دورية أكاديمية
PHYOX2: a pivotal randomized study of nedosiran in primary hyperoxaluria type 1 or 2
| العنوان: | PHYOX2: a pivotal randomized study of nedosiran in primary hyperoxaluria type 1 or 2 |
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| المؤلفون: | Baum, Michelle A., Langman, Craig B., Cochat, Pierre, Lieske, John, Moochhala, Shabbir H., Hamamoto, Shuzo, Ariceta Iraola, Gema |
| المساهمون: | Institut Català de la Salut, Baum MA Division of Nephrology, Boston Children’s Hospital, Boston, Massachusetts, USA. Langman C Department of Pediatrics, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA. Cochat P Reference Centre for Rare Renal Diseases, Hôpital Femme Mère Enfant, Lyon, France. Lieske JC Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota, USA. Moochhala SH UCL Department of Renal Medicine, Royal Free Hospital, London, UK. Hamamoto S Department of Nephro-urology, Nagoya City University, Nagoya, Japan. Ariceta G Servei de Nefrologia Pediàtrica, Vall d’Hebron Hospital Universitari, Barcelona, Spain, Vall d'Hebron Barcelona Hospital Campus |
| المصدر: | Scientia |
| بيانات النشر: | Elsevier |
| سنة النشر: | 2023 |
| مصطلحات موضوعية: | Ronyons - Malalties - Tractament, Malalties congènites - Tractament, Expressió gènica, DISEASES::Congenital, Hereditary, and Neonatal Diseases and Abnormalities::Genetic Diseases, Inborn::Metabolism, Inborn Errors::Carbohydrate Metabolism, Inborn Errors::Hyperoxaluria, Primary, Other subheadings::Other subheadings::Other subheadings::/drug therapy, PHENOMENA AND PROCESSES::Genetic Phenomena::Gene Expression, DISEASES::Male Urogenital Diseases::Urologic Diseases::Kidney Diseases, ENFERMEDADES::enfermedades y anomalías neonatales congénitas y hereditarias::enfermedades genéticas congénitas::alteraciones congénitas del metabolismo::trastornos congénitos del metabolismo de los carbohidratos::hiperoxaluria primaria, Otros calificadores::Otros calificadores::Otros calificadores::/farmacoterapia, FENÓMENOS Y PROCESOS::fenómenos genéticos::expresión génica, ENFERMEDADES::enfermedades urogenitales masculinas::enfermedades urológicas::enfermedades renales |
| الوصف: | Chronic kidney disease; Pediatric nephrology; Urology ; Malaltia renal crònica; Nefrologia pediàtrica; Urologia ; Enfermedad renal crónica; Nefrología pediátrica; Urología ; Nedosiran is an investigational RNA interference agent designed to inhibit expression of hepatic lactate dehydrogenase, the enzyme thought responsible for the terminal step of oxalate synthesis. Oxalate overproduction is the hallmark of all genetic subtypes of primary hyperoxaluria (PH). In this double-blind, placebo-controlled study, we randomly assigned (2:1) 35 participants with PH1 (n = 29) or PH2 (n = 6) with eGFR ≥30 mL/min/1.73 m2 to subcutaneous nedosiran or placebo once monthly for 6 months. The area under the curve (AUC) of percent reduction from baseline in 24-hour urinary oxalate (Uox) excretion (primary endpoint), between day 90–180, was significantly greater with nedosiran vs placebo (least squares mean [SE], +3507 [788] vs −1664 [1190], respectively; difference, 5172; 95% CI 2929–7414; P < 0.001). A greater proportion of participants receiving nedosiran vs placebo achieved normal or near-normal (<0.60 mmol/24 hours; <1.3 × ULN) Uox excretion on ≥2 consecutive visits starting at day 90 (50% vs 0; P = 0.002); this effect was mirrored in the nedosiran-treated PH1 subgroup (64.7% vs 0; P < 0.001). The PH1 subgroup maintained a sustained Uox reduction while on nedosiran, whereas no consistent effect was seen in the PH2 subgroup. Nedosiran-treated participants with PH1 also showed a significant reduction in plasma oxalate versus placebo (P = 0.017). Nedosiran was generally safe and well tolerated. In the nedosiran arm, the incidence of injection-site reactions was 9% (all mild and self-limiting). In conclusion, participants with PH1 receiving nedosiran had clinically meaningful reductions in Uox, the mediator of kidney damage in PH. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 1523-1755 |
| العلاقة: | Kidney International;103(1); https://doi.org/10.1016/j.kint.2022.07.025Test; Baum MA, Langman C, Cochat P, Lieske JC, Moochhala SH, Hamamoto S, et al. PHYOX2: A Pivotal Randomized Study of Nedosiran in Primary Hyperoxaluria Type 1 or 2. Kidney Int. 2023 Jan;103(1):207-17.; https://hdl.handle.net/11351/8992Test |
| DOI: | 10.1016/j.kint.2022.07.025 |
| الإتاحة: | https://doi.org/10.1016/j.kint.2022.07.025Test https://hdl.handle.net/11351/8992Test |
| حقوق: | Attribution 4.0 International ; http://creativecommons.org/licenses/by/4.0Test/ ; info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.9AA57269 |
| قاعدة البيانات: | BASE |
| تدمد: | 15231755 |
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| DOI: | 10.1016/j.kint.2022.07.025 |