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

This study has been completed.
PRA Health Sciences
Information provided by (Responsible Party):
Shire Identifier:
First received: January 22, 2008
Last updated: October 6, 2015
Last verified: February 2014
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.

Condition Intervention Phase
Hunter Syndrome
Mucopolysaccharidosis II
Biological: Idursulfase
Phase 4

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:

Further study details as provided by Shire:

Primary Outcome Measures:
  • Safety Evaluation [ Time Frame: From the start of study treatment until 30 days after the last infusion of idursulfase, up to 53 weeks ] [ Designated as safety issue: Yes ]
    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.

Secondary Outcome Measures:
  • Mean Change From Baseline to Week 53 in Normalized Urinary Glycosaminoglycan (GAG) Levels [ Time Frame: Baseline, Weeks 18, 36 and 53 ] [ Designated as safety issue: No ]
    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).

  • Single- and Repeat-Dose Pharmacokinetics - Maximum Observed Serum Concentration (Cmax) [ Time Frame: Weeks 1 and 27 ] [ Designated as safety issue: No ]
  • Single- and Repeat-Dose Pharmacokinetics - Time of Maximum Observed Serum Concentration (Tmax) [ Time Frame: Weeks 1 and 27 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • Single- and Repeat-Dose Pharmacokinetics - Area Under the Serum Concentration-Time Curve From Time 0 to Infinity (AUCinf) [ Time Frame: Weeks 1 and 27 ] [ Designated as safety issue: No ]
  • Single- and Repeat-Dose Pharmacokinetics - Elimination Half-Life (t1/2) [ Time Frame: Weeks 1 and 27 ] [ Designated as safety issue: No ]
    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.

  • Single- and Repeat-Dose Pharmacokinetics - Mean Residence Time From Time 0 to Infinity (MRTinf) [ Time Frame: Weeks 1 and 27 ] [ Designated as safety issue: No ]
    MRTinf is an average duration of the drug in the body from time zero to infinity, and is expressed in minutes.

  • Single- and Repeat-Dose Pharmacokinetics - Clearance (CL) [ Time Frame: Weeks 1 and 27 ] [ Designated as safety issue: No ]
    Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes.

  • Single- and Repeat-Dose Pharmacokinetics - Volume of Distribution at Steady State (Vss) [ Time Frame: Weeks 1 and 27 ] [ Designated as safety issue: No ]
    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.

Enrollment: 28
Study Start Date: December 2007
Study Completion Date: July 2011
Primary Completion Date: July 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Open-label treatment with idursulfase
Biological: Idursulfase
Solution for intravenous infusion, 0.5 mg/kg weekly
Other Name: Elaprase

Detailed Description:

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.


Ages Eligible for Study:   up to 5 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No

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)


    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.
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Please refer to this study by its identifier: NCT00607386

Hospital de Clinicas de Porto Alegre, Servico de Genetica Medica
Porto Alegre, RS, Brazil, 90035-903
Instytut Pomnik Centrum Zdrowia Dziecka, Klinika Chorob Metaboliczynch, Endokrynologii i Diabetologii
Warsaw, Poland, 04-730
National Taiwan University Hospital, Dept. of Pediatrics and Medical Genetics
Taipei, Taiwan, 10016
Sponsors and Collaborators
PRA Health Sciences
Study Director: Arian Pano, MD, MPH Shire Human Genetic Therapies, Inc.
Principal Investigator: Roberto Giugliani, MD, PhD Hospital de Clinicas de Porto Alegre
Principal Investigator: Wuh-Liang Hwu, MD, PhD National Taiwan University Hospital
Principal Investigator: Anna Tylki-Szymanska, MD, PhD Instytut Pomnik Centrum Zdrowia Dziecka
  More Information

Responsible Party: Shire Identifier: NCT00607386     History of Changes
Other Study ID Numbers: HGT-ELA-038, 2007-006044-22
Study First Received: January 22, 2008
Results First Received: September 3, 2013
Last Updated: October 6, 2015
Health Authority: United States: Food and Drug Administration
Taiwan: Department of Health
Brazil: National Health Surveillance Agency
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products

Keywords provided by Shire:
Hunter syndrome
hunters syndrome
hunter's syndrome
hunter disease
hunters disease
hunter's disease
mps ii therapy
MPS II treatment
iduronate 2 sulfatase
hunter syndrome treatment
hunter's syndrome treatment
hunter syndrome therapy
hunter's disease treatment
lysosomal storage disease
lysosomal storage disorder
chronic ear infection
enlarged adenoids
mps symptoms
mps diagnosis
ert treatment
iduronate sulfatase
enzyme replacement therapy
mps society

Additional relevant MeSH terms:
Mucopolysaccharidosis II
Carbohydrate Metabolism, Inborn Errors
Connective Tissue Diseases
Genetic Diseases, Inborn
Genetic Diseases, X-Linked
Heredodegenerative Disorders, Nervous System
Intellectual Disability
Lysosomal Storage Diseases
Mental Retardation, X-Linked
Metabolic Diseases
Metabolism, Inborn Errors
Nervous System Diseases
Neurobehavioral Manifestations
Neurologic Manifestations
Pathologic Processes processed this record on November 27, 2015