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

NCT02412787 | Completed Phase 2 Results DMC

• 2 other identifiers: SHP609-3022014-004143-13
• Study Type: interventional
• Target: 56
• Locations: 7 countries
• Sites: 9

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.

Conditions

Hunter Syndrome

Outcome Measures

Primary Outcomes (9)

• Number of Participants With Adverse Events (AEs)

  An AE 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.

  Up to 9 years

• Number of Participants With Clinically Significant Changes in Vital Signs

  Participants were assessed for clinically significant changes in vital signs like injection (IT) vital signs and regular vital signs (temperature, pulse, blood pressure \[systolic and diastolic\], oxygen saturation, and respiration rate).

  Up to 9 years

• Number of Participants With Clinically Significant Changes in Laboratory Parameters

  Participants were assessed for clinically significant changes in laboratory parameters such as chemistry, hematology, urinalysis and cerebrospinal fluid (CSF) values.

  Up to 9 years

• Number of Participants With Clinically Significant Changes in 12-lead Electrocardiogram (ECG) Findings

  Participants were assessed for clinically significant changes in 12-lead ECG findings (such as heart rate, PR interval, QRS interval, QT interval, and the corrected QT interval).

  Up to 9 years

• Maximum Observed Serum Concentration (Cmax) of Idursulfase

  Idursulfase concentrations in serum were determined using a validated Enzyme -Linked Immunosorbent Assay (ELISA) method. Concentration for Cmax is presented in this endpoint.

  Predose and at 30 min, 60 min, 120 min, 4 hours, 6 hours, 8 hours, 12 hours, 24 hours, 30 hours and 36 hours post-dose at Week 100 in relation to HGT-HIT-094 (Week 48 of this study)

• Percent Change From Baseline in the Concentration of Glycosaminoglycan (GAG) in CSF at Month 67

  The percent change in concentration of GAG in CSF was assessed. GAGs are long sugar chains that are like building blocks for the body's tissues, especially connective tissues like cartilage, skin, and tendons, and play a crucial role in cell signaling and interactions.

  For participants who began IT treatment in HGT-HIT-094: From Baseline of HGT-HIT-094 up to Month 67 in relation to HGT-HIT-094; For participants who began IT treatment in this study: From Baseline of this study up to Month 55 of this study.

• Percent Change From Baseline in the Concentration of GAG in Urine at Month 67

  The percent change in concentration of GAG in urine was assessed. GAGs are long sugar chains that are like building blocks for the body's tissues, especially connective tissues like cartilage, skin, and tendons, and play a crucial role in cell signaling and interactions.

  For participants who began IT treatment in HGT-HIT-094: From Baseline of HGT-HIT-094 up to Month 67 in relation to HGT-HIT-094; For participants who began IT treatment in this study: From Baseline of this study up to Month 55 of this study.

• Number of Participants Who Reported Positive for Anti-idursulfase Antibodies in CSF

  Up to 9 years

• Number of Participants Who Reported Positive for Anti-idursulfase Antibodies in Serum

  Up to 9 years

Secondary Outcomes (12)

• Change From Baseline in Differential Ability Scales, Second Edition (DAS-II) Standard Cluster Scores at Month 67

  For participants who began IT treatment in HGT-HIT-094: From Baseline of HGT-HIT-094 up to Month 67 in relation to HGT-HIT-094; For participants who began IT treatment in this study: From Baseline of this study up to Month 55 of this study.

• Change From Baseline in Standard Scores of the Vineland Adaptive Behavior Scales, Second Edition (VABS-II) Domains at Month 67

  For participants who began IT treatment in HGT-HIT-094: From Baseline of HGT-HIT-094 up to Month 67 in relation to HGT-HIT-094; For participants who began IT treatment in this study: From Baseline of this study up to Month 55 of this study.

• Change From Baseline in Standard Composite Scores of the VABS-II Domains at Month 67

  For participants who began IT treatment in HGT-HIT-094: From Baseline of HGT-HIT-094 up to Month 67 in relation to HGT-HIT-094; For participants who began IT treatment in this study: From Baseline of this study up to Month 55 of this study.

• Change From Baseline in Age Equivalents Score of the Differential Ability Scales, Second Edition (DAS-II) at Month 61

  For participants who began IT treatment in HGT-HIT-094: From Baseline of HGT-HIT-094 up to Month 61 in relation to HGT-HIT-094; For participants who began IT treatment in this study: From Baseline of this study up to Month 49 of this study.

• Change From Baseline in Developmental Quotients (DQ) of the DAS-II at Month 61

  For participants who began IT treatment in HGT-HIT-094: From Baseline of HGT-HIT-094 up to Month 61 in relation to HGT-HIT-094; For participants who began IT treatment in this study: From Baseline of this study up to Month 49 of this study.

Other Outcomes (3)

• Maximum Observed Concentration (Cmax) of Idursulfase in Cerebrospinal Fluid (CSF)

  Predose each week up to 9 years

• Change From Baseline in Age Equivalent Scores of the Bayley Scales of Infant Development, Third Edition (BSID-III) Domains

  For participants who began IT treatment in HGT-HIT-094: From Baseline of HGT-HIT-094 up to Month 67 in relation to HGT-HIT-094; For participants who began IT treatment in this study: From Baseline of this study up to Month 55 of this study.

• Change From Baseline in Development Quotient (DQ) of the Bayley Scales of Infant Development, Third Edition (BSID-III) Domains

  For participants who began IT treatment in HGT-HIT-094: From Baseline of HGT-HIT-094 up to Month 67 in relation to HGT-HIT-094; For participants who began IT treatment in this study: From Baseline of this study up to Month 55 of this study.

Study Arms (1)

Idursulfase-IT

EXPERIMENTAL

Participants received 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 470 weeks (for participants who began intrathecal \[IT\] treatment in this study) and 480 weeks (for participants who began IT treatment in HGT-HIT-094 and continued to receive IT treatment in this study). Participants who were younger than 3 years of age received an adjusted dose of 7.5 mg (\>8 months to 30 months of age) or 10 mg (\>30 months to 3years of age) of idursulfase-IT.

Drug: Idursulfase-IT; Drug: Elaprase

Interventions

Idursulfase-IT DRUG

Participants received 10 mg of idursulfase-IT intrathecally via IDDD or LP once every 28 days. Participants who were younger than 3 years of age received an adjusted dose of 7.5 mg (\>8 months to 30 months of age) and 10 mg (\>30 months to 3 years of age).

Also known as: HGT-2310

Idursulfase-IT

Elaprase DRUG

Participants received intravenous (IV) Elaprase infusions at a minimum of 48 hours after IT administration of idursulfase-IT.

Idursulfase-IT

Eligibility Criteria

• Age: Up to 18 Years
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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).

You may not qualify if:

• 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:
• The participant has had, or may have, an allergic reaction to the materials of construction of the SOPH-A-PORT Mini S device.
• 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.
• The participant's drug therapy requires substances known to be incompatible with the materials of construction.
• The participant has a known or suspected local or general infection.
• The participant is at risk of abnormal bleeding due to a medical condition or therapy.
• The participant has 1 or more spinal abnormalities that could complicate safe implantation or fixation.
• The participant has a functioning CSF shunt device.
• The participant has shown an intolerance to an implanted device.

Sponsors & Collaborators

• Shire: lead

Study Sites (9)

Children's Hospital and Research Center at Oakland

Oakland, California, 94609, United States

Location

Ann & Robert H Lurie Children's Hospital of Chicago

Chicago, Illinois, 60611, United States

Location

University of North Carolina

Chapel Hill, North Carolina, 27514, United States

Location

Women's and Children's Hospital

Adelaide, 5006, Australia

Location

The Hospital for Sick Children

Toronto, Ontario, M5G 1X8, Canada

Location

Hôpital Femme Mère Enfants

Bron, 69677, France

Location

Instituto Nacional de Pediatría

Coyoacán, Mexico City, 04530, Mexico

Location

Hospital Infantil Universitario Niño Jesus

Madrid, 28009, Spain

Location

Royal Manchester Children's Hospital

Manchester, M13 9WL, United Kingdom

Location

Related Publications (2)

• Yee KS, Chirila C, Davenport E, Mladsi D, Barnett C, Kronenberger WG. A post hoc analysis of Projected Retained Ability Scores (PRAS) for the longitudinal assessment of cognitive functioning in patients with neuronopathic mucopolysaccharidosis II receiving intrathecal idursulfase-IT. Orphanet J Rare Dis. 2023 Nov 2;18(1):343. doi: 10.1186/s13023-023-02957-2.

  PMID: 37915038 DERIVED

• 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.

  PMID: 35961250 DERIVED

Related Links

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

MeSH Terms

Conditions

Mucopolysaccharidosis II

Interventions

idursulfase

Condition Hierarchy (Ancestors)

X-Linked Intellectual Disability; Intellectual Disability; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Genetic Diseases, X-Linked; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Heredodegenerative Disorders, Nervous System; Mucopolysaccharidoses; Carbohydrate Metabolism, Inborn Errors; Metabolism, Inborn Errors; Lysosomal Storage Diseases; Mucinoses; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases

Results Point of Contact

• Title: Study Director
• Organization: Takeda

TrialDisclosures@takeda.com

+1-877-825-3327

Study Officials

• Medical Director

  Takeda

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 1, 2015
• First Posted: April 9, 2015
• Study Start: April 14, 2015
• Primary Completion: April 18, 2024
• Study Completion: April 18, 2024
• Last Updated: June 19, 2025
• Results First Posted: June 19, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• 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.

Locations

FR (1); ES (1); US (3); AU (1); GB (1); ME (1); CA (1)