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Extension Study of HGT-HIT-045 Evaluating Long-Term Safety and Clinical Outcomes of Idursulfase-IT in Conjunction With Elaprase in Pediatric Participants With Hunter Syndrome and Cognitive Impairment

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ClinicalTrials.gov Identifier: NCT01506141
Recruitment Status : Active, not recruiting
First Posted : January 9, 2012
Last Update Posted : February 6, 2019
Sponsor:
Information provided by (Responsible Party):
Shire

Brief Summary:
This extension study of HGT-HIT-045 is designed to collect long-term safety data in pediatric participants with Hunter syndrome and cognitive impairment who are receiving intrathecal (IT) idursulfase-IT and intravenous (IV) Elaprase enzyme replacement therapy.

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

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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
Actual Study Start Date : August 1, 2010
Estimated Primary Completion Date : July 1, 2021
Estimated Study Completion Date : July 1, 2021


Arm Intervention/treatment
Experimental: Idursulfase-IT
Idursulfase-IT will be administered once monthly and weekly IV infusions of Elaprase at the dose used in study HGT-HIT-045 via intrathecal drug delivery device (IDDD).
Drug: Idursulfase-IT
Participants will receive Idursulfase-IT once monthly at the dose used in study HGT-HIT-045 via intrathecal drug delivery device (IDDD).

Drug: Elaprase
Participants will receive weekly IV infusions of commercially available Elaprase.




Primary Outcome Measures :
  1. Number of Participants With Treatment-emergent Adverse Events (TEAEs) [ Time Frame: From start of study drug administration up to follow-up (169 months) ]
    An adverse event (AE) is any noxious, pathologic, or unintended change in anatomical, physiologic, or metabolic function as indicated by physical signs, symptoms, and/or laboratory changes occurring in any phase of a clinical trial, and whether or not considered study drug-related. Treatment-emergent AEs are defined as all AEs occurring on or after the first IDDD surgery date or first dose (whichever is earlier) for the participant (whether it is in this extension study or in HGT HIT-045 [NCT00920647]) and before the end of the study (EOS) visit (+30 days).


Secondary Outcome Measures :
  1. Area Under the Curve Extrapolated to Infinity (AUC0-infinity) of Idursulfase Administered as Intrathecal and in Conjunction With Elaprase [ Time Frame: 15 minutes prior to IT injection, 1, 2, 3, 4, 6, 8, 12, 24, 30 and 36 hours (h) following IT injection on Weeks 3 and 23, Day 2 of Months 19, 31, and 43 ]
    Area under the curve extrapolated to infinity, calculated using the observed value of the last non-zero concentration (AUC0-infinity) of idursulfase will be assessed.

  2. Area Under the Curve From the Time of Dosing to the Last Measureable Concentration (AUC0-t) of Idursulfase Administered as Intrathecal and in Conjunction With Elaprase [ Time Frame: 15 minutes prior to IT injection, 1, 2, 3, 4, 6, 8, 12, 24, 30 and 36 hours (h) following IT injection on Weeks 3 and 23, Day 2 of Months 19, 31, and 43 ]
    Area under the curve from the time of dosing to the last measureable concentration (AUC0-t) of idursulfase will be assessed.

  3. Maximum Observed Concentration (Cmax) of Idursulfase Administered as Intrathecal and in Conjunction With Elaprase [ Time Frame: 15 minutes prior to IT injection, 1, 2, 3, 4, 6, 8, 12, 24, 30 and 36 hours (h) following IT injection on Weeks 3 and 23, Day 2 of Months 19, 31, and 43 ]
    Maximum Observed Concentration (Cmax) of idursulfase will be assessed.

  4. Time of Maximum Observed Concentration (tmax) of Idursulfase Administered in as Intrathecal and in Conjunction With Elaprase [ Time Frame: 15 minutes prior to IT injection, 1, 2, 3, 4, 6, 8, 12, 24, 30 and 36 hours (h) following IT injection on Weeks 3 and 23, Day 2 of Months 19, 31, and 43 ]
    Time of maximum observed concentration (tmax) of idursulfase will be assessed.

  5. Total Body Clearance for Extravascular Administration Divided by the Fraction of Dose Absorbed (Cl/F) of Idursulfase-IT Administered as Intrathecal and in Conjunction With Elaprase [ Time Frame: 15 minutes prior to IT injection, 1, 2, 3, 4, 6, 8, 12, 24, 30 and 36 hours (h) following IT injection on Weeks 3 and 23, Day 2 of Months 19, 31, and 43 ]
    Total body clearance for extravascular administration divided by the fraction of dose absorbed (Cl/F) of idursulfase will be assessed.

  6. Volume of Distribution Associated With the Terminal Slope Following Extravascular Administration Divided by the Fraction of Dose Absorbed (Vz/F) of Idursulfase Administered as Intrathecal and in Conjunction With Elaprase [ Time Frame: 15 minutes prior to IT injection, 1, 2, 3, 4, 6, 8, 12, 24, 30 and 36 hours (h) following IT injection on Weeks 3 and 23, Day 2 of Months 19, 31, and 43 ]
    Volume of distribution associated with the terminal slope following extravascular administration divided by the fraction of dose absorbed (Vz/F) of idursulfase will be assessed.

  7. First Order Rate Constant (Lambda z) of Idursulfase Administered as Intrathecal and in Conjunction With Elaprase [ Time Frame: 15 minutes prior to IT injection, 1, 2, 3, 4, 6, 8, 12, 24, 30 and 36 hours (h) following IT injection on Weeks 3 and 23, Day 2 of Months 19, 31, and 43 ]
    First order rate constant (Lambda z) of idursulfase will be assessed.

  8. Terminal Half-life (t1/2) of Idursulfase Administered as Intrathecal and in Conjunction With Elaprase [ Time Frame: 15 minutes prior to IT injection, 1, 2, 3, 4, 6, 8, 12, 24, 30 and 36 hours (h) following IT injection on Weeks 3 and 23, Day 2 of Months 19, 31, and 43 ]
    Terminal half-life (t1/2) of idursulfase will be assessed.

  9. Total Body Clearance (Cl) of Elaprase [ Time Frame: 15 minutes prior to IT injection, 1, 2, 3, 4, 6, 8, 12, 24, 30 and 36 hours (h) following IT injection on Weeks 3 and 23, Day 2 of Month 19 ]
    Total body clearance (Cl) of Elaprase will be assessed.

  10. Volume of Distribution (Vz) of Elaprase [ Time Frame: 15 minutes prior to IT injection, 1, 2, 3, 4, 6, 8, 12, 24, 30 and 36 hours (h) following IT injection on Weeks 3 and 23, Day 2 of Month 19 ]
    Volume of distribution associated with the terminal slope (Vz) of Elaprase will be assessed.

  11. Observed Steady-state Volume of Distribution (Vss) of Elaprase [ Time Frame: 15 minutes prior to IT injection, 1, 2, 3, 4, 6, 8, 12, 24, 30 and 36 hours (h) following IT injection on Weeks 3 and 23, Day 2 of Month 19 ]
    Observed steady-state volume of distribution (Vss) of Elaprase will be assessed.

  12. Mean Residence Time (MRT) of Elaprase [ Time Frame: 15 minutes prior to IT injection, 1, 2, 3, 4, 6, 8, 12, 24, 30 and 36 hours (h) following IT injection on Weeks 3 and 23, Day 2 of Month 19 ]
    Mean residence time (MRT) of Elaprase will be assessed.

  13. Change From Baseline in CSF Biomarkers [ Time Frame: Baseline, Day 2 of Week 1, Day 2 Pre dose on Weeks 3, 7, 11, 15, 19, 23, 27, Months 7 - 169 ]
    Change from baseline in CSF biomarkers glycosaminoglycan (GAG [HS/DS]) will be assessed.

  14. Change From Baseline in Urinary Glycosaminoglycan (GAG) [ Time Frame: Baseline, Day 1 Pre dose on Weeks 3, 7, 11, 15, 19, 23, 27, Months 7 - 169 ]
    Change from baseline in urinary GAG will be assessed.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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

Inclusion Criteria:

  • Participant 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 participant'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 participant's parent(s) or legally authorized guardian(s) and the participant's assent, as relevant, must be obtained.
  • The participant 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:

  • The participant is enrolled in another clinical study that involves clinical investigations or use of any investigational product (drug or device) other than the PORT-A-CATH IDDD within 30 days prior to study enrollment or at any time during the study.
  • The participant 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.
  • The participant has experienced an adverse reaction to study drug in Study HGT-HIT-045 that contraindicates further treatment with intrathecal idursulfase-IT.
  • The participant has a known hypersensitivity to any of the components of idursulfase-IT.
  • The participant has any known or suspected hypersensitivity to anesthesia or is thought to be at an unacceptably high risk for anesthesia due to airway compromise or other conditions.
  • The participant has a condition that is contraindicated as described in the SOPH-A-PORT Mini S IDDD Instructions for Use, including:

    1. The participant has had, or may have, an allergic reaction to the materials of construction of the SOPH-A-PORT Mini S device
    2. The participant's body size is too small to support the size of the SOPH-A-PORT Mini S Access Port, as judged by the investigator
    3. The participant's drug therapy requires substances known to be incompatible with the materials of construction
    4. The participant has a known or suspected local or general infection
    5. The participant is at risk of abnormal bleeding due to a medical condition or therapy
    6. The participant has one or more spinal abnormalities that could complicate safe implantation or fixation
    7. The participant has a functioning CSF shunt device
    8. The participant has shown an intolerance to an implanted device
  • The participant has an opening CSF pressure upon lumbar puncture that exceeds 30.0 centimeter (cm) water (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 ClinicalTrials.gov identifier (NCT number): NCT01506141


Locations
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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
Shire
Investigators
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Study Director: Shire Physician Shire

Publications:
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Responsible Party: Shire
ClinicalTrials.gov 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 6, 2019
Last Verified: February 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Shire:
MPS II
MPS 2
hunter's syndrome
MPS2
hunters disease
hunter's disease treatment
hunter syndrome therapy
hunter syndrome treatment
hunter's disease
iduronate 2 sulfatase
hunters syndrome
hunter disease
hunter's syndrome treatment
lysosomal storage disorder
mps symptoms
enlarged adenoids
elaprase
iduronate sulfatase
mps society
MPSII
mucopolysaccharides
mps diagnosis
chronic ear infection
ert treatment
lysosomal storage disease
enzyme replacement therapy
idursulfase

Additional relevant MeSH terms:
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Syndrome
Mucopolysaccharidosis II
Cognitive Dysfunction
Disease
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
Mucopolysaccharidoses
Carbohydrate Metabolism, Inborn Errors
Metabolism, Inborn Errors
Lysosomal Storage Diseases
Mucinoses
Connective Tissue Diseases
Metabolic Diseases