Ignite Creation Date:
2024-05-05 @ 5:18 PM
Last Modification Date:
2024-10-26 @ 9:30 AM
Study NCT ID:
NCT00425217
Status:
COMPLETED
Last Update Posted:
2011-02-25
First Post:
2007-01-19
Brief Title:
Rituximab in Membranous Nephropathy
Sponsor:
Mayo Clinic
Organization:
Mayo Clinic
Study Overview
Official Title:
The Use of Rituximab in the Treatment of Idiopathic Membranous Nephropathy
Status:
COMPLETED
Status Verified Date:
2011-02
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Membranous glomerulopathy MN is a common immune-mediated glomerular disease and the leading cause of nephrotic syndrome in Caucasian adults 1 Because of its frequency it remains the second or third cause of end-stage renal disease caused by a primary glomerulonephritis 2 At presentation 70 to 80 of patients have the nephrotic syndrome 1 3 4 Proteinuria greater than 20 grams per day is found in 80 of patients at presentation with greater than 10 grams found in as many as 30 5 The disease affects patients of all ages but it is most often diagnosed in middle age with the peak incidence during the fourth and fifth decades of life There is close to a two-to-one predominance of males to females diagnosed with the disease Idiopathic MN affects all races Current therapeutic options include corticosteroids alone or in combination with alkylating agents cyclosporin A and mycophenolate mofetil The most widely recognized and best-validated regimen is combination therapy with corticosteroids and an alkylating agent but its use is associated with significant adverse effects Recent meta-analysis confirmed that present day treatments are far from ideal 6 Thus it should not come as a surprise that the outcome of MN has not substantially improved over the past 30 years and up to 40 of patients still progress to end-stage renal failure 7 Like in other glomerular diseases the amount of protein in the urine correlates well with long term prognosis Thus this parameter has been used in previous studies and will be used in this study as the primary indicator of effectiveness of therapy We proposed to do a pilot study to test the hypothesis that selective B lymphocyte depletion will result in disappearance of pathogenic antibodies and induction of remission of the nephrotic syndrome in patients with idiopathic membranous nephropathy Our population will be 10 adults The study will be conducted between our Nephrology Divisions at Mayo Clinic Rochester Jacksonville and Scottsdale We will enroll patients with a GFR 25 mlmin as estimated by creatinine clearance and proteinuria 4g24h while receiving an ACEI or ARB and with BP controlled of 13080 mmHg Patients will receive Rituximab 1g on Day 1 and 15 Patients followed for 1 years following completion of treatment The primary outcome will be change in urinary protein excretion at 6 months Secondary outcomes will be changes in serum albumin serum lipids profile the number of partial remissions time to remission and incidence of relapses We will also perform a pharmacokinetic study to evaluate the effect of proteinuria on the bio-availability and effects of the drug
Detailed Description:
There is convincing evidence from both experimental and human studies that MN is mediated by the deposition of IgG antibodies in the subepithelial aspect of the GBM More debatable is the mechanisms of deposition of these antibodies in that location Given the key role of IgG antibodies in MN it is reasonable to postulate that suppression of antibody production by depleting B cells andor plasma cells may improve or even resolve the glomerular pathology as reflected by a reduction in proteinuria There is evidence that this strategy is effective in the treatment of other antibody-mediated diseases and preliminary studies in MN are promising Data from animal studies suggest that immune deposition resulting from B cell activation promote injury to the glomerular filtering barrier and proteinuria103 In humans as discussed above there is evidence that therapy directed against B cells eg cyclophosphamide is effective in MN Cyclophosphamide has striking direct effects on B cell function and suppresses the secretion of immunoglobulins104 Thus a case could be made for using an agent capable of depleting B cells and therefore halting the production of nephrotoxic immunoglobulins This approach could stop the pathogenic events at their initial stages and potentially result in resolution of the pathological process The rationale for using such an approach can be further substantiated by the fact that Th2 pathway for antibody response is activated and that inhibition of B cells and of pathogenic antibodies is strictly associated with beneficial effects of immunosuppressive drugs in experimental MN
This is a open-label Phase III pilot study Patients will receive Rituximab at a total dose of 1g on Day 1 and Day 15 according to infusion guidelines Patient experience complete clinical response as per response criteria outlined below AND Patient subsequently experiences clinical relapse defined as return of proteinuria to 4 g24h and in whom CD20 cell count have normalized will receive a second course of Rituximab Patients who relapse but who remain B cell depleted will not be retreated
This is a open-label Phase III pilot study Patients will receive Rituximab at a total dose of 1g on Day 1 and Day 15 according to infusion guidelines Patient experience complete clinical response as per response criteria outlined below AND Patient subsequently experiences clinical relapse defined as return of proteinuria to 4 g24h and in whom CD20 cell count have normalized will receive a second course of Rituximab Patients who relapse but who remain B cell depleted will not be retreated
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None