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

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by Shire
Sponsor:
Information provided by (Responsible Party):
Shire
ClinicalTrials.gov Identifier:
NCT02055118
First received: January 17, 2014
Last updated: July 10, 2014
Last verified: July 2014
  Purpose

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.


Condition Intervention Phase
Hunter Syndrome
Biological: idursulfase-IT
Other: No IT treatment
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Controlled, Randomized, Two-arm, Open-label, Assessor-blinded, Multicenter Study of Intrathecal Idursulfase-IT Administered in Conjunction With Elaprase® in Pediatric Patients With Hunter Syndrome and Early Cognitive Impairment

Resource links provided by NLM:


Further study details as provided by Shire:

Primary Outcome Measures:
  • Change from baseline in the GCA score after 12 months of treatment at visit week 52, as obtained by DAS-II testing [ Time Frame: Baseline to week 52 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Change from baseline in the adaptive behavior composite (ABC) score after 12 months of treatment at visit week 52, as obtained by VABS-II testing [ Time Frame: Baseline to week 52 ] [ Designated as safety issue: No ]
  • Change from baseline in the GCA score at visit weeks 16, 28 and 40 as obtained by DAS-II testing [ Time Frame: Baseline to week 40 ] [ Designated as safety issue: No ]
  • Change from baseline in the ABC score at visit weeks 16, 28 and 40 as obtained by VABS-II testing [ Time Frame: Baseline to week 40 ] [ Designated as safety issue: No ]
  • Change from baseline in standard scores at visit weeks 16, 28, 40 and 52 in cluster areas of the DAS-II [ Time Frame: Baseline to week 52 ] [ Designated as safety issue: No ]
  • Change from baseline in standard scores at visit weeks 16, 28, 40 and 52 of VABS-II domains [ Time Frame: Baseline to week 52 ] [ Designated as safety issue: No ]
  • Change from baseline in age equivalents at visit weeks 16, 28, 40 and 52 developmental quotients, and T-scores for the subtests of the DAS-II [ Time Frame: Baseline to week 52 ] [ Designated as safety issue: No ]
  • Change from baseline to visit weeks 16, 28, 40 and 52 in age equivalents, developmental quotients, and V-scale scores of the VABS-II subdomains [ Time Frame: Baseline to week 52 ] [ Designated as safety issue: No ]
  • Change from baseline to visit weeks 16, 28, 40 and 52 in the V-scale scores and observed maladaptive levels of the VABS-II Maladaptive Behavior Index and its subscales [ Time Frame: Baseline to week 52 ] [ Designated as safety issue: No ]

Estimated Enrollment: 42
Study Start Date: February 2014
Estimated Study Completion Date: March 2016
Estimated Primary Completion Date: February 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: idursulfase-IT
10 mg administered via IT using IDDD (intrathecal drug delivery device) once a month for 52 weeks. In the USA, up to 9 patients may be enrolled until the IDDD becomes available for use in USA. These patients if randomized to treatment will receive 10 mg investigational idursulfase via IT using LP (Lumbar Puncture) once a month until the IDDD becomes available for use in the USA.
Biological: idursulfase-IT
Other Name: HGT-2310
Nontreatment control
Patients will receive weekly standard of care treatment with IV Elaprase only.
Other: No IT treatment

Detailed Description:

Elaprase, a large molecular protein, is not expected to cross the blood brain barrier when administered intravenously. A revised formulation of idursulfase, idursulfase-IT, that differs from that of the intravenous (IV) formulation, Elaprase, has been developed to be suitable for delivery into the cerebrospinal fluid (CSF) via intrathecal administration.

Mucopolysaccharidosis II (MPS II) is a rare, X-linked, inherited disease that affects males nearly exclusively. The disease is caused by the absence of, or deficiency in, the activity of the lysosomal enzyme, iduronate-2-sulfatase (I2S) which acts to cleave O-linked sulfate moieties from the glycosaminoglycan (GAG) molecules dermatan sulfate and heparan sulfate.

Study HGT-HIT-094 is a controlled, randomized, two-arm, open-label, assessor-blinded, multicenter study 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.

Pediatric patients under 3 years of age will be enrolled into a separate substudy to evaluate the safety and efficacy of idursulfase-IT. The separate substudy is open label and single arm. Patients who are enrolled in the substudy will receive idursulfase-IT treatment and follow the same schedule of study visits.

  Eligibility

Ages Eligible for Study:   up to 18 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria Inclusion Criteria for the Pivotal Study

Patients must meet all of the following criteria to be considered eligible for randomization in the pivotal study:

  1. The patient is male and is ≥3 and <18 years of age at the time of informed consent. Spanish-speaking patients who are to be assessed using the Spanish version of the DAS-II Early Years must be <7 years 8 months of age at the time of informed consent.

    (Patients who are younger than 3 years of age may be enrolled in a separate substudy provided that they meet other inclusion criteria, provided below.)

  2. The patient must have a documented diagnosis of MPS II.
  3. 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):

    1. A GCA score ≥55 and ≤85 OR
    2. 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):

    3. A GCA score of ≥55 and ≤85. AND
    4. There must be evidence of a decrease in GCA score of ≥10 points over 12 months from a previously documented
  4. The patient has received and tolerated a minimum of 4 months of therapy with Elaprase during the period immediately prior to Screening.
  5. 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.
  6. 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.

Inclusion Criteria for the Substudy

Patients must meet all of the following criteria to be considered eligible for enrollment in the separate substudy:

  1. The patient is male and is <3 years of age at the time of informed consent.
  2. The patient must have a documented diagnosis of MPS II.
  3. The patient has evidence at Screening of Hunter syndrome-related cognitive impairment
  4. The patient has received and tolerated a minimum of 4 months of therapy with Elaprase during the period immediately prior to Screening.
  5. 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.
  6. 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) must be obtained prior to the start of any study procedures.

Exclusion Criteria

Patients who meet any of the following criteria are not eligible to be randomized into the pivotal study or enrolled in the separate substudy:

  1. 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.
  2. The patient has a large chromosomal deletion or complex rearrangement that includes a deletion of the FMR1 and/or FMR2 genes.
  3. The patient has a significant medical or psychiatric comorbidity(ies) that might affect study data or confound the integrity of study results.
  4. The patient has contra-indications for performance of lumbar puncture such as musculoskeletal/spinal abnormalities or risk of abnormal bleeding.
  5. 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.
  6. The patient has an opening CSF pressure upon lumbar puncture that exceeds 30.0 cm H2O.
  7. 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.
  8. 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.
  9. The patient has a history of poorly controlled seizure disorder.
  10. 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.
  11. 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.
  12. 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.
  13. 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02055118

Contacts
Contact: MedInfo Shire HGT +1-866-888-0660 US_ShireHGT_Medicalinformation@shire.com

Locations
United States, California
Children's Hospital and Research Center at Oakland Recruiting
Oakland, California, United States, 94609
Contact: Jacqueline Madden, PNP    510-428-3885 ext 5745    jmadden@mail.cho.org   
Principal Investigator: Paul Harmatz         
United States, Illinois
Ann & Robert H Lurie Childrens Hospital of Recruiting
Chicago, Illinois, United States, 60611
Contact: Rachel Katz    312-227-6764    rkatz@luriechildrens.org   
Principal Investigator: Barbara Burton         
United States, North Carolina
University of North Carolina Recruiting
Chapel Hill, North Carolina, United States, 27599
Contact: Heather Preiss    919-843-5731    hpreiss@med.unc.edu   
Principal Investigator: Joseph Muenzer         
Argentina
Hospital Universitario Austral Not yet recruiting
Pilar, Buenos Aires, Argentina, B1629AHJ
Contact: María Julia Cremona    +542304482831    mcremona@cas.austral.edu.ar   
Principal Investigator: Hernán Amartino         
Mexico
Instituto Nacional de Pediatría Not yet recruiting
Coyoacan, Ciudad De México, Mexico, 04530
Contact: Fernando E Ayala Valenzuela    (525) 510-8409 ext x00    dr.fdo.ayala@gmail.com   
Principal Investigator: Matilde Ruiz García         
Spain
Hospital Infantil Universitario Niño Jesus Recruiting
Madrid, Spain, 28009
Contact: Laura Lopez Marin    +34-650-495-878    laural.marin@hotmail.com   
Principal Investigator: Luis González Gutiérrez-Solana         
United Kingdom
Royal Manchester Children's Hospital Recruiting
Manchester, United Kingdom, M13 9WL
Contact: Michaela Turrington    +4401617018313    michaela.turrington@wtcrf.nhs.uk   
Contact: Kathryn Kennedy    +4401612765165    kathryn.kennedy@wtcrf.nhs.uk   
Principal Investigator: Simon Jones         
Sponsors and Collaborators
Shire
Investigators
Study Director: Ann Barbier, MD, PhD Shire
  More Information

No publications provided

Responsible Party: Shire
ClinicalTrials.gov Identifier: NCT02055118     History of Changes
Other Study ID Numbers: HGT-HIT-094, 2013-002885-38
Study First Received: January 17, 2014
Last Updated: July 10, 2014
Health Authority: United States: Food and Drug Administration
Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica
Mexico: Ministry of Health
Spain: Agencia Española de Medicamentos y Productos Sanitarios
United Kingdom: Medicines and Healthcare Products Regulatory Agency

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

Additional relevant MeSH terms:
Mental Retardation, X-Linked
Syndrome
Cognition Disorders
Mucopolysaccharidosis II
Disease
Pathologic Processes
Delirium, Dementia, Amnestic, Cognitive Disorders
Mental Disorders
Intellectual Disability
Neurobehavioral Manifestations
Neurologic Manifestations
Nervous System Diseases
Genetic Diseases, X-Linked
Genetic Diseases, Inborn
Heredodegenerative Disorders, Nervous System
Mucopolysaccharidoses
Carbohydrate Metabolism, Inborn Errors
Metabolism, Inborn Errors
Lysosomal Storage Diseases
Mucinoses
Connective Tissue Diseases
Metabolic Diseases

ClinicalTrials.gov processed this record on September 18, 2014