Efficacy and Safety of Bleselumab in Preventing the Recurrence of Primary Focal Segmental Glomerulosclerosis in Kidney Transplant Recipients: A Phase 2a, Randomized, Multicenter Study.
Shoji, J., et al.Transplantation 2024 [record in progress].
Aims
This study aimed to investigate the effect of Bleselumab in the prevention of recurrent focal segmental glomerulosclerosis (rFSGS) in kidney transplant patients.
Interventions
Participants were randomised to either the Bleselumab group or the standard of care group.
Participants
Adult kidney transplant recipients (≥18 y) who had a history of biopsy-proven primary FSGS as a cause of endstage renal disease in their native kidney; and, for those with a previous transplant, whose current graft failure was also due to biopsy-proven rFSGS.
Outcomes
The primary outcome was the recurrence of FSGS within 3 months post-transplantation. The secondary outcomes were the recurrence of FSGS within 6 to 12 months post-transplantation, biopsy-proven acute rejection, efficacy failure, and biopsy-proven rFSGS.
Follow-up
12 months post-transplantation
CET Conclusions
Bleselumab is a human immunoglobulin G4 anti-CD40 monoclonal antibody, which has been shown to block B-cell CD40 receptors implicated in the pathogenesis of focal segmental glomerulosclerosis (FSGS). This phase 2a, randomised multicentre study investigated the role of Bleselumab in the prevention of FSGS recurrence following renal transplantation. 63 patients with biopsy-proven FSGS were randomised to bleselumab or standard-care. Recurrence of FSGS (the primary endpoint) was defined as nephrotic syndrome-level proteinuria, with death, graft loss or loss to follow-up all imputed as recurrence. Numerical reductions in recurrent FSGS were seen in the bleselumab group compared to controls, both by the study definition and on central histological review, but none of these differences reached statistical significance. The study is open-label and the method of randomisation is not clearly described. No a priori sample size calculation was undertaken, and the study is likely underpowered to the primary endpoint, further hampered by withdrawal of around one third of the patients in each arm due to adverse events. Overall, the study provides enough information to aid the design of a subsequent trial but is far from conclusive.
Data analysis
Per protocol analysis
Trial registration
Clinical trials.gov - NCT02921789