WCN24-683 efficacy of 12-week pegcetacoplan in kidney transplant recipients with recurrent C3 glomerulopathy (C3G) or immune complex membranoproliferative glomerulonephritis (IC-MPGN).

Abstract

Introduction: Pegcetacoplan (PEG; C3 inhibitor) may prevent C3G or IC-MPGN progression. NOBLE (NCT04572854) is the first prospective randomized controlled trial of PEG vs standard of care (SOC) in kidney transplant recipients (KTRs) with primary C3G or IC-MPGN recurrence. Method(s): Adult patients (pts) were randomized 3:1 to subcutaneous PEG 1080 mg twice weekly plus SOC (n=10) or SOC only (n=3). Primary endpoint: reduction in renal biopsy C3c staining (>=2 orders of magnitude [OOM]) from baseline to Week 12 (W12). Additional W12 endpoints: changes in eGFR, uPCR, C3G activity score, serum C3, and serum sC5b-9. Result(s): 9 (69.2%) pts had C3G and 4 (30.8%) had IC-MPGN. At W12, 5 (50%) PEG pts had >=2 OOM reduction in C3c staining (4 had 0 intensity); 8 (80%) had >=1 OOM reduction (Figure). 9 (90%) PEG pts had reduced C3G activity score at W12. In subgroup (>=1000 mg/g), uPCR decreased with PEG (-39.2%) at W12. eGFR remained stable, serum C3 increased, and sC5b-9 decreased with PEG (Table). There were no discontinuations/deaths due to treatment-emergent adverse events. [Formula presented] Conclusion(s): As early as W12, pegcetacoplan reduced C3c staining and proteinuria with stable eGFR, targeted the pathophysiology of C3 dysregulation, and was well tolerated in KTRs with recurrent C3G or IC-MPGN. This abstract was also submitted for the American Society of Nephrology Annual Meeting 2023 congress I have potential conflict of interest to disclose.Copyright © 2024