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Hunter SyndromePhase 1/2NCT01506141

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 study testing Idursulfase-IT and Elaprase in people with Hunter Syndrome, run by Takeda at 9 sites in 3 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 3 to 18 years, men only
Conditions the study is for
Hunter Syndrome
What is being tested?
Idursulfase-IT and Elaprase
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
15 participants
Where
9 sitesin 3 countries
Study dates
1 Aug 2010to 30 Apr 2024
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 3 to 18 years
  • Men only
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • 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.

Who cannot join

  • 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:
Show all 16Show fewer
  • 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).

Trial locations and contacts

9 sites in 3 countries.

9 sites in 3 countries

United States7 sites

  • University of North Carolina at Chapel Hill

    Chapel Hill, North Carolina, 27599

  • Ann & Robert H Lurie Childrens Hospital of Chicago

    Chicago, Illinois, 60611

  • Vanderbilt Children's Hospital

    Nashville, Tennessee, 37232-9559

  • Children's Hospital of Pittsburgh of UPMC

    Pittsburgh, Pennsylvania, 15224

  • Legacy Emanuel Hospital

    Portland, Oregon, 97227

  • University of Utah Hospital

    Salt Lake City, Utah, 84132

  • Seattle Children's Hospital

    Seattle, Washington, 98105

Other trials in United States

Canada1 site

  • British Columbia Children's Hospital

    Vancouver, British Columbia

Other trials in Canada

United Kingdom1 site

  • Birmingham Children's Hospital

    Birmingham, B46NH

Other trials in United Kingdom

About this study

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

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.

Conditions
Hunter Syndrome
Being tested
Idursulfase-IT, Elaprase
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
Medical subject headings
Mucopolysaccharidosis II, Sudden Infant Death, Lysosomal Storage Diseases

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Idursulfase-ITDrug

    Idursulfase-IT once monthly via IDDD.

  • ElapraseDrug

    Weekly IV infusions of commercially available Elaprase.

Study groups in NCT01506141
Study groupRoleWhat they receive
Idursulfase-IT 1 milligram (mg)ExperimentalParticipants 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.
Receives: Drug: Idursulfase-IT; Drug: Elaprase
Idursulfase-IT 10 mgExperimentalParticipants will receive 10 mg idursulfase-IT intrathecally via IDDD or LP once monthly and SoC therapy of Elaprase IV infusions.
Receives: Drug: Idursulfase-IT; Drug: Elaprase
Idursulfase-IT 30 mgExperimentalParticipants will receive 30 mg idursulfase-IT intrathecally via IDDD or LP once monthly and SoC therapy of Elaprase IV infusions.
Receives: Drug: Idursulfase-IT; Drug: Elaprase

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: 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.

    Measured: 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.

    Measured: 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

    Measured: Baseline, Month 163

  5. CSF Chemistries: Change From Baseline in CSF Glucose

    Measured: Baseline, Month 163

  6. CSF Chemistries: Change From Baseline in CSF Protein

    Measured: Baseline, Month 163

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

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

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

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

Secondary outcomes (14)

  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.

    Measured: 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.

    Measured: 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.

    Measured: 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.

    Measured: 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.

    Measured: 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.

    Measured: 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.

    Measured: 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.

    Measured: 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

    Measured: 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

    Measured: 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.

    Measured: 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

    Measured: 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.

    Measured: 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.

    Measured: Baseline, Months 7, 55, and 163

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted9 Jan 2012 (estimated)
  2. Study start1 Aug 2010
  3. Primary completion30 Apr 2024
  4. Study completion30 Apr 2024

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
15 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01506141
Sponsor's protocol ID
HGT-HIT-046
Other IDs
2011-000212-25
Status last verified
Jul 2025
First submitted
15 Dec 2011
Last updated
6 Aug 2025
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
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.

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

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Idursulfase-IT and Elaprase in people with Hunter Syndrome, run by Takeda at 9 sites in 3 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 6 Aug 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 9 sites in United States, Canada, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 6 Aug 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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)). The study lists 8 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01506141, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Aug 2025.

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