Safety and Clinical Outcomes in Hunter Syndrome Patients 5 Years of Age and Younger Receiving Idursulfase Therapy

Study Overview
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Brief Summary
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The objective of this study is to determine the safety of once weekly dosing of idursulfase 0.5 mg/kg administered by intravenous (IV) infusion for male Hunter syndrome patients ≤ 5 years old.

Detailed Description
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This study will provide a basis for evaluating the safety of idursulfase administered to Hunter syndrome patients who are ≤ 5 years old. Additionally, this study will provide a basis for evaluating the idursulfase single- and repeated-dose pharmacokinetic profiles as well as the pharmacodynamic effect (as measured by urinary GAG excretion) in this pediatric population. Additional exploratory measures will include abdominal ultrasound measurements of liver and spleen volumes, assessments of growth with comparisons to normal population growth data, assessments of annualized growth velocity, assessments of routine developmental milestones using the Denver II, and assessments of clinical events, including the first occurrence of certain hearing-related events (e.g., hearing loss, otitis media), respiratory-related events (e.g., upper and lower respiratory infections), and specific surgical procedures (e.g., adenoidectomy, placement of PE tubes). All patients in this open-label study will receive once-weekly infusions of idursulfase at a dose of 0.5 mg/kg.

Official Title
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A Multi-Center, Open-Label Study Evaluating Safety and Clinical Outcomes in Hunter Syndrome Patients 5 Years of Age and Younger Receiving Idursulfase Enzyme Replacement Therapy

Conditions
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Hunter Syndrome, Mucopolysaccharidosis II, MPS II

Intervention / Treatment
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* Biological: Idursulfase


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The patient has a diagnosis of Hunter syndrome based upon biochemical criteria either documented in their medical history or established at Screening: A deficiency in iduronate-2-sulfatase (I2S) enzyme activity of ≤ 10 % of the lower limit of the normal range as measured in plasma, fibroblasts, or leukocytes (based on normal range of measuring laboratory) AND A normal enzyme activity level of one other sulfatase as measured in plasma, fibroblasts, or leukocytes (based on normal range of measuring laboratory). The patient is 5 years of age and under. The patient is male. The patient's parent(s), or patient's legal guardian must have voluntarily signed an Institutional Review Board approved informed consent form after all relevant aspects of the study have been explained and discussed with the patient's parent(s), or the patient's legal guardian. Exclusion Criteria: The patient has received treatment with another investigational therapy within 30 days prior to enrollment. The patient has clinically relevant medical condition(s) making implementation of the protocol difficult. The patient has previously received idursulfase. The patient has known hypersensitivity to any of the components of idursulfase. The patient has had a tracheostomy.

Ages Eligible for Study
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Maximum Age: 5 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Idursulfase<br>Open-label treatment with idursulfase | Biological: Idursulfase<br>* Solution for intravenous infusion, 0.5 mg/kg weekly<br>* Other names: Elaprase;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety Evaluation | An adverse event (AE) was defined as any untoward medical occurrence in a clinical investigation participant administered as a pharmaceutical product that did not necessarily have a causal relationship with this treatment. A serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Number of participants with AEs occurred after start of study treatment until 30 days after the last infusion of idursulfase, were reported. | From the start of study treatment until 30 days after the last infusion of idursulfase, up to 53 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Change From Baseline to Week 53 in Normalized Urinary Glycosaminoglycan (GAG) Levels | Analysis of urinary GAG levels was performed at baseline, Week 18, Week 36, and Week 53 as an assessment of the pharmacodynamic effects of Elaprase (idursulfase). | Baseline, Weeks 18, 36 and 53 | 
| Single- and Repeat-Dose Pharmacokinetics - Maximum Observed Serum Concentration (Cmax) |  | Weeks 1 and 27 | 
| Single- and Repeat-Dose Pharmacokinetics - Time of Maximum Observed Serum Concentration (Tmax) |  | Weeks 1 and 27 | 
| Single- and Repeat-Dose Pharmacokinetics - Area Under the Serum Concentration-Time Curve From Time 0 to the Final Time Point With a Concentration of at Least Lower Limit of Quantitation (AUClast) |  | Weeks 1 and 27 | 
| Single- and Repeat-Dose Pharmacokinetics - Area Under the Serum Concentration-Time Curve From Time 0 to Infinity (AUCinf) |  | Weeks 1 and 27 | 
| Single- and Repeat-Dose Pharmacokinetics - Elimination Half-Life (t1/2) | t1/2 refers to the elimination of the drug. It is the time taken for the blood plasma concentration to reach half the concentration in the terminal phase of elimination. It is expressed in minutes and derived from the terminal slope of the concentration versus time curve. | Weeks 1 and 27 | 
| Single- and Repeat-Dose Pharmacokinetics - Mean Residence Time From Time 0 to Infinity (MRTinf) | MRTinf is an average duration of the drug in the body from time zero to infinity, and is expressed in minutes. | Weeks 1 and 27 | 
| Single- and Repeat-Dose Pharmacokinetics - Clearance (CL) | Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. | Weeks 1 and 27 | 
| Single- and Repeat-Dose Pharmacokinetics - Volume of Distribution at Steady State (Vss) | Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug. Vss is the apparent volume of distribution at steadystate. | Weeks 1 and 27 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hunter syndrome, hunters syndrome, hunter's syndrome, hunter disease, hunters disease, hunter's disease, MPS II, MPSII, MPS2, MPS 2, mucopolysaccharides, lysosomal storage disease, lysosomal storage disorder, chronic ear infection, enlarged adenoids, mps symptoms, mps diagnosis, mps ii therapy, MPS II treatment, ert treatment, elaprase, idursulfase, iduronate sulfatase, iduronate 2 sulfatase, enzyme replacement therapy, hunter syndrome treatment, hunter's syndrome treatment, hunter's disease treatment, mps society, hunter syndrome therapy