Advancing Treatment for C3G; Targeting the Complement System for Personalized Kidney Care - Episode 11
Expert Perspectives on VALIANT: Trial Design and Key Results
Panelists discuss how Andrew S. Bomback, MD, MPH, having been closely involved in the VALIANT trial, outlines the study’s design—a 6-month placebo-controlled period followed by open-label treatment—and highlights its significant outcomes, including over 65% proteinuria reduction, statistically significant glomerular filtration rate (GFR) improvements, and remarkable C3 clearance on kidney biopsies.
Video content above is prompted by the following:
VALIANT Trial – Pegcetacoplan in C3G and Immune Complex MPGN
Study Overview
The VALIANT trial investigated the efficacy and safety of pegcetacoplan, a complement C3 inhibitor, in patients with C3 glomerulopathy (C3G) and immune complex membranoproliferative glomerulonephritis (IC-MPGN). The design included:
- 6-month double-blind phase (pegcetacoplan vs placebo)
- 6-month open-label extension
- Participants: approximately 80% C3G and 20% IC-MPGN
- Included pediatric patients ≥12 years and posttransplant patients
Primary and Secondary End Points
- Primary end point: Reduction in proteinuria at 6 months
- Secondary end points:
- Change in estimated GFR (eGFR)
- Histologic response, particularly C3 staining on kidney biopsy
Key Efficacy Findings
- Proteinuria reduction: >65% in pegcetacoplan-treated group
- eGFR preservation: Statistically significant difference vs placebo
- C3 clearance: >70% of patients achieved 0 C3 staining on repeat biopsy
- Posttransplant results: In the NOBLE study (transplants), 50% achieved 0 C3 staining by 12 weeks
Pediatric and Transplant Populations
- Pegcetacoplan showed comparable efficacy across:
- C3G and IC-MPGN subtypes
- Adolescents and adults
- Native and transplant kidneys
Safety Profile
- Pegcetacoplan was well tolerated:
- No cases of encapsulated Neisseria infections
- No increase in serious infections (eg, COVID-19, influenza, pneumonia)
- No major safety signal or treatment arm imbalance
- All participants were appropriately vaccinated against encapsulated bacteria
Clinical Implications
- The trial demonstrated robust control of complement activity, including dramatic histologic responses
- These results support pegcetacoplan as a promising treatment for C3G and IC-MPGN
- Questions remain regarding treatment duration and long-term management, which will require post-approval data
Conclusion
Pegcetacoplan has shown strong efficacy in reducing proteinuria and complement deposition in both native and transplant kidneys across pediatric and adult populations, with a favorable safety profile. These results position pegcetacoplan as a potentially transformative therapy in C3G and IC-MPGN management.
