Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register   allows you to search for protocol and results information on:
  • interventional clinical trials that were approved in the European Union (EU)/European Economic Area (EEA) under the Clinical Trials Directive 2001/20/EC
  • clinical trials conducted outside the EU/EEA that are linked to European paediatric-medicine development

  • EU/EEA interventional clinical trials approved under or transitioned to the Clinical Trial Regulation 536/2014 are publicly accessible through the
    Clinical Trials Information System (CTIS).

    The EU Clinical Trials Register currently displays   43977   clinical trials with a EudraCT protocol, of which   7312   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

    Phase 1 trials conducted solely on adults and that are not part of an agreed paediatric investigation plan (PIP) are not publicly available (see Frequently Asked Questions ).  
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools

    < Back to search results

    Print Download

    EudraCT Number:2010-020048-36
    Sponsor's Protocol Code Number:HGT-HIT-045
    National Competent Authority:UK - MHRA
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2010-06-17
    Trial results View results
    Expand All   Collapse All
    A. Protocol Information
    A.1Member State ConcernedUK - MHRA
    A.2EudraCT number2010-020048-36
    A.3Full title of the trial
    A Phase I/II, Randomized, Safety and Ascending Dose Ranging Study of Intrathecal Idursulfase-IT administered in conjunction with intravenous Elaprase in Pediatric Patients with Hunter Syndrome and Cognitive Impairment
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A safety, tolerability and preliminary efficacy study of idursulfase-IT in patients with Hunter syndrome associated with learning disability
    A.4.1Sponsor's protocol code numberHGT-HIT-045
    A.7Trial is part of a Paediatric Investigation Plan No
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorShire HGT, Inc
    B.1.3.4CountryUnited States
    B.3.1 and B.3.2Status of the sponsorCommercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportShire Human Genetic Therapies
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationShire Human Genetic Therapies
    B.5.2Functional name of contact pointClinical Project Manager
    B.5.3 Address:
    B.5.3.1Street Address300 Shire Way
    B.5.3.2Town/ cityLexington
    B.5.3.3Post codeMA02421
    B.5.3.4CountryUnited States
    B.5.4Telephone number001 782482 0822
    B.5.5Fax number001782482 2954
    D. IMP Identification
    D.IMP: 1
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation No
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community Yes
    D.2.5.1Orphan drug designation numberEU/3/01/078
    D.3 Description of the IMP
    D.3.1Product nameIdursulfase (I2S)-IT
    D.3.2Product code I2S-IT
    D.3.4Pharmaceutical form Solution for injection
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntrathecal use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNNA
    D.3.9.1CAS number NA
    D.3.9.2Current sponsor codeI2S-IT
    D.3.9.3Other descriptive nameIdursulfase-IT
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number50
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin No
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) Yes
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D. cell therapy medicinal product No
    D. therapy medical product No
    D. Engineered Product No
    D. ATIMP (i.e. one involving a medical device) No
    D. on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy Yes
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product Yes
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product Yes
    D. medicinal product typeIdursulfase-IT, human enzyme produced from genetically engineered human cell line
    D.8 Information on Placebo
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Treatment of Hunter syndrome and cognitive impairment
    E.1.1.1Medical condition in easily understood language
    Hunter Syndrome - Iduronate-2-Sulfatase enzyme defficiency
    E.1.1.2Therapeutic area Body processes [G] - Genetic Phenomena [G05]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 14.1
    E.1.2Level PT
    E.1.2Classification code 10056889
    E.1.2Term Mucopolysaccharidosis II
    E.1.2System Organ Class 10010331 - Congenital, familial and genetic disorders
    E.1.3Condition being studied is a rare disease Yes
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To determine the safety and tolerability of ascending doses of idursulfase-IT administered via a surgically implanted intrathecal drug delivery device (IDDD) once monthly for 6 months in pediatric patients with Hunter syndrome who have cognitive impairment and who have previously received and tolerated a minimum of 6 months of treatment with Elaprase® (idursulfase for intravenous administration)
    E.2.2Secondary objectives of the trial
    The secondary objectives of this study are:

    a) To determine the concentration of idursulfase in cerebrospinal fluid (CSF) and blood after single and repeated doses of intrathecal idursulfase-IT given in conjunction with Elaprase

    b) To determine the effect of intrathecal idursulfase-IT, given in conjunction with Elaprase, on CSF biomarkers (eg, glycosaminoglycans (GAG) and GAG degradation products, sulfated HS/DS oligosaccharides, and markers of lysosomal function)

    c) To determine the effects of intrathecal idursulfase-IT, given in conjunction with Elaprase, on urinary GAG and GAG degradation products
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    Patients must meet all of the following criteria to be considered eligible for enrollment:

    1a) The patient has a deficiency in iduronate-2-sulfatase enzyme activity of ≤10% of the lower limit of the normal range as measured in plasma, fibroblasts, or leukocytes (based on normal range of measuring laboratory)


    1b) The patient has a documented mutation in the iduronate-2-sulfatase gene


    The patient has a normal enzyme activity level of one other sulfatase as measured in plasma, fibroblasts, or leukocytes (based on normal range of measuring laboratory)

    2) The patient is male and is ≥3 and <18 years of age

    3) The patient has evidence at Screening of Hunter syndrome-related cognitive impairment, defined as

    a) The patient has an IQ ≤77


    b) There is evidence of a change of ≥1 (15 IQ points) but ≤2 (30 IQ points) standard deviations decline from a previous protocol-defined neurodevelopmental assessment. The duration of protocol-defined neurologic involvement is at least 3 months but less than 36 months as documented in the patient’s medical history.

    4) The patient has received and tolerated a minimum of 6 months of treatment with weekly intravenous idursulfase, and has received 80% of the total planned infusions within that time frame, including having received 100% of the planned infusions within 4 weeks immediately preceding the surgical implantation of the IDDD.

    5) The patient must have sufficient auditory capacity, with or without hearing aids, to complete the required protocol testing, and be compliant with wearing the aid on scheduled testing days.

    6) The patient, 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 with the patient. The guardians’ consent and patient’s assent, as relevant, must be obtained.
    E.4Principal exclusion criteria
    Patients who meet any of the following criteria are not eligible for this study:

    1) The patient has clinically significant non-Hunter syndrome-related CNS involvement which is judged by the Investigator to be likely to interfere with the accurate administration and interpretation of protocol assessments.

    2) The patient’s IQ is ≥ 78

    3) The patient has a CNS shunt.

    4) 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.

    5) 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.

    6) 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.

    7) The patient or patient’s family has a history of neuroleptic malignant syndrome, malignant hyperthermia, or other anesthesia-related concerns.

    8) The patient has a history of poorly controlled seizure disorder.

    9) The patient has a significant medical or psychiatric comorbidity(ies) that might affect study data or confound the integrity of study results.

    10) The patient is currently receiving chronic psychotropic therapy (eg, neuroleptics, benzodiazepines, antidepressants, anticonvulsants, stimulants) which in the Investigator’s opinion would likely affect the neurocognitive assessments. Intermittent use of selected short half-life agents (benzodiazepine, sedatives, etc) may be permitted as long as there are 5 half-lives between last drug administered and study-related procedures including neurocognitive assessments.

    11) The patient has received treatment with any investigational drug or device within the 30 days prior to study entry.

    12) 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.

    13) 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.

    14) The patient has skeletomuscular/spinal abnormalities or other contraindications for the surgical implantation of the IDDD.

    15) The patient has an opening CSF pressure upon lumbar puncture that exceeds 30.0 cm H2O.
    E.5 End points
    E.5.1Primary end point(s)
    Safety of intrathecal idursulfase-IT administration, by dose group and treatment status.

    Safety will be assessed by adverse events (by type and severity), changes in clinical laboratory testing (serum chemistry including liver function tests, hematology, urinalysis), 12-lead electrocardiograms, CSF chemistries (including cell counts, protein, and glucose), and anti-idursulfase antibodies (in CSF and serum, by isotype: IgG, IgA, IgM, IgE, and antibodies having enzyme neutralizing activity).
    E.5.1.1Timepoint(s) of evaluation of this end point
    Screening Day -60 to Day 0 and Weeks 3, 7,11, 15, 19,
    23, 27 and 30
    E.5.2Secondary end point(s)
    • Single and repeated dose pharmacokinetic parameters of idursulfase, administered as intrathecal idursulfase-IT, given in conjunction with Elaprase, in CSF and blood
    • Change from baseline in CSF biomarkers (eg, GAGs, GAG-degradation products, sulfated HS/DS oligosaccharides) by dose group and in comparison with untreated patients
    • Change from baseline in urinary GAGs and degradation products by dose group and in comparison with untreated patients.
    E.5.2.1Timepoint(s) of evaluation of this end point
    PK Sampling in blood - several timepoints up to 24hrs after I2S IT and after Elaprase i.v.
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis No
    E.6.3Therapy Yes
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic Yes
    E.6.7Pharmacodynamic No
    E.6.8Bioequivalence No
    E.6.9Dose response Yes
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) Yes
    E.7.1.1First administration to humans Yes
    E.7.1.2Bioequivalence study No
    E.7.1.3Other Yes
    E. trial type description
    E.7.2Therapeutic exploratory (Phase II) Yes
    E.7.3Therapeutic confirmatory (Phase III) No
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled Yes
    E.8.1.1Randomised Yes
    E.8.1.2Open Yes
    E.8.1.3Single blind No
    E.8.1.4Double blind No
    E.8.1.5Parallel group No
    E.8.1.6Cross over No
    E.8.1.7Other No
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) No
    E.8.2.2Placebo No
    E.8.2.3Other Yes
    E. description
    Patients previously received and continue to recieve Elaprase
    E.8.2.4Number of treatment arms in the trial4
    E.8.3 The trial involves single site in the Member State concerned Yes
    E.8.4 The trial involves multiple sites in the Member State concerned No
    E.8.4.1Number of sites anticipated in Member State concerned1
    E.8.5The trial involves multiple Member States No
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA Yes
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    United Kingdom
    United States
    E.8.7Trial has a data monitoring committee Yes
    E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial
    Last patient visit
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years2
    E.8.9.1In the Member State concerned months6
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years2
    E.8.9.2In all countries concerned by the trial months6
    E.8.9.2In all countries concerned by the trial days0
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 Yes
    F.1.1Number of subjects for this age range: 20
    F.1.1.1In Utero No
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.3Newborns (0-27 days) No
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.5Children (2-11years) Yes
    F. of subjects for this age range: 10
    F.1.1.6Adolescents (12-17 years) Yes
    F. of subjects for this age range: 10
    F.1.2Adults (18-64 years) No
    F.1.3Elderly (>=65 years) No
    F.2 Gender
    F.2.1Female No
    F.2.2Male Yes
    F.3 Group of trial subjects
    F.3.1Healthy volunteers No
    F.3.2Patients Yes
    F.3.3Specific vulnerable populations Yes
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception Yes
    F.3.3.3Pregnant women Yes
    F.3.3.4Nursing women No
    F.3.3.5Emergency situation No
    F.3.3.6Subjects incapable of giving consent personally No
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state10
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 10
    F.4.2.2In the whole clinical trial 20
    F.5 Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)
    Patients are eligible to participate in an extension study
    G. Investigator Networks to be involved in the Trial
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2010-07-30
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2011-01-31
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2012-10-29
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

    European Medicines Agency © 1995-2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands