Study of Long Term Safety and Clinical Outcomes of Idursulfase IT and Elaprase Treatment in Pediatric Participants Who Have Completed Study HGT-HIT-094

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Hunter Syndrome
• Intervention / Treatment: Drug: Idursulfase-IT; Drug: Elaprase

• Study Type: Interventional
• Enrollment (Actual): 56
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Australia
  • Adelaide, Australia, 5006
    • Women's and Children's Hospital
• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 1X8
      • The Hospital for Sick Children
• France
  • Bron, France, 69677
    • Hopital Femme Mere Enfants
• Mexico
  • Ciudad De México
    • Coyoacan, Ciudad De México, Mexico, 04530
      • Instituto Nacional de Pediatria
• Spain
  • Madrid, Spain, 28009
    • Hospital Infantil Universitario Niño Jesús
• United Kingdom
  • Manchester, United Kingdom, M13 9WL
    • Royal Manchester Children's Hospital
• United States
  • California
    • Oakland, California, United States, 94609
      • Children's Hospital and Research Center at Oakland
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Ann & Robert H Lurie Children's Hospital of Chicago
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27514
      • University of North Carolina

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 18 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Idursulfase-IT; Participants will receive 10 milligrams (mg) of idursulfase-IT intrathecally via intrathecal drug delivery device (IDDD) or lumbar puncture (LP) once every 28 days along with standard-of-care therapy with Elaprase for 480 weeks. Participants who are younger than 3 years of age will receive an adjusted dose of 7.5 mg (greater than [>] 8 months to 30 months of age) and 10 mg (>30 months to 3 years of age) of idursulfase-IT.

Drug: Idursulfase-IT; Participants will receive 10 mg of idursulfase-IT intrathecally via IDDD or LP once every 28 days. Participants who are younger than 3 years of age will receive an adjusted dose of 7.5 mg (>8 months to 30 months of age) and 10 mg (>30 months to 3 years of age).; Other Names: HGT-2310; Drug: Elaprase; Participants will receive intravenous (IV) Elaprase infusions at a minimum of 48 hours after IT administration of idursulfase-IT.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Adverse Events	An adverse event is any noxious, pathologic, or unintended change in anatomical, physiologic, or metabolic function as indicated by physical signs, symptoms, or laboratory changes occurring in any phase of a clinical study, whether or not considered investigational product-related.	From start of study drug administration up to 121 months
Number of Participants With Clinically Significant Changes in Vital Signs, Laboratory Parameters, and 12-lead Electrocardiogram (ECG) Findings	Number of participants with clinically significant changes will be reported.	From start of study drug administration up to 121 months
Maximum Observed Serum Concentration (Cmax) of Idursulfase	The Cmax of Idursulfase will be assessed.	Baseline through Month 121
Maximum Observed Concentration (Cmax) of Idursulfase in Cerebrospinal Fluid (CSF)	The Cmax of Idursulfase in CSF will be assessed.	Baseline through Month 121
Change From Baseline in the Concentration of Glycosaminoglycan (GAG) in Cerebrospinal Fluid (CSF)	Concentration of GAG in CSF will be assessed.	Baseline through Month 121
Change From Baseline in the Concentration of Glycosaminoglycan (GAG) in Urine	Concentration of GAG in urine will be assessed.	Baseline through Month 121
Number of Participants who Report Anti-idursulfase Antibodies in Cerebrospinal Fluid (CSF)	The presence of idursulfase-specific antibodies will be assessed.	From start of study drug administration up to 121 months
Number of Participants who Report Anti-idursulfase Antibodies in Serum	The presence of idursulfase-specific antibodies will be assessed.	From start of study drug administration up to 121 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Differential Ability Scales, Second Edition (DAS-II) Standard Scores and Standard Cluster Scores	The DAS-II will be used to assess all participants of age 2 years, 6 months or older. The DAS-II comprises 2 overlapping batteries. The Early Years battery is designed for children ages 2 years, 6 months through 6 years, 11 months. The Early Years battery is further divided into the Lower Level for children ages 2 years, 6 months through 3 years, 5 months and Upper Level for children ages 3 years 6 months through 6 years, 11 months. The School Age Battery is designed for children ages 7 years, 0 months through 17 years, 11 months. These batteries are fully co-normed for ages 5 years, 0 months, through 8 years, 11 months. The cluster areas include general conceptual ability (GCA), Verbal, Nonverbal, Spatial, and Special Nonverbal Composite (SNC). The cluster area score represents a score (mean = 100 and standard deviation of 15) on which higher scores indicate a higher level of cognitive ability.	Baseline through Month 121
Change From Baseline in Age Equivalent Scores of the Bayley Scales of Infant Development, Third Edition (BSID-III) Domains	Participants who are younger than 2 years, 6 months, will be assessed using the BSID-III. The BSID--III is a series of measurements to assess the motor (fine and gross), language (receptive and expressive), and cognitive development of infants and toddlers and consists of a series of developmental play tasks. Raw scores (range 40-160) will be converted to age- equivalent scores to measure ability, skill, and knowledge, expressed as the age at which most individuals reach the same level (age norm; range: 0, unbound).	Baseline through Month 121
Change From Baseline in Development Quotient (DQ) of the Bayley Scales of Infant Development, Third Edition (BSID-III) Domains	Participants who are younger than 2 years, 6 months, will be assessed using the BSID-III. The BSID--III is a series of measurements to assess the motor (fine and gross), language (receptive and expressive), and cognitive development of infants and toddlers and consists of a series of developmental play tasks. The development quotient (DQ) is a means to express a neurodevelopmental/cognitive delay which will be computed as a ratio and expressed as a percentage using the age equivalent score divided by the age at testing ([age-equivalent score/chronological age] × 100; range: 0-100).	Baseline through Month 121
Change From Baseline in Standard Scores of the Vineland Adaptive Behavior Scales, Second Edition (VABS-II) Domains	The VABS-II test measures adaptive behaviors, including the ability to cope with environmental changes, to learn new everyday skills, and to demonstrate independence. This test measures the following 4 key domains: communication, daily living skills, socialization, motor skills, and the adaptive behaviour composite (a composite of the other 4 domains). The standard scores represent a score (mean = 100 and standard deviation of 15) on which higher scores indicate a higher level of cognitive ability.	Baseline through Month 121
Change From Baseline in Standard Composite Scores of the Vineland Adaptive Behavior Scales, Second Edition (VABS-II) Domains	The VABS-II test measures adaptive behaviors, including the ability to cope with environmental changes, to learn new everyday skills, and to demonstrate independence. This test measures the following 4 key domains: communication, daily living skills, socialization, motor skills, and the adaptive behavior composite (a composite of the other 4 domains). The ABC score ranges from 20 to 160 on which higher scores indicate a higher level of adaptive functioning. A positive change value indicates improvement in adaptive functioning.	Baseline through Month 121
Change From Baseline in Age Equivalents Score of the Differential Ability Scales, Second Edition (DAS-II)	DAS-II will be used to assess all participants of age 2 years (Y), 6 months (M) or older. DAS-II comprises 2 overlapping batteries. Early Years Battery (EYB) is designed for ages 2Y,6M-6Y,11M. School Age Battery is designed for ages 7Y,0M-17Y,11M. These batteries are fully co-normed for age 5Y,0M-8Y,11M. Core subtests include Verbal (V) Comprehension, Picture Similarities, Naming Vocabulary, Pattern Construction (PC), Matrices (M) and Copying for DAS-II Early Y and Recall of Designs, Word Definitions, PC, M, Verbal Similarities, and Sequential and Quantitative Reasoning for DAS-II School Years. Standardized scores will be converted to age equivalent scores (AES) to measure ability, skill, and knowledge expressed as age at which most individuals reach same level. Mean AES will be obtained by averaging out AES. Higher score (HS) indicates greater cognitive ability (CA). Subtests score represent a score (mean=50 and standard deviation of 10) on which HS indicate a higher level of CA.	Baseline through Month 121
Change From Baseline in Developmental Quotients (DQ) of the Differential Ability Scales, Second Edition (DAS-II)	The DAS-II will be used to assess all participants of age 2 years (Y), 6 months (M) or older. The DAS-II comprises 2 overlapping batteries. The Early Years battery (EYB) is designed for children ages (CA) 2Y, 6M, through 6Y, 11M. The EYB is further divided into the Lower Level for CA 2Y, 6M through 3Y, 5M and Upper Level for CA 3Y, 6M through 6Y, 11M. The School Age Battery is designed for CA 7Y, 0M through 17Y, 1M. These batteries are fully co-normed for ages 5Y, 0M, through 8Y, 11M. The core subtests include Verbal Comprehension, Picture Similarities, Naming Vocabulary, Pattern Construction, Matrices, and Copying for the DAS-II Early Y and Recall of Designs, Word Definitions, Pattern Construction, Matrices, Verbal Similarities, and Sequential and Quantitative Reasoning for the DAS-II School Y. The DQ will be computed as a ratio and expressed as a percentage using the age equivalent score (AES) divided by the age at testing ([AES/chronological age] × 100; range, 0-100).	Baseline through Month 121
Change From Baseline in T-scores of the Core Subtests Differential Ability Scales, Second Edition (DAS-II)	The DAS-II will be used to assess all participants of age 2 years (Y), 6 months (M) or older. The DAS-II comprises 2 overlapping batteries. The Early Years battery (EYB) is designed for children ages (CA) 2Y, 6M, through 6Y, 11M. The EYB is further divided into the Lower Level for CA 2Y, 6M through 3Y, 5M and Upper Level for CA 3Y, 6M through 6Y, 11M. The School Age Battery is designed for CA 7Y, 0M through 17Y, 11M. These batteries are fully co-normed for ages 5Y, 0M, through 8Y, 11M. The core subtests (CS) include Verbal Comprehension, Picture Similarities, Naming Vocabulary, Pattern Construction, Matrices, and Copying for the DAS-II Early Years and Recall of Designs, Word Definitions, Pattern Construction, Matrices, Verbal Similarities, and Sequential and Quantitative Reasoning for the DAS-II School Years. The CS score represent a score (mean = 50 and standard deviation of 10) on which higher scores indicate a higher level of cognitive ability.	Baseline through Month 121
Change From Baseline in Age Equivalents Score of the Vineland Adaptive Behavior Scales, Second Edition (VABS-II) Sub Domains	The VABS-II test measures adaptive behaviors, including the ability to cope with environmental changes, to learn new everyday skills, and to demonstrate independence. This test measures the following subdomains of 5 key domains: Communication (Receptive, Expressive, Written), Daily Living Skills (Personal, Domestic, Community), Socialization (Interpersonal Relationships, Play and Leisure Time, Coping Skills), Motor Skills (Gross, Fine). The mean age equivalent score will be obtained by averaging out the age-equivalent scores for the all the sub-domains except for Gross and Fine motor skills (range: 0, unbound).	Baseline through Month 121
Change From Baseline in Developmental Quotients (DQ) of the Vineland Adaptive Behavior Scales, Second Edition (VABS-II) Sub Domains	The VABS-II test measures adaptive behaviors, including the ability to cope with environmental changes, to learn new everyday skills, and to demonstrate independence. This test measures the following subdomains of 5 key domains: Communication (Receptive, Expressive, Written), Daily Living Skills (Personal, Domestic, Community), Socialization (Interpersonal Relationships, Play and Leisure Time, Coping Skills), Motor Skills (Gross, Fine). The DQ will be computed as a ratio and expressed as a percentage using the age-equivalent score divided by the age at testing ([age-equivalent score/chronological age] × 100; range, 0-100).	Baseline through Month 121
Change From Baseline in v-Scores of the Vineland Adaptive Behavior Scales, Second Edition (VABS-II) Sub Domains	The VABS-II test measures adaptive behaviors, including the ability to cope with environmental changes, to learn new everyday skills, and to demonstrate independence. This test measures the following subdomains of 5 key domains: Communication (Receptive, Expressive, Written), Daily Living Skills (Personal, Domestic, Community), Socialization (Interpersonal Relationships, Play and Leisure Time, Coping Skills), Motor Skills (Gross, Fine). The V-scale scores represent a score (mean = 15 and standard deviation of 3; range: 1-24) on which higher scores indicate a higher level of adaptive functioning.	Baseline through Month 121
Change From Baseline in v-Scale Scores of the Vineland Adaptive Behavior Scales, Second Edition (VABS-II) Maladaptive Behavior Index and its Subscales	The VABS-II test measures adaptive behaviors, including the ability to cope with environmental changes, to learn new everyday skills, and to demonstrate independence. Maladaptive behavior index is a composite of the internalizing, externalizing, and other types of undesirable behavior that may interfere with the individual's adaptive functioning. The v-Scale scores represent a score (mean = 15 and standard deviation of 3; range: 1-24) on which higher scores indicate a higher level of adaptive functioning.	Baseline through Month 121
Change From Baseline in Observed Maladaptive Levels of the Vineland Adaptive Behavior Scales, Second Edition (VABS-II) Maladaptive Behavior Index and its Subscales	The VABS-II test measures adaptive behaviors, including the ability to cope with environmental changes, to learn new everyday skills, and to demonstrate independence. Maladaptive behavior index is a composite of the internalizing, externalizing, and other types of undesirable behavior that may interfere with the individual's adaptive functioning. The V scale scores represent a score (mean = 15 and standard deviation of 3; range: 1-24) on which higher scores indicate a higher level of cognitive ability.	Baseline through Month 121
Change From Baseline in Brain Structure Volume as Measured by Magnetic Resonance Imaging (MRI)	Brain structure volume will be assessed from brain total intracranial volume, brain total tissue volume, brain total white matter, brain total gray matter, and total CSF volume as measured by MRI.	Baseline through Month 121

Collaborators and Investigators

• Sponsor: Shire
• Investigators: Study Director: Study Director, Takeda

Publications and helpful links

General Publications

• 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. Erratum In: Mol Genet Metab. 2023 Nov;140(3):107646.

Helpful Links

• To obtain more information on the study, click here/on this link

Study record dates

Study Major Dates

• Study Start (Actual): October 28, 2015
• Primary Completion (Estimated): April 30, 2024
• Study Completion (Estimated): April 30, 2024

Study Registration Dates

• First Submitted: April 1, 2015
• First Submitted That Met QC Criteria: April 6, 2015
• First Posted (Estimated): April 9, 2015

Study Record Updates

• Last Update Posted (Actual): April 5, 2024
• Last Update Submitted That Met QC Criteria: April 4, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Metabolic Diseases; Nervous System Diseases; Neurologic Manifestations; Neurobehavioral Manifestations; Disease; Genetic Diseases, Inborn; Genetic Diseases, X-Linked; Connective Tissue Diseases; Carbohydrate Metabolism, Inborn Errors; Metabolism, Inborn Errors; Lysosomal Storage Diseases; Mucinoses; Mental Retardation, X-Linked; Intellectual Disability; Heredodegenerative Disorders, Nervous System; Mucopolysaccharidoses; Syndrome; Mucopolysaccharidosis II
• Other Study ID Numbers: SHP609-302; 2014-004143-13 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.
• IPD Sharing Access Criteria: IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/. For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR