<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/NCT02995993</url>
  </required_header>
  <id_info>
    <org_study_id>CT-GR-MaGal-01</org_study_id>
    <nct_id>NCT02995993</nct_id>
  </id_info>
  <brief_title>Pharmacokinetics, Pharmacodynamics, and Safety of Moss-aGalactosidase A in Patients With Fabry Disease</brief_title>
  <official_title>An Open-Label, Multi-Center Study to Evaluate the Pharmacokinetics, Pharmacodynamics, and Safety of Moss-aGal in Patients With Fabry Disease</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Greenovation Biotech GmbH</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>FGK Clinical Research GmbH</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Greenovation Biotech GmbH</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Six patients with Fabry disease will be recruited. Patients will receive a single dose of 0.2&#xD;
      mg/kg recombinant human alpha-galactosidase A produced in moss (moss-aGal) as intravenous&#xD;
      infusion. Patients will be hospitalized during the infusion and for at least 24 hours after&#xD;
      the end of the infusion. Treatment will be administered sequentially: if a patient shows no&#xD;
      safety concerns on the treatment day, treatment of the next patient will commence on the&#xD;
      following day.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>November 2016</start_date>
  <completion_date type="Actual">October 9, 2017</completion_date>
  <primary_completion_date type="Actual">October 9, 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>Basic Science</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>AUC0-inf</measure>
    <time_frame>PK sampling for 24 h after moss-aGal administration</time_frame>
    <description>Area under the serum concentration curve extrapolated to infinity</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of patients with drug-related adverse events</measure>
    <time_frame>Adverse event monitoring for 28 days after moss-aGal administration</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Gb3 concentration in plasma</measure>
    <time_frame>Monitoring up to Day 28 after moss-aGal administration</time_frame>
    <description>Globotriaosylceramide concentration in plasma</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Gb3 concentration in morning urine</measure>
    <time_frame>Monitoring up to Day 28 after moss-aGal administration</time_frame>
    <description>Globotriaosylceramide concentration in morning urine</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Lyso-Gb3 concentration in plasma</measure>
    <time_frame>Monitoring up to Day 28 after moss-aGal administration</time_frame>
    <description>Globotriaosylsphingosine concentration in plasma</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">6</enrollment>
  <condition>Fabry Disease</condition>
  <arm_group>
    <arm_group_label>Moss-aGal</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Single administration of 0.2 mg/kg recombinant human alpha-galactosidase A produced in moss (moss-aGal) as intravenous infusion</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Moss-aGal (recombinant human alpha-galactosidase A produced in moss)</intervention_name>
    <description>Single i.v. Infusion of 0.2 mg/kg moss-aGal over 60 minutes</description>
    <arm_group_label>Moss-aGal</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients with Fabry disease evidenced by a deficient α-galactosidase A (α-Gal A)&#xD;
             activity or an α-Gal A gene mutation (the latter is mandatory in women);&#xD;
&#xD;
          -  Treatment naïve Fabry patients or Fabry patients who paused any enzyme replacement&#xD;
             therapy for Fabry disease due to personal reasons for 3 months before study entry;&#xD;
&#xD;
          -  Female and male patients between 18 and &lt;=65 years;&#xD;
&#xD;
          -  At least one of the clinical manifestations of Fabry disease including neuropathic&#xD;
             pain, angiokeratoma, cornea verticillata, cardiomyopathy, hypo- or anhydrosis,&#xD;
             abdominal pain, diarrhea, serum creatinine &gt;1.0 mg/dL, or proteinuria &gt;300 mg/24&#xD;
             hours;&#xD;
&#xD;
          -  Lyso-Gb3 concentrations in plasma above upper limit of normal;&#xD;
&#xD;
          -  Male patients with a female partner of child-bearing potential agree to use a&#xD;
             medically acceptable method of contraception (e.g. condoms, sexual abstinence,&#xD;
             vasectomy), not including the rhythm method for 30 days after administration of the&#xD;
             study medication;&#xD;
&#xD;
          -  Female patients of childbearing potential must apply a highly effective method of&#xD;
             birth control (failure rate less than 1% per year when used consistently and correctly&#xD;
             [e.g. implants, injectables, combined oral contraceptives, some intrauterine&#xD;
             contraceptive devices, sexual abstinence, or a vasectomized partner]). The birth&#xD;
             control method must have been applied for at least one monthly cycle prior to the&#xD;
             first administration of study medication and 30 days after administration of the study&#xD;
             medication.&#xD;
&#xD;
          -  Patient is willing and able (in the opinion of the investigator) to understand and&#xD;
             comply with the procedures and evaluations of the study;&#xD;
&#xD;
          -  Patient must be willing and legally able to give written informed consent.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Treatment with any enzyme replacement therapy for Fabry disease within 3 months before&#xD;
             study entry;&#xD;
&#xD;
          -  Fabry patients who paused any enzyme replacement therapy for Fabry disease due to&#xD;
             intolerability;&#xD;
&#xD;
          -  Patient is positive for anti-alpha-Gal A immunoglobulin G (IgG) at Screening;&#xD;
&#xD;
          -  Participation in any other clinical study with a medical device or investigational&#xD;
             medicinal product concurrently or within 3 months before study start;&#xD;
&#xD;
          -  Patient is currently on dialysis, is expected to begin dialysis during the study, has&#xD;
             received a kidney transplant, or is on the renal transplant waiting list;&#xD;
&#xD;
          -  Patient is unable to comply with the protocol (e.g. clinical relevant medical&#xD;
             condition making implementation of the protocol difficult, unstable social situation,&#xD;
             or otherwise unlikely to complete the study) or is, in the opinion of the&#xD;
             investigator, otherwise unsuited for the study;&#xD;
&#xD;
          -  Known human immunodeficiency virus, hepatitis B surface antigen and/or hepatitis C&#xD;
             infection;&#xD;
&#xD;
          -  Known allergies or intolerabilities to enzyme replacement therapy;&#xD;
&#xD;
          -  Hypersensitivity (like anaphylactic reaction) to the active substance or to any&#xD;
             excipients of moss-aGal;&#xD;
&#xD;
          -  Co-administration of moss-aGal with chloroquine, amiodarone, benoquin or gentamicin;&#xD;
&#xD;
          -  Breast-feeding and pregnant women;&#xD;
&#xD;
          -  Patients with liver impairment;&#xD;
&#xD;
          -  Women with signs of cardiac fibrosis detectable by echocardiography;&#xD;
&#xD;
          -  Other, not Fabry disease-related severe illnesses;&#xD;
&#xD;
          -  Malignancies within the past 5 years;&#xD;
&#xD;
          -  Liver transaminases &gt;=3 times above the upper Limit of normal;&#xD;
&#xD;
          -  Alcohol and/or drug abuse;&#xD;
&#xD;
          -  Weight &gt;100 kg;&#xD;
&#xD;
          -  Employees of the sponsor or patients who are employees or relatives of the&#xD;
             investigator.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Ruhruniversität Bochum, Klinik für Kinder- und Jugendmedizin im St. Josef-Hospital im Katholischen Klinikum Bochum</name>
      <address>
        <city>Bochum</city>
        <zip>44791</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universitätsmedizin Mainz, Zentrum für Kinder- und Jugendmedizin</name>
      <address>
        <city>Mainz</city>
        <zip>55131</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Germany</country>
  </location_countries>
  <reference>
    <citation>Shen JS, Busch A, Day TS, Meng XL, Yu CI, Dabrowska-Schlepp P, Fode B, Niederkruger H, Forni S, Chen S, Schiffmann R, Frischmuth T, Schaaf A. Mannose receptor-mediated delivery of moss-made alpha-galactosidase A efficiently corrects enzyme deficiency in Fabry mice. J Inherit Metab Dis. 2016 Mar;39(2):293-303. doi: 10.1007/s10545-015-9886-9. Epub 2015 Aug 27.</citation>
    <PMID>26310963</PMID>
  </reference>
  <verification_date>December 2017</verification_date>
  <study_first_submitted>December 14, 2016</study_first_submitted>
  <study_first_submitted_qc>December 14, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 19, 2016</study_first_posted>
  <last_update_submitted>December 12, 2017</last_update_submitted>
  <last_update_submitted_qc>December 12, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">December 13, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Fabry Disease</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- 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/NCT02995993
org study id: CT-GR-MaGal-01
nct id: NCT02995993
lead sponsor: 
collaborator: 
has dmc: No
Six patients with Fabry disease will be recruited. Patients will receive a single dose of 0.2
      mg/kg recombinant human alpha-galactosidase A produced in moss (moss-aGal) as intravenous
      infusion. Patients will be hospitalized during the infusion and for at least 24 hours after
      the end of the infusion. Treatment will be administered sequentially: if a patient shows no
      safety concerns on the treatment day, treatment of the next patient will commence on the
      following day.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Basic Science
masking: None (Open Label)
measure: AUC0-inf
time frame: PK sampling for 24 h after moss-aGal administration
description: Area under the serum concentration curve extrapolated to infinity
measure: Number of patients with drug-related adverse events
time frame: Adverse event monitoring for 28 days after moss-aGal administration
measure: Gb3 concentration in plasma
time frame: Monitoring up to Day 28 after moss-aGal administration
description: Globotriaosylceramide concentration in plasma
measure: Gb3 concentration in morning urine
time frame: Monitoring up to Day 28 after moss-aGal administration
description: Globotriaosylceramide concentration in morning urine
measure: Lyso-Gb3 concentration in plasma
time frame: Monitoring up to Day 28 after moss-aGal administration
description: Globotriaosylsphingosine concentration in plasma
arm group label: Moss-aGal
arm group type: Experimental
description: Single administration of 0.2 mg/kg recombinant human alpha-galactosidase A produced in moss (moss-aGal) as intravenous infusion
intervention type: Drug
intervention name: Moss-aGal (recombinant human alpha-galactosidase A produced in moss)
description: Single i.v. Infusion of 0.2 mg/kg moss-aGal over 60 minutes
arm group label: Moss-aGal
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
facility: 
facility: 
country: Germany
citation: Shen JS, Busch A, Day TS, Meng XL, Yu CI, Dabrowska-Schlepp P, Fode B, Niederkruger H, Forni S, Chen S, Schiffmann R, Frischmuth T, Schaaf A. Mannose receptor-mediated delivery of moss-made alpha-galactosidase A efficiently corrects enzyme deficiency in Fabry mice. J Inherit Metab Dis. 2016 Mar;39(2):293-303. doi: 10.1007/s10545-015-9886-9. Epub 2015 Aug 27.
PMID: 26310963
responsible party type: Sponsor
mesh term: Fabry Disease
sharing ipd: No