- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01508468
Evaluate Rituximab Treatment for Idiopathic Membranous Nephropathy (GEMRITUX)
Prospective Randomized Multicentric Open Label Study to Evaluate Rituximab Treatment for Idiopathic Membranous Nephropathy (IMN)
The Membranous Nephropathy is one of the most common cause of Nephrotic Syndrome of adults. In 2/3 of patients the cause of the disease is idiopathic. This can also be referred to as idiopathic membranous nephropathy (IMN).The most of these patients are treated by non immunosuppressive symptomatic treatment (NIST): antiproteinuric and antihypertensive blocking the rennin-angiotensine system. However, the patients resistant to antiproteinuric treatment risk to develop an end stage renal disease (ESRD).
Rituximab has been recently used in patients suffering of nephrotic syndrome related to IMN in four international studies. Rituximab appears effective and safe in reducing proteinuria in nearly 60% of patients.
The primary outcome of the investigators prospective randomized study is to determine whether or not the Rituximab associated with NIST is more effective than non immunologic symptomatic treatment alone in inducing long term remission of proteinuria.
Study Overview
Status
Conditions
Detailed Description
The IMN exposes patients to severe complications which engage the vital prognosis or Nephrotic Syndrome.
The development of well tolerated and effective pathogenesis linked therapies is needed to treat patients with idiopathic Membranous Nephropathy Rituximab, a monoclonal antibody (mAb) against the CD20 present on B cells, has been recently used in patients suffering of nephrotic syndrome related to IMN in four international studies. Rituximab appears effective and safe in reducing proteinuria in nearly 60% of patients.
However, no randomized controlled study has been published to date.
In a previous study, outcome of 28 patients treated with rituximab for idiopathic MN is analysed. Anti-PLA2R antibodies in serum and PLA2R antigen in kidney biopsy were assessed in 10 and 9 patients.
Proteinuria was significantly decreased by 56%, 62% and 87% at 3 months, 6 months and 12 months. At 6 months, 2 patients achieved full remission and 12 partial remission (overall renal response, 50%). At 12 months (n=23), complete remission was achieved in 6 patients and partial remission in 13 patients (overall renal response, 82,6%). Three patients suffered a relapse of nephrotic proteinuria 27 to 50 months after treatment. Univariate analysis suggested that the degree of renal failure (MDRD < 45/ml/min/1.73 m²) is an independent factor that predicts lack of response to rituximab. Anti-PLA2R antibodies were detected in serum in 10 patients, and PLA2R antigen in immune deposits in 8 of 9 patients. Antibodies became negative in all 5 responsive patients with available follow-up. In this retrospective study, a high rate of remission was achieved at 12 months after treatment.
Our trial is a Prospective randomized multicentric open label study. The 2 arms of the study are : Non Immunosuppressive Symptomatic Treatment (NIST) and Rituximab+ NIST Patients randomized to the Rituximab arm will receive 375 mg/m² on days 1 and 8 (+ NIST). Patients in the control arm will be treated only with Non Immunosuppressive Symptomatic Treatment (NIST).
The duration of participation per patient is 6 months for interventional study. An observational follow-up is performed at M9, M12, M18 & M24 for all patients included in study with lab data collection of test done during usual pathology follow-up.
A part of the diagnosis renal biopsy (performed usually as part of health care) is collected for all patients as for the purpose of central analysis.
Our Primary Outcome Measure is evaluation of efficacy of Rituximab associated with NIST in (IMN) in reducing the rate of proteinuria (patients with persistent urinary protein excretion rate ≥3,5g/24 h and albuminemia < 30g/l ).
Study Type
Enrollment (Actual)
Phase
- Phase 3
Contacts and Locations
Study Locations
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Paris, France
- Department of Nephrology , Tenon hospital - APHP
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- At least 18 years old.
- Idiopathic Membranous nephropathy proved by renal biopsy
- Persistent urinary protein excretion rate ≥3,5g/24 h and albuminemia < 30g/l for at least 6 months with full dose of NIST
- Patient receiving a non immunosuppressive conventional treatment (antiproteinuric and antihypertensive blocking the rennin-angiotensine system, lipid-lowering statin) since at least 6 months.
- Patient has given its written consent
- Patient with social coverage (excepting AME)
- Use of an efficient contraception method for women in childbearing age.
Exclusion Criteria:
- Secondary membranous nephropathy
- Patient already in a clinical trial
- Patient received an immunosuppressive treatment within 3 months before the study
- Patient with chronic renal disease defined by estimated GFR by MDRD formula under 30ml/mn/1,73m²
- Pregnancy and breastfeeding
- HIV infection, HCV and HBV active infection
- Severe or evolving infections.
- Allergy or hypersensitivity to Rituximab or any component
Study Plan
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 |
---|---|
ACTIVE_COMPARATOR: active comparator
Non Immunosuppressive Symptomatic Treatment (NIST).
"No specific treatment" Converting Enzyme Inhibitor , Angiotensin II receptor antagonist, Anti-renin, Aldosterone antagonist diuretic, Beta blocker, Calcium inhibitor, statin.
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Converting Enzyme inhibitor , Angiotensin II receptor antagonist, Anti-renin, Aldosterone antagonist diuretic, Beta blocker, Calcium inhibitor, statin.
Other Names:
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EXPERIMENTAL: experimental
NIST and Rituximab: 500 Mg and 100Mg in solution to be diluted for IV infusion (Mabthera®)
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NIST and IV infusion of Rituximab 375mg/m² at day (1) and day (8)
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Evaluation of efficacy of Rituximab associated with Non Immunosuppressive Symptomatic Treatment (NIST) in (IMN) in reducing the rate of proteinuria (patients with persistent urinary protein excretion rate ≥3,5g/24 h and albuminemia < 30g/l )
Time Frame: 6 months
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Evaluation of efficacy of Rituximab associated with Non Immunosuppressive Symptomatic Treatment (NIST) in (IMN) in reducing the rate of proteniuria
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6 months
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Effect of Rituximab on the progression of chronic renal disease
Time Frame: 6 months
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Effect of Rituximab on the progression of chronic renal disease by measuring :
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6 months
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Evaluation of Rituximab tolerance in IMN
Time Frame: 6 months
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Evaluation of Rituximab tolerance in IMN : -Percentage of serious allergic reaction after Rituximab infusion "drop in blood pressure and/or bronchospasm" |
6 months
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serologic diagnosis with identification of anti-NEP and anti-PLA2R antibodies in IMN before and after treatment with Rituximab
Time Frame: 6 months
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serologic diagnosis with identification of anti-NEP and anti-PLA2R antibodies in IMN before and after treatment with Rituximab
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6 months
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genetic analysis
Time Frame: 6 months
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genetic analysis Study of the alleles "HLA-DQA1 and PLA2R1" situated respectively on chromosomes 6p21 and 2q24.
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6 months
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Lymphocyte CD19 dosing at month 3 and month 6.
Time Frame: 6 months
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Lymphocyte CD19 dosing at month 3 and month 6.
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6 months
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Collaborators and Investigators
Investigators
- Principal Investigator: Karine Dahan, MD, Assistance Publique
Publications and helpful links
General Publications
- von Groote TC, Williams G, Au EH, Chen Y, Mathew AT, Hodson EM, Tunnicliffe DJ. Immunosuppressive treatment for primary membranous nephropathy in adults with nephrotic syndrome. Cochrane Database Syst Rev. 2021 Nov 15;11(11):CD004293. doi: 10.1002/14651858.CD004293.pub4.
- Seitz-Polski B, Dahan K, Debiec H, Rousseau A, Andreani M, Zaghrini C, Ticchioni M, Rosenthal A, Benzaken S, Bernard G, Lambeau G, Ronco P, Esnault VLM. High-Dose Rituximab and Early Remission in PLA2R1-Related Membranous Nephropathy. Clin J Am Soc Nephrol. 2019 Aug 7;14(8):1173-1182. doi: 10.2215/CJN.11791018. Epub 2019 Jul 24.
- Dahan K, Debiec H, Plaisier E, Cachanado M, Rousseau A, Wakselman L, Michel PA, Mihout F, Dussol B, Matignon M, Mousson C, Simon T, Ronco P; GEMRITUX Study Group. Rituximab for Severe Membranous Nephropathy: A 6-Month Trial with Extended Follow-Up. J Am Soc Nephrol. 2017 Jan;28(1):348-358. doi: 10.1681/ASN.2016040449. Epub 2016 Jun 27.
Study record dates
Study Major Dates
Study Start (ACTUAL)
Primary Completion (ACTUAL)
Study Completion (ACTUAL)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ESTIMATE)
Study Record Updates
Last Update Posted (ACTUAL)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Immune System Diseases
- Autoimmune Diseases
- Urologic Diseases
- Nephritis
- Glomerulonephritis
- Kidney Diseases
- Glomerulonephritis, Membranous
- Physiological Effects of Drugs
- Adrenergic Antagonists
- Adrenergic Agents
- Neurotransmitter Agents
- Molecular Mechanisms of Pharmacological Action
- Antirheumatic Agents
- Antineoplastic Agents
- Immunologic Factors
- Hormones, Hormone Substitutes, and Hormone Antagonists
- Protease Inhibitors
- Natriuretic Agents
- Antineoplastic Agents, Immunological
- Hormone Antagonists
- Calcium-Regulating Hormones and Agents
- Serine Proteinase Inhibitors
- Diuretics, Potassium Sparing
- Vasoconstrictor Agents
- Rituximab
- Calcium
- Diuretics
- Enzyme Inhibitors
- Mineralocorticoid Receptor Antagonists
- Adrenergic beta-Antagonists
- Angiotensin II
- Giapreza
- Angiotensinogen
Other Study ID Numbers
- P 100115
- AOM 10089 (OTHER: Assistance Publique)
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