دورية أكاديمية
Safety and efficacy of avalglucosidase alfa versus alglucosidase alfa in patients with late-onset Pompe disease (COMET): a phase 3, randomised, multicentre trial ; Jordi Diaz-Manera ; Priya S Kishnani ; Hani Kushlaf ; Shafeeq Ladha ; Tahseen Mozaffar ; Volker Straub ; Antonio Toscano ; Ans T van der Ploeg ; Kenneth I Berger ; Paula R Clemens ; Yin-Hsiu Chien ; John W Day ; Sergey Illarioshkin ; Mark Roberts ; Shahram Attarian ; Joao Lindolfo Borges ; Francoise Bouhour ; Young Chul Choi ; Sevim Erdem-Ozdamar ; Ozlem Goker-Alpan ; Anna Kostera-Pruszczyk ; Kristina An Haack ; Christopher Hug ; Olivier Huynh-Ba ; Judith Johnson ; Nathan Thibault ; Tianyue Zhou ; Mazen M Dimachkie ; Benedikt Schoser ; COMET Investigator Group
| العنوان: | Safety and efficacy of avalglucosidase alfa versus alglucosidase alfa in patients with late-onset Pompe disease (COMET): a phase 3, randomised, multicentre trial ; Jordi Diaz-Manera ; Priya S Kishnani ; Hani Kushlaf ; Shafeeq Ladha ; Tahseen Mozaffar ; Volker Straub ; Antonio Toscano ; Ans T van der Ploeg ; Kenneth I Berger ; Paula R Clemens ; Yin-Hsiu Chien ; John W Day ; Sergey Illarioshkin ; Mark Roberts ; Shahram Attarian ; Joao Lindolfo Borges ; Francoise Bouhour ; Young Chul Choi ; Sevim Erdem-Ozdamar ; Ozlem Goker-Alpan ; Anna Kostera-Pruszczyk ; Kristina An Haack ; Christopher Hug ; Olivier Huynh-Ba ; Judith Johnson ; Nathan Thibault ; Tianyue Zhou ; Mazen M Dimachkie ; Benedikt Schoser ; COMET Investigator Group |
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| المساهمون: | Jordi Diaz-Manera, Priya S Kishnani, Hani Kushlaf, Shafeeq Ladha, Tahseen Mozaffar, Volker Straub, Antonio Toscano, Ans T van der Ploeg, Kenneth I Berger, Paula R Clemens, Yin-Hsiu Chien, John W Day, Sergey Illarioshkin, Mark Roberts, Shahram Attarian, Joao Lindolfo Borges, Francoise Bouhour, Young Chul Choi, Sevim Erdem-Ozdamar, Ozlem Goker-Alpan, Anna Kostera-Pruszczyk, Kristina An Haack, Christopher Hug, Olivier Huynh-Ba, Judith Johnson, Nathan Thibault, Tianyue Zhou, Mazen M Dimachkie, Benedikt Schoser, COMET Investigator Group, Choi, Young Chul |
| بيانات النشر: | Lancet Pub. Group |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Child, Preschool, Double-Blind Method, Enzyme Replacement Therapy / adverse effects, Enzyme Replacement Therapy / methods, Glycogen Storage Disease Type II* / drug therapy, Humans, Treatment Outcome, Walking, alpha-Glucosidases* / adverse effects |
| الوصف: | Background: Pompe disease is a rare, progressive neuromuscular disorder caused by deficiency of acid α-glucosidase (GAA) and accumulation of lysosomal glycogen. We assessed the safety and efficacy of avalglucosidase alfa, a recombinant human GAA enzyme replacement therapy specifically designed for enhanced mannose-6-phosphate-receptor targeting and enzyme uptake aimed at increased glycogen clearance, compared with the current approved standard of care, alglucosidase alfa, in patients with late-onset Pompe disease. Methods: We did a randomised, double-blind, phase 3 trial at 55 sites in 20 countries. We enrolled individuals (aged ≥3 years) with enzymatically confirmed late-onset Pompe disease who had never received treatment. We used a centralised treatment allocation system to randomly allocate participants to either avalglucosidase alfa or alglucosidase alfa. Participants and investigators were unaware of their treatment allocation. The primary outcome measure was change from baseline to week 49 in upright forced vital capacity percent (FVC%) predicted. We used a hierarchical fixed sequential testing strategy, whereby non-inferiority of avalglucosidase alfa compared with alglucosidase alfa was assessed first, with a non-inferiority margin of 1·1. If non-inferiority was seen, then superiority was tested with a 5% significance level. The key secondary objective was effect on functional endurance, measured by the 6-minute walk test (6MWT). Safety was assessed, including treatment-emergent adverse events and infusion-associated reactions. The modified intent-to-treat population was the primary analysis population for all efficacy analyses. The safety population was the analysis population for safety analyses. This trial is registered with ClinicalTrials.gov, NCT02782741. We report results of the 49-week primary analysis period. Findings: Between Nov 2, 2016, and March 29, 2019, 100 participants were randomly allocated avalglucosidase alfa (n=51) or alglucosidase alfa (n=49). Treatment with avalglucosidase alfa ... |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| تدمد: | 1474-4422 1474-4465 |
| العلاقة: | LANCET NEUROLOGY; J02153; OAK-2022-08774; https://ir.ymlib.yonsei.ac.kr/handle/22282913/192383Test; https://www.sciencedirect.com/science/article/pii/S1474442221002416Test; T9992021100; LANCET NEUROLOGY, Vol.20(12) : 1012-1026, 2021-12 |
| DOI: | 10.1016/S1474-4422(21)00241-6 |
| الإتاحة: | https://doi.org/10.1016/S1474-4422Test(21)00241-6 https://ir.ymlib.yonsei.ac.kr/handle/22282913/192383Test https://www.sciencedirect.com/science/article/pii/S1474442221002416Test |
| حقوق: | CC BY-NC-ND 2.0 KR |
| رقم الانضمام: | edsbas.C1AE239 |
| قاعدة البيانات: | BASE |
| تدمد: | 14744422 14744465 |
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| DOI: | 10.1016/S1474-4422(21)00241-6 |