Contributors: Institut Català de la Salut; Wong E National Renal Complement Therapeutics Centre, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle Upon Tyne, UK. Translational and Clinical Research Institute, Newcastle University, Newcastle Upon Tyne, UK. Nester C The University of Iowa Stead Family Children’s Hospital, Iowa City, Iowa, USA. Cavero T Nephrology Department, University Hospital Doce de Octubre, Madrid, Spain. Karras A Department of Nephrology, Hôpital Européen Georges-Pompidou, APHP, Paris, France. Le Quintrec M Service de Néphrologie et Transplantation Rénale, Centre Hospitalier Universitaire de Montpellier, Montpellier, France. Lightstone L Centre for Inflammatory Disease, Department of Immunology and Inflammation, Imperial College London, London, UK. Soler MJ, Garcia-Carro C Servei de Nefrologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. CSUR National Unit of Expertise for Complex Glomerular Diseases of Spain, Barcelona, Spain; Vall d'Hebron Barcelona Hospital Campus
نبذة مختصرة : Complement 3 glomerulopathy; Inflammatory kidney disease; Iptacopan ; Glomerulopatia del complement 3; Malaltia inflamatòria del ronyó; Iptacopan ; Glomerulopatía del complemento 3; Enfermedad inflamatoria del riñón; Iptacopan ; 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 A total of 27 patients (16 native cohort and 11 recurrent KT cohort) were enrolled and all completed the study. In the native cohort, UPCR levels decreased by 45% from baseline to week 12 (P = 0.0003). In the recurrent KT cohort, the median C3 deposit score decreased by 2.50 (scale: 0–12) on day 84 versus baseline (P = 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 ...
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