A randomized, placebo-controlled clinical trial evaluating olipudase alfa enzyme replacement therapy for chronic acid sphingomyelinase deficiency (ASMD) in adults : one-year results
Autor(a) principal: | |
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Data de Publicação: | 2022 |
Outros Autores: | , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UFRGS |
Texto Completo: | http://hdl.handle.net/10183/245616 |
Resumo: | Purpose: This trial aimed to assess the efficacy and safety of olipudase alfa enzyme replacement therapy for non–central nervous system manifestations of acid sphingomyelinase deficiency (ASMD) in adults. Methods: A phase 2/3, 52 week, international, double-blind, placebo-controlled trial (ASCEND; NCT02004691/EudraCT 2015-000371-26) enrolled 36 adults with ASMD randomized 1:1 to receive olipudase alfa or placebo intravenously every 2 weeks with intrapatient dose escalation to 3 mg/kg. Primary efficacy endpoints were percent change from baseline to week 52 in percent predicted diffusing capacity of the lung for carbon monoxide and spleen volume (combined with splenomegaly-related score in the United States). Other outcomes included liver volume/function/sphingomyelin content, pulmonary imaging/function, platelet levels, lipid profiles, and pharmacodynamics. Results: Least square mean percent change from baseline to week 52 favored olipudase alfa over placebo for percent predicted diffusing capacity of the lung for carbon monoxide (22% vs 3.0% increases, P = .0004), spleen volume (39% decrease vs 0.5% increase, P < .0001), and liver volume (28% vs 1.5% decreases, P < .0001). Splenomegaly-related score decreased in both groups (P = .64). Other clinical outcomes improved in the olipudase alfa group compared with the placebo group. There were no treatment-related serious adverse events or adverse event–related discontinuations. Most adverse events were mild. Conclusion: Olipudase alfa was well tolerated and associated with significant and comprehensive improvements in disease pathology and clinically relevant endpoints compared with placebo in adults with ASMD. |
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Wasserstein, Melissa P.Giugliani, RobertoKumar, Monica2022-07-28T04:45:34Z20221530-0366http://hdl.handle.net/10183/245616001145570Purpose: This trial aimed to assess the efficacy and safety of olipudase alfa enzyme replacement therapy for non–central nervous system manifestations of acid sphingomyelinase deficiency (ASMD) in adults. Methods: A phase 2/3, 52 week, international, double-blind, placebo-controlled trial (ASCEND; NCT02004691/EudraCT 2015-000371-26) enrolled 36 adults with ASMD randomized 1:1 to receive olipudase alfa or placebo intravenously every 2 weeks with intrapatient dose escalation to 3 mg/kg. Primary efficacy endpoints were percent change from baseline to week 52 in percent predicted diffusing capacity of the lung for carbon monoxide and spleen volume (combined with splenomegaly-related score in the United States). Other outcomes included liver volume/function/sphingomyelin content, pulmonary imaging/function, platelet levels, lipid profiles, and pharmacodynamics. Results: Least square mean percent change from baseline to week 52 favored olipudase alfa over placebo for percent predicted diffusing capacity of the lung for carbon monoxide (22% vs 3.0% increases, P = .0004), spleen volume (39% decrease vs 0.5% increase, P < .0001), and liver volume (28% vs 1.5% decreases, P < .0001). Splenomegaly-related score decreased in both groups (P = .64). Other clinical outcomes improved in the olipudase alfa group compared with the placebo group. There were no treatment-related serious adverse events or adverse event–related discontinuations. Most adverse events were mild. Conclusion: Olipudase alfa was well tolerated and associated with significant and comprehensive improvements in disease pathology and clinically relevant endpoints compared with placebo in adults with ASMD.application/pdfengGenetics in medicine. New York. Vol. 24 (2021), p. 1425–1436.Doenças de Niemann-PickTerapia de reposição de enzimasDiffusing capacity of the lung for carbon monoxideNiemann-Pick type BNiemann-Pick type A/BOrganomegalyRecombinant human acid sphingomyelinaseA randomized, placebo-controlled clinical trial evaluating olipudase alfa enzyme replacement therapy for chronic acid sphingomyelinase deficiency (ASMD) in adults : one-year resultsEstrangeiroinfo:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UFRGSinstname:Universidade Federal do Rio Grande do Sul (UFRGS)instacron:UFRGSTEXT001145570.pdf.txt001145570.pdf.txtExtracted Texttext/plain53762http://www.lume.ufrgs.br/bitstream/10183/245616/2/001145570.pdf.txtd8f2f42a3eec20910f8daa7e7efe6cd3MD52ORIGINAL001145570.pdfTexto completo (inglês)application/pdf2080248http://www.lume.ufrgs.br/bitstream/10183/245616/1/001145570.pdfeda766860b3a0b42b125dfb0d286c2bdMD5110183/2456162022-07-29 04:51:01.857751oai:www.lume.ufrgs.br:10183/245616Repositório de PublicaçõesPUBhttps://lume.ufrgs.br/oai/requestopendoar:2022-07-29T07:51:01Repositório Institucional da UFRGS - Universidade Federal do Rio Grande do Sul (UFRGS)false |
dc.title.pt_BR.fl_str_mv |
A randomized, placebo-controlled clinical trial evaluating olipudase alfa enzyme replacement therapy for chronic acid sphingomyelinase deficiency (ASMD) in adults : one-year results |
title |
A randomized, placebo-controlled clinical trial evaluating olipudase alfa enzyme replacement therapy for chronic acid sphingomyelinase deficiency (ASMD) in adults : one-year results |
spellingShingle |
A randomized, placebo-controlled clinical trial evaluating olipudase alfa enzyme replacement therapy for chronic acid sphingomyelinase deficiency (ASMD) in adults : one-year results Wasserstein, Melissa P. Doenças de Niemann-Pick Terapia de reposição de enzimas Diffusing capacity of the lung for carbon monoxide Niemann-Pick type B Niemann-Pick type A/B Organomegaly Recombinant human acid sphingomyelinase |
title_short |
A randomized, placebo-controlled clinical trial evaluating olipudase alfa enzyme replacement therapy for chronic acid sphingomyelinase deficiency (ASMD) in adults : one-year results |
title_full |
A randomized, placebo-controlled clinical trial evaluating olipudase alfa enzyme replacement therapy for chronic acid sphingomyelinase deficiency (ASMD) in adults : one-year results |
title_fullStr |
A randomized, placebo-controlled clinical trial evaluating olipudase alfa enzyme replacement therapy for chronic acid sphingomyelinase deficiency (ASMD) in adults : one-year results |
title_full_unstemmed |
A randomized, placebo-controlled clinical trial evaluating olipudase alfa enzyme replacement therapy for chronic acid sphingomyelinase deficiency (ASMD) in adults : one-year results |
title_sort |
A randomized, placebo-controlled clinical trial evaluating olipudase alfa enzyme replacement therapy for chronic acid sphingomyelinase deficiency (ASMD) in adults : one-year results |
author |
Wasserstein, Melissa P. |
author_facet |
Wasserstein, Melissa P. Giugliani, Roberto Kumar, Monica |
author_role |
author |
author2 |
Giugliani, Roberto Kumar, Monica |
author2_role |
author author |
dc.contributor.author.fl_str_mv |
Wasserstein, Melissa P. Giugliani, Roberto Kumar, Monica |
dc.subject.por.fl_str_mv |
Doenças de Niemann-Pick Terapia de reposição de enzimas |
topic |
Doenças de Niemann-Pick Terapia de reposição de enzimas Diffusing capacity of the lung for carbon monoxide Niemann-Pick type B Niemann-Pick type A/B Organomegaly Recombinant human acid sphingomyelinase |
dc.subject.eng.fl_str_mv |
Diffusing capacity of the lung for carbon monoxide Niemann-Pick type B Niemann-Pick type A/B Organomegaly Recombinant human acid sphingomyelinase |
description |
Purpose: This trial aimed to assess the efficacy and safety of olipudase alfa enzyme replacement therapy for non–central nervous system manifestations of acid sphingomyelinase deficiency (ASMD) in adults. Methods: A phase 2/3, 52 week, international, double-blind, placebo-controlled trial (ASCEND; NCT02004691/EudraCT 2015-000371-26) enrolled 36 adults with ASMD randomized 1:1 to receive olipudase alfa or placebo intravenously every 2 weeks with intrapatient dose escalation to 3 mg/kg. Primary efficacy endpoints were percent change from baseline to week 52 in percent predicted diffusing capacity of the lung for carbon monoxide and spleen volume (combined with splenomegaly-related score in the United States). Other outcomes included liver volume/function/sphingomyelin content, pulmonary imaging/function, platelet levels, lipid profiles, and pharmacodynamics. Results: Least square mean percent change from baseline to week 52 favored olipudase alfa over placebo for percent predicted diffusing capacity of the lung for carbon monoxide (22% vs 3.0% increases, P = .0004), spleen volume (39% decrease vs 0.5% increase, P < .0001), and liver volume (28% vs 1.5% decreases, P < .0001). Splenomegaly-related score decreased in both groups (P = .64). Other clinical outcomes improved in the olipudase alfa group compared with the placebo group. There were no treatment-related serious adverse events or adverse event–related discontinuations. Most adverse events were mild. Conclusion: Olipudase alfa was well tolerated and associated with significant and comprehensive improvements in disease pathology and clinically relevant endpoints compared with placebo in adults with ASMD. |
publishDate |
2022 |
dc.date.accessioned.fl_str_mv |
2022-07-28T04:45:34Z |
dc.date.issued.fl_str_mv |
2022 |
dc.type.driver.fl_str_mv |
Estrangeiro info:eu-repo/semantics/article |
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http://hdl.handle.net/10183/245616 |
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1530-0366 |
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001145570 |
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http://hdl.handle.net/10183/245616 |
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eng |
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eng |
dc.relation.ispartof.pt_BR.fl_str_mv |
Genetics in medicine. New York. Vol. 24 (2021), p. 1425–1436. |
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openAccess |
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