VALIANT Trial of Pegcetacoplan for C3G or IC-MPGN

During an oral session at ASN Kidney Week 2024, Carla M. Nester, MD, of the University of Iowa, Stead Family Children’s Hospital, Iowa City, presented results of the VALIANT trial. The session was titled 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).

The trial was designed to examine the efficacy and safety of pegcetacoplan (PEG), a C3/C3b inhibitor, in adolescents (≥12 years of age) and adults with native or post-transplant recurrent C3G or primary IC-MPGN. The primary endpoint of interest was log-transformed ratio of urine protein creatinine ratio (UPCR) at week 26 from baseline as a measure of proteinuria reduction with PEG versus placebo.

Study participants were randomized to receive PEG subcutaneously two times per week (n=63) or placebo (n=61). At week 26, the primary endpoint was met in the PEG group (–67.3%) versus placebo (3.2%); relative reduction, 68.3%; 95% CI, –76.3 to –57.7; P<.001. Results were consistent across all subgroups (disease type, age, and transplant status). There were robust reductions in C3c staining as well as clinically meaningful stabilization in eGFR in the PEG group compared to the placebo group.

Overall, there were four serious infections: three in the PEG group and one in the placebo group. None of them were attributed to encapsulated bacteria. There was one death in the PEG arm; cause of death was COVID-19 pneumonia, unrelated to PEG.

In summary, the authors, said, “PEG, a C3/C3b inhibitor, is the first therapy to achieve significant and clinically meaningful reductions in proteinuria (68.3% vs placebo) and C3c staining and eGFR stabilization, compared with placebo in patients ≥12 years with C3G or primary IC-MPGN and was well tolerated.”

Source: Nester CVM, Bomback AS, Ariceta I, et al. 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). SA-OR92. Abstract of an oral presentation at the American Society of Nephrology Kidney Week 2024; October 26, 2024; San Diego, California.