<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/NCT03300453</url>
  </required_header>
  <id_info>
    <org_study_id>AMT110-CD-001</org_study_id>
    <nct_id>NCT03300453</nct_id>
  </id_info>
  <brief_title>Intracerebral Gene Therapy in Children With Sanfilippo Type B Syndrome</brief_title>
  <official_title>Protocol AMT110-CD-001: A Phase I/II, Open-label, Study of Intracerebral Administration of Adeno-associated Viral Vector Containing the Human Alpha-N-acetylglucosaminidase cDNA in Children With Sanfilippo Type B Syndrome</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>UniQure Biopharma B.V.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Venn Life Sciences</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Institut Pasteur</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>UniQure Biopharma B.V.</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is an open-label, phase I/II study of intra-cerebral administration of&#xD;
      adenovirus-associated viral vector containing the human NAGLU cDNA to children suffering from&#xD;
      Sanfilippo type B syndrome.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is an open-label, phase I/II study of intra-cerebral administration of&#xD;
      adenovirus-associated viral vector containing the human NAGLU cDNA to children suffering from&#xD;
      Sanfilippo type B syndrome.&#xD;
&#xD;
      Four patients, 18 months up to the 5th birthday, have been included.&#xD;
&#xD;
      The inclusion period will be 8 to 12 months. The duration of follow-up for each patient is 1&#xD;
      year post-surgery. The duration of the first extension phase is 18 months. The duration of&#xD;
      the second extension phase is 36 months. Therefore, the maximum time of the follow-up will be&#xD;
      66 months&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">September 17, 2013</start_date>
  <completion_date type="Actual">November 27, 2019</completion_date>
  <primary_completion_date type="Actual">November 27, 2019</primary_completion_date>
  <phase>Phase 1/Phase 2</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>
  </study_design_info>
  <primary_outcome>
    <measure>Number of Participants With Treatment-Related (Serious) Adverse Events as assessed by continuous evaluation of change from baseline</measure>
    <time_frame>Baseline until end of study (Month 66)</time_frame>
    <description>Multiple measurements will be aggregated to derive the number of participants with Abnormal Laboratory Values and/or Adverse Events that are related to Treatment.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of Participants with presence of brain atrophy, white matter lesions and other lesions as assessed by cerebral MRI</measure>
    <time_frame>Baseline until end of study (Month 66)</time_frame>
    <description>MRIs at Baseline, Month 3, Month 12, Month 30, Month 48 and last visit Month 66.&#xD;
Cerebral MRI will be collected for safety assessment to retrospectively evaluate for efficacy at Baseline, D0, Month 3, Month12, Month 30 and last visit Month 66.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">4</enrollment>
  <condition>Sanfilippo Syndrome B</condition>
  <arm_group>
    <arm_group_label>rAAV2/5-hNAGLU</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Each patient will receive 960 µL of vector suspension. The vector suspension will be deposited simultaneously at 16 sites, each deposit containing 2.4x 1011 vg (4x1012 vg in total).</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>rAAV2/5-hNAGLU</intervention_name>
    <description>one-time brain intraparenchymal gene therapy dose</description>
    <arm_group_label>rAAV2/5-hNAGLU</arm_group_label>
    <other_name>AAV5</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion criteria:&#xD;
&#xD;
          -  Age: 18 months up to 60 months (5th birthday);&#xD;
&#xD;
          -  Onset of clinical manifestations related to mucopolysaccharidosis type IIIB (MPSIIIB);&#xD;
&#xD;
          -  NAGLU activity in peripheral blood cell and/or cultured fibroblast extracts of less&#xD;
             than 10% of controls;&#xD;
&#xD;
          -  Patient affiliated to, or covered by a French social security regimen, or European&#xD;
             patients with European Health Insurance Card;&#xD;
&#xD;
          -  Family understanding the procedure and the informed consent;&#xD;
&#xD;
          -  Signed informed consent by both parents or legal representative;&#xD;
&#xD;
          -  Vital laboratory parameters within normal range.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Presence of brain atrophy on baseline MRI judged on a cortico-dural distance of more&#xD;
             than 0.6 cm;&#xD;
&#xD;
          -  Any condition that would contraindicate general anesthesia;&#xD;
&#xD;
          -  Any other permanent medical condition not related to MPSIIIB that could contraindicate&#xD;
             the study participation;&#xD;
&#xD;
          -  No independent walking (ability to walk without help);&#xD;
&#xD;
          -  Any medication aiming at modifying the natural course of MPSIIIB given during the 6&#xD;
             months before vector injection (sleep and mood regulators are accepted);&#xD;
&#xD;
          -  Any condition that would contraindicate treatment with Modigraf®, Cellcept® and&#xD;
             prednisolone (Solupred® and Solumedrol®).&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Months</minimum_age>
    <maximum_age>60 Months</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Kumaran Deiva, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Hopitaux Universitaires Paris-Sud</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Hopitaux Universitaires Paris-Sud</name>
      <address>
        <city>Paris</city>
        <state>Le Kremlin-Bicetre Cedex</state>
        <zip>94275</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <verification_date>October 2018</verification_date>
  <study_first_submitted>June 15, 2016</study_first_submitted>
  <study_first_submitted_qc>October 2, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">October 3, 2017</study_first_posted>
  <last_update_submitted>November 28, 2019</last_update_submitted>
  <last_update_submitted_qc>November 28, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">December 2, 2019</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>Mucopolysaccharidosis III</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/NCT03300453
org study id: AMT110-CD-001
nct id: NCT03300453
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
This is an open-label, phase I/II study of intra-cerebral administration of
      adenovirus-associated viral vector containing the human NAGLU cDNA to children suffering from
      Sanfilippo type B syndrome.
This is an open-label, phase I/II study of intra-cerebral administration of
      adenovirus-associated viral vector containing the human NAGLU cDNA to children suffering from
      Sanfilippo type B syndrome.

      Four patients, 18 months up to the 5th birthday, have been included.

      The inclusion period will be 8 to 12 months. The duration of follow-up for each patient is 1
      year post-surgery. The duration of the first extension phase is 18 months. The duration of
      the second extension phase is 36 months. Therefore, the maximum time of the follow-up will be
      66 months
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Number of Participants With Treatment-Related (Serious) Adverse Events as assessed by continuous evaluation of change from baseline
time frame: Baseline until end of study (Month 66)
description: Multiple measurements will be aggregated to derive the number of participants with Abnormal Laboratory Values and/or Adverse Events that are related to Treatment.
measure: Number of Participants with presence of brain atrophy, white matter lesions and other lesions as assessed by cerebral MRI
time frame: Baseline until end of study (Month 66)
description: MRIs at Baseline, Month 3, Month 12, Month 30, Month 48 and last visit Month 66.
Cerebral MRI will be collected for safety assessment to retrospectively evaluate for efficacy at Baseline, D0, Month 3, Month12, Month 30 and last visit Month 66.
arm group label: rAAV2/5-hNAGLU
arm group type: Experimental
description: Each patient will receive 960 µL of vector suspension. The vector suspension will be deposited simultaneously at 16 sites, each deposit containing 2.4x 1011 vg (4x1012 vg in total).
intervention type: Drug
intervention name: rAAV2/5-hNAGLU
description: one-time brain intraparenchymal gene therapy dose
arm group label: rAAV2/5-hNAGLU
other name: AAV5
criteria: 
gender: All
minimum age: 18 Months
maximum age: 60 Months
healthy volunteers: No
last name: Kumaran Deiva, MD
role: Principal Investigator
affiliation: Hopitaux Universitaires Paris-Sud
facility: 
country: France
responsible party type: Sponsor
mesh term: Mucopolysaccharidosis III
mesh term: Syndrome