Clinical trial NCT00607386: Safety and Clinical Outcomes in Hunter Syndrome Patients 5 Years of Age and Younger Receiving Idursulfase Therapy
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Hunter Syndrome
Mucopolysaccharidosis II
MPS II
Keywords: 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 syndrome therapy
hunter's disease treatment
mps society
Lead sponsor: Takeda
Sponsor class: INDUSTRY
Collaborators: name: Covance
name: PharmaNet
name: PRA Health Sciences
First posted: 2008-02-05
Enrollment: 28
Sex: MALE
Maximum age (years): 5
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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: 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 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.

Primary outcomes:
measure: Safety Evaluation
timeFrame: From the start of study treatment until 30 days after the last infusion of idursulfase, up to 53 weeks
Secondary outcomes:
measure: Mean Change From Baseline to Week 53 in Normalized Urinary Glycosaminoglycan (GAG) Levels
timeFrame: Baseline, Weeks 18, 36 and 53
measure: Single- and Repeat-Dose Pharmacokinetics - Maximum Observed Serum Concentration (Cmax)
timeFrame: Weeks 1 and 27
measure: Single- and Repeat-Dose Pharmacokinetics - Time of Maximum Observed Serum Concentration (Tmax)
timeFrame: Weeks 1 and 27
measure: 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)
timeFrame: Weeks 1 and 27
measure: Single- and Repeat-Dose Pharmacokinetics - Area Under the Serum Concentration-Time Curve From Time 0 to Infinity (AUCinf)
timeFrame: Weeks 1 and 27
measure: Single- and Repeat-Dose Pharmacokinetics - Elimination Half-Life (t1/2)
timeFrame: Weeks 1 and 27
measure: Single- and Repeat-Dose Pharmacokinetics - Mean Residence Time From Time 0 to Infinity (MRTinf)
timeFrame: Weeks 1 and 27
measure: Single- and Repeat-Dose Pharmacokinetics - Clearance (CL)
timeFrame: Weeks 1 and 27
measure: Single- and Repeat-Dose Pharmacokinetics - Volume of Distribution at Steady State (Vss)
timeFrame: Weeks 1 and 27
Other outcomes:
Locations:
city: Porto Alegre
country: Brazil
facility: Hospital de Clinicas de Porto Alegre, Servico de Genetica Medica
state: RS
city: Warsaw
country: Poland
facility: Instytut Pomnik Centrum Zdrowia Dziecka, Klinika Chorob Metaboliczynch, Endokrynologii i Diabetologii
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital, Dept. of Pediatrics and Medical Genetics
Study officials:
affiliation: Takeda
name: Study Director
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.