Clinical trial NCT01506141: 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
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Hunter Syndrome
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
hunters syndrome
ert treatment
lysosomal storage disease
hunter disease
enzyme replacement therapy
idursulfase
hunter's syndrome treatment
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2012-01-09
Enrollment: 25
Sex: MALE
Minimum age (years): 3
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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:

  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).

Primary outcomes:
measure: Number of Participants With Treatment-emergent Adverse Events (TEAEs)
timeFrame: From start of study drug administration up to follow-up (169 months)
Secondary outcomes:
measure: Area Under the Curve Extrapolated to Infinity (AUC0-infinity) of Idursulfase Administered as Intrathecal and in Conjunction With Elaprase
timeFrame: 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
measure: 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
timeFrame: 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
measure: Maximum Observed Concentration (Cmax) of Idursulfase Administered as Intrathecal and in Conjunction With Elaprase
timeFrame: 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
measure: Time of Maximum Observed Concentration (tmax) of Idursulfase Administered in as Intrathecal and in Conjunction With Elaprase
timeFrame: 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
measure: 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
timeFrame: 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
measure: 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
timeFrame: 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
measure: First Order Rate Constant (Lambda z) of Idursulfase Administered as Intrathecal and in Conjunction With Elaprase
timeFrame: 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
measure: Terminal Half-life (t1/2) of Idursulfase Administered as Intrathecal and in Conjunction With Elaprase
timeFrame: 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
measure: Total Body Clearance (Cl) of Elaprase
timeFrame: 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
measure: Volume of Distribution (Vz) of Elaprase
timeFrame: 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
measure: Observed Steady-state Volume of Distribution (Vss) of Elaprase
timeFrame: 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
measure: Mean Residence Time (MRT) of Elaprase
timeFrame: 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
measure: Change From Baseline in CSF Biomarkers
timeFrame: Baseline, Day 2 of Week 1, Day 2 Pre dose on Weeks 3, 7, 11, 15, 19, 23, 27, Months 7 - 169
measure: Change From Baseline in Urinary Glycosaminoglycan (GAG)
timeFrame: Baseline, Day 1 Predose on Weeks 3, 7, 11, 15, 19, 23, 27, Months 7 - 169
Other outcomes:
Locations:
city: Chicago
country: United States
facility: Ann & Robert H Lurie Childrens Hospital of Chicago
state: Illinois
city: Chapel Hill
country: United States
facility: University of North Carolina at Chapel Hill
state: North Carolina
city: Portland
country: United States
facility: Legacy Emanuel Hospital
state: Oregon
city: Pittsburgh
country: United States
facility: Children's Hospital of Pittsburgh of UPMC
state: Pennsylvania
city: Nashville
country: United States
facility: Vanderbilt Children's Hospital
state: Tennessee
city: Salt Lake City
country: United States
facility: University of Utah Hospital
state: Utah
city: Seattle
country: United States
facility: Seattle Children's Hospital
state: Washington
city: Vancouver
country: Canada
facility: British Columbia Children's Hospital
state: British Columbia
city: Birmingham
country: United Kingdom
facility: Birmingham Children's Hospital
Study officials:
affiliation: Takeda
name: Shire Director
role: STUDY_DIRECTOR
References:
citation: 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.
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.
citation: 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.