PMID- 38106570
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20231219
IS  - 2468-0249 (Electronic)
IS  - 2468-0249 (Linking)
VI  - 8
IP  - 12
DP  - 2023 Dec
TI  - Efficacy and Safety of Iptacopan in Patients With C3 Glomerulopathy.
PG  - 2754-2764
LID - 10.1016/j.ekir.2023.09.017 [doi]
AB  - 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 
      identifier: NCT03832114).
CI  - (c) 2023 International Society of Nephrology. Published by Elsevier Inc.
FAU - Wong, Edwin
AU  - Wong E
AD  - National Renal Complement Therapeutics Centre, Newcastle upon Tyne Hospitals NHS 
      Foundation Trust, Newcastle Upon Tyne, UK.
AD  - Translational and Clinical Research Institute, Newcastle University, Newcastle 
      Upon Tyne, UK.
FAU - Nester, Carla
AU  - Nester C
AD  - The University of Iowa Stead Family Children's Hospital, Iowa City, Iowa, USA.
FAU - Cavero, Teresa
AU  - Cavero T
AD  - Nephrology Department, University Hospital Doce de Octubre, Madrid, Spain.
FAU - Karras, Alexandre
AU  - Karras A
AD  - Department of Nephrology, Hopital Europeen Georges-Pompidou, APHP, Paris, France.
FAU - Le Quintrec, Moglie
AU  - Le Quintrec M
AD  - Service de Nephrologie et Transplantation Renale, Centre Hospitalier 
      Universitaire de Montpellier, Montpellier, France.
FAU - Lightstone, Liz
AU  - Lightstone L
AD  - Centre for Inflammatory Disease, Department of Immunology and Inflammation, 
      Imperial College London, London, UK.
FAU - Eisenberger, Ute
AU  - Eisenberger U
AD  - Department of Nephrology, University Hospital Essen, University Duisburg-Essen, 
      Essen, Germany.
FAU - Soler, Maria Jose
AU  - Soler MJ
AD  - Nephrology Department, Vall d'Hebron University Hospital, Vall d'Hebron Institute 
      of Research, CSUR National Unit of Expertise for Complex Glomerular Diseases of 
      Spain, Barcelona, Spain.
FAU - Kavanagh, David
AU  - Kavanagh D
AD  - National Renal Complement Therapeutics Centre, Newcastle upon Tyne Hospitals NHS 
      Foundation Trust, Newcastle Upon Tyne, UK.
AD  - Translational and Clinical Research Institute, Newcastle University, Newcastle 
      Upon Tyne, UK.
FAU - Daina, Erica
AU  - Daina E
AD  - Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milan, Italy.
FAU - Praga, Manuel
AU  - Praga M
AD  - Instituto de Investigacion Hospital 12 de Octubre (i+12), Madrid, Spain.
FAU - Medjeral-Thomas, Nicholas R
AU  - Medjeral-Thomas NR
AD  - Centre for Inflammatory Disease, Department of Immunology and Inflammation, 
      Imperial College London, London, UK.
FAU - Gackler, Anja
AU  - Gackler A
AD  - Department of Nephrology, University Hospital Essen, University Duisburg-Essen, 
      Essen, Germany.
FAU - Garcia-Carro, Clara
AU  - Garcia-Carro C
AD  - Nephrology Department, Vall d'Hebron University Hospital, Vall d'Hebron Institute 
      of Research, CSUR National Unit of Expertise for Complex Glomerular Diseases of 
      Spain, Barcelona, Spain.
FAU - Biondani, Andrea
AU  - Biondani A
AD  - Novartis Institutes for BioMedical Research, Translational Medicine, Novartis AG, 
      Basel, Switzerland.
FAU - Chaperon, Frederique
AU  - Chaperon F
AD  - Novartis Institutes for BioMedical Research, Translational Medicine, Novartis AG, 
      Basel, Switzerland.
FAU - Kulmatycki, Kenneth
AU  - Kulmatycki K
AD  - Novartis Institutes for BioMedical Research, Cambridge, Massachusetts, USA.
FAU - Milojevic, Julie
AU  - Milojevic J
AD  - Novartis Institutes for BioMedical Research, Translational Medicine, Novartis AG, 
      Basel, Switzerland.
FAU - Webb, Nicholas J A
AU  - Webb NJA
AD  - Novartis Institutes for BioMedical Research, Translational Medicine, Novartis AG, 
      Basel, Switzerland.
FAU - Nidamarthy, Prasanna Kumar
AU  - Nidamarthy PK
AD  - Novartis Healthcare Pvt. Ltd., Hyderabad, India.
FAU - Junge, Guido
AU  - Junge G
AD  - Novartis Institutes for BioMedical Research, Translational Medicine, Novartis AG, 
      Basel, Switzerland.
FAU - Remuzzi, Giuseppe
AU  - Remuzzi G
AD  - Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milan, Italy.
LA  - eng
SI  - ClinicalTrials.gov/NCT03832114
PT  - Journal Article
DEP - 20230922
PL  - United States
TA  - Kidney Int Rep
JT  - Kidney international reports
JID - 101684752
PMC - PMC10719607
OTO - NOTNLM
OT  - complement 3 glomerulopathy
OT  - inflammatory kidney disease
OT  - iptacopan
OT  - kidney transplant
OT  - urine protein-to-creatinine ratio
EDAT- 2023/12/18 06:41
MHDA- 2023/12/18 06:42
PMCR- 2023/09/22
CRDT- 2023/12/18 04:42
PHST- 2023/07/14 00:00 [received]
PHST- 2023/08/21 00:00 [revised]
PHST- 2023/09/11 00:00 [accepted]
PHST- 2023/12/18 06:42 [medline]
PHST- 2023/12/18 06:41 [pubmed]
PHST- 2023/12/18 04:42 [entrez]
PHST- 2023/09/22 00:00 [pmc-release]
AID - S2468-0249(23)01510-3 [pii]
AID - 10.1016/j.ekir.2023.09.017 [doi]
PST - epublish
SO  - Kidney Int Rep. 2023 Sep 22;8(12):2754-2764. doi: 10.1016/j.ekir.2023.09.017. 
      eCollection 2023 Dec.