Safety and Clinical Outcomes in Hunter Syndrome Patients 5 Years of Age and Younger Receiving Idursulfase Therapy
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.
|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|
- 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.
- 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.
|Study Start Date:||December 2007|
|Study Completion Date:||July 2011|
|Primary Completion Date:||July 2011 (Final data collection date for primary outcome measure)|
Open-label treatment with idursulfase
Solution for intravenous infusion, 0.5 mg/kg weekly
Other Name: Elaprase
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.
Please refer to this study by its ClinicalTrials.gov 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|
|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|