Table 1.

Summary of completed intravenous idursulfase clinical studies

Study characteristic	TKT008	TKT018	TKT024	TKT024EXT	HGT-ELA-038
Phase; study design	I/II; randomized, double-blind, placebo-controlled, dose-ranging	I/II; open-label extension	II/III; randomized, double-blind, placebo-controlled	II/III; open-label extension	IV; open-label, single-arm
Treatment regimen(s)	Idursulfase 0.15 mg/kg, 0.5 mg/kg or 1.5 mg/kg EOW		Idursulfase 0.5 mg/kg EOW or weekly	Idursulfase 0.5 mg/kg weekly	Idursulfase 0.5 mg/kg weekly
Study duration	6 months	5.5 years	12 months	24 months	12 months
Number of patients	12	12	96	94	28
Patient demographics	6–20 years of age		Stratification by baseline age and total disease score Baseline age groups: 5–11 years, 12–18 years and 19–31 years Baseline total disease score calculated from baseline 6MWT and % predicted FVC		1.4–7.5 years of age
Inclusion/exclusion criteria	≥5 years of age Able to cooperate with taking of study measurements Clinical features consistent with MPS II, including MPS-related hepatosplenomegaly, radiographic evidence of dysostosis multiplex, cardiomyopathy, upper airway obstruction Biochemical criteria: I2S activity in plasma or leukocytes ≤5% of the lower limit of the normal range		Patients 5–31 years of age with a diagnosis of MPS II based on both clinical and biochemical criteria Having any one of the following MPS II-related signs/symptoms: hepatosplenomegaly, radiographic evidence of dysostosis multiplex, valvular heart disease, obstructive airway disease; I2S activity ≤10% of the lower limit of the normal range in plasma, fibroblasts or leukocytes; normal enzyme activity of another sulfatase At baseline, all patients were required to reproducibly perform pulmonary function testing and have an FVC <80% of the predicted value Patients who had a tracheostomy or who had received a bone marrow or cord blood transplant were excluded		Inclusion criteria: Male ≤5 years of age MPS II diagnosis: I2S activity ≤10% of the lower limit of the normal range and normal activity of one other sulfatase Exclusion criteria: Previously treated with another investigational therapy within 30 days before enrollment Previously received idursulfase Clinically relevant medical condition(s) making implementation of the protocol difficult Known hypersensitivity to any of the components of idursulfase Tracheostomy
Primary end point(s)	Change from baseline in uGAG levels		Changes from baseline to the end of the study in 6MWT and % predicted FVC in two-component composite score	Changes from baseline to the end of the study in 6MWT, % predicted FVC and absolute FVC	Safety outcomes, including: Adverse events Anti-idursulfase antibodies Vital signs Physical examination 12-lead electrocardiogram Concomitant medications or procedures Laboratory testing (clinical chemistry, hematology and urinalysis)
Secondary end points	Liver and spleen volumes Walking capacity (6MWT) Pulmonary function (FEV1 and FVC) Joint mobility Heart size and function Oxygen desaturation and frequency of sleep apnea/hypopnea		% predicted FVC Absolute FVC 6MWT Liver and spleen volumes Levels of uGAG excretion Passive joint range of motion	Liver and spleen volume uGAG excretion Joint range of motion Cardiac mass Functional status Linear growth velocity	Exploratory efficacy outcomes, including: uGAG levels Liver or spleen size Developmental milestones Growth indices Pharmacokinetic parameters

Notes: TKT008 and TKT018, data on file, Transkaryotic Therapies, Inc., 2005; TKT024, NCT00069641; TKT024EXT, NCT00630747; HGT-ELA-038, NCT00607386.

Abbreviations: 6MWT, 6-minute walk test; EOW, every other week; FEV₁, forced expiratory volume in 1 second; FVC, forced vital capacity; I2S, iduronate-2-sulfatase; MPS II, mucopolysaccharidosis type II; uGAG, urinary glycosaminoglycan.