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

Mucopolysaccharidosis II Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00607386
• Other study ID #: HGT-ELA-038
• Secondary ID: 2007-006044-22
• Status: Completed
• Phase: Phase 4
• Start date: December 31, 2007
• Est. completion date: July 8, 2011

Study information

• Verified date: May 2021
• Source: Takeda
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 28
• Est. completion date: July 8, 2011
• Est. primary completion date: July 8, 2011
• Accepts healthy volunteers: No
• Gender: Male
• Age group: N/A to 5 Years

Eligibility

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.

Related Conditions & MeSH terms

• Hunter Syndrome
• MPS II
• Mucopolysaccharidoses
• Mucopolysaccharidosis II
• Syndrome

Intervention

Biological:
• Idursulfase
Solution for intravenous infusion, 0.5 mg/kg weekly

Locations

Country	Name	City	State
Brazil	Hospital de Clinicas de Porto Alegre, Servico de Genetica Medica	Porto Alegre	RS
Poland	Instytut Pomnik Centrum Zdrowia Dziecka, Klinika Chorob Metaboliczynch, Endokrynologii i Diabetologii	Warsaw
Taiwan	National Taiwan University Hospital, Dept. of Pediatrics and Medical Genetics	Taipei

Sponsors (4)

Lead Sponsor	Collaborator
Shire	Covance, PharmaNet, PRA Health Sciences

Countries where clinical trial is conducted

Brazil,  Poland,  Taiwan, 

References & Publications (3)

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. — View 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. 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]. — View 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: 10.11 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	From the start of study treatment until 30 days after the last infusion of idursulfase, up to 53 weeks
Secondary	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).	Baseline, Weeks 18, 36 and 53
Secondary	Single- and Repeat-Dose Pharmacokinetics - Maximum Observed Serum Concentration (Cmax)		Weeks 1 and 27
Secondary	Single- and Repeat-Dose Pharmacokinetics - Time of Maximum Observed Serum Concentration (Tmax)		Weeks 1 and 27
Secondary	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)		Weeks 1 and 27
Secondary	Single- and Repeat-Dose Pharmacokinetics - Area Under the Serum Concentration-Time Curve From Time 0 to Infinity (AUCinf)		Weeks 1 and 27
Secondary	Single- and Repeat-Dose Pharmacokinetics - Elimination Half-Life (t1/2)	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.	Weeks 1 and 27
Secondary	Single- and Repeat-Dose Pharmacokinetics - Mean Residence Time From Time 0 to Infinity (MRTinf)	MRTinf is an average duration of the drug in the body from time zero to infinity, and is expressed in minutes.	Weeks 1 and 27
Secondary	Single- and Repeat-Dose Pharmacokinetics - Clearance (CL)	Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes.	Weeks 1 and 27
Secondary	Single- and Repeat-Dose Pharmacokinetics - Volume of Distribution at Steady State (Vss)	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.	Weeks 1 and 27