Principal Investigator: Dave Viskochil
Keywords: Hunter syndrome , MPS II Department: Pediatric Genetics
IRB Number: 00046177 Co Investigator: Nicola Longo
Specialty: Pediatric Genetics
Sub Specialties: Medical Genetics
Recruitment Status: Active, not recruiting

Contact Information

Carrie Bailey

Brief Summary


The primary objective of this study is:
• To collect long-term safety data in pediatric patients with Hunter syndrome and cognitive impairment who are receiving intrathecal idursulfase-IT and intravenous (IV) Elaprase® enzyme replacement therapy
The secondary objectives of this study are:
• To determine the concentration of idursulfase in cerebrospinal fluid (CSF) and blood when given as intrathecal idursulfase-IT and in conjunction with Elaprase
• To determine the effect of intrathecal idursulfase-IT, given in conjunction with Elaprase, on CSF biomarkers (eg, glycosaminoglycans [GAGs] and GAG-degradation products, heparan sulfate [HS]/dermatan sulfate[DS] oligosaccharides, and markers of lysosomal function)
• To determine the effects of intrathecal idursulfase-IT, given in conjunction with Elaprase, on urinary GAGs 
The exploratory objectives of this study are:
  •          To evaluate the long-term effects of intrathecal idursulfase-IT, given in conjunction with Elaprase, on clinical parameters (eg, physiological assessments, neurocognitive assessments, neurologic function, and brain structure volumes)
  •         To evaluate the long-term effects of intrathecal idursulfase-IT, given in conjunction with Elaprase, on functional activities of daily living, as determined by the Scales of Independent Behavior-Revised (SIB-R)
  •         To explore potential relationships between biomarkers and CNS symptomatology
  •         To determine whether monthly idursulfase-IT administrations results in accumulation of idursulfase within the CSF compartment by measuring idursulfase levels in CSF immediately prior to idursulfase-IT administration
  •         To determine the safety and performance of the SOPH-A-PORT Mini S
Study Endpoints:
The primary endpoint of this study is:
• Safety of intrathecal idursulfase-IT administration.
The secondary endpoints include:
• Pharmacokinetic (PK) parameters of idursulfase, administered as intrathecal (IT) idursulfase and in conjunction with Elaprase, in CSF and blood
• Change from baseline in CSF biomarkers (eg, GAGs, GAG-degradation products, sulfated HS/DS oligosaccharides, etc)
• Change from baseline in urinary GAGs and GAG-degradation products
The exploratory endpoints for this study include:
• Change from Baseline in additional clinical parameters (eg, overall clinical status, standardized neurocognitive assessments, neurologic function, brain magnetic resonance imaging [MRI]), and duration and severity of baseline CNS pathology
• Change from Baseline in functional activities of daily living parameters
• Exploration of potential relationships between biomarkers and CNS symptomatology


Inclusion Criteria

Participant Selection Criteria for Local Site:
Inclusion Criteria:
• Signed Consent with the main site, University of North Carolina, Chapel Hill.
• Hunter syndrome with CNS involvement, defined per main site inclusion criteria from prior study HGT-HIT-045.

Participant Selection Criteria for Main Site:
Patients must meet all of the following criteria to be considered eligible for enrollment:
1. Patients must have completed all study requirements and EOS 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.

2. 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.

3. The 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

Exclusion Criteria:
• None for local site


Exclusion Criteria
Patients who meet any of the following criteria are not eligible for participation in this study:
1. The patient has received treatment with any investigational drug (other than idursulfase-IT) or device within 30 days prior to study entry.

2. The 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.

3. The patient has experienced an adverse reaction to study drug in Study HGT-HIT-045 that contraindicates further treatment with intrathecal idursulfase-IT.

4. The patient has a known hypersensitivity to any of the components of idursulfase-IT.

An additional exclusion criterion for patients who were previously untreated with intrathecal idursulfase-IT in Study HGT-HIT-045:
1. The patient has an opening CSF pressure upon lumbar puncture that exceeds 30.0 cm H2O.