Carla Nester, MD, professor at the University of Iowa and lead principal investigator for the VALIANT study, discusses the clinical trial testing pegcetacoplan in patients with C3G and primary IC-MPGN.
Complement 3 glomerulopathy (C3G) and immune-complex membranoproliferative glomerulonephritis (IC-MPGN) are rare kidney diseases. They are characterized by damage to the glomeruli in the kidney that filter blood for toxins and produce urine. Abnormal activation of the complement system 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
Currently, the FDA has not approved any treatments for C3G and IC-MPGN. Management focuses on slowing the progression of kidney damage and addressing symptoms.
Pegcetacoplan is a targeted C3 therapy currently approved for treatment of paroxysmal nocturnal hemoglobinuria (PNH). The therapy targets the excessive activation of the complement cascade, a typical cause of the onset of such diseases and their progression.
VALIANT Clinical Trial
The phase 3 VALIANT study is a randomized, placebo-controlled, double-blind, multi-center trial evaluating the safety and efficacy of pegcetacoplan in patients ages 12 years and older with C3G or primary IC-MPGN. With 124 patients, the study is the largest single trial to be conducted in this disease space and is the only one to include both adolescent and adult patients with native and post-transplant kidneys. Participants received 1080 mg of pegcetacoplan or placebo twice weekly for 26 weeks. Following this controlled period, participants were able to continue a 26-week open-label phase in which all patients were treated with pegcetacoplan.
The primary endpoint of this study was the log transformed ratio of urine protein to creatinine ratio (uPCR) at week 26 compared to baseline. This endpoint was met with a statistically significant 68% proteinuria reduction compared to placebo. Additionally, it was observed that the treatment produced statistically significant results in secondary endpoints of composite renal endpoint and proteinuria reduction of at least 50 percent compared to baseline. The results were consistent across all groups. Favorable safety and tolerability were also demonstrated.
There are plans for the company to submit a supplemental new drug application to the U.S. Food and Drug Administration in early 2025.
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To learn more about C3G and IC-MPGN and other rare kidney diseases, visit https://checkrare.com/diseases/kidney-and-urinary-diseases/
