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NCT Number: NCT01506141

An 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

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.

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Key information

Conditions

Hunter Syndrome Carbohydrate Metabolism, Inborn Errors Congenital, Hereditary, and Neonatal Diseases and Abnormalities Connective Tissue Diseases Death Death, Sudden Genetic Diseases, Inborn Genetic Diseases, X-Linked Heredodegenerative Disorders, Nervous System Infant Death Intellectual Disability Lysosomal Storage Diseases Metabolic Diseases Metabolism, Inborn Errors Mucinoses Mucopolysaccharidoses Mucopolysaccharidosis II Nervous System Diseases Neurobehavioral Manifestations Neurologic Manifestations Nutritional and Metabolic Diseases Pathologic Processes Pathological Conditions, Signs and Symptoms Skin and Connective Tissue Diseases Sudden Infant Death X-Linked Intellectual Disability

Age range

3 year–18 year

Sex eligibility

Male

Study type

Interventional

Phase

Phase 1 / Phase 2

Primary location

British Columbia Children's Hospital, Vancouver, British Columbia, Canada

Loading trial locations.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Eligibility Criteria

Inclusion criteria

  • Participant must have completed all study requirements and End of study (EOS) assessments for study HGT-HIT-045 (NCT00920647) 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 (NCT00920647) 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:
  • The participant has had, or may have, an allergic reaction to the materials of construction of the SOPH-A-PORT Mini S device
  • 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
  • The participant's drug therapy requires substances known to be incompatible with the materials of construction
  • The participant has a known or suspected local or general infection
  • The participant is at risk of abnormal bleeding due to a medical condition or therapy
  • The participant has one or more spinal abnormalities that could complicate safe implantation or fixation
  • The participant has a functioning CSF shunt device
  • The participant has shown an intolerance to an implanted device

An additional exclusion criterion for patients who were previously untreated with intrathecal idursulfase-IT in Study HGT-HIT-045 (NCT00920647):

  • The participant has an opening CSF pressure upon lumbar puncture that exceeds 30.0 centimeter (cm) water (H2O).

Treatment and study plan

Idursulfase-IT

Drug

Idursulfase-IT once monthly via IDDD.

Elaprase

Drug

Weekly IV infusions of commercially available Elaprase.

Primary outcomes

  1. Number of Participants With Treatment-emergent Adverse Events (TEAEs)

    Time frame: From start of study drug administration up to follow-up (up to 165 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. TEAEs were 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). For Idursulfase-IT 1 mg+10 mg arm the summary presented includes only the TEAEs that occurred while the participants were assigned to 10 mg.

  2. Number of Participants With Clinically Significant Changes or Apparent Difference Across Treatment Groups in Laboratory Parameters

    Time frame: From start of study drug administration up to follow-up (up to 165 months)

    Number of participants with clinically significant changes in laboratory parameters (chemistry, hematology, urinalysis and CSF values) were collected.

  3. Number of Participants With Clinically Significant Changes or Apparent Difference Across Treatment Groups in 12-lead Electrocardiogram (ECG) Findings

    Time frame: From start of study drug administration up to follow-up (up to 165 months)

    Number of participants with clinically significant changes in 12-lead Electrocardiogram (ECG) findings (heart rate, PR interval, QRS interval, QT interval and the corrected QT interval) were collected.

  4. CSF Chemistries: Change From Baseline in CSF Total Cell Count

    Time frame: Baseline, Month 163

  5. CSF Chemistries: Change From Baseline in CSF Glucose

    Time frame: Baseline, Month 163

  6. CSF Chemistries: Change From Baseline in CSF Protein

    Time frame: Baseline, Month 163

  7. Number of Participants With Anti-idursulfase Antibodies in CSF

    Time frame: From start of study drug administration up to follow-up (up to 165 months)

  8. Number of Participants With Anti-idursulfase Antibodies in Serum

    Time frame: From start of study drug administration up to follow-up (up to 165 months)

Secondary outcomes

  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, at 1,2,3,4,6,8,12,24,30,36 hours (±1 hour) following IT injection on Day 2 of Weeks 3,23, for 1 mg arm group and on Day 2 of Weeks 3,23, Months 19,31,43,55,67,79 for 10 and 30 mg arm groups

    Area under the curve extrapolated to infinity, calculated using the observed value of the last non-zero concentration (AUC0-infinity) of idursulfase was assessed. Participants in 1 mg arm group were assessed for Pharmacokinetic (PK) analysis in the HGT-HIT-045 study.

  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, at 1,2,3,4,6,8,12,24,30,36 hours (±1 hour) following IT injection on Day 2 of Weeks 3,23, for 1 mg arm group and on Day 2 of Weeks 3,23, Months 19,31,43,55,67,79 for 10 and 30 mg arm groups

    Participants in 1 mg arm group were assessed for PK analysis in the HGT-HIT-045 study.

  3. Maximum Observed Concentration (Cmax) of Idursulfase Administered as Intrathecal and in Conjunction With Elaprase

    Time frame: 15 minutes prior to IT injection, at 1,2,3,4,6,8,12,24,30,36 hours (±1 hour) following IT injection on Day 2 of Weeks 3,23, for 1 mg arm group and on Day 2 of Weeks 3,23, Months 19,31,43,55,67,79 for 10 and 30 mg arm groups

    Participants in 1 mg arm group were assessed for PK analysis in the HGT-HIT-045 study.

  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, at 1,2,3,4,6,8,12,24,30,36 hours (±1 hour) following IT injection on Day 2 of Weeks 3,23, for 1 mg arm group and on Day 2 of Weeks 3,23, Months 19,31,43,55,67,79 for 10 and 30 mg arm groups

    Participants in 1 mg arm group were assessed for PK analysis in the HGT-HIT-045 study.

  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, at 1,2,3,4,6,8,12,24,30,36 hours (±1 hour) following IT injection on Day 2 of Weeks 3,23, for 1 mg arm group and on Day 2 of Weeks 3,23, Months 19,31,43,55,67,79 for 10 and 30 mg arm groups

    Participants in 1 mg arm group were assessed for PK analysis in the HGT-HIT-045 study.

  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, at 1,2,3,4,6,8,12,24,30,36 hours (±1 hour) following IT injection on Day 2 of Weeks 3,23, for 1 mg arm group and on Day 2 of Weeks 3,23, Months 19,31,43,55,67,79 for 10 and 30 mg arm groups

    Participants in 1 mg arm group were assessed for PK analysis in the HGT-HIT-045 study.

  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, at 1,2,3,4,6,8,12,24,30,36 hours (±1 hour) following IT injection on Day 2 of Weeks 3,23, for 1 mg arm group and on Day 2 of Weeks 3,23, Months 19,31,43,55,67,79 for 10 and 30 mg arm groups

    Participants in 1 mg arm group were assessed for PK analysis in the HGT-HIT-045 study.

  8. Terminal Half-life (t1/2) of Idursulfase Administered as Intrathecal and in Conjunction With Elaprase

    Time frame: 15 minutes prior to IT injection, at 1,2,3,4,6,8,12,24,30,36 hours (±1 hour) following IT injection on Day 2 of Weeks 3,23, for 1 mg arm group and on Day 2 of Weeks 3,23, Months 19,31,43,55,67,79 for 10 and 30 mg arm groups

    Participants in 1 mg arm group were assessed for PK analysis in the HGT-HIT-045 study. T1/2 is calculated by dividing 0.693 by Lambda z. Here, 0.693 is the natural logarithm of 2 and Lambda z is the first order rate constant.

  9. Total Body Clearance (CL) of Elaprase

    Time frame: 15 minutes prior to IV infusion, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 9, 11, and 24 hours during/after the IV infusion on Days 3-7 of Weeks 3 and 23

  10. Observed Steady-state Volume of Distribution (Vss) of Elaprase

    Time frame: 15 minutes prior to IV infusion and at multiple timepoint (0.5, 1, 1.5, 2, 2.5, and 3 hours during the infusion; and at 3.5, 4, 5, 6, 7, 9, 11, and 24 hours) following IV infusion on Days 3-7 of Weeks 3 and 23

  11. Volume of Distribution (Vz) of Elaprase

    Time frame: 15 minutes prior to IV infusion and at multiple timepoints (0.5, 1, 1.5, 2, 2.5, and 3 hours during the infusion; and at 3.5, 4, 5, 6, 7, 9, 11, and 24 hours) following IV infusion on Days 3-7 of Weeks 3 and 23

    Volume of distribution associated with the terminal slope (Vz) of Elaprase was assessed.

  12. Mean Residence Time Extrapolated to Infinity (MRT0-inf) of Elaprase

    Time frame: 15 minutes prior to IV infusion and at multiple timepoints (0.5, 1, 1.5, 2, 2.5, and 3 hours during the infusion; and at 3.5, 4, 5, 6, 7, 9, 11, and 24 hours) following IV infusion on Days 3-7 of Weeks 3 and 23

  13. Change From Baseline in CSF Biomarkers

    Time frame: Baseline, Months 7, 55, and 139

    Change from baseline in CSF biomarkers glycosaminoglycan (GAG [heparan sulfate (HS)/dermatan sulfate (DS)]) was assessed.

  14. Change From Baseline in Urinary Glycosaminoglycan (GAG)

    Time frame: Baseline, Months 7, 55, and 163

    mg GAG/mmol creatinine stands for milligrams of GAG per millimole of creatinine.

Sponsors and collaborators

Lead sponsor

Takeda

Industry

Registry information

Official study 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

Important dates

Study start
2010
Primary completion
2024
Study completion
2024
First posted
Jan 9, 2012
Registry last updated
Aug 6, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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