<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/NCT02185651</url>
  </required_header>
  <id_info>
    <org_study_id>IRB201601641</org_study_id>
    <nct_id>NCT02185651</nct_id>
  </id_info>
  <brief_title>A Pilot Study of Zavesca® in Patients With Pompe Disease and Infusion Associated Reaction</brief_title>
  <official_title>A Pilot Study of the Effects of Oral Administration of Zavesca® on Anti-rhGAA Immune Response in Subjects With Pompe Disease Receiving rhGAA Enzyme Replacement Therapy</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Florida</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Amicus Therapeutics</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Florida</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Hypothesis: the effectiveness of treatment of Pompe disease with rhGAA enzyme replacement&#xD;
      therapy (ERT) is limited at least in part because patients develop antibodies against the&#xD;
      provided rhGAA enzyme. Treatment with Zavesca® prior to infusion may dampen or eliminate the&#xD;
      anti-rhGAA immune response in patients receiving ERT, thereby allowing for greater ERT&#xD;
      efficacy.&#xD;
&#xD;
      Treatment with Zavesca® before a enzyme replacement therapy (ERT) may decrease the severity&#xD;
      of, or eliminate infusion associated reactions (IAR) in people with Pompe Disease receiving&#xD;
      ERT.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This Study is designed to assess the effects of Zavesca® as immunomodulatory therapy on&#xD;
      anti-rhGAA immune responses in patients with Pompe disease, as well as their health and&#xD;
      disease progression. Subjects will either receive Zavesca® at 100 mg or 300 mg dosing levels&#xD;
      during study participation (n=3 @ 100 mg dosing; n=3 @ 300 mg dosing).&#xD;
&#xD;
      The first 3 subjects enrolled will be prescribed 100 mg Zavesca® 60 minutes prior to ERT&#xD;
      infusion. The subsequent 3 subjects enrolled will be prescribed 300 mg Zavesca® 60 minutes to&#xD;
      ERT infusion.&#xD;
&#xD;
      Eligible participants are on standard ERT for Pompe disease and have a history of infusion&#xD;
      associated reaction. Travel to the study site in Gainesville, Florida is required for 3&#xD;
      visits. Participants are prescribed medication Zavesca® and have blood tests, punch muscle&#xD;
      biopsy, physical exams, and answer questionnaires over 3 months study participation.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Participants not interested in enrolling.&#xD;
  </why_stopped>
  <start_date type="Actual">October 2016</start_date>
  <completion_date type="Actual">July 2018</completion_date>
  <primary_completion_date type="Actual">July 2018</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Evaluate Pharmacodynamics of ERT with pre-medication Zavesca</measure>
    <time_frame>Baseline, week 0, week 6</time_frame>
    <description>Change in GAA antibody level from Baseline to week 0: GAA antibody titer is reported at timepoints: pre-infusion, and 6, 12, and 24 hours post-infusion start.&#xD;
Change in GAA antibody level from Baseline to week 6: GAA antibody titer is reported at time points: pre-infusion and post-infusion.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Evaluate pharmacokinetics of ERT with pre-medication Zavesca®</measure>
    <time_frame>Baseline, week 0</time_frame>
    <description>Change in ERT half life at baseline (without Zavesca®) compared to week 0 (ERT with pre-medication Zavesca®).&#xD;
Change in Maximum plasma concentration (Cmax) at baseline (without Zavesca®) compared to week 0 (ERT with pre-medication Zavesca®).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Evaluate biodistribution of ERT with pre-medication Zavesca®.</measure>
    <time_frame>Week 0, week 7</time_frame>
    <description>Punch muscle biopsy is performed at week 0 and week 7 for biodistribution: Change in glycogen content and muscle fiber morphology is reported.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">2</enrollment>
  <condition>Pompe Disease</condition>
  <condition>Hypersensitivity Reaction</condition>
  <arm_group>
    <arm_group_label>Zavesca® 100 mg</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>3 study participants are given Zavesca® prescription 100 mg for administration before ERT infusion. Week 0 infusion is completed at study site, with blood collection for anti-GAA antibody level before, during and after the ERT infusion. A punch muscle biopsy is completed the day after ERT infusion with pre-medication Zavesca®. Health Survey is completed.&#xD;
Week 2, 4, and 6 ERT infusion with pre-medication are completed at local/home infusion center. Travel to site for week 7 study visit includes physical exam, blood collection and punch muscle biopsy. Health survey is completed.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Zavesca® 300 mg</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>3 study participants are given Zavesca® prescription 300 mg for administration before ERT infusion. Week 0 infusion is completed at study site, with blood collection for anti-GAA antibody level before, during and after the ERT infusion. A punch muscle biopsy is completed the day after ERT infusion with pre-medication Zavesca®. Health Survey is completed.&#xD;
Week 2, 4, and 6 ERT infusion with pre-medication are completed at local/home infusion center. Travel to site for week 7 study visit includes physical exam, blood collection and punch muscle biopsy. Health survey is completed.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Zavesca® Prescription</intervention_name>
    <description>Following baseline evaluation, Zavesca® prescription is given.&#xD;
Week 2, 4, and 6 ERT infusion with pre-medication are completed at local/home infusion center. Travel to site for week 7 study visit includes physical exam, blood collection and punch muscle biopsy. Health survey is completed.</description>
    <arm_group_label>Zavesca® 100 mg</arm_group_label>
    <arm_group_label>Zavesca® 300 mg</arm_group_label>
    <other_name>miglustat</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Subjects will be patients between the ages of 18 years and 65 years who have been diagnosed&#xD;
        with Pompe Disease, confirmed by mutational analysis and/or GAA enzyme activity assay.&#xD;
&#xD;
          -  Receiving rhGAA ERT&#xD;
&#xD;
          -  Willing to travel to the study site for study assessments&#xD;
&#xD;
          -  Willingness of local medical treatment provider to continue treating study participant&#xD;
             with addition of Zavesca® to treatment plan.&#xD;
&#xD;
          -  Willingness of study participant to modify dietary intake on day of infusion *All&#xD;
             Subjects will continue enzyme replacement therapy as standard of care, as prescribed&#xD;
             by local medical treatment provider during the course of the Study.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Subject is unable to meet the study requirements&#xD;
&#xD;
          -  Subject's medical condition contraindicates participation or Study Investigators feel&#xD;
             that participation is otherwise not in the Subject's best interest&#xD;
&#xD;
          -  Subject does not receive ERT treatment&#xD;
&#xD;
          -  Participation in other interventional studies at the time of enrollment that may&#xD;
             interfere with this study (at the investigator's discretion)&#xD;
&#xD;
          -  Unable to travel to the University of Florida for study visits&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Barry J. Byrne, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Florida</affiliation>
  </overall_official>
  <removed_countries>
    <country>United States</country>
  </removed_countries>
  <verification_date>December 2018</verification_date>
  <study_first_submitted>July 1, 2014</study_first_submitted>
  <study_first_submitted_qc>July 3, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 9, 2014</study_first_posted>
  <last_update_submitted>December 4, 2018</last_update_submitted>
  <last_update_submitted_qc>December 4, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">December 5, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Pompe Disease</keyword>
  <keyword>Enzyme Replacement Therapy</keyword>
  <keyword>Infusion Associated Reaction</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Glycogen Storage Disease Type II</mesh_term>
    <mesh_term>Hypersensitivity</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Miglustat</mesh_term>
  </intervention_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/NCT02185651
org study id: IRB201601641
nct id: NCT02185651
lead sponsor: 
collaborator: 
has dmc: No
Hypothesis: the effectiveness of treatment of Pompe disease with rhGAA enzyme replacement
      therapy (ERT) is limited at least in part because patients develop antibodies against the
      provided rhGAA enzyme. Treatment with Zavesca® prior to infusion may dampen or eliminate the
      anti-rhGAA immune response in patients receiving ERT, thereby allowing for greater ERT
      efficacy.

      Treatment with Zavesca® before a enzyme replacement therapy (ERT) may decrease the severity
      of, or eliminate infusion associated reactions (IAR) in people with Pompe Disease receiving
      ERT.
This Study is designed to assess the effects of Zavesca® as immunomodulatory therapy on
      anti-rhGAA immune responses in patients with Pompe disease, as well as their health and
      disease progression. Subjects will either receive Zavesca® at 100 mg or 300 mg dosing levels
      during study participation (n=3 @ 100 mg dosing; n=3 @ 300 mg dosing).

      The first 3 subjects enrolled will be prescribed 100 mg Zavesca® 60 minutes prior to ERT
      infusion. The subsequent 3 subjects enrolled will be prescribed 300 mg Zavesca® 60 minutes to
      ERT infusion.

      Eligible participants are on standard ERT for Pompe disease and have a history of infusion
      associated reaction. Travel to the study site in Gainesville, Florida is required for 3
      visits. Participants are prescribed medication Zavesca® and have blood tests, punch muscle
      biopsy, physical exams, and answer questionnaires over 3 months study participation.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Evaluate Pharmacodynamics of ERT with pre-medication Zavesca
time frame: Baseline, week 0, week 6
description: Change in GAA antibody level from Baseline to week 0: GAA antibody titer is reported at timepoints: pre-infusion, and 6, 12, and 24 hours post-infusion start.
Change in GAA antibody level from Baseline to week 6: GAA antibody titer is reported at time points: pre-infusion and post-infusion.
measure: Evaluate pharmacokinetics of ERT with pre-medication Zavesca®
time frame: Baseline, week 0
description: Change in ERT half life at baseline (without Zavesca®) compared to week 0 (ERT with pre-medication Zavesca®).
Change in Maximum plasma concentration (Cmax) at baseline (without Zavesca®) compared to week 0 (ERT with pre-medication Zavesca®).
measure: Evaluate biodistribution of ERT with pre-medication Zavesca®.
time frame: Week 0, week 7
description: Punch muscle biopsy is performed at week 0 and week 7 for biodistribution: Change in glycogen content and muscle fiber morphology is reported.
arm group label: Zavesca® 100 mg
arm group type: Active Comparator
description: 3 study participants are given Zavesca® prescription 100 mg for administration before ERT infusion. Week 0 infusion is completed at study site, with blood collection for anti-GAA antibody level before, during and after the ERT infusion. A punch muscle biopsy is completed the day after ERT infusion with pre-medication Zavesca®. Health Survey is completed.
Week 2, 4, and 6 ERT infusion with pre-medication are completed at local/home infusion center. Travel to site for week 7 study visit includes physical exam, blood collection and punch muscle biopsy. Health survey is completed.
arm group label: Zavesca® 300 mg
arm group type: Active Comparator
description: 3 study participants are given Zavesca® prescription 300 mg for administration before ERT infusion. Week 0 infusion is completed at study site, with blood collection for anti-GAA antibody level before, during and after the ERT infusion. A punch muscle biopsy is completed the day after ERT infusion with pre-medication Zavesca®. Health Survey is completed.
Week 2, 4, and 6 ERT infusion with pre-medication are completed at local/home infusion center. Travel to site for week 7 study visit includes physical exam, blood collection and punch muscle biopsy. Health survey is completed.
intervention type: Drug
intervention name: Zavesca® Prescription
description: Following baseline evaluation, Zavesca® prescription is given.
Week 2, 4, and 6 ERT infusion with pre-medication are completed at local/home infusion center. Travel to site for week 7 study visit includes physical exam, blood collection and punch muscle biopsy. Health survey is completed.
arm group label: Zavesca® 100 mg
arm group label: Zavesca® 300 mg
other name: miglustat
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
last name: Barry J. Byrne, MD, PhD
role: Principal Investigator
affiliation: University of Florida
country: United States
responsible party type: Sponsor
mesh term: Glycogen Storage Disease Type II
mesh term: Hypersensitivity
mesh term: Miglustat