Journal article
Trial of Pegcetacoplan in C3 Glomerulopathy and Immune-Complex MPGN
The New England journal of medicine, Vol.393(22), pp.2210-2220
12/04/2025
DOI: 10.1056/NEJMoa2501510
PMID: 41337715
Abstract
C3 glomerulopathy and primary immune-complex membranoproliferative glomerulonephritis (MPGN) generally result in glomerular C3 deposition and irreversible kidney damage. The efficacy and safety of pegcetacoplan, a C3 and C3b inhibitor, in persons with C3 glomerulopathy or primary immune-complex MPGN are unclear.
We conducted a phase 3, double-blind, placebo-controlled trial involving adolescents and adults with C3 glomerulopathy or primary immune-complex MPGN, including those with native kidney disease and those with disease recurrence after transplantation. Patients were randomly assigned in a 1:1 ratio to receive pegcetacoplan or placebo. The primary end point was the log-transformed ratio of the urinary protein-to-creatinine ratio at week 26 as compared with baseline.
A total of 124 patients underwent randomization. The change in proteinuria (as measured by the log-transformed ratio to baseline in the urinary protein-to-creatinine ratio) was significantly greater with pegcetacoplan than with placebo (geometric mean of the urinary protein-to-creatinine ratio, -67.2% [95% confidence interval {CI}, -74.9 to -57.2] vs. 2.9% [95% CI, -8.6 to 15.9]). The difference represents a relative reduction of 68.1% (95% CI, 57.3 to 76.2) as compared with placebo. In hierarchical testing of five secondary end points, significantly higher percentages of patients in the pegcetacoplan group than in the placebo group met the composite renal end-point criteria (stabilization of estimated glomerular filtration rate [eGFR] and ≥50% reduction in urinary protein-to-creatinine ratio) (49% vs. 3%) and had at least a 50% reduction in the protein-to-creatinine ratio (60% vs. 5%). Among 69 patients with evaluable kidney-biopsy samples, the change in the activity score of the C3 glomerulopathy histologic index did not differ significantly between the two groups; subsequent end points (decrease in C3 staining and change in eGFR) were not formally tested. Pegcetacoplan was not associated with more adverse events than placebo. No serious infections from encapsulated bacteria occurred; 1 patient receiving pegcetacoplan died from coronavirus disease 2019 pneumonia. No allograft rejection or loss occurred.
Pegcetacoplan resulted in a significantly greater reduction in proteinuria than placebo among patients with C3 glomerulopathy or primary immune-complex MPGN. (Funded by Apellis Pharmaceuticals and Sobi [Swedish Orphan Biovitrum]; VALIANT ClinicalTrials.gov number, NCT05067127.).
Details
- Title: Subtitle
- Trial of Pegcetacoplan in C3 Glomerulopathy and Immune-Complex MPGN
- Creators
- Fadi Fakhouri - University of LausanneAndrew S Bomback - Columbia University Irving Medical CenterGema Ariceta - Vall d'Hebron Hospital UniversitariYahsou Delmas - Bordeaux Population HealthBradley P Dixon - University of Colorado DenverDaniel P Gale - University College LondonLarry A Greenbaum - Emory UniversitySeung Hyeok Han - Yonsei UniversityNicole Isbel - The University of QueenslandMoglie Le Quintrec - Centre Hospitalier Universitaire de MontpellierChristoph Licht - University of TorontoAntonio Mastrangelo - Fondazione IRCCS Ca' Granda Ospedale Maggiore PoliclinicoMasashi Mizuno - Nagoya UniversityMaria Izabel Neves de Holanda - Hospital Geral de BonsucessoMatthew C Pickering - Imperial College LondonGiuseppe Remuzzi - Istituti di Ricovero e Cura a Carattere ScientificoNicole Van De Kar - Radboud University Medical CenterMarina Vivarelli - Bambino Gesù Children's HospitalPatrick D Walker - Arkana LaboratoriesDean Wallace - Royal Manchester Children's HospitalDaniel Zecher - University Hospital RegensburgCedric Francois - Apellis PharmaceuticalsPascal Deschatelets - Apellis PharmaceuticalsLi Li - Apellis PharmaceuticalsZhongshen Wang - Apellis PharmaceuticalsLydia Abad-Franch - Swedish Orphan BiovitrumNils Kinnman - Swedish Orphan BiovitrumLuis López-Lázaro - Swedish Orphan BiovitrumJohan Szamosi - Swedish Orphan BiovitrumCarla M Nester - University of IowaVALIANT Trial Investigators Group
- Resource Type
- Journal article
- Publication Details
- The New England journal of medicine, Vol.393(22), pp.2210-2220
- DOI
- 10.1056/NEJMoa2501510
- PMID
- 41337715
- NLM abbreviation
- N Engl J Med
- ISSN
- 0028-4793
- eISSN
- 1533-4406
- Publisher
- MASSACHUSETTS MEDICAL SOC
- Grant note
- Apellis Pharmaceuticalshttp://dx.doi.org/10.13039/100019531Swedish Orphan Biovitrumhttp://dx.doi.org/10.13039/501100012112
We thank the patients, investigators, and health care professionals who participated in this trial; Federico Grossi, M.D., Ph.D., and Matthew Ferenc, Ph.D., of Apellis Pharmaceuticals; and Kathryn Fogarty, Ph.D., Jennifer Gibson, Pharm.D., and Sarah Hauze, Ph.D., of Kay Square Scientific for writing the first draft of the manuscript.
- Language
- English
- Date published
- 12/04/2025
- Academic Unit
- Nephrology, Dialysis and Transplantation; Stead Family Department of Pediatrics; Internal Medicine
- Record Identifier
- 9985090626902771
Metrics
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