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

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Overview

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.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Hunter Syndrome

Interventions

Idursulfase-ITDRUG

Idursulfase-IT once monthly via IDDD.

ElapraseDRUG

Weekly IV infusions of commercially available Elaprase.

Eligibility

Sex: MALEMin age: 3 YearsMax age: 18 Years

Medical Language ↔ Plain English

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: 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).

Locations (9)

Ann & Robert H Lurie Childrens Hospital of Chicago

Chicago, Illinois, United States

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, United States

Legacy Emanuel Hospital

Portland, Oregon, United States

Outcomes

Primary Outcomes

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)

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)

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)

CSF Chemistries: Change From Baseline in CSF Total Cell Count

Time frame: Baseline, Month 163

CSF Chemistries: Change From Baseline in CSF Glucose

Time frame: Baseline, Month 163

CSF Chemistries: Change From Baseline in CSF Protein

Data from ClinicalTrials.gov

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Secondary Outcomes

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

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