Phase 2
N=15
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
Hunter Syndrome
Bottom Line
View on ClinicalTrials.gov: NCT01506141 ↗Enrolled (actual)
15
Serious AEs
84.2%
Results posted
Aug 2025
Primary outcome: Primary: Number of Participants With Treatment-emergent Adverse Events (TEAEs) — 4; 10; 5 Participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- Idursulfase-IT (Drug); Elaprase (Drug)
- Age
- Pediatric, Adult · 3+ yrs
- Sex
- Male
- Sponsor
- Takeda
- Primary completion
- Apr 2024
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Participants With Treatment-emergent Adverse Events (TEAEs) |
4; 10; 5 | — |
| PRIMARY Number of Participants With Clinically Significant Changes or Apparent Difference Across Treatment Groups in Laboratory Parameters |
0; 0; 0 | — |
| PRIMARY Number of Participants With Clinically Significant Changes or Apparent Difference Across Treatment Groups in 12-lead Electrocardiogram (ECG) Findings |
0; 0; 0 | — |
| PRIMARY CSF Chemistries: Change From Baseline in CSF Total Cell Count |
1.0; 1.0; 1.0; 7.3 | — |
| PRIMARY CSF Chemistries: Change From Baseline in CSF Glucose |
2.950; 2.850; 3.000; 0.523 | — |
| PRIMARY CSF Chemistries: Change From Baseline in CSF Protein |
0.400; 0.282; 0.530; 0.493 | — |
| PRIMARY Number of Participants With Anti-idursulfase Antibodies in CSF |
3; 1; 1; 3; 5; 1 | — |
| PRIMARY Number of Participants With Anti-idursulfase Antibodies in Serum |
3; 2; 2; 3; 6; 3 | — |
| SECONDARY Area Under the Curve Extrapolated to Infinity (AUC0-infinity) of Idursulfase Administered as Intrathecal and in Conjunction With Elaprase |
NA; 1574.37; 1765; 2869; 5179; 2649 | — |
| SECONDARY 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 |
NA; 1214; 3746; 524.68; 1047; 4855 | — |
| SECONDARY Maximum Observed Concentration (Cmax) of Idursulfase Administered as Intrathecal and in Conjunction With Elaprase |
NA; 43.95; 146.75; 19; 36.10; 173.40 | — |
| SECONDARY Time of Maximum Observed Concentration (Tmax) of Idursulfase Administered in as Intrathecal and in Conjunction With Elaprase |
NA; 24.03; 36.07; 8.03; 12.00; 12.00 | — |
| SECONDARY 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 |
NA; NA; 5.67; 3.59; 6.61; 4.80 | — |
| SECONDARY 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 |
NA; 52.831; 183.31; 94.18; 152.82; 116.91 | — |
| SECONDARY First Order Rate Constant (Lambda z) of Idursulfase Administered as Intrathecal and in Conjunction With Elaprase |
NA; NA; 0.0309; 0.0383; 0.0419; 0.0487 | — |
| SECONDARY Terminal Half-life (t1/2) of Idursulfase Administered as Intrathecal and in Conjunction With Elaprase |
NA; NA; 22.43; 18.20; 16.94; 15.57 | — |
| SECONDARY Total Body Clearance (CL) of Elaprase |
1.94; 3.47 | — |
| SECONDARY Observed Steady-state Volume of Distribution (Vss) of Elaprase |
9.40; 13.19 | — |
| SECONDARY Volume of Distribution (Vz) of Elaprase |
19.91; 34.20 | — |
| SECONDARY Mean Residence Time Extrapolated to Infinity (MRT0-inf) of Elaprase |
6.49; 3.80 | — |
| SECONDARY Change From Baseline in CSF Biomarkers |
1922.34; 1874.00; 1111.92; -807.50; -1526.24; -987.65 | — |
| SECONDARY Change From Baseline in Urinary Glycosaminoglycan (GAG) |
34.07; 23.35; 13.67; 5.22; -4.20; 3.35 | — |
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.
Eligibility Criteria
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).
Data sourced from ClinicalTrials.gov (NCT01506141). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.