Try the modernized ClinicalTrials.gov beta website. Learn more about the modernization effort.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Personalized Medicine for Membranous Nephropathy (PMMN)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03804359
Recruitment Status : Recruiting
First Posted : January 15, 2019
Last Update Posted : February 11, 2020
Sponsor:
Information provided by (Responsible Party):
Centre Hospitalier Universitaire de Nice

Study Description
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
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.

Condition or disease Intervention/treatment Phase
Idiopathic Membranous Nephropathy Drug: Rituximab Phase 2

Study Design
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 64 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Personalized Medicine for Membranous Nephropathy
Actual Study Start Date : January 14, 2020
Estimated Primary Completion Date : September 2023
Estimated Study Completion Date : September 2023

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Kidney Diseases
Drug Information available for: Rituximab

Arms and Interventions
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

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.


Outcome Measures
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Primary Outcome Measures :
  1. 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%


Secondary Outcome Measures :
  1. Immunological remission [ Time Frame: 6 months ]
    full PLA2R1 depletion measured by ELISA (titer<14RU (relative units) /ml)


Eligibility Criteria
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
Contacts and Locations
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03804359


Contacts
Layout table for location contacts
Contact: Barbara SEITZ-POLSKI, MD 04 92 03 55 02 seitz-polski.b@chu-nice.fr
Contact: Céline FERNANDEZ fernandez.c3@chu-nice.fr

Locations
Show Show 19 study locations
Sponsors and Collaborators
Centre Hospitalier Universitaire de Nice
Investigators
Layout table for investigator information
Principal Investigator: Barbara SEITZ-POLSKI Centre Hospitalier Universitaire de Nice
More Information
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
Publications of Results:

Other Publications:

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Layout table for additonal information
Responsible Party: Centre Hospitalier Universitaire de Nice
ClinicalTrials.gov Identifier: NCT03804359    
Other Study ID Numbers: 17-APN-01
First Posted: January 15, 2019    Key Record Dates
Last Update Posted: February 11, 2020
Last Verified: February 2020

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Centre Hospitalier Universitaire de Nice:
Nephrotic Syndrome
PLA2R1-antibodies
Epitope spreading
Rituximab
Additional relevant MeSH terms:
Layout table for MeSH terms
Kidney Diseases
Glomerulonephritis, Membranous
Urologic Diseases
Glomerulonephritis
Nephritis
Autoimmune Diseases
Immune System Diseases
 Rituximab
Antineoplastic Agents, Immunological
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents