Year: 2023
Type: article
Study design: Clinical Trial
Abstract: Introduction: Complement 3 glomerulopathy (C3G) is a rare inflammatory kidney disease mediated by dysregulation of the alternative complement pathway. No targeted therapy exists for this aggressive glomerulonephritis. Efficacy, safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) (measured by complement biomarkers) of iptacopan were assessed in patients with C3G. Methods: In this phase 2, multicenter, open-label, single-arm, nonrandomized study, adults with biopsy-proven, native kidney C3G (native cohort) and kidney transplant recipients with C3G recurrence (recurrent kidney transplant [KT] cohort) received iptacopan twice daily (bid) for 84 days (days 1-21: 10-100 mg; days 22-84: 200 mg). The primary end point was the urine protein-to-creatinine ratio (UPCR; native cohort) and the change in the C3 deposit score of kidney biopsy (recurrent KT cohort). The complement pathway measures included Wieslab assay, soluble C5b9, and serum C3 levels. Results: = 0.03). Serum C3 levels were normalized in most patients; complement hyperactivity observed pretreatment was reduced. Severe adverse events (AEs) included post-biopsy hematuria and hyperkalemia. No deaths occurred during the study. Conclusion: Iptacopan resulted in statistically significant and clinically important reductions in UPCR and normalization of serum C3 levels in the native cohort and reduced C3 deposit scores in the recurrent KT cohort with favorable safety and tolerability. (ClinicalTrials.gov identifier: NCT03832114).
Source: Kidney International Reports
Authors: Edwin Wong, Carla Nester, Teresa Cavero, Alexandre Karras, Moglie Le Quintrec, Liz Lightstone, Ute Eisenberger, Maria Jose Soler, David Kavanagh, Erica Daina, Manuel Praga, Nicholas R. Medjeral-Thomas, Anja Gäckler, Clara Garcia-Carro, Andrea Biondani, Frederique Chaperon, Kenneth Kulmatycki, Julie Milojevic, Nicholas J.A. Webb, Prasanna Kumar Nidamarthy, Guido Junge, Giuseppe Remuzzi
Institutions: Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne Hospital, Newcastle University, University of Iowa Stead Family Children’s Hospital, Hospital Universitario 12 De Octubre, Hôpital Européen Georges-Pompidou, Centre Hospitalier Universitaire de Montpellier, Imperial College London, Essen University Hospital, University of Duisburg-Essen, Vall d'Hebron Institut de Recerca, Vall d'Hebron Hospital Universitari, Mario Negri Institute for Pharmacological Research, Research Institute Hospital 12 de Octubre, Novartis (Switzerland), Novartis Institutes for BioMedical Research, Novartis (India)
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,625
Funders: Novartis, Novartis Pharma
OpenAlex ID: W4386964882