NCT03804359

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
68

participants targeted

Target at P50-P75 for phase_2

Timeline
Completed

Started Jan 2020

Longer than P75 for phase_2

Geographic Reach
1 country

19 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

January 11, 2019

Completed
4 days until next milestone

First Posted

Study publicly available on registry

January 15, 2019

Completed
12 months until next milestone

Study Start

First participant enrolled

January 14, 2020

Completed
4.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

September 30, 2024

Completed
1 month until next milestone

Study Completion

Last participant's last visit for all outcomes

November 5, 2024

Completed
Last Updated

July 25, 2025

Status Verified

July 1, 2025

Enrollment Period

4.7 years

First QC Date

January 11, 2019

Last Update Submit

July 24, 2025

Conditions

Idiopathic Membranous Nephropathy

Keywords

Nephrotic SyndromePLA2R1-antibodiesEpitope spreadingRituximab

Outcome Measures

Primary Outcomes (1)

  • 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 Outcomes (1)

  • Immunological remission

    6 months

Study Arms (2)

GEMRITUX protocol

NO INTERVENTION

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

EXPERIMENTAL

* 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.

Drug: Rituximab

Interventions

RituximabDRUG

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

Personalized treatment

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (19)

CHU D'amiens Hôpital Sud

Amiens, 80800, France

Location

CHU Besançon

Besançon, 25000, France

Location

Hôpital universitaire La Cavale Blanche

Brest, 29069, France

Location

CHU de Caen

Caen, 14033, France

Location

CHU Gabriel Montpied

Clermont-Ferrand, 63000, France

Location

CHU Henri Mondor

Créteil, 94010, France

Location

CHRU de LILLE

Lille, 59037, France

Location

CHU de LYON NORD

Lyon, 69437, France

Location

AP-HM

Marseille, 13005, France

Location

CHRU de Montpellier

Montpellier, 34295, France

Location

CHU de NANTES

Nantes, 44093, France

Location

Dr Barbara SEITZ-POLSKI

Nice, 06000, France

Location

CHU Carémeau

Nîmes, 30029, France

Location

Hôpital Necker

Paris, 75015, France

Location

Le Kremlin Bicêtre

Paris, 94275, France

Location

Hôpital de la maison blanche

Reims, 51092, France

Location

CHU de Strasbourg

Strasbourg, 67091, France

Location

CHU de Toulouse

Toulouse, 31059, France

Location

CHU de Tours

Tours, 37044, France

Location

Related Publications (6)

  • Simon N, Courouce AM, Lemarrec N, Trepo C, Ducamp S. A twelve year natural history of hepatitis C virus infection in hemodialyzed patients. Kidney Int. 1994 Aug;46(2):504-11. doi: 10.1038/ki.1994.301.

    PMID: 7967364BACKGROUND

  • 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. doi: 10.1111/j.1523-1755.2004.00834.x.

    PMID: 15327379BACKGROUND

  • Ponticelli C. Membranous nephropathy. J Nephrol. 2007 May-Jun;20(3):268-87.

    PMID: 17557260BACKGROUND

  • 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.

    PMID: 20378220BACKGROUND

  • 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.2014.08.002. Epub 2014 Nov 1.

    PMID: 25457107RESULT

  • Brglez V, Boyer-Suavet S, Zorzi K, Fernandez C, Fontas E, Esnault V, Seitz-Polski B. Personalized Medicine for PLA2R1-Related Membranous Nephropathy: A Multicenter Randomized Control Trial. Front Med (Lausanne). 2020 Aug 13;7:412. doi: 10.3389/fmed.2020.00412. eCollection 2020.

    PMID: 32903623DERIVED

MeSH Terms

Conditions

Glomerulonephritis, MembranousNephrotic Syndrome

Interventions

Rituximab

Condition Hierarchy (Ancestors)

GlomerulonephritisNephritisKidney DiseasesUrologic DiseasesFemale Urogenital DiseasesFemale Urogenital Diseases and Pregnancy ComplicationsUrogenital DiseasesMale Urogenital DiseasesAutoimmune DiseasesImmune System DiseasesNephrosis

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-DerivedAntibodies, MonoclonalAntibodiesImmunoglobulinsImmunoproteinsBlood ProteinsProteinsAmino Acids, Peptides, and ProteinsSerum GlobulinsGlobulins

Study Officials

  • Barbara SEITZ-POLSKI

    Centre Hospitalier Universitaire de Nice

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

January 11, 2019

First Posted

January 15, 2019

Study Start

January 14, 2020

Primary Completion

September 30, 2024

Study Completion

November 5, 2024

Last Updated

July 25, 2025

Record last verified: 2025-07

Locations

FR(19)