One-year results of a clinical trial of olipudase alfa enzyme replacement therapy in pediatric patients with acid sphingomyelinase deficiency.
Journal
Genetics in medicine : official journal of the American College of Medical Genetics
ISSN: 1530-0366
Titre abrégé: Genet Med
Pays: United States
ID NLM: 9815831
Informations de publication
Date de publication:
08 2021
08 2021
Historique:
received:
19
01
2021
accepted:
10
03
2021
revised:
09
03
2021
pubmed:
21
4
2021
medline:
14
9
2021
entrez:
20
4
2021
Statut:
ppublish
Résumé
To assess olipudase alfa enzyme replacement therapy for non-central nervous system manifestations of acid sphingomyelinase deficiency (ASMD) in children. 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 (DL 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 DL 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.
Identifiants
pubmed: 33875845
doi: 10.1038/s41436-021-01156-3
pii: S1098-3600(21)05062-0
pmc: PMC8354848
doi:
Substances chimiques
Recombinant Proteins
0
Sphingomyelin Phosphodiesterase
EC 3.1.4.12
olipudase alfa
EC 3.1.4.12
Banques de données
ClinicalTrials.gov
['NCT02292654']
Types de publication
Clinical Trial, Phase I
Clinical Trial, Phase II
Journal Article
Multicenter Study
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1543-1550Commentaires et corrections
Type : ErratumIn
Informations de copyright
© 2021. The Author(s).
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