Study of Intrathecal Idursulfase-IT Administered in Conjunction With Elaprase® in Pediatric Patients With Hunter Syndrome and Early Cognitive Impairment

NCT02055118 | Completed Phase 2 Results DMC

• 2 other identifiers: HGT-HIT-0942013-002885-38
• Study Type: interventional
• Target: 58
• Locations: 7 countries
• Sites: 9

Brief Summary

Study HGT-HIT-094 is a multicenter study designed to determine the effect on clinical parameters of neurodevelopmental status of monthly IT administration of idursulfase-IT 10 mg for 12 months in pediatric patients with Hunter syndrome and cognitive impairment who have previously received and tolerated a minimum of 4 months of therapy with Elaprase.

Conditions

Hunter Syndrome

Keywords

hunters disease; MPS II; lysosomal storage disorder; hunters syndrome; ert treatment; hunter's disease; iduronate sulfatase; MPS society; mps 2; enlarged adenoids; hunter's syndrome; iduronate 2 sulfatase; chronic ear infection; mucopolysaccharides; hunter syndrome therapy; hunter's syndrome treatment; enzyme replacement therapy; hunter syndrome treatment; elaprase; MPSII; lysosomal storage disease; mps diagnosis; mps symptoms; idursulfase; hunter disease; hunter's disease treatment; MPS2

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in the Differential Ability Scales, Second Edition (DAS-II) General Conceptual Ability (GCA) Standard Score at Week 52

  The DAS-II was used to assess cognitive development in all randomized participants. The GCA standard score of the DAS-II was used to obtain a general measure of cognitive ability. The GCA score represent a score (mean = 100 and standard deviation of 15) on which higher scores indicate a higher level of cognitive ability. The score ranges from 30 to 170. A positive change value indicates improvement in cognitive ability.

  Baseline, Week 52

Secondary Outcomes (31)

• Change From Baseline in the Vineland Adaptive Behavior Scales, Second Edition (VABS-II) Adaptive Behavior Composite (ABC) Score at Week 52

  Baseline, Week 52

• Change From Baseline in the Differential Ability Scales, Second Edition (DAS-II) General Conceptual Ability (GCA) Standard Score at Weeks 16, 28 and 40

  Baseline, Week 16, Week 28 and Week 40

• Change From Baseline in the Vineland Adaptive Behavior Scales, Second Edition (VABS-II) Adaptive Behavior Composite (ABC) Score at Week 16, 28 and 40

  Baseline, Week 16, Week 28 and Week 40

• Change From Baseline in Differential Ability Scales, Second Edition (DAS-II) Cluster Standard Scores at Weeks 16, 28, 40 and 52

  Baseline, Week 16, Week 28, Week 40 and Week 52

• Change From Baseline in Vineland Adaptive Behavior Scales, Second Edition (VABS-II) Standard Scores of Other Domains at Weeks 16, 28, 40, 52

  Baseline, Week 16, Week 28, Week 40 and Week 52

Study Arms (2)

idursulfase-IT

EXPERIMENTAL

10 mg administered via IT using IDDD (intrathecal drug delivery device) once a month for 52 weeks.

Biological: idursulfase-IT

Nontreatment control

OTHER

Patients will receive weekly standard of care treatment with IV Elaprase only.

Other: No IT treatment

Interventions

idursulfase-IT BIOLOGICAL

10mg

idursulfase-IT

No IT treatment OTHER

Standard of Care

Also known as: Non-treatment Control

Nontreatment control

Eligibility Criteria

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

You may qualify if:

• Patients must meet all of the following criteria to be considered eligible for randomization in the pivotal study:
• The patient is male and is ≥3 and \<18 years of age at the time of informed consent.
• The patient must have a documented diagnosis of MPS II.
• The patient has evidence at Screening of Hunter syndrome-related cognitive impairment defined as follows:
• A patient who is ≥3 and \<13 years of age must have one of the following criteria (3a OR 3b):
• A GCA score ≥55 and ≤85 OR
• If the patient has a GCA score at Screening \>85, there must be evidence of a decrease in GCA score of ≥10 points over 12 months from a previously documented test result in observational study HGT-HIT-090.
• A patient who is ≥13 and \<18 years of age must have both of the following criteria (3c AND 3d):
• A GCA score of ≥55 and ≤85. AND
• There must be evidence of a decrease in GCA score of ≥10 points over 12 months from a previously documented
• The patient has received and tolerated a minimum of 4 months of therapy with Elaprase during the period immediately prior to Screening.
• The patient must have sufficient auditory capacity, with a hearing aid(s), if needed, in the Investigator's judgment to complete the required protocol testing and must be compliant with wearing the hearing aid(s), if needed, on scheduled testing days.
• The patient's parent(s) or legally authorized guardian(s) must have voluntarily signed an Institutional Review Board/Independent Ethics Committee approved informed consent form after all relevant aspects of the study have been explained and discussed. Consent of the patient's parent(s) or legally authorized guardian(s) and the patient's assent, if applicable, must be obtained prior to the start of any study procedures.
• Patients must meet all of the following criteria to be considered eligible for enrollment in the separate substudy:
• The patient is male and is \<3 years of age at the time of informed consent.

You may not qualify if:

• Patients who meet any of the following criteria are not eligible to be randomized into the pivotal study or enrolled in the separate substudy:
• The patient has clinically significant non-Hunter syndrome-related CNS involvement (such as Fragile-X syndrome) which is judged by the Investigator to be likely to interfere with the accurate administration and interpretation of protocol assessments.
• The patient has a large chromosomal deletion or complex rearrangement that includes a deletion of the FMR1 and/or FMR2 genes.
• The patient has a significant medical or psychiatric comorbidity(ies) that might affect study data or confound the integrity of study results.
• The patient has contra-indications for performance of lumbar puncture such as musculoskeletal/spinal abnormalities or risk of abnormal bleeding.
• The patient has a history of complications from previous lumbar punctures or technical challenges in conducting lumbar punctures such that the potential risks would exceed possible benefits for the patient.
• The patient has an opening CSF pressure upon lumbar puncture that exceeds 30.0 cm H2O.
• The patient has experienced infusion-related anaphylactoid event(s) or has evidence of consistent severe adverse events related to treatment with Elaprase which, in the Investigator's opinion, may pose an unnecessary risk to the patient.
• The patient has received a cord blood or bone marrow transplant at any time or has received blood product transfusions within 90 days prior to Screening.
• The patient has a history of poorly controlled seizure disorder.
• The patient is unable to comply with the protocol (eg, has significant hearing or vision impairment, a clinically relevant medical condition making implementation of the protocol difficult, unstable social situation, known clinically significant psychiatric/behavioral instability, is unable to return for safety evaluations, or is otherwise unlikely to complete the study), as determined by the Investigator.
• The patient is enrolled in another clinical study that involves clinical investigation 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 patient 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 patient has a condition that is contraindicated as described in the SOPH-A-PORT Mini S IDDD Instructions for Use (IFU), including but not limited to the presence of a CSF shunt device in the patient.

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, 27599, United States

Location

Women's and Children's Hospital, 72 King William Road

North Adelaide, 5006, Australia

Location

The Hospital for Sick Children

Toronto, Ontario, M5G 1X8, Canada

Location

Hôpital Femme Mère Enfant

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 (3)

• 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; HGT-HIT-094 Study Group. Intrathecal idursulfase-IT in patients with neuronopathic mucopolysaccharidosis II: Results from a phase 2/3 randomized study. Mol Genet Metab. 2022 Sep-Oct;137(1-2):127-139. doi: 10.1016/j.ymgme.2022.07.017. Epub 2022 Aug 2.

  PMID: 36027721 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

MeSH Terms

Conditions

Mucopolysaccharidosis II; Sudden Infant Death; Lysosomal Storage Diseases

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; Mucinoses; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases; Death, Sudden; Death; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Infant Death

Results Point of Contact

• Title: Study Director
• Organization: Shire

ClinicalTransparency@shire.com

+1 866 842 5335

Study Officials

• Study Director

  Takeda

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

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

Study Record Dates

• First Submitted: January 17, 2014
• First Posted: February 4, 2014
• Study Start: March 24, 2014
• Primary Completion: September 28, 2017
• Study Completion: September 28, 2017
• Last Updated: June 11, 2021
• Results First Posted: December 13, 2018

Record last verified: 2021-05

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

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