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Successful treatment with avacopan (CCX168) in a pediatric patient with C3 glomerulonephritis

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Abstract

Background

C3 glomerulonephritis (C3GN) is a subtype of C3 glomerulopathy (C3G), characterized by dysregulation of the alternative pathway of complement and by dominant C3 by immunofluorescence on the kidney biopsy. There is no approved treatment for patients with C3G. Immunosuppressive drugs as well as biologics have been used with limited success. In recent decades, substantial advances in the understanding of the complement system have led to the development of new complement inhibitors. Avacopan (CCX168) is an orally administered small-molecule C5aR antagonist that blocks the effects of C5a, one of the most potent pro-inflammatory mediators of the complement system.

Case report

We describe a child with biopsy-proven C3GN treated with avacopan. She was enrolled in the ACCOLADE double-blind placebo-controlled Phase 2 study (NCT03301467), where during the first 26 weeks she was randomized to receive an avacopan-matching placebo orally twice daily, while in the following 26 weeks, the study was open-label and she received avacopan. After a wash-out period, she was restarted on avacopan through an expanded access program.

Conclusions

In this case, use of avacopan in a pediatric patient with C3GN was safe and well tolerated. On avacopan, the patient was able to discontinue mycophenolate mofetil (MMF) while maintaining remission.

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Abbreviations

ACE-I:

Angiotensin-converting enzyme inhibitor

C3GN:

C3 glomerulonephritis

C3G:

C3 glomerulopathy

C5aR:

Complement C5a receptor

CYA:

Cyclosporin A

CP:

Cyclophosphamide

DDD:

Dense deposit disease

EU:

European Union

i.v.:

Intravenous

MAC:

Membrane attack complex

ME:

Electron microscopy

MMF:

Mycophenolate mofetil

PDN:

Prednisone

UPCR:

Urinary protein/creatinine ratio

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Acknowledgements

Vifor Renal Pharma Ltd. provided financial support for the expanded access program. Vifor Fresenius Medical Care Renal Pharma Ltd. has the exclusive right to commercialize avacopan in Italy pursuant to a license agreement with ChemoCentryx, Inc., a wholly owned subsidiary of Amgen, Inc.

This work was supported also by the Italian Ministry of Health with "Current Research funds”.

Funding

The authors declare that they have no relevant financial interests.

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Authors and Affiliations

  1. Division of Nephrology and Dialysis, Department of Pediatric Subspecialties, Bambino Gesù Pediatric Hospital IRCCS, Piazza S. Onofrio 4, 00165, Rome, Italy

    Federica Zotta, Antonio Gargiulo, Andrea Cappoli, Francesco Emma & Marina Vivarelli

  2. Department of Laboratories, Pathology Unit, Bambino Gesù Pediatric Hospital IRCCS, Rome, Italy

    Francesca Diomedi-Camassei

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  1. Federica Zotta
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  2. Francesca Diomedi-Camassei
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  3. Antonio Gargiulo
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  4. Andrea Cappoli
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  5. Francesco Emma
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  6. Marina Vivarelli
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Correspondence to Federica Zotta.

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Zotta, F., Diomedi-Camassei, F., Gargiulo, A. et al. Successful treatment with avacopan (CCX168) in a pediatric patient with C3 glomerulonephritis. Pediatr Nephrol 38, 4197–4201 (2023). https://doi.org/10.1007/s00467-023-06035-4

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  • DOI: https://doi.org/10.1007/s00467-023-06035-4

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