A randomized, placebo-controlled clinical trial evaluating olipudase alfa enzyme replacement therapy for chronic acid sphingomyelinase deficiency (ASMD) in adults: One-year results.
Genet Med
; 24(7): 1425-1436, 2022 07.
Article
em En
| MEDLINE
| ID: mdl-35471153
ABSTRACT
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 11 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.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Doença de Niemann-Pick Tipo A
Tipo de estudo:
Clinical_trials
/
Prognostic_studies
Limite:
Adult
/
Humans
Idioma:
En
Revista:
Genet Med
Assunto da revista:
GENETICA MEDICA
Ano de publicação:
2022
Tipo de documento:
Article