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 Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01506141
• Other study ID #: HGT-HIT-046
• Secondary ID: 2011-000212-25
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: August 1, 2010
• Est. completion date: April 30, 2024

Study information

• Verified date: May 2024
• Source: Takeda
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 25
• Est. completion date: April 30, 2024
• Est. primary completion date: April 30, 2024
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 3 Years to 18 Years

Eligibility

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).

Related Conditions & MeSH terms

• Cognitive Dysfunction
• Hunter Syndrome
• Mucopolysaccharidosis II
• Syndrome

Intervention

Drug:
• Idursulfase-IT
Participants will receive Idursulfase-IT once monthly at the dose used in study HGT-HIT-045 via intrathecal drug delivery device (IDDD).
• Elaprase
Participants will receive weekly IV infusions of commercially available Elaprase.

Locations

Country	Name	City	State
Canada	British Columbia Children's Hospital	Vancouver	British Columbia
United Kingdom	Birmingham Children's Hospital	Birmingham
United States	University of North Carolina at Chapel Hill	Chapel Hill	North Carolina
United States	Ann & Robert H Lurie Childrens Hospital of Chicago	Chicago	Illinois
United States	Vanderbilt Children's Hospital	Nashville	Tennessee
United States	Children's Hospital of Pittsburgh of UPMC	Pittsburgh	Pennsylvania
United States	Legacy Emanuel Hospital	Portland	Oregon
United States	University of Utah Hospital	Salt Lake City	Utah
United States	Seattle Children's Hospital	Seattle	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Shire

Countries where clinical trial is conducted

United States,  Canada,  United Kingdom, 

References & Publications (2)

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. — View Citation

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. Erratum In: Genet Med. 2006 Sep;8(9):599. Wendt, Suzanne [corrected to Wendt, Susanne]; Puga, Antonio [corrected to Puga, Ana Cristina]; Conway, Ann Marie [corrected to Conway, Anne Marie]. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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. Treatment-emergent AEs are 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).	From start of study drug administration up to follow-up (169 months)
Secondary	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 will be assessed.	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
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	Area under the curve from the time of dosing to the last measureable concentration (AUC0-t) of idursulfase will be assessed.	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	Maximum Observed Concentration (Cmax) of Idursulfase Administered as Intrathecal and in Conjunction With Elaprase	Maximum Observed Concentration (Cmax) of idursulfase will be assessed.	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	Time of Maximum Observed Concentration (tmax) of Idursulfase Administered in as Intrathecal and in Conjunction With Elaprase	Time of maximum observed concentration (tmax) of idursulfase will be assessed.	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	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	Total body clearance for extravascular administration divided by the fraction of dose absorbed (Cl/F) of idursulfase will be assessed.	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	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	Volume of distribution associated with the terminal slope following extravascular administration divided by the fraction of dose absorbed (Vz/F) of idursulfase will be assessed.	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	First Order Rate Constant (Lambda z) of Idursulfase Administered as Intrathecal and in Conjunction With Elaprase	First order rate constant (Lambda z) of idursulfase will be assessed.	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	Terminal Half-life (t1/2) of Idursulfase Administered as Intrathecal and in Conjunction With Elaprase	Terminal half-life (t1/2) of idursulfase will be assessed.	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	Total Body Clearance (Cl) of Elaprase	Total body clearance (Cl) of Elaprase will be assessed.	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
Secondary	Volume of Distribution (Vz) of Elaprase	Volume of distribution associated with the terminal slope (Vz) of Elaprase will be assessed.	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
Secondary	Observed Steady-state Volume of Distribution (Vss) of Elaprase	Observed steady-state volume of distribution (Vss) of Elaprase will be assessed.	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
Secondary	Mean Residence Time (MRT) of Elaprase	Mean residence time (MRT) of Elaprase will be assessed.	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
Secondary	Change From Baseline in CSF Biomarkers	Change from baseline in CSF biomarkers glycosaminoglycan (GAG [HS/DS]) will be assessed.	Baseline, Day 2 of Week 1, Day 2 Pre dose on Weeks 3, 7, 11, 15, 19, 23, 27, Months 7 - 169
Secondary	Change From Baseline in Urinary Glycosaminoglycan (GAG)	Change from baseline in urinary GAG will be assessed.	Baseline, Day 1 Predose on Weeks 3, 7, 11, 15, 19, 23, 27, Months 7 - 169

External Links

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