VALIANT: A Randomized, Multicenter, Double-Blind, Placebo (PBO)-Controlled, Phase 3 Trial of Pegcetacoplan for Patients with Native or Post-transplant Recurrent Glomerulopathy (C3G) or Primary Immune Complex Membranoproliferative Glomerulonephritis (IC-MPGN)
Carla Nester, Andrew S. Bomback, María Gema Ariceta Iraola, Yahsou Delmas, Bradley P. Dixon, Daniel P. Gale, Larry A. Greenbaum, Seung Hyeok Han, Nicole M. Isbel, Christoph Licht, Antonio Mastrangelo, Masashi Mizuno, Maria Izabel Neves de Holanda, Matthew C. Pickering, Giuseppe Remuzzi, Nicole C. A. J. van de Kar, Marina Vivarelli, Patrick D. Walker, Dean Wallace, Daniel Zecher, Li Li, Zhongshen Wang, Luis López Lázaro, Johan Szamosi, Fádi Fakhouri
Abstract
Background: VALIANT (NCT05067127) is a double-blind, PBO-controlled trial investigating the efficacy/safety of pegcetacoplan (PEG), a C3/C3b inhibitor, in adolescents (≥12 yrs) and adults with native or post-transplant recurrent C3G or primary IC-MPGN. Methods: Patients (pts) received PEG (SC infusion 2x/wk) or PBO (randomized 1:1) for 26 wks. The primary endpoint was log-transformed ratio of uPCR at wk 26 vs. baseline to measure proteinuria reduction vs. PBO. Results: 124 pts were randomized to PEG (n=63) or PBO (n=61). The primary endpoint was met:68.3% (95% CI –76.3, –57.7) uPCR reduction in PEG vs. PBO arms at wk 26 (p<0.0001; Table). Results were consistent across all subgroups (disease type, age, and transplant status). Robust reductions in C3c staining and clinically meaningful eGFR stabilization were observed with PEG vs. PBO (Table). Treatment-emergent AE frequency and severity were similar between arms. None of the 4 serious infections (3 PEG; 1 PBO) were attributed to encapsulated bacteria. 1 death occurred in the PEG arm due to COVID-19 pneumonia (unrelated to PEG). Conclusion: PEG, a C3/C3b inhibitor, is the first therapy to achieve significant and clinically meaningful reductions in proteinuria (68.3% vs. PBO) and C3c staining and eGFR stabilization, compared with PBO in pts ≥12 yrs with C3G or primary IC-MPGN and was well tolerated.