Evaluate Rituximab Treatment for Idiopathic Membranous Nephropathy

NCT01508468 | Completed Phase 3 DMC

• 2 other identifiers: P 100115AOM 10089
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Idiopathic Membranous Nephropathy

Keywords

Rituximab; membranous nephropathy; anti-PLA2R antibody

Outcome Measures

Primary Outcomes (1)

• 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 )

  Evaluation of efficacy of Rituximab associated with Non Immunosuppressive Symptomatic Treatment (NIST) in (IMN) in reducing the rate of proteniuria

  6 months

Secondary Outcomes (5)

• Effect of Rituximab on the progression of chronic renal disease

  6 months

• Evaluation of Rituximab tolerance in IMN

  6 months

• serologic diagnosis with identification of anti-NEP and anti-PLA2R antibodies in IMN before and after treatment with Rituximab

  6 months

• genetic analysis

  6 months

• Lymphocyte CD19 dosing at month 3 and month 6.

  6 months

Study Arms (2)

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.

Drug: symptomatic treatment (Converting Enzyme inhibitor, Angiotensin II, Anti-renin, Aldosterone antagonist diuretic, Beta blocker, Calcium inhibitor, statin)

experimental

EXPERIMENTAL

NIST and Rituximab: 500 Mg and 100Mg in solution to be diluted for IV infusion (Mabthera®)

Drug: experimental (Non Immunosuppressive Symptomatic Treatment (NIST) and Rituximab)

Interventions

symptomatic treatment (Converting Enzyme inhibitor, Angiotensin II, Anti-renin, Aldosterone antagonist diuretic, Beta blocker, Calcium inhibitor, statin) DRUG

Converting Enzyme inhibitor , Angiotensin II receptor antagonist, Anti-renin, Aldosterone antagonist diuretic, Beta blocker, Calcium inhibitor, statin.

Also known as: symptomatic treatment (no specific)

active comparator

experimental (Non Immunosuppressive Symptomatic Treatment (NIST) and Rituximab) DRUG

NIST and IV infusion of Rituximab 375mg/m² at day (1) and day (8)

Also known as: experimental

experimental

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead

Study Sites (1)

Department of Nephrology , Tenon hospital - APHP

Paris, France

Location

Related Publications (3)

• 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.

  PMID: 34778952 DERIVED

• 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.

  PMID: 31340979 DERIVED

• 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.

  PMID: 27352623 DERIVED

MeSH Terms

Conditions

Glomerulonephritis, Membranous

Interventions

Angiotensin II; Adrenergic beta-Antagonists; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Rituximab

Condition Hierarchy (Ancestors)

Glomerulonephritis; Nephritis; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Angiotensins; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Oligopeptides; Nerve Tissue Proteins; Proteins; Autacoids; Inflammation Mediators; Biological Factors; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Physiological Effects of Drugs; Anticholesteremic Agents; Hypolipidemic Agents; Antimetabolites; Enzyme Inhibitors; Lipid Regulating Agents; Therapeutic Uses; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins

Study Officials

• Karine Dahan, MD

  Assistance Publique

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 9, 2011
• First Posted: January 12, 2012
• Study Start: January 17, 2012
• Primary Completion: August 31, 2016
• Study Completion: August 31, 2016
• Last Updated: October 26, 2021

Record last verified: 2021-10

Locations

FR (1)