Phase 3; NCT05067127) evaluated the efficacy and safety of pegcetacoplan in adolescents (12 years) and adults with native or posttransplant C3G or primary IC-MPGN. At Week 26, patients treated with pegcetacoplan demonstrated a significant reduction in proteinuria compared with placebo, along with stable estimated glomerular filtration rate (eGFR) and evidence of glomerular C3c clearance. In the subsequent 26-week open-label period (OLP), all patients received pegcetacoplan. Here, we report treatment responses in key patient subgroups, stratified by baseline proteinuria and concomitant immunosuppressant (IS) use, across both the randomized controlled period (RCP) and the OLP. Methods: 59 of 63 pegcetacoplan-to-pegcetacoplan and 55 of 61 placebo-to-pegcetacoplan patients completed OLP. Efficacy end points included changes from baseline in proteinuria and estimated glomerular filtration rate (eGFR). Treatment-emergent adverse events were recorded. Results: Patients receiving pegcetacoplan for 52 weeks had sustained proteinuria decrease (mean 95% CI change: week 26, -67. 2% -74. 9, -57. 2; week 52, -67. 2% -75. 8, -55. 4). Results were consistent with overall population regardless of IS use and baseline nephrotic proteinuria (Figure). eGFR was stable for overall pegcetacoplan-treated population (least squares mean SE change, mL/min/1. 73m2: week 26, -1. 5 2. 2; week 52, -3. 7 2. 7). No new safety signals were identified. Conclusion: Proteinuria reductions and eGFR stabilization in the VALIANT RCP were maintained regardless of baseline proteinuria and IS use, confirming pegcetacoplan's durable and consistent efficacy. eGFR was stable. The safety profile of pegcetacoplan was consistent with previous studies.
Okabayashi et al. (Wed,) studied this question.