Targeting the Alternative Complement Pathway With Iptacopan to Treat IgA Nephropathy: Design and Rationale of the APPLAUSE-IgAN Study
Introduction: Targeting the alternative complement pathway (AP) is an attractive therapeutic strategy because of its role in immunoglobulin A nephropathy (IgAN) pathophysiology. Iptacopan (LNP023), a proximal complement inhibitor that specifically binds to factor B and inhibits the AP, reduced prote...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-05-01
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| Series: | Kidney International Reports |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2468024923000505 |
| _version_ | 1797833655250321408 |
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| author | Dana V. Rizk Brad H. Rovin Hong Zhang Naoki Kashihara Bart Maes Hernán Trimarchi Vlado Perkovic Matthias Meier Dmitrij Kollins Olympia Papachristofi Alan Charney Jonathan Barratt |
| author_facet | Dana V. Rizk Brad H. Rovin Hong Zhang Naoki Kashihara Bart Maes Hernán Trimarchi Vlado Perkovic Matthias Meier Dmitrij Kollins Olympia Papachristofi Alan Charney Jonathan Barratt |
| author_sort | Dana V. Rizk |
| collection | DOAJ |
| description | Introduction: Targeting the alternative complement pathway (AP) is an attractive therapeutic strategy because of its role in immunoglobulin A nephropathy (IgAN) pathophysiology. Iptacopan (LNP023), a proximal complement inhibitor that specifically binds to factor B and inhibits the AP, reduced proteinuria and attenuated AP activation in a Phase 2 study of patients with IgAN, thereby supporting the rationale for its evaluation in a Phase 3 study. Methods: APPLAUSE-IgAN (NCT04578834) is a multicenter, randomized, double-blind, placebo-controlled, parallel-group, Phase 3 study enrolling approximately 450 adult patients (aged ≥18 years) with biopsy-confirmed primary IgAN at high risk of progression to kidney failure despite optimal supportive treatment. Eligible patients receiving stable and maximally tolerated doses of angiotensin-converting enzyme inhibitors (ACEis) or angiotensin receptor blockers (ARBs) will be randomized 1:1 to either iptacopan 200 mg or placebo twice daily for a 24-month treatment period. A prespecified interim analysis (IA) will be performed when approximately 250 patients from the main study population complete the 9-month visit. The primary objective is to demonstrate superiority of iptacopan over placebo in reducing 24-hour urine protein-to-creatinine ratio (UPCR) at the IA and demonstrate the superiority of iptacopan over placebo in slowing the rate of estimated glomerular filtration rate (eGFR) decline (total eGFR slope) estimated over 24 months at study completion. The effect of iptacopan on patient-reported outcomes, safety, and tolerability will be evaluated as secondary outcomes. Conclusions: APPLAUSE-IgAN will evaluate the benefits and safety of iptacopan, a novel targeted therapy for IgAN, in reducing complement-mediated kidney damage and thus slowing or preventing disease progression. |
| first_indexed | 2024-04-09T14:26:35Z |
| format | Article |
| id | doaj.art-e273eb3d888049e0b8276461498c3f08 |
| institution | Directory Open Access Journal |
| issn | 2468-0249 |
| language | English |
| last_indexed | 2024-04-09T14:26:35Z |
| publishDate | 2023-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Kidney International Reports |
| spelling | doaj.art-e273eb3d888049e0b8276461498c3f082023-05-04T04:12:54ZengElsevierKidney International Reports2468-02492023-05-0185968979Targeting the Alternative Complement Pathway With Iptacopan to Treat IgA Nephropathy: Design and Rationale of the APPLAUSE-IgAN StudyDana V. Rizk0Brad H. Rovin1Hong Zhang2Naoki Kashihara3Bart Maes4Hernán Trimarchi5Vlado Perkovic6Matthias Meier7Dmitrij Kollins8Olympia Papachristofi9Alan Charney10Jonathan Barratt11Division of Nephrology, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA; Correspondence: Dana V. Rizk, Division of Nephrology, Department of Medicine, University of Alabama at Birmingham, 1720 2nd Ave S, ZRB 614, Birmingham, Alabama 35294-0007, USA.Division of Nephrology, The Ohio State University Wexner Medical Center, Columbus, Ohio, USARenal Division, Peking University First Hospital, Peking University Institute of Nephrology, Beijing, People’s Republic of ChinaDepartment of Nephrology and Hypertension, Kawasaki Medical School, Kurashiki, JapanDepartment of Nephrology, AZ Delta, Roeselare, BelgiumNephrology Service and Kidney Transplantation Unit, Hospital Británico de Buenos Aires, Buenos Aires, ArgentinaUniversity of New South Wales, Sydney, New South Wales, AustraliaNovartis Pharma AG, Basel, SwitzerlandNovartis Pharma AG, Basel, SwitzerlandNovartis Pharma AG, Basel, SwitzerlandNovartis Pharmaceuticals Corporation, East Hanover, New Jersey, USADepartment of Cardiovascular Sciences, University of Leicester and The John Walls Renal Unit, University Hospitals of Leicester NHS Trust, Leicester, UKIntroduction: Targeting the alternative complement pathway (AP) is an attractive therapeutic strategy because of its role in immunoglobulin A nephropathy (IgAN) pathophysiology. Iptacopan (LNP023), a proximal complement inhibitor that specifically binds to factor B and inhibits the AP, reduced proteinuria and attenuated AP activation in a Phase 2 study of patients with IgAN, thereby supporting the rationale for its evaluation in a Phase 3 study. Methods: APPLAUSE-IgAN (NCT04578834) is a multicenter, randomized, double-blind, placebo-controlled, parallel-group, Phase 3 study enrolling approximately 450 adult patients (aged ≥18 years) with biopsy-confirmed primary IgAN at high risk of progression to kidney failure despite optimal supportive treatment. Eligible patients receiving stable and maximally tolerated doses of angiotensin-converting enzyme inhibitors (ACEis) or angiotensin receptor blockers (ARBs) will be randomized 1:1 to either iptacopan 200 mg or placebo twice daily for a 24-month treatment period. A prespecified interim analysis (IA) will be performed when approximately 250 patients from the main study population complete the 9-month visit. The primary objective is to demonstrate superiority of iptacopan over placebo in reducing 24-hour urine protein-to-creatinine ratio (UPCR) at the IA and demonstrate the superiority of iptacopan over placebo in slowing the rate of estimated glomerular filtration rate (eGFR) decline (total eGFR slope) estimated over 24 months at study completion. The effect of iptacopan on patient-reported outcomes, safety, and tolerability will be evaluated as secondary outcomes. Conclusions: APPLAUSE-IgAN will evaluate the benefits and safety of iptacopan, a novel targeted therapy for IgAN, in reducing complement-mediated kidney damage and thus slowing or preventing disease progression.http://www.sciencedirect.com/science/article/pii/S2468024923000505alternative complement pathwayeGFR slopeFactor BIgANiptacopan (LNP023)proteinuria |
| spellingShingle | Dana V. Rizk Brad H. Rovin Hong Zhang Naoki Kashihara Bart Maes Hernán Trimarchi Vlado Perkovic Matthias Meier Dmitrij Kollins Olympia Papachristofi Alan Charney Jonathan Barratt Targeting the Alternative Complement Pathway With Iptacopan to Treat IgA Nephropathy: Design and Rationale of the APPLAUSE-IgAN Study Kidney International Reports alternative complement pathway eGFR slope Factor B IgAN iptacopan (LNP023) proteinuria |
| title | Targeting the Alternative Complement Pathway With Iptacopan to Treat IgA Nephropathy: Design and Rationale of the APPLAUSE-IgAN Study |
| title_full | Targeting the Alternative Complement Pathway With Iptacopan to Treat IgA Nephropathy: Design and Rationale of the APPLAUSE-IgAN Study |
| title_fullStr | Targeting the Alternative Complement Pathway With Iptacopan to Treat IgA Nephropathy: Design and Rationale of the APPLAUSE-IgAN Study |
| title_full_unstemmed | Targeting the Alternative Complement Pathway With Iptacopan to Treat IgA Nephropathy: Design and Rationale of the APPLAUSE-IgAN Study |
| title_short | Targeting the Alternative Complement Pathway With Iptacopan to Treat IgA Nephropathy: Design and Rationale of the APPLAUSE-IgAN Study |
| title_sort | targeting the alternative complement pathway with iptacopan to treat iga nephropathy design and rationale of the applause igan study |
| topic | alternative complement pathway eGFR slope Factor B IgAN iptacopan (LNP023) proteinuria |
| url | http://www.sciencedirect.com/science/article/pii/S2468024923000505 |
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