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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT00607386
Recruitment Status : Completed
First Posted : February 5, 2008
Results First Posted : November 7, 2013
Last Update Posted : October 28, 2015
Sponsor:
Collaborators:
Covance
PharmaNet
PRA Health Sciences
Information provided by (Responsible Party):
Shire

Tracking Information
First Submitted Date  ICMJE January 22, 2008
First Posted Date  ICMJE February 5, 2008
Results First Submitted Date  ICMJE September 3, 2013
Results First Posted Date  ICMJE November 7, 2013
Last Update Posted Date October 28, 2015
Study Start Date  ICMJE December 2007
Actual Primary Completion Date July 2011   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 31, 2015)
Safety Evaluation [ Time Frame: From the start of study treatment until 30 days after the last infusion of idursulfase, up to 53 weeks ]
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.
Original Primary Outcome Measures  ICMJE
 (submitted: January 22, 2008)
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 ]
Change History Complete list of historical versions of study NCT00607386 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: July 31, 2015)
  • Mean Change From Baseline to Week 53 in Normalized Urinary Glycosaminoglycan (GAG) Levels [ Time Frame: Baseline, Weeks 18, 36 and 53 ]
    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 ]
  • Single- and Repeat-Dose Pharmacokinetics - Time of Maximum Observed Serum Concentration (Tmax) [ Time Frame: Weeks 1 and 27 ]
  • 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 ]
  • Single- and Repeat-Dose Pharmacokinetics - Area Under the Serum Concentration-Time Curve From Time 0 to Infinity (AUCinf) [ Time Frame: Weeks 1 and 27 ]
  • Single- and Repeat-Dose Pharmacokinetics - Elimination Half-Life (t1/2) [ Time Frame: Weeks 1 and 27 ]
    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 ]
    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 ]
    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 ]
    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.
Original Secondary Outcome Measures  ICMJE
 (submitted: January 22, 2008)
  • Mean change from Baseline to Week 53 in urinary GAG clearance (normalized for μg GAG/mg creatinine) [ Time Frame: One year ]
  • Single-dose and repeat-dose pharmacokinetic parameters [ Time Frame: Weeks 1 and 27 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Safety and Clinical Outcomes in Hunter Syndrome Patients 5 Years of Age and Younger Receiving Idursulfase Therapy
Official Title  ICMJE 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
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Hunter Syndrome
  • Mucopolysaccharidosis II
  • MPS II
Intervention  ICMJE Biological: Idursulfase
Solution for intravenous infusion, 0.5 mg/kg weekly
Other Name: Elaprase
Study Arms  ICMJE Idursulfase
Open-label treatment with idursulfase
Intervention: Biological: Idursulfase
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: October 10, 2011)
28
Original Estimated Enrollment  ICMJE
 (submitted: January 22, 2008)
30
Actual Study Completion Date  ICMJE July 2011
Actual Primary Completion Date July 2011   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: Male
Ages  ICMJE up to 5 Years   (Child)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Brazil,   Poland,   Taiwan
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00607386
Other Study ID Numbers  ICMJE HGT-ELA-038
2007-006044-22 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Shire
Study Sponsor  ICMJE Shire
Collaborators  ICMJE
  • Covance
  • PharmaNet
  • PRA Health Sciences
Investigators  ICMJE
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
PRS Account Shire
Verification Date February 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP