<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03292887</url>
  </required_header>
  <id_info>
    <org_study_id>HOS</org_study_id>
    <nct_id>NCT03292887</nct_id>
  </id_info>
  <brief_title>Hunter Outcome Survey (HOS)</brief_title>
  <acronym>HOS</acronym>
  <official_title>Hunter Outcome Survey: A Global, Multi-Center, Long-Term, Observational Registry of Patients With Hunter Syndrome (Mucopolysaccharidosis Type II, MPS II)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Shire</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Takeda</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to collect data that will increase understanding of Hunter&#xD;
      syndrome. The data from HOS may provide guidance to healthcare professionals about disease&#xD;
      treatment options.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">August 1, 2005</start_date>
  <completion_date type="Actual">February 16, 2023</completion_date>
  <primary_completion_date type="Actual">February 16, 2023</primary_completion_date>
  <study_type>Observational [Patient Registry]</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Other</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <target_duration>20 Years</target_duration>
  <primary_outcome>
    <measure>Number of Participants With Infusion-related Reactions (IRRs)</measure>
    <time_frame>Baseline to year 17</time_frame>
    <description>An Infusion-related reaction (IRR) is an adverse event (AE) that occurs during or within 24 hours of an infusion and with evidence of a causal relationship with Elaprase.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)</measure>
    <time_frame>Baseline to year 17</time_frame>
    <description>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 the registry, whether or not considered product-related. This includes an exacerbation of a pre-existing condition. An AE or adverse drug reaction (ADR) that meets one or more of the following criteria/outcomes is classified as serious whether considered to be related to the pharmaceutical product or not: death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalizations, a persistent or significant disability or incapacity, a congenital anomaly or birth defect and important medical events.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of Participants With Positive Antibody Response</measure>
    <time_frame>Baseline to year 17</time_frame>
    <description>Immunogenicity is determined by time to first positive antibody response (antibody level and isotype), antibody titer, isotype, and neutralizing antibodies.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in Urinary Glycosaminoglycan (GAG) Levels</measure>
    <time_frame>Baseline to year 17</time_frame>
    <description>Change in urinary GAG levels from the start of ERT is reported.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in Height</measure>
    <time_frame>Baseline to year 17</time_frame>
    <description>Change in height from the start of ERT will be reported.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in Weight</measure>
    <time_frame>Baseline to year 17</time_frame>
    <description>Change in weight from the start of ERT will be reported.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in Head Circumference and Corresponding Calculated Z-scores</measure>
    <time_frame>Baseline to year 17</time_frame>
    <description>Change in head circumference with the corresponding Z-scores from the start of ERT will be reported.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in Distance Walked in the 6-minute Walk Test</measure>
    <time_frame>Baseline to year 17</time_frame>
    <description>Change in distance walked in 6-minute walk test from the start of ERT is reported.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Left Ventricular Mass Index (LVMI)</measure>
    <time_frame>Baseline to year 17</time_frame>
    <description>Change in LVMI will be assessed as calculated by echocardiography.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in Forced Expiratory Volume in 1 Second (FEV1)</measure>
    <time_frame>Baseline to year 17</time_frame>
    <description>Change in pulmonary function from the start of ERT will be reported as measured by forced expiratory volume in 1 second (FEV1).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in Forced Vital Capacity (FVC)</measure>
    <time_frame>Baseline to year 17</time_frame>
    <description>Change in pulmonary function from the start of ERT will be reported as measured by forced vital capacity (FVC).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in Liver and Spleen Size</measure>
    <time_frame>Baseline to year 17</time_frame>
    <description>Change in liver and spleen size as estimated by palpation will be reported.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Prevalence of Cardiac and Pulmonary-related Hospitalizations</measure>
    <time_frame>Baseline to year 17</time_frame>
    <description>Prevalence of cardiac and pulmonary-related hospitalizations will be reported.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Age at the Time of Death</measure>
    <time_frame>Baseline to year 17</time_frame>
    <description>Age at the time of death will be reported.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Cause of Death</measure>
    <time_frame>Baseline to year 17</time_frame>
    <description>Causes of death will be reported</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Natural History of Untreated Participants With Hunter Syndrome</measure>
    <time_frame>Baseline to year 17</time_frame>
    <description>Evaluation of signs and symptoms for the natural history of disease: hepatosplenomegaly, central nervous system involvement, skeletal involvement, ear, nose, and throat signs and symptoms, pulmonary signs and symptoms and cardiac signs and symptoms will be reported.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Dosing Regimens of Elaprase for Prescribed Dose in Participants With Hunter Syndrome</measure>
    <time_frame>Baseline to year 17</time_frame>
    <description>Dosing regiments of Elaprase will be evaluated for prescribed dose.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Dosing Regimens of Elaprase for Administered Dose in Participants With Hunter Syndrome</measure>
    <time_frame>Baseline to year 17</time_frame>
    <description>Dosing regiments of Elaprase will be evaluated for administered dose.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Dosing Regimens of Elaprase for Total Infusion Time in Participants With Hunter Syndrome</measure>
    <time_frame>Baseline to year 17</time_frame>
    <description>Dosing regiments of Elaprase will be evaluated for total infusion time.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Dosing Regimens of Elaprase for Missed Infusions in Participants With Hunter Syndrome</measure>
    <time_frame>Baseline to year 17</time_frame>
    <description>Dosing regiments of Elaprase will be evaluated for missed infusions.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Dosing Regimens of Elaprase for Reason for Missed Infusions.</measure>
    <time_frame>Baseline to year 17</time_frame>
    <description>Dosing regiments of Elaprase will be evaluated for reason for missed infusions.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Assessment of Hunter Syndrome on Health-related Quality of Life (HRQL) Using Hunter Syndrome-Functional Outcomes for Clinical Understanding Scale (HS-FOCUS)</measure>
    <time_frame>Baseline to year 17</time_frame>
    <description>HS-FOCUS was developed as disease-specific measure of the impact of Hunter syndrome on HRQL. The HS-FOCUS is designed to gather information on the participant's daily life and wellbeing, satisfaction with treatment, and hospitalizations, as well as on how Hunter syndrome impacts participant's general quality of life. HS-FOCUS includes 2 validated components: a parent version and a patient self-reported version for those over age 12 years. The HS-FOCUS Version 2.0 contains 6 functional status domains: Walking/Standing, Reach/Grip, Sleeping, Schooling/Work, Activities, and Breathing. Items are scored using a response scale from 0 to 4, with =&quot;0&quot; expressing being able to complete the activity-related functions &quot;without any difficulty&quot; and &quot;4&quot; as &quot;unable to do so. Scores are averaged to calculate the 6 function domain scores and the Overall Function Score, with higher scores corresponding to a higher degree of incapacity.</description>
  </secondary_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Actual">2000</enrollment>
  <condition>Hunter Syndrome</condition>
  <arm_group>
    <arm_group_label>Elaprase Treated</arm_group_label>
    <description>Participants with Hunters Syndrome received or receiving treatment with Elaprase as prescribed by their physician following locally approved prescribing information.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Elaprase Non-Treated</arm_group_label>
    <description>Participants received no treatment for Hunters Syndrome.</description>
  </arm_group>
  <eligibility>
    <study_pop>
      <textblock>
        The HOS registry is open to all participants (both alive and deceased) with Hunter syndrome&#xD;
        who are untreated or who are receiving/received treatment with Elaprase, including&#xD;
        participants who are alive at HOS enrollment (referred to as &quot;Prospective Patients&quot;) and&#xD;
        participants who are deceased at HOS enrollment (referred to as &quot;Historical Patients&quot;).&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Diagnosis of Hunter syndrome (biochemically and/or genetically)&#xD;
&#xD;
          2. Signed and dated written informed consent, as per either a or b below:&#xD;
&#xD;
               1. Prospective Participants: Signed and dated written informed consent from the&#xD;
                  participant or, for participants aged less than (&lt;) 18 years (&lt;16 years in&#xD;
                  Scotland), parent and/or participant's legally authorized representative (LAR),&#xD;
                  and assent of the minor where applicable.&#xD;
&#xD;
                  informed consent must be obtained from LARs for cognitively impaired&#xD;
                  participants, where applicable.&#xD;
&#xD;
                  OR&#xD;
&#xD;
               2. Historical Participants: Signed and dated informed consent from the participant's&#xD;
                  LAR (where allowed by relevant individual country or site regulations/laws). .&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Participants enrolled in an interventional clinical trial are not eligible.&#xD;
             Participants may re-enroll once they have completed or withdrawn from the other&#xD;
             clinical study.&#xD;
&#xD;
          2. Participants receiving treatment for Hunter syndrome with an ERT product other than&#xD;
             Elaprase are not eligible. Participants may enroll or re-enroll once they have stopped&#xD;
             treatment with another ERT.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Study Director</last_name>
    <role>Study Director</role>
    <affiliation>Shire</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Shire</name>
      <address>
        <city>Lexington</city>
        <state>Massachusetts</state>
        <zip>02421</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>https://clinicaltrials.takeda.com/study-detail/5f6b5fcf4db2bf003ab46821</url>
    <description>To obtain more information on the study, click here/on this link</description>
  </link>
  <verification_date>February 2023</verification_date>
  <study_first_submitted>September 18, 2017</study_first_submitted>
  <study_first_submitted_qc>September 20, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 26, 2017</study_first_posted>
  <last_update_submitted>February 27, 2023</last_update_submitted>
  <last_update_submitted_qc>February 27, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">February 28, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Mucopolysaccharidosis II</keyword>
  <keyword>Hunter Syndrome</keyword>
  <keyword>Enzyme Replacement Therapy</keyword>
  <keyword>Lysosomal</keyword>
  <keyword>Glycosaminoglycans</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Mucopolysaccharidosis II</mesh_term>
    <mesh_term>Mucopolysaccharidoses</mesh_term>
    <mesh_term>Syndrome</mesh_term>
  </condition_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03292887
org study id: HOS
nct id: NCT03292887
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The purpose of this study is to collect data that will increase understanding of Hunter
      syndrome. The data from HOS may provide guidance to healthcare professionals about disease
      treatment options.
observational model: Other
time perspective: Prospective
measure: Number of Participants With Infusion-related Reactions (IRRs)
time frame: Baseline to year 17
description: An Infusion-related reaction (IRR) is an adverse event (AE) that occurs during or within 24 hours of an infusion and with evidence of a causal relationship with Elaprase.
measure: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
time frame: Baseline to year 17
description: 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 the registry, whether or not considered product-related. This includes an exacerbation of a pre-existing condition. An AE or adverse drug reaction (ADR) that meets one or more of the following criteria/outcomes is classified as serious whether considered to be related to the pharmaceutical product or not: death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalizations, a persistent or significant disability or incapacity, a congenital anomaly or birth defect and important medical events.
measure: Number of Participants With Positive Antibody Response
time frame: Baseline to year 17
description: Immunogenicity is determined by time to first positive antibody response (antibody level and isotype), antibody titer, isotype, and neutralizing antibodies.
measure: Change in Urinary Glycosaminoglycan (GAG) Levels
time frame: Baseline to year 17
description: Change in urinary GAG levels from the start of ERT is reported.
measure: Change in Height
time frame: Baseline to year 17
description: Change in height from the start of ERT will be reported.
measure: Change in Weight
time frame: Baseline to year 17
description: Change in weight from the start of ERT will be reported.
measure: Change in Head Circumference and Corresponding Calculated Z-scores
time frame: Baseline to year 17
description: Change in head circumference with the corresponding Z-scores from the start of ERT will be reported.
measure: Change in Distance Walked in the 6-minute Walk Test
time frame: Baseline to year 17
description: Change in distance walked in 6-minute walk test from the start of ERT is reported.
measure: Left Ventricular Mass Index (LVMI)
time frame: Baseline to year 17
description: Change in LVMI will be assessed as calculated by echocardiography.
measure: Change in Forced Expiratory Volume in 1 Second (FEV1)
time frame: Baseline to year 17
description: Change in pulmonary function from the start of ERT will be reported as measured by forced expiratory volume in 1 second (FEV1).
measure: Change in Forced Vital Capacity (FVC)
time frame: Baseline to year 17
description: Change in pulmonary function from the start of ERT will be reported as measured by forced vital capacity (FVC).
measure: Change in Liver and Spleen Size
time frame: Baseline to year 17
description: Change in liver and spleen size as estimated by palpation will be reported.
measure: Prevalence of Cardiac and Pulmonary-related Hospitalizations
time frame: Baseline to year 17
description: Prevalence of cardiac and pulmonary-related hospitalizations will be reported.
measure: Age at the Time of Death
time frame: Baseline to year 17
description: Age at the time of death will be reported.
measure: Cause of Death
time frame: Baseline to year 17
description: Causes of death will be reported
measure: Natural History of Untreated Participants With Hunter Syndrome
time frame: Baseline to year 17
description: Evaluation of signs and symptoms for the natural history of disease: hepatosplenomegaly, central nervous system involvement, skeletal involvement, ear, nose, and throat signs and symptoms, pulmonary signs and symptoms and cardiac signs and symptoms will be reported.
measure: Dosing Regimens of Elaprase for Prescribed Dose in Participants With Hunter Syndrome
time frame: Baseline to year 17
description: Dosing regiments of Elaprase will be evaluated for prescribed dose.
measure: Dosing Regimens of Elaprase for Administered Dose in Participants With Hunter Syndrome
time frame: Baseline to year 17
description: Dosing regiments of Elaprase will be evaluated for administered dose.
measure: Dosing Regimens of Elaprase for Total Infusion Time in Participants With Hunter Syndrome
time frame: Baseline to year 17
description: Dosing regiments of Elaprase will be evaluated for total infusion time.
measure: Dosing Regimens of Elaprase for Missed Infusions in Participants With Hunter Syndrome
time frame: Baseline to year 17
description: Dosing regiments of Elaprase will be evaluated for missed infusions.
measure: Dosing Regimens of Elaprase for Reason for Missed Infusions.
time frame: Baseline to year 17
description: Dosing regiments of Elaprase will be evaluated for reason for missed infusions.
measure: Assessment of Hunter Syndrome on Health-related Quality of Life (HRQL) Using Hunter Syndrome-Functional Outcomes for Clinical Understanding Scale (HS-FOCUS)
time frame: Baseline to year 17
description: HS-FOCUS was developed as disease-specific measure of the impact of Hunter syndrome on HRQL. The HS-FOCUS is designed to gather information on the participant's daily life and wellbeing, satisfaction with treatment, and hospitalizations, as well as on how Hunter syndrome impacts participant's general quality of life. HS-FOCUS includes 2 validated components: a parent version and a patient self-reported version for those over age 12 years. The HS-FOCUS Version 2.0 contains 6 functional status domains: Walking/Standing, Reach/Grip, Sleeping, Schooling/Work, Activities, and Breathing. Items are scored using a response scale from 0 to 4, with ="0" expressing being able to complete the activity-related functions "without any difficulty" and "4" as "unable to do so. Scores are averaged to calculate the 6 function domain scores and the Overall Function Score, with higher scores corresponding to a higher degree of incapacity.
arm group label: Elaprase Treated
description: Participants with Hunters Syndrome received or receiving treatment with Elaprase as prescribed by their physician following locally approved prescribing information.
arm group label: Elaprase Non-Treated
description: Participants received no treatment for Hunters Syndrome.
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: N/A
maximum age: N/A
healthy volunteers: No
last name: Study Director
role: Study Director
affiliation: Shire
facility: 
country: United States
url: https://clinicaltrials.takeda.com/study-detail/5f6b5fcf4db2bf003ab46821
description: To obtain more information on the study, click here/on this link
responsible party type: Sponsor
mesh term: Mucopolysaccharidosis II
mesh term: Mucopolysaccharidoses
mesh term: Syndrome