Personalized Medicine for Membranous Nephropathy (PMMN)
Idiopathic Membranous Nephropathy
About this trial
This is an interventional treatment trial for Idiopathic Membranous Nephropathy focused on measuring Nephrotic Syndrome, PLA2R1-antibodies, Epitope spreading, Rituximab
Eligibility Criteria
Inclusion Criteria:
- Age 18 years or more
- Anti-PLA2R1 activity detected by ELISA or Euroimmune Immunofluorescence Assay
- Nephrotic syndrome defined by proteinuria > 3.5 g/24h (or UPCR > 3.5 g/g) and serum albumin < 30 g/L at diagnosis
- eGFR (CKD-EPI) > 30 ml/min/1,73 m2 at diagnosis
- Symptomatic treatment according to KDIGO guidelines: maximal tolerated dose of NIAT : Non Immunosuppressive Antiproteinuric Treatment (angiotensin-converting enzyme inhibitor and/or angiotensin 2 receptor blockers, diuretics and statins)
- Medical insurance
- Signed informed consent
- Having understood and accepted the need for long-term medical follow-up
- Woman of child-bearing age must be using an effective method of contraception
Exclusion Criteria:
- Secondary Membranous Nephropathy: Membranous Nephropathy related to cancer, infectious, systemic lupus erythematosis, drug
- Anti-PLA2R1 antibodies not confirmed by central analysis (in this case the patient will be replaced)
- Pregnancy or breastfeeding
- Immunosuppressive treatment in the 3 last months
- Cancer under treatment
- Patient with complicated nephrotic syndrome that would require early immunosuppressive treatment (thrombosis, acute renal failure…)
- Patients with active, severe infections or active hepatitis B
- Hypersensitivity to the active substance or to murine proteins, or to any of the other excipients
- Patients in a severely immunocompromised state
- Severe heart failure (New York Heart Association Class IV) or severe, uncontrolled cardiac disease
- Patients unable to give an informed consent
Sites / Locations
- CHU D'amiens Hôpital Sud
- CHU Besançon
- Hôpital universitaire La Cavale Blanche
- CHU de Caen
- CHU Gabriel Montpied
- CHU Henri Mondor
- CHRU de LILLE
- CHU de LYON NORD
- AP-HM
- CHRU de Montpellier
- CHU de NANTES
- Dr Barbara SEITZ-POLSKIRecruiting
- CHU CarémeauRecruiting
- Hôpital Necker
- Le Kremlin Bicêtre
- Hôpital de la maison blanche
- CHU de Strasbourg
- CHU de Toulouse
- CHU de Tours
Arms of the Study
Arm 1
Arm 2
No Intervention
Experimental
GEMRITUX protocol
Personalized treatment
6 months of symptomatic antihypertensive and antiproteinuric therapy, and if the nephrotic syndrome persists at month-6 (urinary protein/creatinine ratio (UPCR) remains > 3.5 g/g and albuminemia < 30 g/l), two 375 mg/m2 rituximab infusions at 1-week interval.
restricted anti-CysR activity at inclusion : 6-month symptomatic antihypertensive and antiproteinuric treatment (KDIGO) restricted anti-CysR activity after 6 months of symptomatic treatment with persisting nephrotic syndrome (UPCR remains > 3.5 g/g and albuminemia < 30 g/l): two 375 mg/m2 rituximab infusions at 1-week interval; Anti-CTLD1/7 activity at inclusion or after 6 months with persisting nephrotic syndrome (UPCR remains > 3.5 g/g and albuminemia < 30 g/l): two 1g rituximab infusions at 2-week interval at month 0 and/or month 6.