Focal Segmental Glomerulosclerosis Patient Baseline Characteristics in the Sparsentan Phase 3 DUPLEX Study
Introduction: The phase 3 DUPLEX trial is evaluating sparsentan, a novel, nonimmunosuppressive, single-molecule dual endothelin angiotensin receptor antagonist, in patients with focal segmental glomerulosclerosis (FSGS). Methods: DUPLEX (NCT03493685) is a global, multicenter, randomized, double-blin...
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Elsevier
2024-04-01
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| Series: | Kidney International Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2468024924000421 |
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| author | Howard Trachtman Jai Radhakrishnan Michelle N. Rheault Charles E. Alpers Jonathan Barratt Hiddo J.L. Heerspink Irene L. Noronha Vlado Perkovic Brad Rovin Hernán Trimarchi Muh Geot Wong Alex Mercer Jula Inrig William Rote Ed Murphy Patricia W. Bedard Sandra Roth Stewart Bieler Radko Komers |
| author_facet | Howard Trachtman Jai Radhakrishnan Michelle N. Rheault Charles E. Alpers Jonathan Barratt Hiddo J.L. Heerspink Irene L. Noronha Vlado Perkovic Brad Rovin Hernán Trimarchi Muh Geot Wong Alex Mercer Jula Inrig William Rote Ed Murphy Patricia W. Bedard Sandra Roth Stewart Bieler Radko Komers |
| author_sort | Howard Trachtman |
| collection | DOAJ |
| description | Introduction: The phase 3 DUPLEX trial is evaluating sparsentan, a novel, nonimmunosuppressive, single-molecule dual endothelin angiotensin receptor antagonist, in patients with focal segmental glomerulosclerosis (FSGS). Methods: DUPLEX (NCT03493685) is a global, multicenter, randomized, double-blind, parallel-group, active-controlled study evaluating the efficacy and safety of sparsentan 800 mg once daily versus irbesartan 300 mg once daily in patients aged 8 to 75 years (USA/UK) and 18 to 75 years (ex-USA/UK) weighing ≥20 kg with biopsy-proven FSGS or documented genetic mutation in a podocyte protein associated with FSGS, and urine protein-to-creatinine ratio (UP/C) ≥1.5 g/g. Baseline characteristics blinded to treatment allocation are reported descriptively. Results: The primary analysis population includes 371 patients (336 adult, 35 pediatric [<18 years]) who were randomized and received study drug (median age, 42 years). Patients were White (73.0%), Asian (13.2%), Black/African American (6.7%), or Other race (7.0%); and from North America (38.8%), Europe (36.1%), South America (12.7%), or Asia Pacific (12.4%). Baseline median UP/C was 3.0 g/g; 42.6% in nephrotic-range (UP/C >3.5 g/g [adults]; >2.0 g/g [pediatrics]). Patients were evenly distributed across estimated glomerular filtration rate (eGFR) categories corresponding to chronic kidney disease (CKD) stages 1 to 3b. Thirty-three patients (9.4% of 352 evaluable samples) had pathogenic or likely pathogenic (P/LP) variants of genes essential to podocyte structural integrity and function, 27 (7.7%) had P/LP collagen gene (COL4A3/4/5) variants, and 14 (4.0%) had high-risk APOL1 genotypes. Conclusions: Patient enrollment in DUPLEX, the largest interventional study in FSGS to date, will enable important characterization of the treatment effect of sparsentan in a geographically broad and clinically diverse FSGS population. |
| format | Article |
| id | doaj-art-88d1185da86c4b8f8decb8bb524f012e |
| institution | DOAJ |
| issn | 2468-0249 |
| language | English |
| publishDate | 2024-04-01 |
| publisher | Elsevier |
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| series | Kidney International Reports |
| spelling | doaj-art-88d1185da86c4b8f8decb8bb524f012e2025-08-20T03:20:19ZengElsevierKidney International Reports2468-02492024-04-01941020103010.1016/j.ekir.2024.01.032Focal Segmental Glomerulosclerosis Patient Baseline Characteristics in the Sparsentan Phase 3 DUPLEX StudyHoward Trachtman0Jai Radhakrishnan1Michelle N. Rheault2Charles E. Alpers3Jonathan Barratt4Hiddo J.L. Heerspink5Irene L. Noronha6Vlado Perkovic7Brad Rovin8Hernán Trimarchi9Muh Geot Wong10Alex Mercer11Jula Inrig12William Rote13Ed Murphy14Patricia W. Bedard15Sandra Roth16Stewart Bieler17Radko Komers18Division of Nephrology, Department of Pediatrics, University of Michigan, Ann Arbor, Michigan, USA; Correspondence: Howard Trachtman, Division of Nephrology, Department of Pediatrics, University of Michigan, Ann Arbor, Michigan 48109, USA.Division of Nephrology, Columbia University, New York, New York, USA; Jai Radhakrishnan, Division of Nephrology, Columbia University, New York, New York, USA.Division of Pediatric Nephrology, University of Minnesota Medical School, Minneapolis, Minnesota, USA; Michelle Rheault, Department of Pediatrics, Division of Nephrology, University of Minnesota Masonic Children’s Hospital, Minneapolis, Minnesota, USA.Department of Laboratory Medicine and Pathology, University of Washington, Seattle, Washington, USADepartment of Cardiovascular Sciences, University of Leicester General Hospital, Leicester, UKDepartment of Clinical Pharmacy and Pharmacology, University of Medical Center Groningen, University of Groningen, Groningen, the Netherlands; The George Institute for Global Health, Sydney, AustraliaDivision of Nephrology, University of São Paulo School of Medicine, São Paulo, BrazilFaculty of Medicine, University of New South Wales Sydney, Sydney, New South Wales, AustraliaDivision of Nephrology, Ohio State University Wexner Medical Center, Columbus, Ohio, USANephrology Service, Hospital Británico de Buenos Aires, Buenos Aires, ArgentinaThe George Institute for Global Health, Sydney, Australia; Concord Clinical School, University of Sydney, Concord, New South Wales, AustraliaJAMCO Pharma Consulting, Stockholm, SwedenTravere Therapeutics Inc., San Diego, California, USATravere Therapeutics Inc., San Diego, California, USATravere Therapeutics Inc., San Diego, California, USATravere Therapeutics Inc., San Diego, California, USATravere Therapeutics Inc., San Diego, California, USATravere Therapeutics Inc., San Diego, California, USATravere Therapeutics Inc., San Diego, California, USAIntroduction: The phase 3 DUPLEX trial is evaluating sparsentan, a novel, nonimmunosuppressive, single-molecule dual endothelin angiotensin receptor antagonist, in patients with focal segmental glomerulosclerosis (FSGS). Methods: DUPLEX (NCT03493685) is a global, multicenter, randomized, double-blind, parallel-group, active-controlled study evaluating the efficacy and safety of sparsentan 800 mg once daily versus irbesartan 300 mg once daily in patients aged 8 to 75 years (USA/UK) and 18 to 75 years (ex-USA/UK) weighing ≥20 kg with biopsy-proven FSGS or documented genetic mutation in a podocyte protein associated with FSGS, and urine protein-to-creatinine ratio (UP/C) ≥1.5 g/g. Baseline characteristics blinded to treatment allocation are reported descriptively. Results: The primary analysis population includes 371 patients (336 adult, 35 pediatric [<18 years]) who were randomized and received study drug (median age, 42 years). Patients were White (73.0%), Asian (13.2%), Black/African American (6.7%), or Other race (7.0%); and from North America (38.8%), Europe (36.1%), South America (12.7%), or Asia Pacific (12.4%). Baseline median UP/C was 3.0 g/g; 42.6% in nephrotic-range (UP/C >3.5 g/g [adults]; >2.0 g/g [pediatrics]). Patients were evenly distributed across estimated glomerular filtration rate (eGFR) categories corresponding to chronic kidney disease (CKD) stages 1 to 3b. Thirty-three patients (9.4% of 352 evaluable samples) had pathogenic or likely pathogenic (P/LP) variants of genes essential to podocyte structural integrity and function, 27 (7.7%) had P/LP collagen gene (COL4A3/4/5) variants, and 14 (4.0%) had high-risk APOL1 genotypes. Conclusions: Patient enrollment in DUPLEX, the largest interventional study in FSGS to date, will enable important characterization of the treatment effect of sparsentan in a geographically broad and clinically diverse FSGS population.http://www.sciencedirect.com/science/article/pii/S2468024924000421dual endothelin angiotensin receptor antagonistfocal segmental glomerulosclerosispediatricracerandomized controlled clinical trialsparsentan |
| spellingShingle | Howard Trachtman Jai Radhakrishnan Michelle N. Rheault Charles E. Alpers Jonathan Barratt Hiddo J.L. Heerspink Irene L. Noronha Vlado Perkovic Brad Rovin Hernán Trimarchi Muh Geot Wong Alex Mercer Jula Inrig William Rote Ed Murphy Patricia W. Bedard Sandra Roth Stewart Bieler Radko Komers Focal Segmental Glomerulosclerosis Patient Baseline Characteristics in the Sparsentan Phase 3 DUPLEX Study Kidney International Reports dual endothelin angiotensin receptor antagonist focal segmental glomerulosclerosis pediatric race randomized controlled clinical trial sparsentan |
| title | Focal Segmental Glomerulosclerosis Patient Baseline Characteristics in the Sparsentan Phase 3 DUPLEX Study |
| title_full | Focal Segmental Glomerulosclerosis Patient Baseline Characteristics in the Sparsentan Phase 3 DUPLEX Study |
| title_fullStr | Focal Segmental Glomerulosclerosis Patient Baseline Characteristics in the Sparsentan Phase 3 DUPLEX Study |
| title_full_unstemmed | Focal Segmental Glomerulosclerosis Patient Baseline Characteristics in the Sparsentan Phase 3 DUPLEX Study |
| title_short | Focal Segmental Glomerulosclerosis Patient Baseline Characteristics in the Sparsentan Phase 3 DUPLEX Study |
| title_sort | focal segmental glomerulosclerosis patient baseline characteristics in the sparsentan phase 3 duplex study |
| topic | dual endothelin angiotensin receptor antagonist focal segmental glomerulosclerosis pediatric race randomized controlled clinical trial sparsentan |
| url | http://www.sciencedirect.com/science/article/pii/S2468024924000421 |
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