Treatment trials- Rituximab plus cyclosporine for MN and Belimumab plus rituximab for MN (REBOOT)

National Institute Of Diabetes And Digestive And Kidney Diseases

Investigators

Abstract

The purpose of the pilot study using a combination of Rituximab plus cyclosporine is to test if there are greater number of remissions of the nephrotic syndrome and more sustained remissions than is expected with cyclosporine alone. Although each of these medications has been used separately in membranous nephropathy, the potential benefits and risks of this combination have not yet been formally explored. Subjects enrolled in this study will receive two doses of intravenous infusion of rituximab given two weeks apart. Subjects will also take cyclosporine twice a day. After 6 months, the dose of cyclosporine will be tapered over several weeks and then discontinued. Subjects will be retreated with a second course of Rituximab (two doses of intravenous infusion given two weeks apart) at least 6 months have passed since the first rituximab course and CD+B cells have recovered >5 cells/uL. The primary objective of REBOOT which combines belimumab and rituximab is to evaluate the effectiveness of belimumab and intravenous rituximab co-administration at inducing a complete or partial remission (CR or PR) compared to rituximab alone in primary membranous nephropathy. Participants randomized to the belimumab and rituximab arm will receive subcutaneous belimumab 400 mg once weekly from weeks 0-3, and then 200 mg once weekly from weeks 4-51.Participants randomized to the belimumab placebo and rituximab arm will receive subcutaneous belimumab placebo according to the same dose and schedule. Participants in both arms will receive rituximab 1000 mg IV at weeks 4 and 6. At week 30, participants will be assessed for a response to study treatment. Participants who meet at least two of the following three criteria at week 30 will be considered to have an inadequate response to study treatment and, defined as fulfilling at least two of the following three criteria at week 30, will receive a second course of rituximab (1000 mg IV at weeks 34 and 36): [Anti-PLA2R levels is ≥ 25% of baseline; Proteinuria is ≥ 50% of baseline; Serum albumin is < 2.8 g/dL]. After the 52 week treatment period, all participants will be followed on no study medication with assessment of the primary endpoint (CR or PR) at week 104.