Personalized Medicine for Membranous Nephropathy

Phase 2

• Conditions: Idiopathic Membranous Nephropathy
• Interventions: Drug: Rituximab

• Registration Number: NCT03804359
• Lead Sponsor: Centre Hospitalier Universitaire de Nice

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2019-01-11
• Study First Submitted QC: 2019-01-11
• Study First Posted: 2019-01-15
• Study Start: 2020-01-14
• Status Verified: 2020-02
• Last Update Submitted: 2020-02-07
• Last Update Posted: 2020-02-11
• Primary Completion: 2023-09
• Study Completion: 2023-09

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 64

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Personalized treatment	Rituximab	* 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.

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
Immunological remission	6 months	full PLA2R1 depletion measured by ELISA (titer\<14RU (relative units) /ml)

Trial Locations

Locations (19)

CHU D'amiens Hôpital Sud; 🇫🇷 Amiens, France

CHU Gabriel Montpied; 🇫🇷 Clermont-Ferrand, France

CHU Carémeau; 🇫🇷 Nîmes, France

CHU Henri Mondor; 🇫🇷 Créteil, France

CHU Besançon; 🇫🇷 Besançon, France

Le Kremlin Bicêtre; 🇫🇷 Paris, France

CHU de Toulouse; 🇫🇷 Toulouse, France

Hôpital universitaire La Cavale Blanche; 🇫🇷 Brest, France

CHRU de Montpellier; 🇫🇷 Montpellier, France

CHU de Caen; 🇫🇷 Caen, France

CHU de LYON NORD; 🇫🇷 Lyon, France

Dr Barbara SEITZ-POLSKI; 🇫🇷 Nice, France

AP-HM; 🇫🇷 Marseille, France

CHU de NANTES; 🇫🇷 Nantes, France

CHU de Strasbourg; 🇫🇷 Strasbourg, France

Hôpital Necker; 🇫🇷 Paris, France

Hôpital de la maison blanche; 🇫🇷 Reims, France

CHRU de LILLE; 🇫🇷 Lille, France

CHU de Tours; 🇫🇷 Tours, France