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CompletedNCT01506141Updated Aug 6, 2025Results posted

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

A Phase 1/2 interventional study of Idursulfase-IT and Elaprase in Hunter Syndrome, sponsored by Takeda. Completed at 9 sites in 3 countries. Open to male participants aged 3 Years to 18 Years. Per ClinicalTrials.gov, last updated 2025-08-06.

Sponsored by Takeda · Phase 1/2, Interventional, and Treatment

From the registry’s dates

  • Registered 1 year 4 months after the study started (first participant enrolled Aug 2010, registered Dec 2011).
Phase
Phase 1/2
Study type
Interventional
Enrollment
15
Allocation
Non-randomized
Ages
3 Years to 18 Years
Sex
Male
01

Study 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.

02

Conditions studied

  • Hunter Syndrome

Keywords

  • MPS II
  • MPS 2
  • lysosomal storage disorder
  • mps symptoms
  • enlarged adenoids
  • elaprase
  • hunter's syndrome
  • MPS2
  • hunters disease
  • hunter's disease treatment
  • hunter syndrome therapy
  • iduronate sulfatase
  • mps society
  • MPSII
  • hunter syndrome treatment
  • hunter's disease
  • iduronate 2 sulfatase
  • mucopolysaccharides
  • mps diagnosis
  • chronic ear infection
  • hunters syndrome
  • ert treatment
  • lysosomal storage disease
  • hunter disease
  • enzyme replacement therapy
  • idursulfase
  • hunter's syndrome treatment
03

In context

Mucopolysaccharidosis II

71 studies on the registry are indexed under Mucopolysaccharidosis II; 8 are open to participants now.

This study's enrollment of 15 is below the median of 20 across 43 interventional studies indexed under Mucopolysaccharidosis II.

Browse Mucopolysaccharidosis II studies →

Lead sponsor

Takeda is the lead sponsor of 1,002 studies on the registry; 92 are open to participants now.

Of its 173 completed or terminated interventional studies of FDA-regulated products, 149 (86%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
3 Years to 18 Years
Sexes eligible
Male
Accepts healthy volunteers
No

Eligibility Criteria

Inclusion 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

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:

    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

      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).
05

Study design

Phase
Phase 1 / Phase 2
Primary purpose
Treatment
Allocation
Non-randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
15 participants (actual)

Study arms

  • Experimental
    Idursulfase-IT 1 milligram (mg)

    Participants will receive 1 mg idursulfase-IT intrathecally via intrathecal drug delivery device (IDDD) or lumbar puncture (LP) once monthly and standard-of-care (SoC) therapy of Elaprase intravenous (IV) infusions.

    Drug: Idursulfase-IT · Drug: Elaprase

  • Experimental
    Idursulfase-IT 10 mg

    Participants will receive 10 mg idursulfase-IT intrathecally via IDDD or LP once monthly and SoC therapy of Elaprase IV infusions.

    Drug: Idursulfase-IT · Drug: Elaprase

  • Experimental
    Idursulfase-IT 30 mg

    Participants will receive 30 mg idursulfase-IT intrathecally via IDDD or LP once monthly and SoC therapy of Elaprase IV infusions.

    Drug: Idursulfase-IT · Drug: Elaprase

Interventions

  • DrugIdursulfase-IT

    Idursulfase-IT once monthly via IDDD.

  • DrugElaprase

    Weekly IV infusions of commercially available Elaprase.

06

What researchers measure

Primary outcomes

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

    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.

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

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

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

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

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

    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.

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

  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

    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.

    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

  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

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

    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

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

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

    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

  4. Time of Maximum Observed Concentration (Tmax) of Idursulfase Administered in as Intrathecal and in Conjunction With Elaprase

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

    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

  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

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

    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

  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

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

    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

  7. First Order Rate Constant (Lambda z) of Idursulfase Administered as Intrathecal and in Conjunction With Elaprase

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

    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

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

    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.

    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

  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

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

    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

  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

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

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

  14. Change From Baseline in Urinary Glycosaminoglycan (GAG)

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

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

07

Results

Posted Aug 6, 2025

Participant flow

Participants took part in the study at various investigative sites in the United States (US) and the United Kingdom (UK) from 01 August 2010 to 30 April 2024.

Participant flow — Overall Study
MilestoneIdursulfase-IT 10 mgIdursulfase-IT 30 mg
Started105
Transferred from 1 mg arm40
Completed30
Not completed75
Withdrew: Adverse event02
Withdrew: Participation terminated by investigator11
Withdrew: Site terminated by sponsor20
Withdrew: Reason not specified42

Outcome measures

PrimaryNumber of Participants With Treatment-emergent Adverse Events (TEAEs)

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.

Time frame:
From start of study drug administration up to follow-up (up to 165 months)
Reported as:
Count of participants · Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
ParticipantsIdursulfase-IT 1 mgIdursulfase-IT 10 mgIdursulfase-IT 30 mg
Number of Participants With Treatment-emergent Adverse Events (TEAEs)4105
PrimaryNumber of Participants With Clinically Significant Changes or Apparent Difference Across Treatment Groups in Laboratory Parameters

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

Time frame:
From start of study drug administration up to follow-up (up to 165 months)
Reported as:
Count of participants · Participants
Number of Participants With Clinically Significant Changes or Apparent Difference Across Treatment Groups in Laboratory Parameters
ParticipantsIdursulfase-IT 1 mgIdursulfase-IT 10 mgIdursulfase-IT 30 mg
Number of Participants With Clinically Significant Changes or Apparent Difference Across Treatment Groups in Laboratory Parameters000
PrimaryNumber of Participants With Clinically Significant Changes or Apparent Difference Across Treatment Groups in 12-lead Electrocardiogram (ECG) Findings

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.

Time frame:
From start of study drug administration up to follow-up (up to 165 months)
Reported as:
Count of participants · Participants
Number of Participants With Clinically Significant Changes or Apparent Difference Across Treatment Groups in 12-lead Electrocardiogram (ECG) Findings
ParticipantsIdursulfase-IT 1 mgIdursulfase-IT 10 mgIdursulfase-IT 30 mg
Number of Participants With Clinically Significant Changes or Apparent Difference Across Treatment Groups in 12-lead Electrocardiogram (ECG) Findings000
PrimaryCSF Chemistries: Change From Baseline in CSF Total Cell Count
Time frame:
Baseline, Month 163
Reported as:
Mean · 10^6 cells/Liter (L)
CSF Chemistries: Change From Baseline in CSF Total Cell Count
10^6 cells/Liter (L)Idursulfase-IT 1 mgIdursulfase-IT 10 mgIdursulfase-IT 30 mg
Baseline1.0 ± 0.001.0 ± 0.001.0 ± 0.00
Change From Baseline in CSF Total Cell Count at Month 163—7.3 ± 11.85—
PrimaryCSF Chemistries: Change From Baseline in CSF Glucose
Time frame:
Baseline, Month 163
Reported as:
Mean · millimoles per liter (mmol/L)
CSF Chemistries: Change From Baseline in CSF Glucose
millimoles per liter (mmol/L)Idursulfase-IT 1 mgIdursulfase-IT 10 mgIdursulfase-IT 30 mg
Baseline2.950 ± 0.2652.850 ± 0.2173.000 ± 0.200
Change from Baseline in CSF Glucose at Month 163—0.523 ± 0.436—
PrimaryCSF Chemistries: Change From Baseline in CSF Protein
Time frame:
Baseline, Month 163
Reported as:
Mean · grams per liter (g/L)
CSF Chemistries: Change From Baseline in CSF Protein
grams per liter (g/L)Idursulfase-IT 1 mgIdursulfase-IT 10 mgIdursulfase-IT 30 mg
Baseline0.400 ± 0.1940.282 ± 0.1440.530 ± 0.368
Change from Baseline in CSF Protein at Month 163—0.493 ± 0.229—
PrimaryNumber of Participants With Anti-idursulfase Antibodies in CSF
Time frame:
From start of study drug administration up to follow-up (up to 165 months)
Reported as:
Count of participants · Participants
Number of Participants With Anti-idursulfase Antibodies in CSF
ParticipantsIdursulfase-IT 1 mgIdursulfase-IT 10 mgIdursulfase-IT 30 mg
At Baseline311
Post-Baseline351
PrimaryNumber of Participants With Anti-idursulfase Antibodies in Serum
Time frame:
From start of study drug administration up to follow-up (up to 165 months)
Reported as:
Count of participants · Participants
Number of Participants With Anti-idursulfase Antibodies in Serum
ParticipantsIdursulfase-IT 1 mgIdursulfase-IT 10 mgIdursulfase-IT 30 mg
At Baseline322
Post-Baseline363
SecondaryArea Under the Curve Extrapolated to Infinity (AUC0-infinity) of Idursulfase Administered as Intrathecal and in Conjunction With Elaprase

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.

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
Reported as:
Mean · hours*nanograms per milliliter(h*ng/mL)
Area Under the Curve Extrapolated to Infinity (AUC0-infinity) of Idursulfase Administered as Intrathecal and in Conjunction With Elaprase
hours*nanograms per milliliter(h*ng/mL)Idursulfase-IT 1 mgIdursulfase-IT 10 mgIdursulfase-IT 30 mg
Week 3: Day 2NA ± NA——
Week 23: Day 21574.37 ± NA1765 ± NA—
Month 19: Day 2—2869 ± 563.15179 ± 2579.8
Month 31: Day 2—2649 ± 1334.84766 ± NA
Month 43—2324 ± 203.04395 ± 733.1
Month 55—1636 ± 351.42445 ± 1770.8
Month 67—1649 ± 167.43270 ± 801.6
Month 79—1865 ± 775.2—
SecondaryArea 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

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

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
Reported as:
Mean · h*ng/mL
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
h*ng/mLIdursulfase-IT 1 mgIdursulfase-IT 10 mgIdursulfase-IT 30 mg
Week 3: Day 2NA ± NA1214 ± NA3746 ± NA
Week 23: Day 2524.68 ± NA1047 ± NA4855 ± NA
Month 19: Day 2—1633 ± 976.63525 ± 835.5
Month 31: Day 2—2031 ± 1081.93586 ± 1056.9
Month 43—1944 ± 295.83141 ± 979.7
Month 55—1356 ± 235.31466 ± 1511.8
Month 67—1247 ± 204.02415 ± 394.8
Month 79—1500 ± 347.1—
SecondaryMaximum Observed Concentration (Cmax) of Idursulfase Administered as Intrathecal and in Conjunction With Elaprase

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

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
Reported as:
Mean · nanograms per milliliter (ng/mL)
Maximum Observed Concentration (Cmax) of Idursulfase Administered as Intrathecal and in Conjunction With Elaprase
nanograms per milliliter (ng/mL)Idursulfase-IT 1 mgIdursulfase-IT 10 mgIdursulfase-IT 30 mg
Week 3: Day 2NA ± NA43.95 ± NA146.75 ± NA
Week 23: Day 219 ± NA36.10 ± NA173.40 ± NA
Month 19: Day 2—76.39 ± 51.386156.80 ± 33.054
Month 31: Day 2—143.52 ± 122.774175.20 ± 70.083
Month 43—90.57 ± 28.720144.35 ± 44.434
Month 55—61.50 ± 19.33093.43 ± 61.406
Month 67—56.73 ± 12.69099.20 ± 19.762
Month 79—64.08 ± 7.835—
SecondaryTime of Maximum Observed Concentration (Tmax) of Idursulfase Administered in as Intrathecal and in Conjunction With Elaprase

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

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
Reported as:
Median · hours
Time of Maximum Observed Concentration (Tmax) of Idursulfase Administered in as Intrathecal and in Conjunction With Elaprase
hoursIdursulfase-IT 1 mgIdursulfase-IT 10 mgIdursulfase-IT 30 mg
Week 3: Day 2NA (NA to NA)24.03 (NA to NA)36.07 (NA to NA)
Week 23: Day 28.03 (NA to NA)12.00 (NA to NA)12.00 (NA to NA)
Month 19: Day 2—12.00 (6.00 to 36.2)24.00 (2.00 to 30.0)
Month 31: Day 2—9.99 (1.12 to 12.0)17.98 (6.00 to 30.1)
Month 43—12.00 (8.00 to 12.0)10.02 (6.03 to 12.0)
Month 55—12.00 (6.00 to 12.0)7.97 (2.00 to 8.00)
Month 67—12.00 (6.00 to 12.0)12.00 (6.00 to 30.0)
Month 79—10.00 (8.00 to 12.00)—
SecondaryTotal 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

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

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
Reported as:
Mean · liters per hour (L/h)
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
liters per hour (L/h)Idursulfase-IT 1 mgIdursulfase-IT 10 mgIdursulfase-IT 30 mg
Week 3: Day 2NA ± NA——
Week 23: Day 2NA ± NA5.67 ± NA—
Month 19: Day 2—3.59 ± 0.7636.61 ± 3.295
Month 31: Day 2—4.80 ± 2.6676.29 ± NA
Month 43—4.33 ± 0.3776.92 ± 1.154
Month 55—6.33 ± 1.5488.25 ± 0.191
Month 67—6.10 ± 0.6199.46 ± 2.319
Month 79—5.96 ± 2.207—
SecondaryVolume 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

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

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
Reported as:
Mean · liters
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
litersIdursulfase-IT 1 mgIdursulfase-IT 10 mgIdursulfase-IT 30 mg
Week 3: Day 2NA ± NA——
Week 23: Day 252.831 ± NA183.31 ± NA—
Month 19: Day 2—94.18 ± 21.961152.82 ± 45.153
Month 31: Day 2—116.91 ± 84.881128.63 ± NA
Month 43—68.06 ± 21.783104.93 ± 44.848
Month 55—130.84 ± 15.624127.77 ± 11.009
Month 67—115.31 ± 29.260206.92 ± 11.864
Month 79—79.22 ± 8.364—
SecondaryFirst Order Rate Constant (Lambda z) of Idursulfase Administered as Intrathecal and in Conjunction With Elaprase

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

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
Reported as:
Mean · per hour (/h)
First Order Rate Constant (Lambda z) of Idursulfase Administered as Intrathecal and in Conjunction With Elaprase
per hour (/h)Idursulfase-IT 1 mgIdursulfase-IT 10 mgIdursulfase-IT 30 mg
Week 3: Day 2NA ± NA——
Week 23: Day 2NA ± NA0.0309 ± NA—
Month 19: Day 2—0.0383 ± 0.002600.0419 ± 0.00917
Month 31: Day 2—0.0487 ± 0.019960.0489 ± NA
Month 43—0.0677 ± 0.018290.0700 ± 0.01892
Month 55—0.0486 ± 0.011260.0649 ± 0.00708
Month 67—0.0539 ± 0.008310.0455 ± 0.00860
Month 79—0.0772 ± 0.03550—
SecondaryTerminal Half-life (t1/2) of Idursulfase Administered as Intrathecal and in Conjunction With Elaprase

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.

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
Reported as:
Median · hours
Terminal Half-life (t1/2) of Idursulfase Administered as Intrathecal and in Conjunction With Elaprase
hoursIdursulfase-IT 1 mgIdursulfase-IT 10 mgIdursulfase-IT 30 mg
Week 3: Day 2NA (NA to NA)——
Week 23: Day 2NA (NA to NA)22.43 (NA to NA)—
Month 19: Day 2—18.20 (16.9 to 19.4)16.94 (14.3 to 19.6)
Month 31: Day 2—15.57 (8.35 to 29.8)14.16 (NA to NA)
Month 43—10.28 (8.21 to 14.7)10.28 (8.31 to 12.2)
Month 55—14.21 (11.6 to 18.6)10.75 (9.92 to 11.6)
Month 67—13.01 (11.6 to 14.4)15.52 (13.4 to 17.6)
Month 79—9.68 (6.02 to 15.4)—
SecondaryTotal 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
Reported as:
Mean · liters per hour (L/h)
Total Body Clearance (CL) of Elaprase
liters per hour (L/h)Elaprase IV Infusion 0.5 mg/kg
Week 3: Day 3-71.94 ± 1.677
Week 23: Day 3-73.47 ± NA
SecondaryObserved 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
Reported as:
Mean · liters
Observed Steady-state Volume of Distribution (Vss) of Elaprase
litersElaprase IV Infusion 0.5 mg/kg
Week 3: Day 3-79.40 ± 3.464
Week 23: Day 3-713.19 ± NA
SecondaryVolume of Distribution (Vz) of Elaprase

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

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
Reported as:
Mean · liters
Volume of Distribution (Vz) of Elaprase
litersElaprase IV Infusion 0.5 mg/kg
Week 3: Day 3-719.91 ± 13.874
Week 23: Day 3-734.20 ± NA
SecondaryMean 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
Reported as:
Mean · hours
Mean Residence Time Extrapolated to Infinity (MRT0-inf) of Elaprase
hoursElaprase IV Infusion 0.5 mg/kg
Week 3: Day 3-76.49 ± 3.817
Week 23: Day 3-73.80 ± NA
SecondaryChange From Baseline in CSF Biomarkers

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

Time frame:
Baseline, Months 7, 55, and 139
Reported as:
Mean · ng/mL
Change From Baseline in CSF Biomarkers
ng/mLIdursulfase-IT 1 mgIdursulfase-IT 10 mgIdursulfase-IT 30 mg
Baseline1922.34 ± 1164.6791874.00 ± 979.4591111.92 ± 485.898
Change from Baseline at Month 7-807.50 ± 569.461-1526.24 ± 638.893-987.65 ± 437.885
Change from Baseline at Month 55—-1575.63 ± 906.621-974.07 ± 558.075
Change from Baseline at Month 139—-1169.25 ± 530.781-1135.51 ± NA
SecondaryChange From Baseline in Urinary Glycosaminoglycan (GAG)

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

Time frame:
Baseline, Months 7, 55, and 163
Reported as:
Mean · mg GAG/mmol creatinine
Change From Baseline in Urinary Glycosaminoglycan (GAG)
mg GAG/mmol creatinineIdursulfase-IT 1 mgIdursulfase-IT 10 mgIdursulfase-IT 30 mg
Baseline34.07 ± 20.13223.35 ± 13.79913.67 ± 7.200
Change from Baseline at Month 75.22 ± 6.084-4.20 ± 4.2783.35 ± 1.324
Change from Baseline at Month 55—-6.83 ± 5.8376.33 ± 7.387
Change from Baseline at Month 163—-13.88 ± 5.163—

Adverse events

Collected over From start of study drug administration up to follow-up (up to 165 months). Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Idursulfase-IT 1 mg0/4 (0%)3/4 (75%)4/4 (100%)
Idursulfase-IT 10 mg0/10 (0%)9/10 (90%)10/10 (100%)
Idursulfase-IT 30 mg0/5 (0%)4/5 (80%)5/5 (100%)
Most frequent serious events
Showing 10 of 68
Most frequent serious events
EventIdursulfase-IT 1 mgIdursulfase-IT 10 mgIdursulfase-IT 30 mg
Device failureGeneral disorders0/45/102/5
Device breakageGeneral disorders1/44/101/5
Device dislocationGeneral disorders1/44/100/5
Device malfunctionGeneral disorders1/44/102/5
Implant site infectionInfections and infestations1/40/102/5
ConvulsionNervous system disorders0/43/100/5
PyrexiaGeneral disorders0/43/100/5
Vascular complication associated with deviceGeneral disorders0/43/101/5
DehydrationMetabolism and nutrition disorders1/40/100/5
Device difficult to useGeneral disorders1/40/100/5
Most frequent other events
Showing 10 of 534
Most frequent other events
EventIdursulfase-IT 1 mgIdursulfase-IT 10 mgIdursulfase-IT 30 mg
Procedural painInjury, poisoning and procedural complications4/48/105/5
PyrexiaGeneral disorders3/49/105/5
Vascular complication associated with deviceGeneral disorders1/47/105/5
VomitingGastrointestinal disorders2/410/104/5
AgitationPsychiatric disorders1/48/103/5
Blood pressure diastolic decreasedInvestigations2/48/102/5
Blood pressure diastolic increasedInvestigations1/48/102/5
Blood pressure systolic increasedInvestigations2/48/102/5
Cardiac murmurInvestigations1/44/104/5
ContusionInjury, poisoning and procedural complications1/48/103/5

Baseline characteristics

Safety Population included all eligible participants from HGT-HIT-045 who had agreed to participate in the extension study and have had either surgical implantation of an IDDD or intrathecal administration of study drug in the extension study. Baseline characteristics are reported according to participant's initial treatment arms.

Age, Continuous
Age, Continuous(years)Idursulfase-IT 1 mgIdursulfase-IT 10 mgIdursulfase-IT 30 mgTotal
Mean5.61 ± 1.7995.68 ± 2.5017.94 ± 2.7066.41 ± 2.502
Sex: Female, Male
Sex: Female, Male(Participants)Idursulfase-IT 1 mgIdursulfase-IT 10 mgIdursulfase-IT 30 mgTotal
Female0000
Male46515
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)Idursulfase-IT 1 mgIdursulfase-IT 10 mgIdursulfase-IT 30 mgTotal
Hispanic or Latino0101
Not Hispanic or Latino44412
Unknown or Not Reported0112
Race (NIH/OMB)
Race (NIH/OMB)(Participants)Idursulfase-IT 1 mgIdursulfase-IT 10 mgIdursulfase-IT 30 mgTotal
American Indian or Alaska Native0000
Asian0011
Native Hawaiian or Other Pacific Islander0000
Black or African American0000
White24410
More than one race0000
Unknown or Not Reported2204
08

Study locations

9 sites
  • Ann & Robert H Lurie Childrens Hospital of Chicago
    Chicago, Illinois 60611, United States
  • University of North Carolina at Chapel Hill
    Chapel Hill, North Carolina 27599, United States
  • Legacy Emanuel Hospital
    Portland, Oregon 97227, United States
  • Children's Hospital of Pittsburgh of UPMC
    Pittsburgh, Pennsylvania 15224, United States
  • Vanderbilt Children's Hospital
    Nashville, Tennessee 37232-9559, United States
  • University of Utah Hospital
    Salt Lake City, Utah 84132, United States
  • Seattle Children's Hospital
    Seattle, Washington 98105, United States
  • British Columbia Children's Hospital
    Vancouver, British Columbia, Canada
  • Birmingham Children's Hospital
    Birmingham, B46NH, United Kingdom
09

References and documents

Publications

  • Muenzer J, Gucsavas-Calikoglu M, McCandless SE, Schuetz TJ, Kimura A. A phase I/II clinical trial of enzyme replacement therapy in mucopolysaccharidosis II (Hunter syndrome). Mol Genet Metab. 2007 Mar;90(3):329-37. doi: 10.1016/j.ymgme.2006.09.001. Epub 2006 Dec 20. PubMed 17185020 ↗
  • Muenzer J, Wraith JE, Beck M, Giugliani R, Harmatz P, Eng CM, Vellodi A, Martin R, Ramaswami U, Gucsavas-Calikoglu M, Vijayaraghavan S, Wendt S, Puga AC, Ulbrich B, Shinawi M, Cleary M, Piper D, Conway AM, Kimura A. A phase II/III clinical study of enzyme replacement therapy with idursulfase in mucopolysaccharidosis II (Hunter syndrome). Genet Med. 2006 Aug;8(8):465-73. doi: 10.1097/01.gim.0000232477.37660.fb. PubMed 16912578 ↗
  • Muenzer J, Vijayaraghavan S, Stein M, Kearney S, Wu Y, Alexanderian D. Long-term open-label phase I/II extension study of intrathecal idursulfase-IT in the treatment of neuronopathic mucopolysaccharidosis II. Genet Med. 2022 Jul;24(7):1437-1448. doi: 10.1016/j.gim.2022.04.002. Epub 2022 May 20. PubMed 35588317 ↗

Study documents

  • Study protocol · Aug 17, 2021
  • Statistical analysis plan · Feb 21, 2023

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: Yes — Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.

Supporting information: Study protocol, Sap, Icf, Csr

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Aug 6, 2025, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT01506141
Lead sponsor
Takeda
Responsible party
Sponsor
First posted
Jan 9, 2012
Start date
Aug 1, 2010
Primary completion
Apr 30, 2024
Completion
Apr 30, 2024
Results posted
Aug 6, 2025
Last update
Aug 6, 2025

Study contacts

Study Director
study director · Takeda

Oversight

Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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