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

• Register: ClinicalTrials.gov
• Last refreshed on: 22 April 2024
• Main ID: NCT01506141
• Date of registration: 15/12/2011
• Prospective Registration: No
• Primary sponsor: Shire
• Public title: 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
• Scientific 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
• Date of first enrolment: August 1, 2010
• Target sample size: 25
• Recruitment status: Active, not recruiting
• URL: https://clinicaltrials.gov/ct2/show/NCT01506141
• Study type: Interventional
• Study design: Allocation: N/A. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 1/Phase 2

Countries of recruitment

Canada, United Kingdom, United States

Contacts

• Name: Shire Director
• Affiliation: Takeda

Key inclusion & exclusion 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:

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).



Age minimum: 3 Years
Age maximum: 18 Years
Gender: Male

Health Condition(s) or Problem(s) studied

Hunter Syndrome

Intervention(s)

Drug: Elaprase

Drug: Idursulfase-IT

Primary Outcome(s)

Number of Participants With Treatment-emergent Adverse Events (TEAEs) [Time Frame: From start of study drug administration up to follow-up (169 months)]

Secondary Outcome(s)

Mean Residence Time (MRT) 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 Weeks 3 and 23]

Terminal Half-life (t1/2) of Idursulfase Administered as Intrathecal and in Conjunction With Elaprase [Time Frame: 15 minutes prior to IT injection, 1, 2, 3, 4, 6, 8, 12, 24, 30 and 36 hours following IT injection on Weeks 3 and 23, Day 2 of Months 19, 31, and 43]

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, 1, 2, 3, 4, 6, 8, 12, 24, 30 and 36 hours following IT injection on Weeks 3 and 23, Day 2 of Months 19, 31, and 43]

First Order Rate Constant (Lambda z) of Idursulfase Administered as Intrathecal and in Conjunction With Elaprase [Time Frame: 15 minutes prior to IT injection, 1, 2, 3, 4, 6, 8, 12, 24, 30 and 36 hours following IT injection on Weeks 3 and 23, Day 2 of Months 19, 31, and 43]

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, 1, 2, 3, 4, 6, 8, 12, 24, 30 and 36 hours following IT injection on Weeks 3 and 23, Day 2 of Months 19, 31, and 43]

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 Weeks 3 and 23]

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, 1, 2, 3, 4, 6, 8, 12, 24, 30 and 36 hours following IT injection on Weeks 3 and 23, Day 2 of Months 19, 31, and 43]

Volume of Distribution (Vz) 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 Weeks 3 and 23]

Change From Baseline in CSF Biomarkers [Time Frame: Baseline, Day 2 of Week 1, Day 2 Pre dose on Weeks 3, 7, 11, 15, 19, 23, 27, Months 7 - 169]

Maximum Observed Concentration (Cmax) of Idursulfase Administered as Intrathecal and in Conjunction With Elaprase [Time Frame: 15 minutes prior to IT injection, 1, 2, 3, 4, 6, 8, 12, 24, 30 and 36 hours following IT injection on Weeks 3 and 23, Day 2 of Months 19, 31, and 43]

Observed Steady-state Volume of Distribution (Vss) 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 Weeks 3 and 23]

Change From Baseline in Urinary Glycosaminoglycan (GAG) [Time Frame: Baseline, Day 1 Predose on Weeks 3, 7, 11, 15, 19, 23, 27, Months 7 - 169]

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, 1, 2, 3, 4, 6, 8, 12, 24, 30 and 36 hours (h) following IT injection on Weeks 3 and 23, Day 2 of Months 19, 31, and 43]

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, 1, 2, 3, 4, 6, 8, 12, 24, 30 and 36 hours following IT injection on Weeks 3 and 23, Day 2 of Months 19, 31, and 43]

Secondary ID(s)

2011-000212-25

HGT-HIT-046

Source(s) of Monetary Support

Please refer to primary and secondary sponsors