Journal article
Efficacy and Safety of Iptacopan in Patients with C3 Glomerulopathy
Kidney international reports, Vol.8(12), pp.2754-2764
12/2023
DOI: 10.1016/j.ekir.2023.09.017
PMCID: PMC10719607
PMID: 38106570
Abstract
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, and pharmacodynamics (measured by complement biomarkers) of iptacopan were assessed in patients with C3G.
In this Phase 2, multicenter, open-label, single-arm, non-randomized study, adults with biopsy-proven, native kidney C3G (native cohort) and kidney transplant recipients with C3G recurrence (recurrent KT cohort) received iptacopan twice daily for 84 days (Days 1-21: 10–100-mg; Days 22–84: 200-mg). The primary endpoint 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.
27 patients (16 native cohort/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) at Day 84 versus baseline (P = 0.03). Serum C3 levels were normalized in most patients; complement hyperactivity observed pretreatment was reduced. Severe adverse events included post-biopsy hematuria and hyperkalemia. No deaths occurred during the study.
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)
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Details
- Title: Subtitle
- Efficacy and Safety of Iptacopan in Patients with C3 Glomerulopathy
- Creators
- Edwin Wong - Newcastle upon Tyne Hospitals NHS Foundation TrustCarla Nester - University of IowaTeresa Cavero - Nephrology Department, University Hospital Doce de Octubre, Madrid, SpainAlexandre Karras - Hôpital EuropéenMoglie Le Quintrec - Centre Hospitalier Universitaire de MontpellierLiz Lightstone - Imperial College LondonUte Eisenberger - University of Duisburg-EssenMaria Jose Soler - Vall d'Hebron Hospital UniversitariDavid Kavanagh - University of Newcastle AustraliaErica Daina - Mario Negri Institute for Pharmacological ResearchManuel Praga - Research Institute Hospital 12 de OctubreNicholas R. Medjeral-Thomas - Imperial College LondonAnja Gäckler - University of Duisburg-EssenClara Garcia-Carro - Vall d'Hebron Hospital UniversitariAndrea Biondani - Novartis (Switzerland)Frederique Chaperon - Novartis (Switzerland)Kenneth Kulmatycki - Novartis (United States)Julie Milojevic - Novartis (Switzerland)Nicholas J.A. Webb - Novartis (Switzerland)Prasanna Kumar Nidamarthy - Novartis (India)Guido Junge - Novartis (Switzerland)Giuseppe Remuzzi - Mario Negri Institute for Pharmacological Research
- Resource Type
- Journal article
- Publication Details
- Kidney international reports, Vol.8(12), pp.2754-2764
- DOI
- 10.1016/j.ekir.2023.09.017
- PMID
- 38106570
- PMCID
- PMC10719607
- NLM abbreviation
- Kidney Int Rep
- ISSN
- 2468-0249
- eISSN
- 2468-0249
- Publisher
- Elsevier Inc
- Grant note
- DOI: 10.13039/100004336, name: Novartis
- Language
- English
- Electronic publication date
- 09/2023
- Date published
- 12/2023
- Academic Unit
- Nephrology, Dialysis and Transplantation; Stead Family Department of Pediatrics; Internal Medicine
- Record Identifier
- 9984471941502771
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