Abstract: PUB226
Safety and Efficacy of Avacopan (CCX168) in a Pediatric Patient with C3 Glomerulopathy
Session Information
Category: Glomerular Diseases
- 1203 Glomerular Diseases: Clinical, Outcomes, and Trials
Authors
- Vivarelli, Marina, Division of Nephrology and Dialysis - Bambino Gesù Pediatreic Hospital IRCCS, Rome, RM, Italy
- Arena, Maria, Division of Nephrology and Dialysis - Bambino Gesù Pediatreic Hospital IRCCS, Rome, RM, Italy
- Zotta, Federica Fz, Division of Nephrology and Dialysis - Bambino Gesù Pediatreic Hospital IRCCS, Rome, RM, Italy
- Cappoli, Andrea, Division of Nephrology and Dialysis - Bambino Gesù Pediatreic Hospital IRCCS, Rome, RM, Italy
- L'Erario, Ines Dr, Division of Nephrology and Dialysis - Bambino Gesù Pediatreic Hospital IRCCS, Rome, RM, Italy
- Busutti, Marco, Division of Nephrology and Dialysis - Bambino Gesù Pediatreic Hospital IRCCS, Rome, RM, Italy
- Emma, Francesco, Division of Nephrology and Dialysis - Bambino Gesù Pediatreic Hospital IRCCS, Rome, RM, Italy
Introduction
C3 glomerulonephritis (C3GN) is a subtype of C3 glomerulopathy, characterized by alternative pathway complement activation and intense C3 immunofluorescence on renal biopsy.
C5a is a potent pro-inflammatory mediator of the complement system, whose chemotactic effects are mainly mediated by the interaction with complement C5a receptor (C5aR) expressed on the cell surface.
Avacopan is an orally administered selective inhibitor of C5aR.
Case Description
An 11-year-old female with biopsy-proven C3GN was initially treated with three intravenous (IV) boluses of methylprednisolone then tapered to oral prednisone (PDN) given with mycophenolate mofetil (MMF) and an angiotensin-converting enzyme inhibitor (ACE-i). Complete remission was achieved, PDN was stopped, and MMF and ACE-i were maintained. Twelve months following remission, due to relapse of proteinuria (urinary protein/creatinine ratio [UPCR] 1.19 mg/mg), a second course of PDN therapy was started and cyclosporin (CyA) was added to the therapy. A high level of C5b9 was found.
Since the patient never achieved complete remission, she was enrolled in the ChemoCentryx ACCOLADE study, which was a randomized, double blind, placebo controlled study. Patients received avacopan or matching placebo for the first 26 weeks, followed by open-label avacopan in all patients for the following 26 weeks.
At the end of the open-label phase, her UPCR was 2.09 mg/mg. Following avacopan, a progressive reduction of proteinuria of approximately 0.5 mg/mg was observed. In the last 4 weeks of the study, avacopan was discontinued, and an increase in proteinuria (UPCR 0.7 mg/mg) was observed, which continued to >1 mg/mg in the subsequent weeks. The patient also reported increased fatigue.
After about 3 months, authorization for compassionate use of avacopan was obtained and the patient experienced improvement in her physical well-being and a reduction of proteinuria of approximately 0.5 mg/mg. CyA was discontinued, but it was rapidly reintroduced due to a transient increase of proteinuria. In the following months, proteinuria remained low despite the interruption of MMF. At the last follow up (+16 months from open-label start) UPCR was 0.29 mg/mg and the drug was well tolerated.
Discussion
To the best of our knowledge, this is the first report on the use of avacopan in a pediatric case of C3GN.