Personalized Medicine for Membranous Nephropathy (PMMN)

February 7, 2020 updated by: Centre Hospitalier Universitaire de Nice

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Anticipated)

64

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • France
      • Amiens, France, 80800
        • Not yet recruiting
        • CHU D'amiens Hôpital Sud
        • Contact:
          • Gabriel CHOUKROUN
      • Besançon, France, 25000
        • Not yet recruiting
        • CHU Besançon
        • Contact:
          • Céline COURNIVAUD
      • Brest, France, 29069
        • Not yet recruiting
        • Hôpital universitaire La Cavale Blanche
        • Contact:
          • Emilie CORNEC-LE GALL
      • Caen, France, 14033
        • Not yet recruiting
        • CHU de Caen
        • Contact:
          • Antoine LANOT
      • Clermont-Ferrand, France, 63000
        • Not yet recruiting
        • Chu Gabriel Montpied
      • Créteil, France, 94010
        • Not yet recruiting
        • CHU Henri Mondor
        • Contact:
          • Vincent AUDARD
      • Lille, France, 59037
        • Not yet recruiting
        • CHRU de Lille
        • Contact:
          • Céline LEBAS
      • Lyon, France, 69437
        • Not yet recruiting
        • CHU de LYON NORD
        • Contact:
          • Fitsum GUEBRE-EGZIABHER
      • Marseille, France, 13005
        • Not yet recruiting
        • AP-HM
        • Contact:
          • Noémie JOURDE-CHICHE
      • Montpellier, France, 34295
        • Not yet recruiting
        • CHRU de Montpellier
      • Nantes, France, 44093
        • Not yet recruiting
        • CHU de Nantes
        • Contact:
          • Fadi FAKHOURI
      • Nice, France, 06000
        • Recruiting
        • Dr Barbara SEITZ-POLSKI
        • Contact:
        • Contact:
        • Sub-Investigator:
          • Vincent ESNAULT, MD; PhD
      • Nîmes, France, 30029
        • Recruiting
        • CHU Caremeau
        • Contact:
          • Olivier MORANNE
      • Paris, France, 75015
        • Not yet recruiting
        • Hôpital Necker
        • Contact:
          • Bertrand KNEBELMANN
      • Paris, France, 94275
        • Not yet recruiting
        • Le Kremlin Bicetre
        • Contact:
          • Antoine DURRBACH
      • Reims, France, 51092
        • Not yet recruiting
        • Hopital de La Maison Blanche
      • Strasbourg, France, 67091
        • Not yet recruiting
        • CHU de Strasbourg
        • Contact:
          • Thierry KRUMMEL
      • Toulouse, France, 31059
        • Not yet recruiting
        • CHU de Toulouse
        • Contact:
          • Dominique CHAUVEAU
      • Tours, France, 37044
        • Not yet recruiting
        • CHU de Tours

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
NO_INTERVENTION: 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.
EXPERIMENTAL: 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-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
In the "personalized arm", the patient will be treated in function of the CysR activity result during the inclusion visit.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Clinical remission will be defined as a composite criterion combining (KDIGO definitions)
Time Frame: 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%
6 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Immunological remission
Time Frame: 6 months
full PLA2R1 depletion measured by ELISA (titer<14RU (relative units) /ml)
6 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Centre Hospitalier Universitaire de Nice

Investigators

  • Principal Investigator: Barbara SEITZ-POLSKI, Centre Hospitalier Universitaire de Nice

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

January 14, 2020

Primary Completion (ANTICIPATED)

September 1, 2023

Study Completion (ANTICIPATED)

September 1, 2023

Study Registration Dates

First Submitted

January 11, 2019

First Submitted That Met QC Criteria

January 11, 2019

First Posted (ACTUAL)

January 15, 2019

Study Record Updates

Last Update Posted (ACTUAL)

February 11, 2020

Last Update Submitted That Met QC Criteria

February 7, 2020

Last Verified

February 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 17-APN-01

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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