One-year results of a clinical trial of olipudase alfa enzyme replacement therapy in pediatric patients with acid sphingomyelinase deficiency
Autor(a) principal: | |
---|---|
Data de Publicação: | 2021 |
Outros Autores: | , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UFRGS |
Texto Completo: | http://hdl.handle.net/10183/234517 |
Resumo: | PURPOSE: To assess olipudase alfa enzyme replacement therapy for non–central nervous system manifestations of acid sphingomyelinase deficiency (ASMD) in children. METHODS: This phase 1/2, international, multicenter, open-label trial (ASCEND-Peds/NCT02292654) administered intravenous olipudase alfa every 2 weeks with intrapatient dose escalation to 3 mg/kg. Primary outcome was safety through week 64. Secondary outcomes included pharmacokinetics, spleen and liver volumes, lung diffusing capacity (DLCO), lipid profiles, and height through week 52. RESULTS: Twenty patients were enrolled: four adolescents (12–17 years), nine children (6–11 years), and seven infants/early child (1–5 years). Most adverse events were mild or moderate, including infusion-associated reactions (primarily urticaria, pyrexia, and/or vomiting) in 11 patients. Three patients had serious treatment-related events: one with transient asymptomatic alanine aminotransferase increases, another with urticaria and rash (antidrug antibody positive [ADA+]), and a third with an anaphylactic reaction (ADA+) who underwent desensitization and reached the 3 mg/kg maintenance dose. Mean splenomegaly and hepatomegaly improved by >40% (p < 0.0001). Mean % predicted DLCO improved by 32.9% (p = 0.0053) in patients able to perform the test. Lipid profiles and elevated liver transaminase levels normalized. Mean height Z-scores improved by 0.56 (p < 0.0001). CONCLUSION: In this study in children with chronic ASMD, olipudase alfa was generally well-tolerated with significant, comprehensive improvements in disease pathology across a range of clinically relevant endpoints. |
id |
UFRGS-2_e9ef14e30e80d32d6bb4e571dac57173 |
---|---|
oai_identifier_str |
oai:www.lume.ufrgs.br:10183/234517 |
network_acronym_str |
UFRGS-2 |
network_name_str |
Repositório Institucional da UFRGS |
repository_id_str |
|
spelling |
Diaz, George A.Jones, Simon A.Scarpa, MaurizioMengel, Karl EugenGiugliani, RobertoGuffon, NathalieBatsu, IsabelaFraser, Patricia A.Jing, LiQi, ZhangRenon, Catherine Ortemann2022-01-27T04:33:10Z20211530-0366http://hdl.handle.net/10183/234517001135853PURPOSE: To assess olipudase alfa enzyme replacement therapy for non–central nervous system manifestations of acid sphingomyelinase deficiency (ASMD) in children. METHODS: This phase 1/2, international, multicenter, open-label trial (ASCEND-Peds/NCT02292654) administered intravenous olipudase alfa every 2 weeks with intrapatient dose escalation to 3 mg/kg. Primary outcome was safety through week 64. Secondary outcomes included pharmacokinetics, spleen and liver volumes, lung diffusing capacity (DLCO), lipid profiles, and height through week 52. RESULTS: Twenty patients were enrolled: four adolescents (12–17 years), nine children (6–11 years), and seven infants/early child (1–5 years). Most adverse events were mild or moderate, including infusion-associated reactions (primarily urticaria, pyrexia, and/or vomiting) in 11 patients. Three patients had serious treatment-related events: one with transient asymptomatic alanine aminotransferase increases, another with urticaria and rash (antidrug antibody positive [ADA+]), and a third with an anaphylactic reaction (ADA+) who underwent desensitization and reached the 3 mg/kg maintenance dose. Mean splenomegaly and hepatomegaly improved by >40% (p < 0.0001). Mean % predicted DLCO improved by 32.9% (p = 0.0053) in patients able to perform the test. Lipid profiles and elevated liver transaminase levels normalized. Mean height Z-scores improved by 0.56 (p < 0.0001). CONCLUSION: In this study in children with chronic ASMD, olipudase alfa was generally well-tolerated with significant, comprehensive improvements in disease pathology across a range of clinically relevant endpoints.application/pdfengGenetics in medicine. New York. Vol. 23 (2021), p. 1543–1550.Terapia de reposição de enzimasDoenças de Niemann-PickCriançaOne-year results of a clinical trial of olipudase alfa enzyme replacement therapy in pediatric patients with acid sphingomyelinase deficiencyEstrangeiroinfo: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:UFRGSTEXT001135853.pdf.txt001135853.pdf.txtExtracted Texttext/plain49449http://www.lume.ufrgs.br/bitstream/10183/234517/2/001135853.pdf.txtaefeef0d1d83d5201e6c20526b8a4836MD52ORIGINAL001135853.pdfTexto completo (inglês)application/pdf632093http://www.lume.ufrgs.br/bitstream/10183/234517/1/001135853.pdf4529664d87c9b043a712f52399c33a91MD5110183/2345172022-07-15 04:48:00.261032oai:www.lume.ufrgs.br:10183/234517Repositório de PublicaçõesPUBhttps://lume.ufrgs.br/oai/requestopendoar:2022-07-15T07:48Repositório Institucional da UFRGS - Universidade Federal do Rio Grande do Sul (UFRGS)false |
dc.title.pt_BR.fl_str_mv |
One-year results of a clinical trial of olipudase alfa enzyme replacement therapy in pediatric patients with acid sphingomyelinase deficiency |
title |
One-year results of a clinical trial of olipudase alfa enzyme replacement therapy in pediatric patients with acid sphingomyelinase deficiency |
spellingShingle |
One-year results of a clinical trial of olipudase alfa enzyme replacement therapy in pediatric patients with acid sphingomyelinase deficiency Diaz, George A. Terapia de reposição de enzimas Doenças de Niemann-Pick Criança |
title_short |
One-year results of a clinical trial of olipudase alfa enzyme replacement therapy in pediatric patients with acid sphingomyelinase deficiency |
title_full |
One-year results of a clinical trial of olipudase alfa enzyme replacement therapy in pediatric patients with acid sphingomyelinase deficiency |
title_fullStr |
One-year results of a clinical trial of olipudase alfa enzyme replacement therapy in pediatric patients with acid sphingomyelinase deficiency |
title_full_unstemmed |
One-year results of a clinical trial of olipudase alfa enzyme replacement therapy in pediatric patients with acid sphingomyelinase deficiency |
title_sort |
One-year results of a clinical trial of olipudase alfa enzyme replacement therapy in pediatric patients with acid sphingomyelinase deficiency |
author |
Diaz, George A. |
author_facet |
Diaz, George A. Jones, Simon A. Scarpa, Maurizio Mengel, Karl Eugen Giugliani, Roberto Guffon, Nathalie Batsu, Isabela Fraser, Patricia A. Jing, Li Qi, Zhang Renon, Catherine Ortemann |
author_role |
author |
author2 |
Jones, Simon A. Scarpa, Maurizio Mengel, Karl Eugen Giugliani, Roberto Guffon, Nathalie Batsu, Isabela Fraser, Patricia A. Jing, Li Qi, Zhang Renon, Catherine Ortemann |
author2_role |
author author author author author author author author author author |
dc.contributor.author.fl_str_mv |
Diaz, George A. Jones, Simon A. Scarpa, Maurizio Mengel, Karl Eugen Giugliani, Roberto Guffon, Nathalie Batsu, Isabela Fraser, Patricia A. Jing, Li Qi, Zhang Renon, Catherine Ortemann |
dc.subject.por.fl_str_mv |
Terapia de reposição de enzimas Doenças de Niemann-Pick Criança |
topic |
Terapia de reposição de enzimas Doenças de Niemann-Pick Criança |
description |
PURPOSE: To assess olipudase alfa enzyme replacement therapy for non–central nervous system manifestations of acid sphingomyelinase deficiency (ASMD) in children. METHODS: This phase 1/2, international, multicenter, open-label trial (ASCEND-Peds/NCT02292654) administered intravenous olipudase alfa every 2 weeks with intrapatient dose escalation to 3 mg/kg. Primary outcome was safety through week 64. Secondary outcomes included pharmacokinetics, spleen and liver volumes, lung diffusing capacity (DLCO), lipid profiles, and height through week 52. RESULTS: Twenty patients were enrolled: four adolescents (12–17 years), nine children (6–11 years), and seven infants/early child (1–5 years). Most adverse events were mild or moderate, including infusion-associated reactions (primarily urticaria, pyrexia, and/or vomiting) in 11 patients. Three patients had serious treatment-related events: one with transient asymptomatic alanine aminotransferase increases, another with urticaria and rash (antidrug antibody positive [ADA+]), and a third with an anaphylactic reaction (ADA+) who underwent desensitization and reached the 3 mg/kg maintenance dose. Mean splenomegaly and hepatomegaly improved by >40% (p < 0.0001). Mean % predicted DLCO improved by 32.9% (p = 0.0053) in patients able to perform the test. Lipid profiles and elevated liver transaminase levels normalized. Mean height Z-scores improved by 0.56 (p < 0.0001). CONCLUSION: In this study in children with chronic ASMD, olipudase alfa was generally well-tolerated with significant, comprehensive improvements in disease pathology across a range of clinically relevant endpoints. |
publishDate |
2021 |
dc.date.issued.fl_str_mv |
2021 |
dc.date.accessioned.fl_str_mv |
2022-01-27T04:33:10Z |
dc.type.driver.fl_str_mv |
Estrangeiro info:eu-repo/semantics/article |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10183/234517 |
dc.identifier.issn.pt_BR.fl_str_mv |
1530-0366 |
dc.identifier.nrb.pt_BR.fl_str_mv |
001135853 |
identifier_str_mv |
1530-0366 001135853 |
url |
http://hdl.handle.net/10183/234517 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.ispartof.pt_BR.fl_str_mv |
Genetics in medicine. New York. Vol. 23 (2021), p. 1543–1550. |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.source.none.fl_str_mv |
reponame:Repositório Institucional da UFRGS instname:Universidade Federal do Rio Grande do Sul (UFRGS) instacron:UFRGS |
instname_str |
Universidade Federal do Rio Grande do Sul (UFRGS) |
instacron_str |
UFRGS |
institution |
UFRGS |
reponame_str |
Repositório Institucional da UFRGS |
collection |
Repositório Institucional da UFRGS |
bitstream.url.fl_str_mv |
http://www.lume.ufrgs.br/bitstream/10183/234517/2/001135853.pdf.txt http://www.lume.ufrgs.br/bitstream/10183/234517/1/001135853.pdf |
bitstream.checksum.fl_str_mv |
aefeef0d1d83d5201e6c20526b8a4836 4529664d87c9b043a712f52399c33a91 |
bitstream.checksumAlgorithm.fl_str_mv |
MD5 MD5 |
repository.name.fl_str_mv |
Repositório Institucional da UFRGS - Universidade Federal do Rio Grande do Sul (UFRGS) |
repository.mail.fl_str_mv |
|
_version_ |
1801225049609338880 |