title: Safety and physiological effects of two different doses of elosulfase alfa in patients with morquio a syndrome: A randomized, double-blind, pilot study.
abstract: The primary treatment outcomes of a phase 2, randomized, double-blind, pilot study evaluating safety, physiological, and pharmacological effects of elosulfase alfa in patients with Morquio A syndrome are herewith presented. Patients aged ≥7 years and able to walk ≥200 m in the 6-min walk test (6MWT) were randomized to elosulfase alfa 2.0 or 4.0 mg/kg/week for 27 weeks. The primary objective was to evaluate the safety of both doses. Secondary objectives were to evaluate effects on endurance (6MWT and 3-min stair climb test [3MSCT]), exercise capacity (cardio-pulmonary exercise test [CPET]), respiratory function, muscle strength, cardiac function, pain, and urine keratan sulfate (uKS) levels, and to determine pharmacokinetic parameters. Twenty-five patients were enrolled (15 randomized to 2.0 mg/kg/week and 10 to 4.0 mg/kg/week). No new or unexpected safety signals were observed. After 24 weeks, there were no improvements versus baseline in the 6MWT, yet numerical improvements were seen in the 3MSCT with 4.0 mg/kg/week. uKS and pharmacokinetic data suggested no linear relationship over the 2.0-4.0 mg/kg dose range. Overall, an abnormal exercise capacity (evaluated in 10 and 5 patients in the 2.0 and 4.0 mg/kg/week groups, respectively), impaired muscle strength, and considerable pain were observed at baseline, and there were trends towards improvements in all domains after treatment. In conclusion, preliminary data of this small study in a Morquio A population with relatively good endurance confirmed the acceptable safety profile of elosulfase alfa and showed a trend of increased exercise capacity and muscle strength and decreased pain.
authors.affiliation: Ann and Robert H. Lurie Children's Hospital, Chicago, Illinois.|Northwestern University Feinberg School of Medicine, Chicago, Illinois.
authors.forename: Barbara K
authors.initials: BK
authors.lastname: Burton
authors.affiliation: New York University School of Medicine, New York, New York.
authors.forename: Kenneth I
authors.initials: KI
authors.lastname: Berger
authors.affiliation: Massachusetts General Hospital, Boston, Massachusetts.
authors.forename: Gregory D
authors.initials: GD
authors.lastname: Lewis
authors.affiliation: McMaster University Medical Center, Hamilton, Ontario, Canada.
authors.forename: Mark
authors.initials: M
authors.lastname: Tarnopolsky
authors.affiliation: UCSF Benioff Children's Hospital Oakland, Oakland, California.
authors.forename: Marsha
authors.initials: M
authors.lastname: Treadwell
authors.affiliation: Montreal Children's Hospital, Montreal, Quebec, Canada.
authors.forename: John J
authors.initials: JJ
authors.lastname: Mitchell
authors.affiliation: University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Nicole
authors.initials: N
authors.lastname: Muschol
authors.affiliation: Willink Unit, St. Mary's Hospital, CMFT, MAHSC, University of Manchester, Manchester, United Kingdom.
authors.forename: Simon A
authors.initials: SA
authors.lastname: Jones
authors.affiliation: Texas Children's Hospital, Houston, Texas.|Baylor College of Medicine, Houston, Texas.
authors.forename: V Reid
authors.initials: VR
authors.lastname: Sutton
authors.affiliation: New York University School of Medicine, New York, New York.|Mater Misericordiae University Hospital, Dublin, Ireland.
authors.forename: Gregory M
authors.initials: GM
authors.lastname: Pastores
authors.affiliation: New York University School of Medicine, New York, New York.
authors.forename: Heather
authors.initials: H
authors.lastname: Lau
authors.affiliation: Alberta Children's Hospital, Calgary, Alberta, Canada.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Sparkes
authors.affiliation: BioMarin Pharmaceutical Inc., Novato, California.
authors.forename: Fred
authors.initials: F
authors.lastname: Genter
authors.affiliation: BioMarin Pharmaceutical Inc., Novato, California.
authors.forename: Adam J
authors.initials: AJ
authors.lastname: Shaywitz
authors.affiliation: UCSF Benioff Children's Hospital Oakland, Oakland, California.
authors.forename: Paul
authors.initials: P
authors.lastname: Harmatz
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002811:Chondroitinsulfatases / Q000235:genetics* / Q000378:metabolism / Q000627:therapeutic use*; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D056947:Enzyme Replacement Therapy; D005080:Exercise Test; D005260:Female; D006334:Heart Function Tests; D006801:Humans; D007632:Keratan Sulfate / Q000652:urine; D008297:Male; D009085:Mucopolysaccharidosis IV / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D053580:Muscle Strength; D061214:Patient Safety; D010865:Pilot Projects; D011994:Recombinant Proteins / Q000627:therapeutic use; D012129:Respiratory Function Tests; D016896:Treatment Outcome; D016138:Walking
chemical_list: D011994:Recombinant Proteins; D007632:Keratan Sulfate; D002811:Chondroitinsulfatases; C102295:GALNS protein, human
keywords: GALNS protein; cardiopulmonary exercise test; enzyme replacement therapy; human [supplementary concept]; mucopolysaccharidosis IV; muscle strength; physical endurance; respiratory function tests; safety