Fadi Fakhouri, MD, PhD, Professor of Nephrology at Lausanne University, discusses the results from a phase 2 clinical trial testing the safety and efficacy of pegcetacoplan in patients with C3G and IC-MPGN.
Complement 3 glomerulopathy (C3G) and immune-complex membranoproliferative glomerulonephritis (IC-MPGN) are rare kidney diseases characterized by damage to the glomeruli in the kidney that filter blood for toxins and produce urine. Abnormal activation of the complement system, which Dr. Fakhouri describes as the first line of protection against infection, can be caused by genetic mutations or the absence of regulatory proteins. This leads to the destruction of C3 proteins. When these proteins get lodged in the kidney, glomeruli get injured and buildup of toxins and reduced urine production occur. This can ultimately lead to declined kidney function. Common signs and symptoms include:
- Hematuria
- Proteinuria
- Reduced glomerular filtration rate and increased creatinine levels
- Fatigue
- Edema of the hands, feet, and ankles
There are currently no FDA approved treatments for C3G and IC-MPGN so management focuses on slowing the progression of kidney damage and addressing symptoms.
Clinical Trial
The NOBLE trial is a phase 2, multicenter, open-label, randomized, controlled study evaluating the safety and efficacy of pegcetacoplan in patients with post-transplant recurrence of C3G or IC-MPGN. Pegcetacoplan is a targeted C3 therapy that regulates excessive activation of the complement system.
11 patients were treated with pegcetacoplan for one year. At this year mark, it was observed that 64% of patients had a reduction in C3c staining by two or more orders of magnitude of intensity from baseline and 55% of patients showed no C3c staining intensity, indicating that C3c deposits were cleared. 64% of patients also showed zero inflammation. The treatment also showed improvements in proteinuria and stabilization of kidney function.
An ongoing phase 3 study, VALIANT, is further evaluating the potential of pegcetacoplan in all patients with C3G and IC-MPGN.
To learn more about C3G, IC-MPGN, and other rare kidney diseases, visit https://checkrare.com/diseases/kidney-and-urinary-diseases/