Clinical Trial: Extension of HGT-HIT-045 Evaluating Long-Term Safety and Clinical Outcomes of Idursulfase (IT)in Conjunction With Elaprase in Pediatric Patients With Hunter Syndrome and Cognitive Impairment

Study Status: Active, not recruiting
Recruit Status: Active, not recruiting
Study Type: Interventional

Official Title: An Open Label Extension of Study HGT-HIT-045 Evaluating Long-Term Safety and Clinical Outcomes of Intrathecal Idursulfase-IT Administered in Conjunction With Intravenous Elaprase® in Pediatric Pa

Brief Summary:

Elaprase, a large molecular protein, is not expected to cross the blood brain barrier when administered intravenously. A revised 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 extension study of HGT-HIT-045 is designed to collect long-term safety data in pediatric patients with Hunter syndrome and cognitive impairment who are receiving intrathecal idursulfase-IT and intravenous Elaprase enzyme replacement therapy.


Detailed Summary:
Sponsor: Shire

Current Primary Outcome: Safety of intrathecal idursulfase-IT administration [ Time Frame: 30 Months ]

Safety of intrathecal administration of idursulfase-IT will be measured by type and severity of adverse events (AEs), changes in clinical laboratory testing (serum chemistry including liver function tests, hematology, urinalysis), 12-lead ECG, CSF chemistries, and anti-idursulfase antibodies (in CSF and serum by isotype: immunoglobulin (Ig) IgG, IgA, IgM, IgE and antibodies having enzyme neutralizing activity.


Original Primary Outcome: Safety of intrathecal idursulfase-IT administration [ Time Frame: 30 Months ]

Safety of intrathecal administration of idursulfase-IT will be measured by type and severity of adverse events (AEs), changes in clinical laboratory testing (serum chemistry including liver function tests, hematology, urinalysis), 12-lead ECG, CSF chemistries, and anti-idursulfase anitbodies (in CSF and serum by isotype: immunoglobulin (Ig) IgG, IgA, IgM, IgE and antibodies having enzyme neutralizing activity.


Current Secondary Outcome:

  • Pharmacokinetic (PK) parameters of idursulfase-IT administered in conjunction with Elaprase in CSF and blood. [ Time Frame: PK in blood at time 0, 1, 2, 3, 4, 6, 8, 12, 24 30 and 36 hours every 12 months upon initiation of study, CSF at time immediately prior to each monthly dose out to 30 months. ]
    Single and multiple-dose PK profiles for idursulfase following IT and IV infusions will be established by analyzing standard PK parameters including: area under the curve (AUC), maximum serum concentration (Cmax), time to maximum serum concentration (Tmax), serum clearance normalized for body weight (CL), apparent volume of distribution at steady-state (Vss), Vss normalized for body weight (Vss %BW), mean residence time (MRT) and elimination half life (t1/2).
  • Change from baseline in CSF biomarkers. [ Time Frame: 30 months ]
    Change from baseline and percent change from baseline in CSF biomarker (glycosaminoglycans (GAGs), GAG-degradation products, sulfated HS/DS oligosaccharides) values.
  • Change from baseline in urinary GAGs and GAG-degradation products [ Time Frame: 30 months ]
    Change from baseline and percent change from baseline in observed urinary GAG biomarker values.


Original Secondary Outcome: Same as current

Information By: Shire

Dates:
Date Received: December 15, 2011
Date Started: August 2010
Date Completion: July 2021
Last Updated: February 14, 2017
Last Verified: February 2017