<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/NCT02262338</url>
  </required_header>
  <id_info>
    <org_study_id>AGT-182-101</org_study_id>
    <nct_id>NCT02262338</nct_id>
  </id_info>
  <brief_title>Safety and Dose Ranging Study of Insulin Receptor MoAb-IDS Fusion Protein in Patients With Hunter Syndrome</brief_title>
  <official_title>A Phase 1 Safety and Dose-Finding Study of a Human Insulin Receptor Monoclonal Antibody-Human Iduronate 2-Sulfatase (IDS) Fusion Protein, AGT-182 in Adult Patients With Mucopolysaccharidosis II (MPS II, Hunter Syndrome)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>ArmaGen, Inc</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>ArmaGen, Inc</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      AGT-182 is a fusion protein containing idursulfase that is intended to deliver the enzyme&#xD;
      peripherally and to the brain, when administered intravenously. This study is a safety and&#xD;
      dose ranging study to obtain safety and exposure data, as well as information on the&#xD;
      biological activity of the investigational drug.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a sequential, open-label, dose escalation, multi-dose study in adults with Hunter&#xD;
      syndrome. Two dose levels, assuming tolerability, are planned sequentially, with safety data&#xD;
      from the previous cohort being reviewed prior to escalation to the next higher dose cohort.&#xD;
      Subjects will receive weekly doses of AGT-182 for 8 weeks if ERT-naive or agreeing to a&#xD;
      6-week ERT washout, or for 13 weeks if currently taking ERT and not agreeing to washout.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">April 2015</start_date>
  <completion_date type="Actual">March 27, 2017</completion_date>
  <primary_completion_date type="Actual">March 27, 2017</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
    <masking_description>Open Label</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>number of participants with adverse events as a measure of safety and tolerability</measure>
    <time_frame>8 weeks (ERT-naive) or 13 weeks (ERT)</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>plasma pharmacokinetic parameters (maximal concentration, half-life, area under the curve, mean residence time, volume of distribution and clearance of AGT-182)</measure>
    <time_frame>8 weeks (ERT-naive) or 13 weeks (ERT)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>change in urinary or plasma glycosaminoglycans (GAGs)</measure>
    <time_frame>8 weeks (ERT-naive) or 13 weeks (ERT)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>change in liver or spleen size</measure>
    <time_frame>8 weeks (ERT-naive) or 13 weeks (ERT)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>change in cerebrospinal fluid (CSF) glycosaminoglycans (GAGs)</measure>
    <time_frame>8 weeks (ERT-naive) or 13 weeks (ERT)</time_frame>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">6</enrollment>
  <condition>Mucopolysaccharidosis II</condition>
  <arm_group>
    <arm_group_label>Treated subjects</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>AGT-182 solution for infusion will be administered intravenously at doses of 1.0 mg/kg or 3.0 mg/kg weekly for 8-13 weeks.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>AGT-182</intervention_name>
    <description>Recombinant HIRMAb-IDS</description>
    <arm_group_label>Treated subjects</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Male age 18 years or older&#xD;
&#xD;
          -  Diagnosis of Hunter Syndrome (documented fibroblast or leukocyte IDS enzyme activity&#xD;
             level of less than 10% of the lower limit of the normal range of the measuring&#xD;
             laboratory - or any level of enzyme deficiency together with the presence of a&#xD;
             pathogenic mutation in the IDS gene - and documentation of normal enzymatic activity&#xD;
             of at least 1 other sulfatase.)&#xD;
&#xD;
          -  Must fall into one of the following groups:&#xD;
&#xD;
               -  currently receiving standard enzyme replacement therapy (ERT) and be willing to&#xD;
                  discontinue it for the study duration, taking AGT-182 instead&#xD;
&#xD;
               -  have not received standard ERT for at least 3 months and have elevated uGAGs of&#xD;
                  at least 3.5 fold above age-related normals at study screening&#xD;
&#xD;
               -  have never received ERT&#xD;
&#xD;
          -  Voluntary written consent&#xD;
&#xD;
          -  Sexually mature males must be advised to use a medically accepted method of&#xD;
             contraception throughout the study.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Refusal to complete screening/baseline evaluations&#xD;
&#xD;
          -  Receipt of an investigational drug within the prior 90 days&#xD;
&#xD;
          -  Any medical condition or other circumstances that may significantly interfere with&#xD;
             study compliance&#xD;
&#xD;
          -  Clinically significant spinal cord compression, evidence of cervical instability&#xD;
&#xD;
          -  Known hypersensitivity to idursulfase or any of the components of AGT-182&#xD;
&#xD;
          -  Known to be nonresponsive to standard ERT treatment (i.e., high uGAG values despite&#xD;
             taking full dose standard ERT)&#xD;
&#xD;
          -  History of diabetes mellitus or hypoglycemia&#xD;
&#xD;
          -  Contraindication to lumbar puncture, if the patient agrees to this optional assessment&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Patrice Rioux, MD PhD</last_name>
    <role>Study Director</role>
    <affiliation>ArmaGen, Inc</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Children's Hospital Oakland</name>
      <address>
        <city>Oakland</city>
        <state>California</state>
        <zip>94609</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Children's Hospital of Orange County</name>
      <address>
        <city>Orange</city>
        <state>California</state>
        <zip>92868</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Emory University</name>
      <address>
        <city>Decatur</city>
        <state>Georgia</state>
        <zip>30033</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>ZKJM MC University of Mainz</name>
      <address>
        <city>Mainz</city>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Institute of Human Genetics, National Inst of Health, University of the Philippines</name>
      <address>
        <city>Manila</city>
        <country>Philippines</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Germany</country>
    <country>Philippines</country>
    <country>United States</country>
  </location_countries>
  <removed_countries>
    <country>Netherlands</country>
  </removed_countries>
  <verification_date>September 2018</verification_date>
  <study_first_submitted>October 2, 2014</study_first_submitted>
  <study_first_submitted_qc>October 10, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 13, 2014</study_first_posted>
  <last_update_submitted>September 16, 2018</last_update_submitted>
  <last_update_submitted_qc>September 16, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">September 18, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>MPS II</keyword>
  <keyword>Hunter Syndrome</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>
  </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/NCT02262338
org study id: AGT-182-101
nct id: NCT02262338
lead sponsor: 
has dmc: Yes
AGT-182 is a fusion protein containing idursulfase that is intended to deliver the enzyme
      peripherally and to the brain, when administered intravenously. This study is a safety and
      dose ranging study to obtain safety and exposure data, as well as information on the
      biological activity of the investigational drug.
This is a sequential, open-label, dose escalation, multi-dose study in adults with Hunter
      syndrome. Two dose levels, assuming tolerability, are planned sequentially, with safety data
      from the previous cohort being reviewed prior to escalation to the next higher dose cohort.
      Subjects will receive weekly doses of AGT-182 for 8 weeks if ERT-naive or agreeing to a
      6-week ERT washout, or for 13 weeks if currently taking ERT and not agreeing to washout.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
masking description: Open Label
measure: number of participants with adverse events as a measure of safety and tolerability
time frame: 8 weeks (ERT-naive) or 13 weeks (ERT)
measure: plasma pharmacokinetic parameters (maximal concentration, half-life, area under the curve, mean residence time, volume of distribution and clearance of AGT-182)
time frame: 8 weeks (ERT-naive) or 13 weeks (ERT)
measure: change in urinary or plasma glycosaminoglycans (GAGs)
time frame: 8 weeks (ERT-naive) or 13 weeks (ERT)
measure: change in liver or spleen size
time frame: 8 weeks (ERT-naive) or 13 weeks (ERT)
measure: change in cerebrospinal fluid (CSF) glycosaminoglycans (GAGs)
time frame: 8 weeks (ERT-naive) or 13 weeks (ERT)
arm group label: Treated subjects
arm group type: Experimental
description: AGT-182 solution for infusion will be administered intravenously at doses of 1.0 mg/kg or 3.0 mg/kg weekly for 8-13 weeks.
intervention type: Drug
intervention name: AGT-182
description: Recombinant HIRMAb-IDS
arm group label: Treated subjects
criteria: 
gender: Male
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Patrice Rioux, MD PhD
role: Study Director
affiliation: ArmaGen, Inc
facility: 
facility: 
facility: 
facility: 
facility: 
country: Germany
country: Philippines
country: United States
country: Netherlands
responsible party type: Sponsor
mesh term: Mucopolysaccharidosis II
mesh term: Mucopolysaccharidoses