Background In VALIANT (phase 3; NCT05067127), pegcetacoplan (C3/C3b inhibitor) led to significant proteinuria reduction (>68% vs placebo) and estimated glomerular filtration rate (eGFR) stabilization in native kidney and posttransplant recurrent C3 glomerulopathy (C3G) and primary immune complex membranoproliferative glomerulonephritis (IC-MPGN). Here, we describe results for adolescents (12–17 years) in VALIANT. Methods Patients (randomized 1:1) received pegcetacoplan twice weekly or placebo for 26 weeks. For overall population, the primary endpoint was baseline-to-week 26 change in log-transformed urine protein-to-creatinine ratio (UPCR) in pegcetacoplan vs placebo arms. Key secondary endpoints were: patients achieving composite renal endpoint (≤15% eGFR reduction and ≥50% UPCR reduction), patients achieving ≥50% UPCR reduction, and eGFR change. Results Twenty-eight adolescents received pegcetacoplan; 27 received placebo. Consistent with overall population, pegcetacoplan-treated adolescents achieved clinically meaningful UPCR reduction (relative reduction, 75% 95% confidence interval (CI), 59 to 84; nominal P < 0.001). More adolescents in pegcetacoplan vs placebo arms achieved the composite endpoint (57% vs 4%; nominal P = 0.002) and ≥50% UPCR reduction (71% vs 4%; nominal P < 0.001). eGFR was stable for pegcetacoplan-treated adolescents (adjusted least squares mean difference 95% vs placebo, +9.7 -0.026 to 19.382 mL/min/1.73 m 2 ; nominal P = 0.05). Three adolescents in each group experienced serious treatment-emergent adverse events (pyrexia in 1 pegcetacoplan-treated patient was considered treatment related). None experienced infection caused by encapsulated bacteria. Conclusions Pegcetacoplan induced clinically meaningful proteinuria reduction and eGFR stabilization compared with placebo in adolescents with C3G or primary IC-MPGN and was well tolerated.
Vivarelli et al. (Thu,) studied this question.