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NCT Number: NCT06341205

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

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.

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Key information

Conditions

Membranous Nephropathy Autoimmune Diseases Female Urogenital Diseases Female Urogenital Diseases and Pregnancy Complications Glomerulonephritis Glomerulonephritis, Membranous Immune System Diseases Kidney Diseases Male Urogenital Diseases Nephritis Urogenital Diseases Urologic Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

CHU de BESANCON, Besançon, France

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

RiTUXimab Injection

Drug

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

Primary outcomes

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

    Time frame: 6 months

    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%).

Secondary outcomes

  1. Complete clinical remission after 12 months of rituximab initiation

    Time frame: 12 months

    Complete remission: 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

  2. Partial clinical remission after 12 months of rituximab initiation

    Time frame: 12 months

    Partial remission: 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%).

  3. Immunological remission: anti-PLA2R1 depletion

    Time frame: 12 months

    Immunological remission: anti-PLA2R1 depletion (i.e., PLA2R1 titer < 14 RU/mL by ELISA method) at month-3, month-6 and month-12

  4. Change in urine protein/creatinine ratio (UPCR)

    Time frame: 12 months

    Percentage of change in urine albumin/creatinine ratio (mg/g) from day-0 to month-3, month-6, month-9, month-12

  5. Change in serum creatinine

    Time frame: 12 months

    Percentage of change in serum creatinine (μmol/L) from day-0 to month-3, month-6, month-9, month-12

  6. Change in renal function

    Time frame: 12 months

    Percentage of change in Glomerular Filtration Rate estimated by CKD-EPI formula (mL/min/1.73m²) from day-0 to month-3, month-6, month-9, month-12

  7. Change in the immunological status of the disease

    Time frame: 12 months

    Percentage of change in anti-PLA2R1 titer (RU/mL) by ELISA (EUROIMMUN Kit) from day-0 to month-3, month-6, month-9, month-12

  8. Appearance of anti-drug antibodies after rituximab treatment

    Time frame: 12 months

    Serum anti-rituximab antibodies (ng/mL) at month-3, month-6, month-9, month-12

  9. Rituximab underdosed patients

    Time frame: 3 months

    Percentage of patients with serum rituximab (μg/mL) >2 μg/mL 3 months after the last infusion

  10. Serious adverse events

    Time frame: 84 months

    Occurence of Serious adverse events reported

  11. Adaptation of symptomatic treatment

    Time frame: 84 months

    Number of dose modification of non-immunosuppressive anti-proteinuric treatment during study follow-up

  12. Model improvement through machine learning

    Time frame: 6 months

    serum creatinine and serum albumin levels, weight, anti-PLA2R1 and rituximab level will be combined to report the risk of having undetectable rituximab level after 3 months (in %) at day-0, day-15, day-30, day-45, month-3, month-6

  13. Effect of rituximab on immune profiles

    Time frame: 6 months

    Cytokine levels in pg/mL (IFN-γ, IFN-α, IL-12p70, IL-17A, IL-4, IL-5, IL-10, IL-1, IL-6) at day-0 and month-6

Study contacts

Contact information is provided by the study sponsor or research team.

Barbara SEITZ-POLSKI, MD, PhD

CONTACT

[email protected]

+33492038828

Céline FERNANDEZ

CONTACT

[email protected]

+33492038828

Sponsors and collaborators

Lead sponsor

Centre Hospitalier Universitaire de Nice

Other

Registry information

Official study title

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

Acronym: iRITUX

Important dates

Study start
2025
Primary completion
2031
Study completion
2031
First posted
Apr 2, 2024
Registry last updated
Jun 22, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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