Personalized Rituximab Treatment Based on Artificial Intelligence in Membranous Nephropathy (iRITUX)

NCT06341205 | Recruiting Phase 3

• 1 other identifier: 22-APN-01
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 13

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.

Conditions

Membranous Nephropathy

Outcome Measures

Primary Outcomes (1)

• Clinical remission (complete or partial) after 6 months of rituximab initiation

  Clinical remission (complete or partial) according to KDIGO and French guidelines: * Complete: urine protein/creatinine ratio (UPCR) \<0.3 g/g and serum albumin\>30 g/L and Glomerular Filtration Rate (estimated by CKD-EPI formula) \>60 ml/min/1.73m2 * Partial: UPCR \<3.5 g/g with a decrease \>50% from baseline (i.e., at first rituximab infusion) and serum albumin improvement or normalization and stable serum creatinine (or increase \<30%).

  6 months

Secondary Outcomes (13)

• Complete clinical remission after 12 months of rituximab initiation

  12 months

• Partial clinical remission after 12 months of rituximab initiation

  12 months

• Immunological remission: anti-PLA2R1 depletion

  12 months

• Change in urine protein/creatinine ratio (UPCR)

  12 months

• Change in serum creatinine

  12 months

Study Arms (2)

Standard-of-care

ACTIVE COMPARATOR

rituximab treatment 1gram x 2 (day-0, day-15)

Drug: RiTUXimab Injection

Personalised treatment

EXPERIMENTAL

personalized treatment based on the algorithm for assessing the risk of having undetectable rituximab level after 3 months: * Patients with a risk between 0 and 50% will receive 1gram x2 (day-0, day-15) * Patients with a risk between 51 and 75% will receive 1gram x 3 (day-0, day-15, day-30) * Patients with a risk between 76 and 100% will receive 1gram x 4 (day-0, day-15, day-30, day-45)

Drug: RiTUXimab Injection

Interventions

RiTUXimab Injection DRUG

Dose administered will depend on randomisation and for experimental Arm on the risk of having undetectable rituximab level after 3 months

Personalised treatment; Standard-of-care

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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%)

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Centre Hospitalier Universitaire de Nice: lead

Study Sites (13)

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

Related Publications (1)

• Teisseyre M, Destere A, Cremoni M, Zorzi K, Brglez V, Benito S, Bailly L, Fernandez C, Seitz-Polski B. Artificial intelligence-based personalised rituximab treatment protocol in membranous nephropathy (iRITUX): protocol for a multicentre randomised control trial. BMJ Open. 2025 Apr 2;15(4):e093920. doi: 10.1136/bmjopen-2024-093920.

  PMID: 40180405 DERIVED

MeSH Terms

Conditions

Glomerulonephritis, Membranous

Interventions

Rituximab

Condition Hierarchy (Ancestors)

Glomerulonephritis; Nephritis; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Central Study Contacts

Barbara SEITZ-POLSKI, MD, PhD

CONTACT

+33492038828; seitz-polski.b@chu-nice.fr

Céline FERNANDEZ

CONTACT

+33492038828; fernandez.c3@chu-nice.fr

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 27, 2024
• First Posted: April 2, 2024
• Study Start: February 4, 2025
• Primary Completion (Estimated): August 31, 2031
• Study Completion (Estimated): September 30, 2031
• Last Updated: September 11, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

FR (13)