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

Shire28 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Hunter Syndrome Mucopolysaccharidosis II MPS II

Interventions

IdursulfaseBIOLOGICAL

Solution for intravenous infusion, 0.5 mg/kg weekly

Eligibility

Sex: MALEMax age: 5 Years

Medical Language ↔ Plain English

Inclusion Criteria: * The patient has a diagnosis of Hunter syndrome based upon biochemical criteria either documented in their medical history or established at Screening: 1. 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 2. 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.

Locations (3)

Hospital de Clinicas de Porto Alegre, Servico de Genetica Medica

Porto Alegre, Rio Grande do Sul, Brazil

Instytut Pomnik Centrum Zdrowia Dziecka, Klinika Chorob Metaboliczynch, Endokrynologii i Diabetologii

Warsaw, Poland

National Taiwan University Hospital, Dept. of Pediatrics and Medical Genetics

Taipei, Taiwan

Outcomes

Primary Outcomes

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.

Time frame: From the start of study treatment until 30 days after the last infusion of idursulfase, up to 53 weeks

Secondary Outcomes

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).

Time frame: Baseline, Weeks 18, 36 and 53

Single- and Repeat-Dose Pharmacokinetics - Maximum Observed Serum Concentration (Cmax)

Time frame: Weeks 1 and 27

Single- and Repeat-Dose Pharmacokinetics - Time of Maximum Observed Serum Concentration (Tmax)

Time frame: 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)

Time frame: Weeks 1 and 27

Single- and Repeat-Dose Pharmacokinetics - Area Under the Serum Concentration-Time Curve From Time 0 to Infinity (AUCinf)

Time frame: Weeks 1 and 27

Data from ClinicalTrials.gov

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