Rituximab in the Treatment of Idiopathic Membranous Nephropathy

This study has been completed.
Sponsor:
Collaborator:
Genentech
Information provided by (Responsible Party):
Fernando Fervenza, Mayo Clinic
ClinicalTrials.gov Identifier:
NCT00405340
First received: November 29, 2006
Last updated: September 7, 2012
Last verified: September 2012
  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
Phase 0

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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 Mayo Clinic:

Primary Outcome Measures:
  • Primary endpoint. [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Complete and partial remission rates at 6, 9, and 12 months [ Time Frame: 6, 9, and 12 months ] [ Designated as safety issue: No ]
  • Pharmacokinetics/bioavailability [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • Rate of decline in urinary protein [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • Frequency of relapse after CR [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • Toxicity [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
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
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00405340

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

No publications provided

Responsible Party: Fernando Fervenza, M.D., Ph.D., Mayo Clinic
ClinicalTrials.gov Identifier: NCT00405340     History of Changes
Other Study ID Numbers: 06-004833
Study First Received: November 29, 2006
Last Updated: September 7, 2012
Health Authority: United States: Institutional Review Board

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

ClinicalTrials.gov processed this record on September 18, 2014