Clinical trial NCT02412787: Study of Long Term Safety and Clinical Outcomes of Idursulfase IT and Elaprase Treatment in Pediatric Participants Who Have Completed Study HGT-HIT-094
Official title: An Open Label Extension of Study HGT-HIT-094 Evaluating Long Term Safety and Clinical Outcomes of Intrathecal Idursulfase Administered in Conjunction With Elaprase® in Patients With Hunter Syndrome and Cognitive Impairment
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Hunter Syndrome
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2015-04-09
Enrollment: 56
Sex: MALE
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 will allow participants that completed Study HGT-HIT-094 to continue receiving Elaprase treatment in conjunction with idursulfase IT or to continue receiving Elaprase treatment and begin concurrent IT treatment for those that did not receive idursulfase IT treatment in Study HGT-HIT-094.


Eligibility criteria: Inclusion Criteria:

* Participants must have completed Visit Week 52 assessments in Study HGT-HIT-094 (NCT02055118).
* 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 consent/assent, as relevant, must be obtained.
* The participant has continued to receive Elaprase on a regular basis in Study HGT-HIT-094 (NCT02055118).

Exclusion Criteria:

* The participant has experienced, in the opinion of the investigator, a safety or medical issue that contraindicates treatment with idursulfase-IT, including, but not limited to, uncontrolled seizure disorder, bleeding disorder, and clinically relevant hypertension.
* The participant has a known hypersensitivity to any of the components of idursulfase-IT.
* The participant has clinically relevant intracranial hypertension.
* The participant is enrolled in another clinical study, other than HGT-HIT-094 (NCT02055118), that involves clinical investigations or use of any investigational product (drug or \[intrathecal/spinal\] device) within 30 days prior to study enrollment or at any time during the study.
* The participant has any known or suspected hypersensitivity to anesthesia or is thought to be at an unacceptably high risk for anesthesia due to compromised airways or other conditions.
* The participant has a condition that is contraindicated as described in the SOPH-A-PORT® Mini S, Implantable Access Port, Spinal, Mini Unattached, with Guidewire (SOPH-A-PORT Mini S) intrathecal drug delivery device (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 1 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.

Primary outcomes:
measure: Number of Participants With Adverse Events
timeFrame: From start of study drug administration up to 121 months
measure: Number of Participants With Clinically Significant Changes in Vital Signs, Laboratory Parameters, and 12-lead Electrocardiogram (ECG) Findings
timeFrame: From start of study drug administration up to 121 months
measure: Maximum Observed Serum Concentration (Cmax) of Idursulfase
timeFrame: Baseline through Month 121
measure: Maximum Observed Concentration (Cmax) of Idursulfase in Cerebrospinal Fluid (CSF)
timeFrame: Baseline through Month 121
measure: Change From Baseline in the Concentration of Glycosaminoglycan (GAG) in Cerebrospinal Fluid (CSF)
timeFrame: Baseline through Month 121
measure: Change From Baseline in the Concentration of Glycosaminoglycan (GAG) in Urine
timeFrame: Baseline through Month 121
measure: Number of Participants who Report Anti-idursulfase Antibodies in Cerebrospinal Fluid (CSF)
timeFrame: From start of study drug administration up to 121 months
measure: Number of Participants who Report Anti-idursulfase Antibodies in Serum
timeFrame: From start of study drug administration up to 121 months
Secondary outcomes:
measure: Change From Baseline in Differential Ability Scales, Second Edition (DAS-II) Standard Scores and Standard Cluster Scores
timeFrame: Baseline through Month 121
measure: Change From Baseline in Age Equivalent Scores of the Bayley Scales of Infant Development, Third Edition (BSID-III) Domains
timeFrame: Baseline through Month 121
measure: Change From Baseline in Development Quotient (DQ) of the Bayley Scales of Infant Development, Third Edition (BSID-III) Domains
timeFrame: Baseline through Month 121
measure: Change From Baseline in Standard Scores of the Vineland Adaptive Behavior Scales, Second Edition (VABS-II) Domains
timeFrame: Baseline through Month 121
measure: Change From Baseline in Standard Composite Scores of the Vineland Adaptive Behavior Scales, Second Edition (VABS-II) Domains
timeFrame: Baseline through Month 121
measure: Change From Baseline in Age Equivalents Score of the Differential Ability Scales, Second Edition (DAS-II)
timeFrame: Baseline through Month 121
measure: Change From Baseline in Developmental Quotients (DQ) of the Differential Ability Scales, Second Edition (DAS-II)
timeFrame: Baseline through Month 121
measure: Change From Baseline in T-scores of the Core Subtests Differential Ability Scales, Second Edition (DAS-II)
timeFrame: Baseline through Month 121
measure: Change From Baseline in Age Equivalents Score of the Vineland Adaptive Behavior Scales, Second Edition (VABS-II) Sub Domains
timeFrame: Baseline through Month 121
measure: Change From Baseline in Developmental Quotients (DQ) of the Vineland Adaptive Behavior Scales, Second Edition (VABS-II) Sub Domains
timeFrame: Baseline through Month 121
measure: Change From Baseline in v-Scores of the Vineland Adaptive Behavior Scales, Second Edition (VABS-II) Sub Domains
timeFrame: Baseline through Month 121
measure: Change From Baseline in v-Scale Scores of the Vineland Adaptive Behavior Scales, Second Edition (VABS-II) Maladaptive Behavior Index and its Subscales
timeFrame: Baseline through Month 121
measure: Change From Baseline in Observed Maladaptive Levels of the Vineland Adaptive Behavior Scales, Second Edition (VABS-II) Maladaptive Behavior Index and its Subscales
timeFrame: Baseline through Month 121
measure: Change From Baseline in Brain Structure Volume as Measured by Magnetic Resonance Imaging (MRI)
timeFrame: Baseline through Month 121
Other outcomes:
Locations:
city: Oakland
country: United States
facility: Children's Hospital and Research Center at Oakland
state: California
city: Chicago
country: United States
facility: Ann & Robert H Lurie Children's Hospital of Chicago
state: Illinois
city: Chapel Hill
country: United States
facility: University of North Carolina
state: North Carolina
city: Adelaide
country: Australia
facility: Women's and Children's Hospital
city: Toronto
country: Canada
facility: The Hospital for Sick Children
state: Ontario
city: Bron
country: France
facility: Hôpital Femme Mère Enfants
city: Coyoacan
country: Mexico
facility: Instituto Nacional de Pediatría
state: Ciudad De México
city: Madrid
country: Spain
facility: Hospital Infantil Universitario Niño Jesus
city: Manchester
country: United Kingdom
facility: Royal Manchester Children's Hospital
Study officials:
affiliation: Takeda
name: Study Director
role: STUDY_DIRECTOR
References:
citation: Muenzer J, Burton BK, Harmatz P, Gutierrez-Solana LG, Ruiz-Garcia M, Jones SA, Guffon N, Inbar-Feigenberg M, Bratkovic D, Hale M, Wu Y, Yee KS, Whiteman DAH, Alexanderian D; SHP609-302 study group. Long-term open-label extension study of the safety and efficacy of intrathecal idursulfase-IT in patients with neuronopathic mucopolysaccharidosis II. Mol Genet Metab. 2022 Sep-Oct;137(1-2):92-103. doi: 10.1016/j.ymgme.2022.07.016. Epub 2022 Aug 2.