Pegcetacoplan for Adolescents with C3 Glomerulopathy or Primary Immune Complex Membranoproliferative GN: Phase 3...

Adolescents with C3 glomerulopathy/primary immune complex membranoproliferative GN received pegcetacoplan. Proteinuria reduction and stable eGFR in adolescents were consistent with the overall VALIANT population. Pegcetacoplan may resolve pathophysiology underlying C3 glomerulopathy/primary immune complex membranoproliferative GN and prevent long-term kidney damage in a key patient population.

In VALIANT (phase 3; NCT05067127 ), pegcetacoplan (C3/C3b inhibitor) led to significant proteinuria reduction (>68% versus placebo) and eGFR stabilization in native kidney and posttransplant recurrent C3 glomerulopathy and primary immune complex membranoproliferative GN. Here, we describe results for adolescents (12-17 years) in VALIANT.

Patients (randomized 1:1) received pegcetacoplan twice weekly or placebo for 26 weeks. For overall population, the primary end point was baseline-to-week 26 change in log-transformed urine protein-to-creatinine ratio (UPCR) in pegcetacoplan versus placebo arms. Key secondary end points were patients achieving composite renal end point (≤15% eGFR reduction and ≥50% UPCR reduction), patients achieving ≥50% UPCR reduction, and eGFR change.

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], 59 to 84; nominal P < 0.001). More adolescents in pegcetacoplan versus placebo arms achieved the composite end point (57% versus 4%; nominal P = 0.002) and ≥50% UPCR reduction (71% versus 4%; nominal P < 0.001). eGFR was stable for pegcetacoplan-treated adolescents (adjusted least squares mean difference [95% confidence interval] versus placebo, +9.7 [-0.026 to 19.382] ml/min per 1.73 m 2 ; nominal P = 0.05). Three adolescents in each group experienced serious treatment-emergent adverse events (pyrexia in one pegcetacoplan-treated patient was considered treatment related). None experienced infection caused by encapsulated bacteria.

Pegcetacoplan induced clinically meaningful proteinuria reduction and eGFR stabilization compared with placebo in adolescents with C3 glomerulopathy or primary immune complex membranoproliferative GN and was well tolerated.

ClincialTrials.gov, NCT05067127 .