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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Shire
ClinicalTrials.gov Identifier:
NCT01506141
First received: December 15, 2011
Last updated: March 6, 2014
Last verified: March 2014

December 15, 2011
March 6, 2014
August 2010
October 2015   (final data collection date for primary outcome measure)
Safety of intrathecal idursulfase-IT administration [ Time Frame: 30 Months ] [ Designated as safety issue: No ]
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.
Safety of intrathecal idursulfase-IT administration [ Time Frame: 30 Months ] [ Designated as safety issue: No ]
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.
Complete list of historical versions of study NCT01506141 on ClinicalTrials.gov Archive Site
  • 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. ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    Change from baseline and percent change from baseline in observed urinary GAG biomarker values.
Same as current
Not Provided
Not Provided
 
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
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 Patients With Hunter Syndrome and Cognitive Impairment

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.

Not Provided
Interventional
Phase 1
Phase 2
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Hunter Syndrome
Drug: Idursulfase-IT
Idursulfase-IT administered once monthly at the dose used in study HGT-HIT-045 via intrathecal drug delivery device (IDDD)
Experimental: Idursulfase-IT
Idursulfase-IT administered once monthly at the dose used in study HGT-HIT-045 via intrathecal drug delivery device (IDDD)
Intervention: Drug: Idursulfase-IT

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
20
November 2015
October 2015   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Patient must have completed all study requirements and end of study assessments for study HGT-HIT-045 prior to enrolling in Study HGT-HIT-046 and must have no safety or medical issues that contraindicate participation.
  • The patient's parent(s) or legally authorized guardian(s) must have voluntarily signed an Institutional Review Board (IRB)/Independent Ethics Committee(IEC)-approved informed consent form after all relevant aspects of the study have been explained and discussed. Consent of the patient's parent(s) or legally authorized guardian(s) and the patient's assent, as relevant, must be obtained.
  • That patient has received and tolerated a minimum of 12 months of treatment with weekly IV infusions of Elaprase and has received 80% of the total planned infusions within the last 6 months.

Exclusion Criteria:

  • Patient has received treatment with any investigational drug (other than idursulfase-IT) or device within 30 days prior to study entry.
  • Patient is unable to comply with the protocol (eg, is unable to return for safety evaluations, or is otherwise unlikely to complete the study) as determined by the investigator.
  • Patient has experienced an adverse reaction to study drug in Study HGT-HIT-045 that contraindicates further treatment with intrathecal idursulfase-IT.
  • Patient has a known hypersensitivity to any of the components of idursulfase-IT.
  • For patients who were previously untreated with intrathecal idursulfase-IT in Study HGT-HIT-045, the patient has an opening CSF pressure upon lumbar puncture that exceeds 30.0 cm H2O
Male
3 Years to 18 Years
No
Contact information is only displayed when the study is recruiting subjects
United States,   United Kingdom
 
NCT01506141
HGT-HIT-046
No
Shire
Shire
Not Provided
Principal Investigator: Joseph Muenzer, MD, PhD University of North Carolina, Chapel Hill
Shire
March 2014

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