Rituximab Versus Steroids and Cyclophosphamide in the Treatment of Idiopathic Membranous Nephropathy
Status:
Unknown status
Trial end date:
2019-12-01
Target enrollment:
Participant gender:
Summary
Idiopathic Membranous nephropathy (IMN) is an auto-immune glomerular disease. Recent studies
suggest that circulating auto-antibodies against the podocyte surface antigens phospholipase
A2 receptor1 (PLA2R1) and thrombospondin type 1 domain-containing 7A (THSD7A) cause the
disease in the majority of the patients. Additional autoantibodies, directed to podocyte
neo-expressed cytoplasm proteins have been described, including aldose reductase (AR),
Mn-superoxide dismutase (SOD2) and alpha-enolase (alpha-ENO).
The commonest presentation of IMN is nephrotic syndrome. Data from placebo arms of
interventional studies show that 30-40% of the untreated patients with persistent nephrotic
syndrome (NS) progress to end-stage renal disease (ESRD).
The best-validated treatment regimen of IMN is combination therapy with steroids and
cyclophosphamide, capable to induce remission of protenuria in two-third of the patients.
Despite this evidence of efficacy, there are concerns about the use of cyclophosphamide,
since it may be associated with adverse events, including bone marrow suppression, gonadal
toxicity, infections and oncogenic effects. Thus, the availability of alternative therapies
highly effective but with a greater safety profile is desirable.
Given the key role of IgG antibodies in IMN, B cell depletion may favourably impact the
glomerular disease. The anti-CD20 monoclonal antibody Rituximab is a selective B cell
depleting agent. There is evidence that Rituximab is effective in the treatment of other
diseases in which B cells play a key role, such as ANCA-related vasculitis. Observational
studies in IMN provided encouraging data; in addition, the drug seems well tolerated.
Head-to-head comparisons between Rituximab and steroid plus ciclophosphamide in randomized
clinical trials are missing.
The investigators propose this study in order to test, in a randomized controlled trial, the
hypothesis that Rituximab is more effective than cyclical steroid/alkylating-agent therapy in
inducing remission in patients with IMN and NS undergoing the initial treatment. In addition,
the levels of the above-mentioned pathogenetic autoantibodies will be measured at baseline
and during treatment. Finally, the study will compare the safety profile of steroid plus
cyclophosphamide and Rituximab by evaluating the rate and severity of adverse events
Phase:
Phase 3
Details
Lead Sponsor:
Azienda Ospedaliera Spedali Civili di Brescia Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia
Collaborators:
Azienda Ospedaliera Brotzu Azienda Ospedaliera Universitaria di Bologna Policlinico S. Orsola Malpighi Azienda Ospedaliera Universitaria Policlinico Azienda Sanitaria Locale Roma E Fondazione Salvatore Maugeri Humanitas Hospital, Italy IRCCS Azienda Ospedaliero-Universitaria di Bologna Istituto Giannina Gaslini Regione Piemonte Universita di Verona University of Alberta University of Bari University of Bern University of Bologna University of Chieti University of Messina University of Milan University of Milano Bicocca University of Modena and Reggio Emilia University of Pisa