Idiopathic Membranous Nephropathy
Conditions
Keywords
Nephrotic Syndrome, PLA2R1-antibodies, Epitope spreading, Rituximab
Brief summary
Randomized, open label, multicentre (20 sites), prospective trial comparing the efficacy of two therapeutic strategies to obtain clinical remission 1 year after diagnosis of Idiopathic Membranous Nephropathy with nephrotic syndrome and anti-PLA2R1 (phospholipase A2 receptor 1) antibodies: * GEMRITUX protocol: 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. * Personalized treatment: * 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-CTLD (C-type lectin domains ) 1/7 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.
Interventions
DRUGRituximab
In the personalized arm, the patient will be treated in function of the CysR activity result during the inclusion visit.
Sponsors
Centre Hospitalier Universitaire de Nice
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Clinical remission will be defined as a composite criterion combining (KDIGO definitions) | 6 months | * Complete clinical remission: urinary protein/creatinine ratio (UPCR)\<0.3 g/g in spot morning urine samples and serum albumin \> 35 g/L and eGFR (epidermal growth factor receptor) \> 60 ml/min/1.73 m2 * Partial clinical remission: UPCR \< 3.5 g/g with a decrease greater than 50% from baseline and serum albumin \> 30 g/L and increase of serum creatinine lower than 20% |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Immunological remission | 6 months | full PLA2R1 depletion measured by ELISA (titer\<14RU (relative units) /ml) |
Countries
France
Outcome results
None listed