PMID- 26331768
OWN - NLM
STAT- MEDLINE
DCOM- 20160927
LR  - 20181113
IS  - 1530-0447 (Electronic)
IS  - 0031-3998 (Print)
IS  - 0031-3998 (Linking)
VI  - 78
IP  - 6
DP  - 2015 Dec
TI  - Safety and clinical activity of elosulfase alfa in pediatric patients with 
      Morquio A syndrome (mucopolysaccharidosis IVA) less than 5 y.
PG  - 717-22
LID - 10.1038/pr.2015.169 [doi]
AB  - BACKGROUND: Previous studies have shown that elosulfase alfa has a favorable 
      efficacy/safety profile in Morquio A patients aged >/=5 y. This study evaluated 
      safety and impact on urine keratan sulfate (uKS) levels and growth velocity in 
      younger patients. METHODS: Fifteen Morquio A patients aged <5 y received 
      elosulfase alfa 2.0 mg/kg/week for 52 wk during the primary treatment phase of a 
      phase II, open-label, multinational study. Primary endpoint was safety and 
      tolerability; secondary endpoints were change in uKS and growth velocity over 
      52 wk. RESULTS: All 15 patients completed the primary treatment phase. Six of 743 
      infusions (0.8%) administered led to adverse events (AEs) requiring infusion 
      interruption and medical intervention. Eleven patients (73.3%) had >/=1 study 
      drug-related AE, mostly infusion-associated reactions. Mean z-score growth rate 
      per year numerically improved from -0.6 at baseline to -0.4 at week 52. 
      Comparison to untreated subjects of similar age in the Morquio A Clinical 
      Assessment Program study showed a smaller decrease in height z-scores for treated 
      than for untreated patients. Mean percent change from baseline in uKS was -30.2% 
      at 2 wk and -43.5% at 52 wk. CONCLUSION: Early intervention with elosulfase alfa 
      is well-tolerated and produces a decrease in uKS and a trend toward improvement 
      in growth.
FAU - Jones, Simon A
AU  - Jones SA
AD  - Willink Unit, Manchester Centre for Genomic Medicine, St Mary's Hospital, 
      Manchester Academic Health Sciences Centre, University of Manchester, Central 
      Manchester University Hospital National Health Service Foundation Trust, 
      Manchester, UK.
FAU - Bialer, Martin
AU  - Bialer M
AD  - North Shore LIJ Health System, Department of Pediatrics, Manhasset, New York.
FAU - Parini, Rossella
AU  - Parini R
AUID- ORCID: 0000-0003-4505-1306
AD  - Azienda Ospedaliera San Gerardo, Unita Operativa Semplice Malattie Metaboliche 
      Rare, Monza, Italy.
FAU - Martin, Ken
AU  - Martin K
AD  - BioMarin Pharmaceutical Inc., Novato, California.
FAU - Wang, Hui
AU  - Wang H
AD  - BioMarin Pharmaceutical Inc., Novato, California.
FAU - Yang, Ke
AU  - Yang K
AD  - BioMarin Pharmaceutical Inc., Novato, California.
FAU - Shaywitz, Adam J
AU  - Shaywitz AJ
AD  - BioMarin Pharmaceutical Inc., Novato, California.
FAU - Harmatz, Paul
AU  - Harmatz P
AD  - UCSF Benioff Children's Hospital Oakland, Department of Gastroenterology, 
      Oakland, California.
LA  - eng
SI  - ClinicalTrials.gov/NCT01515956
GR  - UL1 TR000004/TR/NCATS NIH HHS/United States
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Multicenter Study
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20150902
PL  - United States
TA  - Pediatr Res
JT  - Pediatric research
JID - 0100714
RN  - 0 (Biomarkers)
RN  - 0 (Recombinant Proteins)
RN  - 9056-36-4 (Keratan Sulfate)
RN  - EC 3.1.6.- (Chondroitinsulfatases)
RN  - EC 3.1.6.4 (GALNS protein, human)
SB  - IM
MH  - Age Factors
MH  - Biomarkers/urine
MH  - Body Height/drug effects
MH  - Child Development/drug effects
MH  - Child, Preschool
MH  - Chondroitinsulfatases/*administration & dosage/adverse effects
MH  - Drug Administration Schedule
MH  - Early Medical Intervention
MH  - *Enzyme Replacement Therapy/adverse effects
MH  - Europe
MH  - Female
MH  - Humans
MH  - Infant
MH  - Infusions, Intravenous
MH  - Keratan Sulfate/urine
MH  - Male
MH  - Mucopolysaccharidosis IV/diagnosis/*drug therapy/enzymology/physiopathology/urine
MH  - Recombinant Proteins/administration & dosage
MH  - Time Factors
MH  - Treatment Outcome
MH  - United Kingdom
PMC - PMC4700045
EDAT- 2015/09/04 06:00
MHDA- 2016/09/28 06:00
PMCR- 2016/01/05
CRDT- 2015/09/03 06:00
PHST- 2015/01/23 00:00 [received]
PHST- 2015/06/09 00:00 [accepted]
PHST- 2015/09/03 06:00 [entrez]
PHST- 2015/09/04 06:00 [pubmed]
PHST- 2016/09/28 06:00 [medline]
PHST- 2016/01/05 00:00 [pmc-release]
AID - pr2015169 [pii]
AID - 10.1038/pr.2015.169 [doi]
PST - ppublish
SO  - Pediatr Res. 2015 Dec;78(6):717-22. doi: 10.1038/pr.2015.169. Epub 2015 Sep 2.