Idiopathic Membranous Nephropathy MedDRA version: 20.0 Level: LLT Classification code 10027170 Term: Membranous nephropathy System Organ Class: 100000004857
Conditions
Interventions
Trade Name: TRUXIMA
Product Name: TRUXIMAB
Pharmaceutical Form: Solution for infusion
Sponsors
CHU de Nice
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Age 18 years or more - Anti-PLA2R1 activity detected by ELISA or Euroimmune IFA - Nephrotic syndrome defined by proteinuria > 3.5 g/24h (or UPCR > 3.5 g/g) and serum albumin 30 ml/min/1,73 m2 at diagnosis - Symptomatic treatment according to KDIGO guidelines: maximal tolerated dose of NIAT (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 Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 60 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 4
Exclusion criteria
Exclusion criteria: - Secondary MN: MN 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 |
|---|---|
| Main Objective: To compare the efficacy of a personalized treatment of nephrotic iMN driven by anti-PLA2R1 antibody epitope profile at month 0 and month 6 with the GEMRITUX therapeutic protocol to induce clinical remission of the nephrotic syndrome at month-12. ;Secondary Objective: To compare between a personalized treatment of iMN driven by anti-PLA2R1 antibody epitope profiles and the GEMRITUX therapeutic protocol: -Complete clinical and immunological remissions at M6, M12, M18, M24 -Partial clinical remission at M6, M12, M18, M24 -Proteinuria and albuminuria at M6, M12, M18, M24 -Changes in proteinuria and albuminuria from baseline at M6, M12, M18, M24 -Serum creatinine and estimated glomerular filtration rate (eGFR) at M6, M12, M18 -Changes in serum creatinine and eGFR from baseline at M6, M12 and M18 -PLA2R1-Ab titers at M6, M12 and M18 -Severe infections serious adverse And to compare between responders versus non responders at month-12 and between relapsers versus non relapsers: -Lymphocyte counts: B cells (CD19, transitional, mature and memory) and T cells (CD3, CD4, CD8 and TReg) at J0, M3, M6, M12 post-rituximab infusion -Serum level of IL-35 at J0, M3, M6, M12 post-rituximab infusion -Residual serum rituximab levels at M3 ;Primary end point(s): Clinical remission at month-12 (KDIGO definition): -complete: UPCR 35 g/L and eGFR > 60 ml/min/1.73 m2 -partial: UPCR 30 g/L and increase of serum creatinine lower than 20%;Timepoint(s) of evaluation of this end point: After 12 months of treatment | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Complete clinical remission as defined above 2. Partial clinical remission as defined above 3. Immunological remission: full PLA2R1 depletion measured by ELISA (titer 3.5 g/g after remission at M12. Patients from both groups will be analysed jointly. The risk factors studied will be the same as above measured at J0, M3, M6 and M12 post-rituximab infusion.;Timepoint(s) of evaluation of this end point: After 12 months of treatment | — |
Countries
France
Contacts
Public ContactDRCI
CHU de Nice
Outcome results
None listed