Rituximab in the Treatment of Idiopathic Membranous Nephropathy
This study has been completed.
First Posted: November 30, 2006
Last Update Posted: October 27, 2015
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Information provided by (Responsible Party):
Fernando Fervenza, Mayo Clinic
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.
Early Phase 1
||Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
||Rituximab in the Treatment of Idiopathic Membranous Nephropathy
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 ]
| Study Start Date:
| Study Completion Date:
| Primary Completion Date:
||July 2010 (Final data collection date for primary outcome measure)
Patients will received rituximab 4 weekly doses of rituximab 375 mg/m2 at baseline. Patients will be retreated at 6 months.