Clinical Trials Logo

Clinical Trial Summary

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


Clinical Trial Description

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 (IgG) 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 nephrotic syndrome (NS) and be safer than any current therapeutic regimen used to treat MN.

Based on this rationale, the investigators 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 <130 millimeter of mercury (mmHg). 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 12 months (mean ± SD). In the fourteen patients who completed a 12 months follow-up complete remission (proteinuria <0.3g/24h) was achieved in 2 patients and partial remission (<3g/24h) in 7 patients. In 5 of these 7 patients, proteinuria was <1.5g/24h and follow up at 18 months showed that 3 of these 7 patients on PR achieved CR of proteinuria. Five patients did not respond. The mean drop in proteinuria from baseline to 12 months was 6.2± 5.1g (p=.002, paired t-test). There were a limited number of minor side-effects. Initial cluster of differentiation 20 (CD20)+ B cell depletion was seen in all patients. However, at 3 months, CD20+ B cells were starting to recover with five patients >35 cells/µl (range 35-152).(50) These data contrasts with previous work by Ruggenenti et al. using RTX given weekly (375 mg/m2) for 4 weeks. Pharmacokinetic (PK) analysis showed that RTX levels in this 2-dose regimen were 50% lower compared to non-proteinuric patients, which could potentially result in undertreatment.

Based on these results, the investigators recently conducted a study postulating that in patients with MN, 4 weekly doses of RTX would result in more effective B cell depletion, a higher remission rate and maintaining of the same safety profile compared to patients treated with RTX dosed at 1g x 2. ;


Study Design


Related Conditions & MeSH terms


NCT number NCT01180036
Study type Interventional
Source Mayo Clinic
Contact
Status Completed
Phase Phase 2/Phase 3
Start date November 2011
Completion date October 1, 2017

See also
  Status Clinical Trial Phase
Recruiting NCT06245707 - the Effects of Different Treatment Schemes on Cognitive Function of Patients With Idiopathic Membranous Nephropathy N/A
Recruiting NCT03864250 - Tacrolimus Monotherapy for Idiopathic Membranous Nephropathy N/A
Completed NCT01845688 - Clinical Study of QingReMoShen Granule to Treat Idiopathic Membranous Nephropathy N/A
Withdrawn NCT01093781 - Aliskiren in Patients With Idiopathic Membranous Nephropathy N/A
Completed NCT00362531 - Tacrolimus Combined With Prednisone Treatment of Idiopathic Membranous Nephropathy and Nephrotic Syndrome Phase 2/Phase 3
Recruiting NCT05839314 - Effect of Huaier Granule on the Treatment of Idiopathic Membranous Nephropathy Phase 4
Completed NCT00302523 - Tacrolimus Treatment of Patients With Idiopathic Membranous Nephropathy N/A
Terminated NCT03466801 - The Efficacy of Prednisone and Combination Therapy With Methylprednisolone and Cyclophosphamide on IMN in Stage I. N/A
Terminated NCT03475602 - Membranous Nephropathy-associated Serological Antibody Predict the Prognosis of Idiopathic Membranous Nephropathy
Not yet recruiting NCT05850845 - Study on the Application of Hyperspectral Imaging Technique in CTX Treatment of IMN
Not yet recruiting NCT05667922 - Prognostic Model of TAC in the Treatment of MN
Not yet recruiting NCT05667896 - Prognostic Model of GC/TAC in the Treatment of MN
Not yet recruiting NCT05667883 - Prognostic Model of GC/CTX in the Treatment of MN
Not yet recruiting NCT05667909 - Prognostic Model of Rituximab in the Treatment of MN
Recruiting NCT02173106 - A Controlled Study of Steroids Plus Cyclosporin Therapy for Patients of Idiopathic Membranous Nephropathy Phase 2
Completed NCT01161459 - Treatment of Idiopathic Membranous Nephropathy With Tripterygium Wilfordii Plus Steroid vs Tacrolimus Plus Steroid N/A
Recruiting NCT03549663 - Tacrolimus Monotherapy for Idiopathic Membranous Nephropathy (IMN) N/A
Not yet recruiting NCT05845762 - Obinutuzumab in the Management of Idiopathic Membranous Nephropathy
Completed NCT00694863 - Treatment With Synthetic ACTH in High Risk Patients With Membranous Nephropathy Phase 2
Recruiting NCT03170323 - Mycophenolate Mofetil Plus Steroid in the Treatment Of Patients With Progressive Idiopathic Membranous Nephropathy Phase 4