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

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. Identifier: NCT01506141
Recruitment Status : Active, not recruiting
First Posted : January 9, 2012
Last Update Posted : February 15, 2017
Information provided by (Responsible Party):

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.

Condition or disease Intervention/treatment Phase
Hunter Syndrome Drug: Idursulfase-IT Phase 1 Phase 2

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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 Patients With Hunter Syndrome and Cognitive Impairment
Study Start Date : August 2010
Estimated Primary Completion Date : July 2021
Estimated Study Completion Date : July 2021

Arm Intervention/treatment
Experimental: Idursulfase-IT
Idursulfase-IT administered once monthly at the dose used in study HGT-HIT-045 via intrathecal drug delivery device (IDDD)
Drug: Idursulfase-IT
Idursulfase-IT administered once monthly at the dose used in study HGT-HIT-045 via intrathecal drug delivery device (IDDD)

Primary Outcome Measures :
  1. 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.

Secondary Outcome Measures :
  1. 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).

  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.

  3. 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.

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Ages Eligible for Study:   3 Years to 18 Years   (Child, Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01506141

United States, Illinois
Ann & Robert H Lurie Childrens Hospital of Chicago
Chicago, Illinois, United States, 60611
United States, North Carolina
University of North Carolina at Chapel Hill
Chapel Hill, North Carolina, United States, 27599
United States, Oregon
Legacy Emanuel Hospital
Portland, Oregon, United States, 97227
United States, Pennsylvania
Children's Hospital of Pittsburgh of UPMC
Pittsburgh, Pennsylvania, United States, 15224
United States, Tennessee
Vanderbilt Children's Hospital
Nashville, Tennessee, United States, 37232-9559
United States, Utah
University of Utah Hospital
Salt Lake City, Utah, United States, 84132
United States, Washington
Seattle Children's Hospital
Seattle, Washington, United States, 98105
Canada, British Columbia
British Columbia Children's Hospital
Vancouver, British Columbia, Canada
United Kingdom
Birmingham Children's Hospital
Birmingham, United Kingdom, B46NH
Sponsors and Collaborators
Study Director: Shire Physician Shire

Responsible Party: Shire Identifier: NCT01506141     History of Changes
Other Study ID Numbers: HGT-HIT-046
2011-000212-25 ( EudraCT Number )
First Posted: January 9, 2012    Key Record Dates
Last Update Posted: February 15, 2017
Last Verified: February 2017

Keywords provided by Shire:
lysosomal storage disorder
mps symptoms
enlarged adenoids
hunter's syndrome
hunters disease
hunter's disease treatment
hunter syndrome therapy
iduronate sulfatase
mps society
hunter syndrome treatment
hunter's disease
iduronate 2 sulfatase
mps diagnosis
chronic ear infection
hunters syndrome
ert treatment
lysosomal storage disease
hunter disease
enzyme replacement therapy
hunter's syndrome treatment

Additional relevant MeSH terms:
Cognitive Dysfunction
Mucopolysaccharidosis II
Pathologic Processes
Cognition Disorders
Neurocognitive Disorders
Mental Disorders
Mental Retardation, X-Linked
Intellectual Disability
Neurobehavioral Manifestations
Neurologic Manifestations
Nervous System Diseases
Genetic Diseases, X-Linked
Genetic Diseases, Inborn
Heredodegenerative Disorders, Nervous System
Carbohydrate Metabolism, Inborn Errors
Metabolism, Inborn Errors
Lysosomal Storage Diseases
Connective Tissue Diseases
Metabolic Diseases