Membranous NephropathyPhase 3iRITUXNCT06341205
Personalized Rituximab Treatment Based on Artificial Intelligence in Membranous Nephropathy (iRITUX)
A Phase 3 study testing RiTUXimab Injection in people with Membranous Nephropathy, run by Centre Hospitalier Universitaire de Nice at 14 sites in France.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Membranous Nephropathy
- What is being tested?
- RiTUXimab Injection
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 120 participants
- Where
- 14 sitesFrance
- Study dates
- 4 Feb 2025to 30 Sep 2031
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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%)
Who cannot join
- 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
Show all 10Show fewer
- Patients with active, severe infections
- Hypersensitivity to the active substance or excipients
- Patients severely immunocompromised
- Severe heart failure or severe, uncontrolled cardiac disease
Trial locations and contacts
14 sites in 1 country. Contact the study team or a site near you to ask about taking part.
14 sites in 1 country
France14 sites, 14 recruiting
- Recruiting
CHU de BESANCON
Besançon
Thomas CREPIN
- Recruiting
CHU de BORDEAUX - Hôpital Pellegrin
Bordeaux
Claire RIGOTHIER
- Recruiting
CHU de CAEN
Caen
Antoine LANOT
- Recruiting
AP-HP - Hôpital H. Mondor
Créteil
Vincent AUDARD
- Recruiting
HCL - Hôpital E. Herriot
Lyon
Fitsum GUEBRE-EGZIABHER
- Recruiting
AP-HM - Hôpital de la Conception
Marseille
Noémie JOURDE-CHICHE
- Recruiting
CHU de NICE
Nice
Céline FERNANDEZ, 0492038828, fernandez.c3@chu-nice.fr
Barbara SEITZ-POLSKI
- Recruiting
CHU de Nîmes - Hôpital CAREMEAU
Nîmes
Olivier MORANNE
- Recruiting
AP-HP - Hôpital Européen Georges Pompidou
Paris
Alexandre KARRAS
- Recruiting
AP-HP - Hôpital Necker
Paris
KNEBELMANN Bertrand
- Not yet recruiting
Hôpital Tenon
Paris
Jean-Jacques BOFFA, +331 56 01 60 29, jean-jacques.boffa@aphp.fr
- Recruiting
CHU de TOULOUSE - Hôpital Rangueil
Toulouse
Dominique CHAUVEAU
- Recruiting
CHRU de TOURS - Hôpital Bretonneau
Tours
Christelle BARBET
- Recruiting
CH de Valenciennes
Valenciennes
Claire CATERY
About this study
Official title: Study of Artificial Intelligence-based Personalized Rituximab Treatment Protocol in Membranous Nephropathy
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.
Read more
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
- Being tested
- RiTUXimab Injection
- Medical subject headings
- Glomerulonephritis, Membranous
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RiTUXimab InjectionDrug
Dose administered will depend on randomisation and for experimental Arm on the risk of having undetectable rituximab level after 3 months
| Study group | Role | What they receive |
|---|---|---|
| Standard-of-care | Active comparator | rituximab treatment 1gram x 2 (day-0, day-15) Receives: 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) Receives: Drug: RiTUXimab Injection |
What is being measured
The primary outcome is the main question the study is designed to answer.
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%).
Measured: 6 months
Secondary outcomes (13)
Complete clinical remission after 12 months of rituximab initiation
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
Measured: 12 months
Partial clinical remission after 12 months of rituximab initiation
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%).
Measured: 12 months
Immunological remission: anti-PLA2R1 depletion
Immunological remission: anti-PLA2R1 depletion (i.e., PLA2R1 titer < 14 RU/mL by ELISA method) at month-3, month-6 and month-12
Measured: 12 months
Change in urine protein/creatinine ratio (UPCR)
Percentage of change in urine albumin/creatinine ratio (mg/g) from day-0 to month-3, month-6, month-9, month-12
Measured: 12 months
Change in serum creatinine
Percentage of change in serum creatinine (μmol/L) from day-0 to month-3, month-6, month-9, month-12
Measured: 12 months
Change in renal function
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
Measured: 12 months
Change in the immunological status of the disease
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
Measured: 12 months
Appearance of anti-drug antibodies after rituximab treatment
Serum anti-rituximab antibodies (ng/mL) at month-3, month-6, month-9, month-12
Measured: 12 months
Rituximab underdosed patients
Percentage of patients with serum rituximab (μg/mL) >2 μg/mL 3 months after the last infusion
Measured: 3 months
Serious adverse events
Occurence of Serious adverse events reported
Measured: 84 months
Adaptation of symptomatic treatment
Number of dose modification of non-immunosuppressive anti-proteinuric treatment during study follow-up
Measured: 84 months
Model improvement through machine learning
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
Measured: 6 months
Effect of rituximab on immune profiles
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
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Apr 2024
- Study start4 Feb 2025
- Primary completion31 Aug 2031 (estimated)
- Study completion30 Sep 2031 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Membranous NephropathyStudies of the same condition, open and under way.
- More trials run by Centre Hospitalier Universitaire de NiceThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 120 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Centre Hospitalier Universitaire de Nice
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06341205
- Sponsor's protocol ID
- 22-APN-01
- Acronym
- iRITUX
- Status last verified
- Jun 2026
- First submitted
- 27 Feb 2024
- Last updated
- 22 Jun 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: not planed
Publications
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.
PubMed 40180405
Study at a glance
From the registry record, last updated by the sponsor on 22 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Study of Artificial Intelligence-based Personalized Rituximab Treatment Protocol in Membranous Nephropathy
- ClinicalTrials.gov ID
- NCT06341205
- Acronym / sponsor ID
- iRITUX / 22-APN-01
- Conditions
- Membranous Nephropathy
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 120 participants (estimated)
- Lead sponsor
- Centre Hospitalier Universitaire de NiceUniversity, hospital or other
- Study start
- 4 Feb 2025 (actual)
- Primary completion
- 31 Aug 2031 (estimated)
- Study completion
- 30 Sep 2031 (estimated)
- First posted
- 2 Apr 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Standard-of-care | Active comparator | Drug: RiTUXimab Injectionrituximab treatment 1gram x 2 (day-0, day-15) |
| Personalised treatment | Experimental | Drug: RiTUXimab Injectionpersonalized 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) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (10 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RiTUXimab InjectionDose administered will depend on randomisation and for experimental Arm on the risk of having undetectable rituximab level after 3 months | Drug | Personalised treatment, Standard-of-care |
Primary outcome
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%).
13 secondary outcomes
Complete clinical remission after 12 months of rituximab initiation
Time frame: 12 months
Partial clinical remission after 12 months of rituximab initiation
Time frame: 12 months
Immunological remission: anti-PLA2R1 depletion
Time frame: 12 months
Change in urine protein/creatinine ratio (UPCR)
Time frame: 12 months
Change in serum creatinine
Time frame: 12 months
Change in renal function
Time frame: 12 months
Change in the immunological status of the disease
Time frame: 12 months
Appearance of anti-drug antibodies after rituximab treatment
Time frame: 12 months
Rituximab underdosed patients
Time frame: 3 months
Serious adverse events
Time frame: 84 months
Adaptation of symptomatic treatment
Time frame: 84 months
Model improvement through machine learning
Time frame: 6 months
Effect of rituximab on immune profiles
Time frame: 6 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Jun 2026.
- Derived from this study: PubMed 40180405Teisseyre 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.
- Individual participant dataSharing planned: No. not planed
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
14 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing RiTUXimab Injection in people with Membranous Nephropathy, run by Centre Hospitalier Universitaire de Nice at 14 sites in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 22 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 14 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Barbara SEITZ-POLSKI, MD, PhD (+33492038828, seitz-polski.b@chu-nice.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Clinical remission (complete or partial) after 6 months of rituximab initiation (time frame: 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06341205, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Jun 2026.