- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00607386
Safety and Clinical Outcomes in Hunter Syndrome Patients 5 Years of Age and Younger Receiving Idursulfase Therapy
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
Study Overview
Status
Conditions
Intervention / Treatment
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.
Study Type
Enrollment (Actual)
Phase
- Phase 4
Contacts and Locations
Study Locations
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RS
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Porto Alegre, RS, Brazil, 90035-903
- Hospital de Clinicas de Porto Alegre, Servico de Genetica Medica
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Warsaw, Poland, 04-730
- Instytut Pomnik Centrum Zdrowia Dziecka, Klinika Chorob Metaboliczynch, Endokrynologii i Diabetologii
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Taipei, Taiwan, 10016
- National Taiwan University Hospital, Dept. of Pediatrics and Medical Genetics
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Other: Idursulfase
Open-label treatment with idursulfase
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Solution for intravenous infusion, 0.5 mg/kg weekly
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Safety Evaluation
Time Frame: From the start of study treatment until 30 days after the last infusion of idursulfase, up to 53 weeks
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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.
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From the start of study treatment until 30 days after the last infusion of idursulfase, up to 53 weeks
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Mean Change From Baseline to Week 53 in Normalized Urinary Glycosaminoglycan (GAG) Levels
Time Frame: Baseline, Weeks 18, 36 and 53
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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).
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Baseline, Weeks 18, 36 and 53
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Single- and Repeat-Dose Pharmacokinetics - Maximum Observed Serum Concentration (Cmax)
Time Frame: Weeks 1 and 27
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Weeks 1 and 27
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Single- and Repeat-Dose Pharmacokinetics - Time of Maximum Observed Serum Concentration (Tmax)
Time Frame: Weeks 1 and 27
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Weeks 1 and 27
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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
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Weeks 1 and 27
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Single- and Repeat-Dose Pharmacokinetics - Area Under the Serum Concentration-Time Curve From Time 0 to Infinity (AUCinf)
Time Frame: Weeks 1 and 27
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Weeks 1 and 27
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Single- and Repeat-Dose Pharmacokinetics - Elimination Half-Life (t1/2)
Time Frame: Weeks 1 and 27
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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.
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Weeks 1 and 27
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Single- and Repeat-Dose Pharmacokinetics - Mean Residence Time From Time 0 to Infinity (MRTinf)
Time Frame: Weeks 1 and 27
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MRTinf is an average duration of the drug in the body from time zero to infinity, and is expressed in minutes.
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Weeks 1 and 27
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Single- and Repeat-Dose Pharmacokinetics - Clearance (CL)
Time Frame: Weeks 1 and 27
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Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes.
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Weeks 1 and 27
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Single- and Repeat-Dose Pharmacokinetics - Volume of Distribution at Steady State (Vss)
Time Frame: Weeks 1 and 27
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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.
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Weeks 1 and 27
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Collaborators and Investigators
Sponsor
Publications and helpful links
General Publications
- Muenzer J, Gucsavas-Calikoglu M, McCandless SE, Schuetz TJ, Kimura A. A phase I/II clinical trial of enzyme replacement therapy in mucopolysaccharidosis II (Hunter syndrome). Mol Genet Metab. 2007 Mar;90(3):329-37. doi: 10.1016/j.ymgme.2006.09.001. Epub 2006 Dec 20.
- Muenzer J, Wraith JE, Beck M, Giugliani R, Harmatz P, Eng CM, Vellodi A, Martin R, Ramaswami U, Gucsavas-Calikoglu M, Vijayaraghavan S, Wendt S, Puga AC, Ulbrich B, Shinawi M, Cleary M, Piper D, Conway AM, Kimura A. A phase II/III clinical study of enzyme replacement therapy with idursulfase in mucopolysaccharidosis II (Hunter syndrome). Genet Med. 2006 Aug;8(8):465-73. doi: 10.1097/01.gim.0000232477.37660.fb. Erratum In: Genet Med. 2006 Sep;8(9):599. Wendt, Suzanne [corrected to Wendt, Susanne]; Puga, Antonio [corrected to Puga, Ana Cristina]; Conway, Ann Marie [corrected to Conway, Anne Marie].
- Pano A, Barbier AJ, Bielefeld B, Whiteman DA, Amato DA. Immunogenicity of idursulfase and clinical outcomes in very young patients (16 months to 7.5 years) with mucopolysaccharidosis II (Hunter syndrome). Orphanet J Rare Dis. 2015 Apr 24;10:50. doi: 10.1186/s13023-015-0265-2.
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
- enzyme replacement therapy
- MPS II
- Hunter syndrome
- lysosomal storage disorder
- lysosomal storage disease
- MPS 2
- mps symptoms
- enlarged adenoids
- elaprase
- hunter's syndrome
- MPS2
- hunters disease
- hunter's disease treatment
- hunter syndrome therapy
- iduronate sulfatase
- mps society
- MPSII
- hunter syndrome treatment
- hunter's disease
- iduronate 2 sulfatase
- mucopolysaccharides
- mps diagnosis
- chronic ear infection
- hunters syndrome
- ert treatment
- hunter disease
- idursulfase
- hunter's syndrome treatment
- mps ii therapy
- MPS II treatment
Additional Relevant MeSH Terms
- Pathologic Processes
- Metabolic Diseases
- Nervous System Diseases
- Neurologic Manifestations
- Neurobehavioral Manifestations
- Disease
- Genetic Diseases, Inborn
- Genetic Diseases, X-Linked
- Connective Tissue Diseases
- Carbohydrate Metabolism, Inborn Errors
- Metabolism, Inborn Errors
- Lysosomal Storage Diseases
- Mucinoses
- Mental Retardation, X-Linked
- Intellectual Disability
- Heredodegenerative Disorders, Nervous System
- Syndrome
- Mucopolysaccharidosis II
- Mucopolysaccharidoses
Other Study ID Numbers
- HGT-ELA-038
- 2007-006044-22 (EudraCT Number)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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