes Eligible for Study

All

Accepts Healthy Volunteers

No

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

Primary Purpose

Treatment

Allocation

Randomized

Interventional Model

Parallel Assignment

Masking

None (Open Label)

Lead Sponsor

Centre Hospitalier Universitaire de NiceOTHER

fernandez.c3@chu-nice.fr0492038828