Clinical Trial: A Safety and Dose Ranging Study of Idursulfase (Intrathecal) Administration Via an Intrathecal Drug Delivery Device in Pediatric Patients With Hunter Syndrome Who Have Central Nervous System Involvement and Are Receiving Treatment With Elaprase®

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: A Phase I/II, Randomized, Safety and Ascending Dose Ranging Study of Intrathecal Idursulfase-IT Administered in Conjunction With Intravenous Elaprase in Pediatric Patients With H

Brief Summary:

Elaprase (idursulfase), a large molecular protein, is not expected to cross the blood brain barrier at therapeutic levels when administered intravenously. A new formulation of idursulfase, idursulfase-IT, that differs from that of the intravenous (IV) formulation, Elaprase, has been developed to be suitable for delivery into the cerebrospinal fluid (CSF) via intrathecal administration.

This Phase I/II study is designed to obtain necessary safety and exposure data, as well as secondary and exploratory outcome measures, to be interpreted and used in the design of subsequent clinical trials.


Detailed Summary:
Sponsor: Shire

Current Primary Outcome:

  • Number of Serious Adverse Event (SAE) [ Time Frame: 6 months ]
  • Number of Treatment Emergent Adverse Event (AE) [ Time Frame: Baseline to week 23 ]
    ITT patient population
  • Safety Changes in Cerebrospinal Fluid (CSF)- White Blood Cells (WBC) [ Time Frame: 6 months ]
    White blood cell count in CSF was monitored throughout the study as a way of assessing any potential inflammation of the meninges induced by idursulfase-IT.
  • Safety: Development of Anti-idursulfase Antibodies (CSF) [ Time Frame: 6 months ]
    Reflects development of anti-idursulfase antibodies post baseline.
  • Safety: Development of Anti-idursulfase Antibodies (Serum) [ Time Frame: 6 months ]
  • Clinically Significant ECG Findings at Any Time During the Study. [ Time Frame: 6 months ]
    Electrocardiogram (ECG) parameters included: heart rate, sinus rhythm, atrial/ventricular hypertrophy, PR, QRS, QT and QTc intervals.


Original Primary Outcome:

  • Safety of intrathecal idursulfase administration as assessed by AEs, changes in clinical laboratory testing, 12-lead electrocardiograms, CSF chemistries, and anti-idursulfase antibodies [ Time Frame: 6 months ]
  • Safety, tolerability, and long term patency of the IDDD in the pediatric Hunter syndrome population [ Time Frame: 6 months ]


Current Secondary Outcome:

  • Change From Baseline in CSF Glycosaminoglycans [GAGs] at Week 27 [ Time Frame: Baseline to Week 27 ]
    Percent Change from Baseline to Week 27
  • Level of Idursulfase in the CSF Compartment Resulting From Monthly Idursulfase IT Administrations [ Time Frame: Week 27 (end of study) ]
    Samples collected from patients treated at doses of 1 mg and 30 mg, as well as the control group, were below the lower limit of detection of the bioanalytical method (3.13 ng/mL)
  • Concentration of Idursulfase in Serum After Single Administration (Week 3) in Conjunction With Elaprase [ Time Frame: Weeks 3 ]
    Values below lower limit of quantitation (LLOQ) are listed as 0.
  • Concentration of Idursulfase in Serum After Repeated Doses of Intrathecal Idursulfase-IT Given in Conjunction With Elaprase [ Time Frame: Weeks 23 ]
  • % Change From Baseline in Urinary GAG [ Time Frame: Baseline to Week 27 ]


Original Secondary Outcome:

  • Single and repeated dose pharmacokinetic parameters of idursulfase-IT, given in conjunction with Elaprase, in CSF and blood [ Time Frame: Weeks 3 and 23 ]
  • Change from baseline in CSF biomarkers by dose group and in comparison with untreated patients [ Time Frame: 6 months ]
  • Change from baseline in urinary GAG and degradation byproducts by dose group and in comparison with untreated patients [ Time Frame: 6 months ]


Information By: Shire

Dates:
Date Received: June 12, 2009
Date Started: November 2009
Date Completion:
Last Updated: October 6, 2015
Last Verified: April 2014