Efficacy and Safety of Pegcetacoplan in Kidney Transplant Recipients With Recurrent Complement 3 Glomerulopathy or Primary Immune Complex Membranoproliferative Glomerulonephritis.
Bomback, A. S., et al.KI Reports 2025; 10(1): 87-98.
Aims
The aim of this paper was to report the 12-week results of the NOBLE randomised controlled trial which investigated the role of pegcetacoplan in post-kidney transplant patients with recurrent complement 3 glomerulopathy (C3G) or immune complex membranoproliferative glomerulonephritis (IC-MPGN).
Interventions
Participants were randomised to either the pegcetacoplan group or standard-of-care (SOC) only group.
Participants
13 adult post-kidney transplant recipients with recurrent C3G or primary IC-MPGN from the NOBLE trial.
Outcomes
The primary efficacy outcome was the proportion of patients that showed a reduction in C3c immunofluorescence staining on renal biopsy. The main secondary efficacy outcomes were the changes in eGFR and serum creatinine concentration over time, and changes from baseline biopsy in C3c staining over time. Safety outcomes were the number and incidence of rejection episodes and graft loss; and the number, incidence, severity and seriousness of treatment-emergent adverse events (TEAEs).
Follow-up
12 weeks
CET Conclusions
Complement 3 glomerulopathy (C3G) and primary immune complex membranoproliferative glomerulonephritis (IC-MPGN) are rare causes of renal failure, but with a high recurrence rate. Pegcetacoplan, a C3 inhibitor which is used for paroxysmal nocturnal haematuria, has been assessed as a potential treatment for C3G and IC-MPGN recurrence. This exploratory study evaluated the efficacy and adverse effect profile of Pegcetacoplan in patients with biopsy proven disease recurrence. Patients were randomized to Pegcetacoplan and standard of care (SOC) vs SOC only administered over a 12-week period. Outcomes included reduction in C3 staining, stability of renal function and rate of treatment emergent adverse events (TEAE). 10 patients were randomized to the treatment group and 3 to the control group. A significant reduction in C3 staining was found in the Pegcetacoplan group but with no difference in renal function. There was no difference in TEAEs. Intended as a ‘proof of concept’ trial, the authors acknowledge that the small patient number and short follow-up period preclude reaching meaningful conclusions. There are other limitations which are not highlighted, and will affect the next phase of the study (12 month follow-up). Patients in the Pegcetacoplan group were recruited at a much earlier stage in their treatment journey (1.9 years vs 5.5 years after kidney transplant), which could underestimate the efficacy of SOC. Half of the patients in the treatment group also received systemic steroid therapy vs none in the SOC group. Finally, the SOC is not described in the methodology, which makes safety analysis difficult to intrepid.
Data analysis
Strict intention-to-treat analysis
Trial registration
ClinicalTrials.gov - NCT04572854