search
Back to results

Personalized Medicine for Membranous Nephropathy (PMMN)

Primary Purpose

Idiopathic Membranous Nephropathy

Status
Unknown status
Phase
Phase 2
Locations
France
Study Type
Interventional
Intervention
Rituximab
Sponsored by
Centre Hospitalier Universitaire de Nice
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Idiopathic Membranous Nephropathy focused on measuring Nephrotic Syndrome, PLA2R1-antibodies, Epitope spreading, Rituximab

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • CHU D'amiens Hôpital Sud
  • CHU Besançon
  • Hôpital universitaire La Cavale Blanche
  • CHU de Caen
  • CHU Gabriel Montpied
  • CHU Henri Mondor
  • CHRU de LILLE
  • CHU de LYON NORD
  • AP-HM
  • CHRU de Montpellier
  • CHU de NANTES
  • Dr Barbara SEITZ-POLSKIRecruiting
  • CHU CarémeauRecruiting
  • Hôpital Necker
  • Le Kremlin Bicêtre
  • Hôpital de la maison blanche
  • CHU de Strasbourg
  • CHU de Toulouse
  • CHU de Tours

Arms of the Study

Arm 1

Arm 2

Arm Type

No Intervention

Experimental

Arm Label

GEMRITUX protocol

Personalized treatment

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

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%

Secondary Outcome Measures

Immunological remission
full PLA2R1 depletion measured by ELISA (titer<14RU (relative units) /ml)

Full Information

First Posted
January 11, 2019
Last Updated
February 7, 2020
Sponsor
Centre Hospitalier Universitaire de Nice
search

1. Study Identification

Unique Protocol Identification Number
NCT03804359
Brief Title
Personalized Medicine for Membranous Nephropathy
Acronym
PMMN
Official Title
Personalized Medicine for Membranous Nephropathy
Study Type
Interventional

2. Study Status

Record Verification Date
February 2020
Overall Recruitment Status
Unknown status
Study Start Date
January 14, 2020 (Actual)
Primary Completion Date
September 2023 (Anticipated)
Study Completion Date
September 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Centre Hospitalier Universitaire de Nice

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Idiopathic Membranous Nephropathy
Keywords
Nephrotic Syndrome, PLA2R1-antibodies, Epitope spreading, Rituximab

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
64 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
GEMRITUX protocol
Arm Type
No Intervention
Arm Description
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.
Arm Title
Personalized treatment
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Rituximab
Intervention Description
In the "personalized arm", the patient will be treated in function of the CysR activity result during the inclusion visit.
Primary Outcome Measure Information:
Title
Clinical remission will be defined as a composite criterion combining (KDIGO definitions)
Description
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%
Time Frame
6 months
Secondary Outcome Measure Information:
Title
Immunological remission
Description
full PLA2R1 depletion measured by ELISA (titer<14RU (relative units) /ml)
Time Frame
6 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Barbara SEITZ-POLSKI, MD
Phone
04 92 03 55 02
Email
seitz-polski.b@chu-nice.fr
First Name & Middle Initial & Last Name or Official Title & Degree
Céline FERNANDEZ
Email
fernandez.c3@chu-nice.fr
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Barbara SEITZ-POLSKI
Organizational Affiliation
Centre Hospitalier Universitaire de Nice
Official's Role
Principal Investigator
Facility Information:
Facility Name
CHU D'amiens Hôpital Sud
City
Amiens
ZIP/Postal Code
80800
Country
France
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Gabriel CHOUKROUN
Facility Name
CHU Besançon
City
Besançon
ZIP/Postal Code
25000
Country
France
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Céline COURNIVAUD
Facility Name
Hôpital universitaire La Cavale Blanche
City
Brest
ZIP/Postal Code
29069
Country
France
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Emilie CORNEC-LE GALL
Facility Name
CHU de Caen
City
Caen
ZIP/Postal Code
14033
Country
France
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Antoine LANOT
Facility Name
CHU Gabriel Montpied
City
Clermont-Ferrand
ZIP/Postal Code
63000
Country
France
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Anne-Elisabeth HENG
Facility Name
CHU Henri Mondor
City
Créteil
ZIP/Postal Code
94010
Country
France
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Vincent AUDARD
Facility Name
CHRU de LILLE
City
Lille
ZIP/Postal Code
59037
Country
France
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Céline LEBAS
Facility Name
CHU de LYON NORD
City
Lyon
ZIP/Postal Code
69437
Country
France
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Fitsum GUEBRE-EGZIABHER
Facility Name
AP-HM
City
Marseille
ZIP/Postal Code
13005
Country
France
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Noémie JOURDE-CHICHE
Facility Name
CHRU de Montpellier
City
Montpellier
ZIP/Postal Code
34295
Country
France
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Moglie LE QUINTREC
Facility Name
CHU de NANTES
City
Nantes
ZIP/Postal Code
44093
Country
France
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Fadi FAKHOURI
Facility Name
Dr Barbara SEITZ-POLSKI
City
Nice
ZIP/Postal Code
06000
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Barbara SEITZ-POLSKI, MD
Phone
04 92 03 55 02
Email
seitz-polski.b@chu-nice.fr
First Name & Middle Initial & Last Name & Degree
Céline FERNANDEZ
Phone
04 92 03 88 28
Email
fernandez.c3@chu-nice.fr
First Name & Middle Initial & Last Name & Degree
Vincent ESNAULT, MD; PhD
Facility Name
CHU Carémeau
City
Nîmes
ZIP/Postal Code
30029
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Olivier MORANNE
Facility Name
Hôpital Necker
City
Paris
ZIP/Postal Code
75015
Country
France
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Bertrand KNEBELMANN
Facility Name
Le Kremlin Bicêtre
City
Paris
ZIP/Postal Code
94275
Country
France
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Antoine DURRBACH
Facility Name
Hôpital de la maison blanche
City
Reims
ZIP/Postal Code
51092
Country
France
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Philippe RIEU
Facility Name
CHU de Strasbourg
City
Strasbourg
ZIP/Postal Code
67091
Country
France
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Thierry KRUMMEL
Facility Name
CHU de Toulouse
City
Toulouse
ZIP/Postal Code
31059
Country
France
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Dominique CHAUVEAU
Facility Name
CHU de Tours
City
Tours
ZIP/Postal Code
37044
Country
France
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jean-Michel HALIMI

12. IPD Sharing Statement

Citations:
PubMed Identifier
7967364
Citation
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.
Results Reference
background
PubMed Identifier
15327379
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. doi: 10.1111/j.1523-1755.2004.00834.x.
Results Reference
background
PubMed Identifier
17557260
Citation
Ponticelli C. Membranous nephropathy. J Nephrol. 2007 May-Jun;20(3):268-87.
Results Reference
background
PubMed Identifier
20378220
Citation
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.
Results Reference
background
PubMed Identifier
25457107
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.2014.08.002. Epub 2014 Nov 1.
Results Reference
result
PubMed Identifier
32903623
Citation
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.
Results Reference
derived

Learn more about this trial

Personalized Medicine for Membranous Nephropathy

We'll reach out to this number within 24 hrs