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

Purpose

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 MPS 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:

Genetics Home Reference related topics: MECP2 duplication syndrome mucopolysaccharidosis type II PPM-X syndrome Renpenning syndrome Schindler disease

Drug Information available for: Idursulfase

U.S. FDA Resources

Further study details as provided by Shire Human Genetic Therapies, Inc.:

Primary Outcome Measures:

Incidence of adverse events (including infusion-related adverse events), changes in 12-lead ECG, vital signs, standard laboratory parameters, and anti-idursulfase antibody status. [ Time Frame: One year ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Mean change from Baseline to Week 53 in urinary GAG clearance (normalized for μg GAG/mg creatinine) [ Time Frame: One year ] [ Designated as safety issue: No ]
Single-dose and repeat-dose pharmacokinetic parameters [ Time Frame: Weeks 1 and 27 ] [ Designated as safety issue: No ]

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
Idursulfase 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.

Eligibility

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

Criteria

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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00607386

Locations

Brazil
Hospital de Clinicas de Porto Alegre, Servico de Genetica Medica
Porto Alegre, RS, Brazil, 90035-903
Poland
Instytut Pomnik Centrum Zdrowia Dziecka, Klinika Chorob Metaboliczynch, Endokrynologii i Diabetologii
Warsaw, Poland, 04-730
Taiwan
National Taiwan University Hospital, Dept. of Pediatrics and Medical Genetics
Taipei, Taiwan, 10016

Sponsors and Collaborators

Shire Human Genetic Therapies, Inc.

Covance

PharmaNet

PRA International

Investigators

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

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. 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. 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].

Responsible Party:	Shire Human Genetic Therapies, Inc.
ClinicalTrials.gov Identifier:	NCT00607386 History of Changes
Other Study ID Numbers:	HGT-ELA-038
Study First Received:	January 22, 2008
Last Updated:	October 10, 2011
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 Human Genetic Therapies, Inc.:

Hunter syndrome
hunters syndrome
hunter's syndrome
hunter disease
hunters disease
hunter's disease
MPS II
MPSII
MPS2
MPS 2
mps 2
mps ii
mucopolysaccharides
lysosomal storage disease
lysosomal storage disorder

chronic ear infection
enlarged adenoids
mps symptoms
mps diagnosis
mps ii therapy
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

Additional relevant MeSH terms:

Mucopolysaccharidoses
Mucopolysaccharidosis II
Carbohydrate Metabolism, Inborn Errors
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Lysosomal Storage Diseases
Mucinoses
Connective Tissue Diseases

Metabolic Diseases
Mental Retardation, X-Linked
Mental Retardation
Neurobehavioral Manifestations
Neurologic Manifestations
Nervous System Diseases
Genetic Diseases, X-Linked
Heredodegenerative Disorders, Nervous System

ClinicalTrials.gov processed this record on May 22, 2013