Personalized Medicine for Membranous Nephropathy

Idiopathic Membranous Nephropathy Clinical Trial

— PMMN  

Official title:

Personalized Medicine for Membranous Nephropathy

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03804359
• Other study ID #: 17-APN-01
• Status: Recruiting
• Phase: Phase 2
• Start date: January 14, 2020
• Est. completion date: September 2023

Study information

• Verified date: February 2020
• Source: Centre Hospitalier Universitaire de Nice
• Contact: Barbara SEITZ-POLSKI, MD
• Phone: 04 92 03 55 02
• Email: seitz-polski.b[@]chu-nice.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 64
• Est. completion date: September 2023
• Est. primary completion date: September 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Glomerulonephritis, Membranous
• Idiopathic Membranous Nephropathy
• Kidney Diseases

Intervention

Drug:
• Rituximab
In the "personalized arm", the patient will be treated in function of the CysR activity result during the inclusion visit.

Locations

Country	Name	City	State
France	CHU D'amiens Hôpital Sud	Amiens
France	CHU Besançon	Besançon
France	Hôpital universitaire La Cavale Blanche	Brest
France	CHU de Caen	Caen
France	CHU Gabriel Montpied	Clermont-Ferrand
France	CHU Henri Mondor	Créteil
France	CHRU de LILLE	Lille
France	CHU de LYON NORD	Lyon
France	AP-HM	Marseille
France	CHRU de Montpellier	Montpellier
France	CHU de NANTES	Nantes
France	Dr Barbara SEITZ-POLSKI	Nice
France	CHU Carémeau	Nîmes
France	Hôpital Necker	Paris
France	Le Kremlin Bicêtre	Paris
France	Hôpital de la maison blanche	Reims
France	CHU de Strasbourg	Strasbourg
France	CHU de Toulouse	Toulouse
France	CHU de Tours	Tours

Sponsors (1)

Lead Sponsor	Collaborator
Centre Hospitalier Universitaire de Nice

Country where clinical trial is conducted

France, 

References & Publications (5)

Glassock RJ. The pathogenesis of idiopathic membranous nephropathy: a 50-year odyssey. Am J Kidney Dis. 2010 Jul;56(1):157-67. doi: 10.1053/j.ajkd.2010.01.008. Epub 2010 Apr 8. Review. — View Citation

Lassalle M, Ayav C, Frimat L, Jacquelinet C, Couchoud C; Au Nom du Registre REIN. The essential of 2012 results from the French Renal Epidemiology and Information Network (REIN) ESRD registry. Nephrol Ther. 2015 Apr;11(2):78-87. doi: 10.1016/j.nephro.2014 — View Citation

Ponticelli C. Membranous nephropathy. J Nephrol. 2007 May-Jun;20(3):268-87. Review. — View Citation

Simon N, Couroucé AM, Lemarrec N, Trépo C, Ducamp S. A twelve year natural history of hepatitis C virus infection in hemodialyzed patients. Kidney Int. 1994 Aug;46(2):504-11. — View Citation

Simon P, Ramee MP, Boulahrouz R, Stanescu C, Charasse C, Ang KS, Leonetti F, Cam G, Laruelle E, Autuly V, Rioux N. Epidemiologic data of primary glomerular diseases in western France. Kidney Int. 2004 Sep;66(3):905-8. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Clinical remission will be defined as a composite criterion combining (KDIGO definitions)	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%	6 months
Secondary	Immunological remission	full PLA2R1 depletion measured by ELISA (titer<14RU (relative units) /ml)	6 months