Efficacy and Safety of Iptacopan in Patients With C3 Glomerulopathy
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) (...
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| Autor*in: |
Edwin Wong [verfasserIn] Carla Nester [verfasserIn] Teresa Cavero [verfasserIn] Alexandre Karras [verfasserIn] Moglie Le Quintrec [verfasserIn] Liz Lightstone [verfasserIn] Ute Eisenberger [verfasserIn] Maria Jose Soler [verfasserIn] David Kavanagh [verfasserIn] Erica Daina [verfasserIn] Manuel Praga [verfasserIn] Nicholas R. Medjeral-Thomas [verfasserIn] Anja Gäckler [verfasserIn] Clara Garcia-Carro [verfasserIn] Andrea Biondani [verfasserIn] Frederique Chaperon [verfasserIn] Kenneth Kulmatycki [verfasserIn] Julie Milojevic [verfasserIn] Nicholas J.A. Webb [verfasserIn] Prasanna Kumar Nidamarthy [verfasserIn] Guido Junge [verfasserIn] Giuseppe Remuzzi [verfasserIn] |
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| Format: |
E-Artikel |
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| Sprache: |
Englisch |
| Erschienen: |
2023 |
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| Schlagwörter: |
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| Übergeordnetes Werk: |
In: Kidney International Reports - Elsevier, 2016, 8(2023), 12, Seite 2754-2764 |
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| Übergeordnetes Werk: |
volume:8 ; year:2023 ; number:12 ; pages:2754-2764 |
| Links: |
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| DOI / URN: |
10.1016/j.ekir.2023.09.017 |
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| Katalog-ID: |
DOAJ100138179 |
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| 245 | 1 | 0 | |a Efficacy and Safety of Iptacopan in Patients With C3 Glomerulopathy |
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| 520 | |a 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). | ||
| 650 | 4 | |a complement 3 glomerulopathy | |
| 650 | 4 | |a inflammatory kidney disease | |
| 650 | 4 | |a iptacopan | |
| 650 | 4 | |a kidney transplant | |
| 650 | 4 | |a urine protein-to-creatinine ratio | |
| 653 | 0 | |a Diseases of the genitourinary system. Urology | |
| 700 | 0 | |a Carla Nester |e verfasserin |4 aut | |
| 700 | 0 | |a Teresa Cavero |e verfasserin |4 aut | |
| 700 | 0 | |a Alexandre Karras |e verfasserin |4 aut | |
| 700 | 0 | |a Moglie Le Quintrec |e verfasserin |4 aut | |
| 700 | 0 | |a Liz Lightstone |e verfasserin |4 aut | |
| 700 | 0 | |a Ute Eisenberger |e verfasserin |4 aut | |
| 700 | 0 | |a Maria Jose Soler |e verfasserin |4 aut | |
| 700 | 0 | |a David Kavanagh |e verfasserin |4 aut | |
| 700 | 0 | |a Erica Daina |e verfasserin |4 aut | |
| 700 | 0 | |a Manuel Praga |e verfasserin |4 aut | |
| 700 | 0 | |a Nicholas R. Medjeral-Thomas |e verfasserin |4 aut | |
| 700 | 0 | |a Anja Gäckler |e verfasserin |4 aut | |
| 700 | 0 | |a Clara Garcia-Carro |e verfasserin |4 aut | |
| 700 | 0 | |a Andrea Biondani |e verfasserin |4 aut | |
| 700 | 0 | |a Frederique Chaperon |e verfasserin |4 aut | |
| 700 | 0 | |a Kenneth Kulmatycki |e verfasserin |4 aut | |
| 700 | 0 | |a Julie Milojevic |e verfasserin |4 aut | |
| 700 | 0 | |a Nicholas J.A. Webb |e verfasserin |4 aut | |
| 700 | 0 | |a Prasanna Kumar Nidamarthy |e verfasserin |4 aut | |
| 700 | 0 | |a Guido Junge |e verfasserin |4 aut | |
| 700 | 0 | |a Giuseppe Remuzzi |e verfasserin |4 aut | |
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10.1016/j.ekir.2023.09.017 doi (DE-627)DOAJ100138179 (DE-599)DOAJ4142dfa19bbe4b318478e3240af7c53c DE-627 ger DE-627 rakwb eng RC870-923 Edwin Wong verfasserin aut Efficacy and Safety of Iptacopan in Patients With C3 Glomerulopathy 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier 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). complement 3 glomerulopathy inflammatory kidney disease iptacopan kidney transplant urine protein-to-creatinine ratio Diseases of the genitourinary system. Urology Carla Nester verfasserin aut Teresa Cavero verfasserin aut Alexandre Karras verfasserin aut Moglie Le Quintrec verfasserin aut Liz Lightstone verfasserin aut Ute Eisenberger verfasserin aut Maria Jose Soler verfasserin aut David Kavanagh verfasserin aut Erica Daina verfasserin aut Manuel Praga verfasserin aut Nicholas R. Medjeral-Thomas verfasserin aut Anja Gäckler verfasserin aut Clara Garcia-Carro verfasserin aut Andrea Biondani verfasserin aut Frederique Chaperon verfasserin aut Kenneth Kulmatycki verfasserin aut Julie Milojevic verfasserin aut Nicholas J.A. Webb verfasserin aut Prasanna Kumar Nidamarthy verfasserin aut Guido Junge verfasserin aut Giuseppe Remuzzi verfasserin aut In Kidney International Reports Elsevier, 2016 8(2023), 12, Seite 2754-2764 (DE-627)881695580 (DE-600)2887223-X 24680249 nnns volume:8 year:2023 number:12 pages:2754-2764 https://doi.org/10.1016/j.ekir.2023.09.017 kostenfrei https://doaj.org/article/4142dfa19bbe4b318478e3240af7c53c kostenfrei http://www.sciencedirect.com/science/article/pii/S2468024923015103 kostenfrei https://doaj.org/toc/2468-0249 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2088 GBV_ILN_2106 GBV_ILN_2110 GBV_ILN_2112 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4700 AR 8 2023 12 2754-2764 |
| spelling |
10.1016/j.ekir.2023.09.017 doi (DE-627)DOAJ100138179 (DE-599)DOAJ4142dfa19bbe4b318478e3240af7c53c DE-627 ger DE-627 rakwb eng RC870-923 Edwin Wong verfasserin aut Efficacy and Safety of Iptacopan in Patients With C3 Glomerulopathy 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier 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). complement 3 glomerulopathy inflammatory kidney disease iptacopan kidney transplant urine protein-to-creatinine ratio Diseases of the genitourinary system. Urology Carla Nester verfasserin aut Teresa Cavero verfasserin aut Alexandre Karras verfasserin aut Moglie Le Quintrec verfasserin aut Liz Lightstone verfasserin aut Ute Eisenberger verfasserin aut Maria Jose Soler verfasserin aut David Kavanagh verfasserin aut Erica Daina verfasserin aut Manuel Praga verfasserin aut Nicholas R. Medjeral-Thomas verfasserin aut Anja Gäckler verfasserin aut Clara Garcia-Carro verfasserin aut Andrea Biondani verfasserin aut Frederique Chaperon verfasserin aut Kenneth Kulmatycki verfasserin aut Julie Milojevic verfasserin aut Nicholas J.A. Webb verfasserin aut Prasanna Kumar Nidamarthy verfasserin aut Guido Junge verfasserin aut Giuseppe Remuzzi verfasserin aut In Kidney International Reports Elsevier, 2016 8(2023), 12, Seite 2754-2764 (DE-627)881695580 (DE-600)2887223-X 24680249 nnns volume:8 year:2023 number:12 pages:2754-2764 https://doi.org/10.1016/j.ekir.2023.09.017 kostenfrei https://doaj.org/article/4142dfa19bbe4b318478e3240af7c53c kostenfrei http://www.sciencedirect.com/science/article/pii/S2468024923015103 kostenfrei https://doaj.org/toc/2468-0249 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2088 GBV_ILN_2106 GBV_ILN_2110 GBV_ILN_2112 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4700 AR 8 2023 12 2754-2764 |
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10.1016/j.ekir.2023.09.017 doi (DE-627)DOAJ100138179 (DE-599)DOAJ4142dfa19bbe4b318478e3240af7c53c DE-627 ger DE-627 rakwb eng RC870-923 Edwin Wong verfasserin aut Efficacy and Safety of Iptacopan in Patients With C3 Glomerulopathy 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier 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). complement 3 glomerulopathy inflammatory kidney disease iptacopan kidney transplant urine protein-to-creatinine ratio Diseases of the genitourinary system. Urology Carla Nester verfasserin aut Teresa Cavero verfasserin aut Alexandre Karras verfasserin aut Moglie Le Quintrec verfasserin aut Liz Lightstone verfasserin aut Ute Eisenberger verfasserin aut Maria Jose Soler verfasserin aut David Kavanagh verfasserin aut Erica Daina verfasserin aut Manuel Praga verfasserin aut Nicholas R. Medjeral-Thomas verfasserin aut Anja Gäckler verfasserin aut Clara Garcia-Carro verfasserin aut Andrea Biondani verfasserin aut Frederique Chaperon verfasserin aut Kenneth Kulmatycki verfasserin aut Julie Milojevic verfasserin aut Nicholas J.A. Webb verfasserin aut Prasanna Kumar Nidamarthy verfasserin aut Guido Junge verfasserin aut Giuseppe Remuzzi verfasserin aut In Kidney International Reports Elsevier, 2016 8(2023), 12, Seite 2754-2764 (DE-627)881695580 (DE-600)2887223-X 24680249 nnns volume:8 year:2023 number:12 pages:2754-2764 https://doi.org/10.1016/j.ekir.2023.09.017 kostenfrei https://doaj.org/article/4142dfa19bbe4b318478e3240af7c53c kostenfrei http://www.sciencedirect.com/science/article/pii/S2468024923015103 kostenfrei https://doaj.org/toc/2468-0249 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2088 GBV_ILN_2106 GBV_ILN_2110 GBV_ILN_2112 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4700 AR 8 2023 12 2754-2764 |
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10.1016/j.ekir.2023.09.017 doi (DE-627)DOAJ100138179 (DE-599)DOAJ4142dfa19bbe4b318478e3240af7c53c DE-627 ger DE-627 rakwb eng RC870-923 Edwin Wong verfasserin aut Efficacy and Safety of Iptacopan in Patients With C3 Glomerulopathy 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier 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). complement 3 glomerulopathy inflammatory kidney disease iptacopan kidney transplant urine protein-to-creatinine ratio Diseases of the genitourinary system. Urology Carla Nester verfasserin aut Teresa Cavero verfasserin aut Alexandre Karras verfasserin aut Moglie Le Quintrec verfasserin aut Liz Lightstone verfasserin aut Ute Eisenberger verfasserin aut Maria Jose Soler verfasserin aut David Kavanagh verfasserin aut Erica Daina verfasserin aut Manuel Praga verfasserin aut Nicholas R. Medjeral-Thomas verfasserin aut Anja Gäckler verfasserin aut Clara Garcia-Carro verfasserin aut Andrea Biondani verfasserin aut Frederique Chaperon verfasserin aut Kenneth Kulmatycki verfasserin aut Julie Milojevic verfasserin aut Nicholas J.A. Webb verfasserin aut Prasanna Kumar Nidamarthy verfasserin aut Guido Junge verfasserin aut Giuseppe Remuzzi verfasserin aut In Kidney International Reports Elsevier, 2016 8(2023), 12, Seite 2754-2764 (DE-627)881695580 (DE-600)2887223-X 24680249 nnns volume:8 year:2023 number:12 pages:2754-2764 https://doi.org/10.1016/j.ekir.2023.09.017 kostenfrei https://doaj.org/article/4142dfa19bbe4b318478e3240af7c53c kostenfrei http://www.sciencedirect.com/science/article/pii/S2468024923015103 kostenfrei https://doaj.org/toc/2468-0249 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2088 GBV_ILN_2106 GBV_ILN_2110 GBV_ILN_2112 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4700 AR 8 2023 12 2754-2764 |
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10.1016/j.ekir.2023.09.017 doi (DE-627)DOAJ100138179 (DE-599)DOAJ4142dfa19bbe4b318478e3240af7c53c DE-627 ger DE-627 rakwb eng RC870-923 Edwin Wong verfasserin aut Efficacy and Safety of Iptacopan in Patients With C3 Glomerulopathy 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier 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). complement 3 glomerulopathy inflammatory kidney disease iptacopan kidney transplant urine protein-to-creatinine ratio Diseases of the genitourinary system. Urology Carla Nester verfasserin aut Teresa Cavero verfasserin aut Alexandre Karras verfasserin aut Moglie Le Quintrec verfasserin aut Liz Lightstone verfasserin aut Ute Eisenberger verfasserin aut Maria Jose Soler verfasserin aut David Kavanagh verfasserin aut Erica Daina verfasserin aut Manuel Praga verfasserin aut Nicholas R. Medjeral-Thomas verfasserin aut Anja Gäckler verfasserin aut Clara Garcia-Carro verfasserin aut Andrea Biondani verfasserin aut Frederique Chaperon verfasserin aut Kenneth Kulmatycki verfasserin aut Julie Milojevic verfasserin aut Nicholas J.A. Webb verfasserin aut Prasanna Kumar Nidamarthy verfasserin aut Guido Junge verfasserin aut Giuseppe Remuzzi verfasserin aut In Kidney International Reports Elsevier, 2016 8(2023), 12, Seite 2754-2764 (DE-627)881695580 (DE-600)2887223-X 24680249 nnns volume:8 year:2023 number:12 pages:2754-2764 https://doi.org/10.1016/j.ekir.2023.09.017 kostenfrei https://doaj.org/article/4142dfa19bbe4b318478e3240af7c53c kostenfrei http://www.sciencedirect.com/science/article/pii/S2468024923015103 kostenfrei https://doaj.org/toc/2468-0249 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2088 GBV_ILN_2106 GBV_ILN_2110 GBV_ILN_2112 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4700 AR 8 2023 12 2754-2764 |
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Edwin Wong @@aut@@ Carla Nester @@aut@@ Teresa Cavero @@aut@@ Alexandre Karras @@aut@@ Moglie Le Quintrec @@aut@@ Liz Lightstone @@aut@@ Ute Eisenberger @@aut@@ Maria Jose Soler @@aut@@ David Kavanagh @@aut@@ Erica Daina @@aut@@ Manuel Praga @@aut@@ Nicholas R. Medjeral-Thomas @@aut@@ Anja Gäckler @@aut@@ Clara Garcia-Carro @@aut@@ Andrea Biondani @@aut@@ Frederique Chaperon @@aut@@ Kenneth Kulmatycki @@aut@@ Julie Milojevic @@aut@@ Nicholas J.A. Webb @@aut@@ Prasanna Kumar Nidamarthy @@aut@@ Guido Junge @@aut@@ Giuseppe Remuzzi @@aut@@ |
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<?xml version="1.0" encoding="UTF-8"?><collection xmlns="http://www.loc.gov/MARC21/slim"><record><leader>01000naa a22002652 4500</leader><controlfield tag="001">DOAJ100138179</controlfield><controlfield tag="003">DE-627</controlfield><controlfield tag="005">20240414065935.0</controlfield><controlfield tag="007">cr uuu---uuuuu</controlfield><controlfield tag="008">240414s2023 xx |||||o 00| ||eng c</controlfield><datafield tag="024" ind1="7" ind2=" "><subfield code="a">10.1016/j.ekir.2023.09.017</subfield><subfield code="2">doi</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-627)DOAJ100138179</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-599)DOAJ4142dfa19bbe4b318478e3240af7c53c</subfield></datafield><datafield tag="040" ind1=" " ind2=" "><subfield code="a">DE-627</subfield><subfield code="b">ger</subfield><subfield code="c">DE-627</subfield><subfield code="e">rakwb</subfield></datafield><datafield tag="041" ind1=" " ind2=" "><subfield code="a">eng</subfield></datafield><datafield tag="050" ind1=" " ind2="0"><subfield code="a">RC870-923</subfield></datafield><datafield tag="100" ind1="0" ind2=" "><subfield code="a">Edwin Wong</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="245" ind1="1" ind2="0"><subfield code="a">Efficacy and Safety of Iptacopan in Patients With C3 Glomerulopathy</subfield></datafield><datafield tag="264" ind1=" " ind2="1"><subfield code="c">2023</subfield></datafield><datafield tag="336" ind1=" " ind2=" "><subfield code="a">Text</subfield><subfield code="b">txt</subfield><subfield code="2">rdacontent</subfield></datafield><datafield tag="337" ind1=" " ind2=" "><subfield code="a">Computermedien</subfield><subfield code="b">c</subfield><subfield code="2">rdamedia</subfield></datafield><datafield tag="338" ind1=" " ind2=" "><subfield code="a">Online-Ressource</subfield><subfield code="b">cr</subfield><subfield code="2">rdacarrier</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">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. 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RC870-923 Efficacy and Safety of Iptacopan in Patients With C3 Glomerulopathy complement 3 glomerulopathy inflammatory kidney disease iptacopan kidney transplant urine protein-to-creatinine ratio |
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misc RC870-923 misc complement 3 glomerulopathy misc inflammatory kidney disease misc iptacopan misc kidney transplant misc urine protein-to-creatinine ratio misc Diseases of the genitourinary system. Urology |
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Efficacy and Safety of Iptacopan in Patients With C3 Glomerulopathy |
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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 |
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efficacy and safety of iptacopan in patients with c3 glomerulopathy |
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Efficacy and Safety of Iptacopan in Patients With C3 Glomerulopathy |
| 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: 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). |
| abstractGer |
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). |
| abstract_unstemmed |
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). |
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Efficacy and Safety of Iptacopan in Patients With C3 Glomerulopathy |
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https://doi.org/10.1016/j.ekir.2023.09.017 https://doaj.org/article/4142dfa19bbe4b318478e3240af7c53c http://www.sciencedirect.com/science/article/pii/S2468024923015103 https://doaj.org/toc/2468-0249 |
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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 |
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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 |
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10.1016/j.ekir.2023.09.017 |
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2024-07-04T01:42:37.745Z |
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| score |
7.402128 |