Clinical Trial: MEmbranous Nephropathy Trial Of Rituximab

Study Status: Active, not recruiting
Recruit Status: Active, not recruiting
Study Type: Interventional

Official Title: "A Randomized Controlled Trial of Rituximab Versus Cyclosporine in the Treatment of Idiopathic Membranous Nephropathy (IMN)"

Brief Summary: The primary outcome of this study is to determine whether or not the B cell targeting with Rituximab is more effective than Cyclosporine in inducing long term remission of proteinuria.

Detailed Summary:

In IMN, experimental data suggests that B cells are involved in the pathogenesis of the disease. To date, the best proven therapy for patients with MN consists of the combined use of corticosteroids and cyclophosphamide (CYC). Since the mechanism of action of CYC includes suppression of various stages of the B cell cycle including B cell activation, proliferation, and differentiation and inhibition of immunoglobulin secretion, it lends credence to the hypothesis that B cells abnormalities are involved in the pathogenesis of MN. Given the key role of IgG antibodies in MN, it is reasonable to postulate that suppression of antibody production by depleting B cells may improve or even resolve the glomerular pathology and be reflected by a reduction in proteinuria. Thus, a case could be made for using an agent capable of selectively depleting B cells, and therefore halting the production of immunoglobulins against antigens potentially present in the glomeruli. This approach could stop the initiating sequence of pathogenic events and result in resolution of the. The P.I. believes that the application of selective B cell targeting with Rituximab (RTX) will prove at least equal, or even superior, both in the production of short term and long term control of the NS and be safer than any current therapeutic regimen used to treat MN.

Based on this rationale, we conducted a pilot trial in 15 newly-biopsied patients (<3 years) with IMN and proteinuria >5g/24h despite ACEi/ARB use for >3months and systolic BP <130mmHg. Mean baseline creatinine was 1.4 mg/dl. Thirteen males and 2 females, median age 47 (range 33-63), were treated with RTX (1g) on days 1 and 15. At six months, patients who remained with proteinuria >3g/24 received a second identical course of RTX. Baseline proteinuria of 13.0±5.7g/24h (range 8.4-23.5) decreased to 6.0±7.0 g/24h (range 0.2-20) at 1
Sponsor: Mayo Clinic

Current Primary Outcome: Remission status [ Time Frame: 24 months after randomization ]

Complete remission or partial remission at 24 months after randomization will be the primary endpoint.


Original Primary Outcome: Remission status [ Time Frame: After 27 months ]

The primary outcome is to determine whether or not the B cell targeting with Rituximab is more effective than Cyclosporine in inducing long term remission of proteinuria.


Current Secondary Outcome: Remission Status [ Time Frame: 6-24 months after randomization ]

Relapse state at month 24 after randomization (Urine Protein) (UP) >3.5 after earlier CR or PR; CR(Complete Remission) or PR (Partial Remission), and CR alone at 6, 12, 18, and 24 after randomization; Time to CR or PR; Anti-PLA2R levels; Quality of life as measured by modified KDQOL; Adverse events; ESRD


Original Secondary Outcome: Remission Status [ Time Frame: 6-27 months ]

CR(Complete Remission) or PR (Partial Remission), and CR alone at 6, 12, 18, 24, and 27 months Frequency of and time to relapse Rate of change in urinary protein at 6 and 12 months and beyond Time to CR or PR and to CR alone. Toxicity Quality of life as measured by SF-36 Frequency of PRA2 antibodies and its relation to therapy and proteinuria response


Information By: Mayo Clinic

Dates:
Date Received: August 10, 2010
Date Started: November 2011
Date Completion: October 2017
Last Updated: March 21, 2017
Last Verified: November 2016