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Rituximab in the Treatment of Idiopathic Membranous Nephropathy

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT00405340
First Posted: November 30, 2006
Last Update Posted: October 27, 2015
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. Read our disclaimer for details.
Collaborator:
Genentech, Inc.
Information provided by (Responsible Party):
Fernando Fervenza, Mayo Clinic
  Purpose
Membranous glomerulopathy (MN) is still the most common glomerular disease associated with nephrotic proteinuria (NS). Up to 40% of patients reach end stage renal failure (ESRD), making MN the 2nd or 3rd most common cause of ESRD caused by a primary glomerulopathy. Current treatment options include corticosteroids, alkylating agents, and cyclosporin, but their use is controversial and the associated adverse effects and high cost temper their usage. Experimental data in MN suggests that B cell activation results in immunoglobulin deposition along the glomerular basement membrane causing injury to the membrane and subsequent proteinuria. Drugs that non-selectively inhibit B cells and, these pathogenic antibodies, are closely associated with improved outcomes. Based on the rationale that selective depletion of B cells in humans would prevent the production of ?nephrotoxic? immunoglobulins and subsequent renal injury we recently treated 15 patients with MN with rituximab 1g i.v. twice (day 1 and day 15). Baseline proteinuria of 13.0±5.5g/24h decreased to 9.1±7g, 9.7±8g and 6.5±6 g/24h at 3, 6, and 9 months, respectively (mean ± SD). Analysis of the pharmacokinetic data obtained from this study, however, suggests that in heavily nephrotic patients, rituximab dosed in this fashion results in patients being under-treated. The present study propose to test the hypothesis that rituximab, given in accordance to the standard lymphoma protocol (375mg/m2 x 4), will result in a more effective and profound depletion of B cells, a more complete suppression of pathogenic antibodies, and a higher remission rate of the NS while maintaining a favorable safety profile.

Condition Intervention Phase
Membranous Nephropathy Drug: Rituximab Early Phase 1

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Rituximab in the Treatment of Idiopathic Membranous Nephropathy

Resource links provided by NLM:


Further study details as provided by Fernando Fervenza, Mayo Clinic:

Primary Outcome Measures:
  • Primary endpoint. [ Time Frame: 12 months ]

Secondary Outcome Measures:
  • Complete and partial remission rates at 6, 9, and 12 months [ Time Frame: 6, 9, and 12 months ]
  • Pharmacokinetics/bioavailability [ Time Frame: 12 months ]
  • Rate of decline in urinary protein [ Time Frame: 12 months ]
  • Frequency of relapse after CR [ Time Frame: 12 months ]
  • Toxicity [ Time Frame: 12 months ]

Enrollment: 20
Study Start Date: October 2006
Study Completion Date: April 2012
Primary Completion Date: July 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Drug
Rituximab
Drug: Rituximab
Patients will received rituximab 4 weekly doses of rituximab 375 mg/m2 at baseline. Patients will be retreated at 6 months.

  Show Detailed Description

  Eligibility

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria
  • Idiopathic MN with diagnostic biopsy performed within the past 24 months.
  • Age > 18 years
  • If female, must be post-menopausal, surgically sterile or practicing a medically approved method of contraception
  • Patients need to be treated with an ACEI and/or ARB, for at least 4 months prior to rituximab treatment and have adequately controlled blood pressure (BP <130/75 mm Hg in >75% of the readings).
  • Proteinuria as measured by urinary proteinuria / urinary creatinine > 5.0 on a spot sample aliquot from a 24-hour urine collection.
  • Estimated GFR &#8805; 30 ml/min/1.73m2 while taking ACEI/ARB therapy.
  Contacts and Locations
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): NCT00405340


Locations
United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905
Sponsors and Collaborators
Mayo Clinic
Genentech, Inc.
Investigators
Principal Investigator: Fernando C. Fervenza, M.D., Ph.D. Mayo Clinic
  More Information

Responsible Party: Fernando Fervenza, M.D., Ph.D., Mayo Clinic
ClinicalTrials.gov Identifier: NCT00405340     History of Changes
Other Study ID Numbers: 06-004833
First Submitted: November 29, 2006
First Posted: November 30, 2006
Last Update Posted: October 27, 2015
Last Verified: October 2015

Additional relevant MeSH terms:
Kidney Diseases
Glomerulonephritis, Membranous
Urologic Diseases
Glomerulonephritis
Nephritis
Autoimmune Diseases
Immune System Diseases
Rituximab
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents