<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/NCT03784287</url>
  </required_header>
  <id_info>
    <org_study_id>AX 250-202</org_study_id>
    <nct_id>NCT03784287</nct_id>
  </id_info>
  <brief_title>A Treatment Extension Study of Mucopolysaccharidosis Type IIIB</brief_title>
  <official_title>A Multicenter, Multinational, Extension Study to Evaluate the Long Term Safety and Efficacy of Intracerebroventricular AX 250 in Patients With Mucopolysaccharidosis Type IIIB (MPS IIIB, Sanfilippo Syndrome Type B)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Allievex Corporation</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Allievex Corporation</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>Yes</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      The primary objectives of this study are to evaluate the long-term safety and tolerability of&#xD;
      AX 250 administered to subjects with MPS IIIB by an implanted ICV reservoir and catheter and&#xD;
      to evaluate the impact of long-term AX 250 treatment on cognitive function in patients with&#xD;
      MPS IIIB as assessed by developmental quotient (DQ).&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">February 19, 2018</start_date>
  <completion_date type="Anticipated">February 2025</completion_date>
  <primary_completion_date type="Anticipated">January 2025</primary_completion_date>
  <phase>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>Evaluate the Long-term safety and tolerability of AX 250 administered in up to 33 subjects with MPS IIIB by assessing the number of participants with abnormal clinical laboratory values and/or Adverse Events related to the treatment</measure>
    <time_frame>Entire study period, up to 240 weeks</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Evaluating the impact of long-term AX 250 treatment on cognitive function in up to 33 patients with MPS IIIB as assessed by developmental quotient (DQ)</measure>
    <time_frame>Entire study period, up to 240 weeks</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Evaluate the impact of long-term AX 250 treatment on cognitive function in up to 33 patients with MPS IIIB as assessed by age equivalent score (AEq)</measure>
    <time_frame>Entire study period, up to 240 weeks</time_frame>
    <description>Age equivalent score is derived from neurocognitive tests (Bayley Scales of Infant Development, 3rd edition OR Kaufman Assessment battery for Children, 2nd edition)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Characterize immunogenicity as measured by IgE levels, formation of anti-AX 250, IGF1 and IGF2 antibodies in Cerebrospinal fluid (CSF) and serum.</measure>
    <time_frame>Entire study period, up to 240 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Evaluate the impact of long-term AX 250 treatment on Heparan sulfate (HS) levels in cerebrospinal fluid (CSF), serum and urine.</measure>
    <time_frame>Entire study period, up to 240 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Evaluate the impact of long-term AX 250 treatment on brain structure assessed by magnetic resonance imaging (MRI)</measure>
    <time_frame>Entire study period, up to 240 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Evaluate the impact of long-term AX 250 treatment on adaptive function derived from the Vineland Adaptive Behavior Scales, 2nd edition (VABS-II)</measure>
    <time_frame>Entire study period, up to 240 weeks</time_frame>
    <description>VABS-II is a measure of adaptive behavior and can be used to assess the level of subjects' functioning at various ages. Scale ranges from 0-4 (0 meaning never performs the behavior, and 4 meaning almost always performs the behavior independently)</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">20</enrollment>
  <condition>Mucopolysaccharidosis Type IIIB</condition>
  <condition>MPS III B</condition>
  <arm_group>
    <arm_group_label>AX 250</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>All subjects will receive AX 250 at the MTTD established in 250-201, 300mg administered weekly by ICV infusion that will continue for up to 240 weeks.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>AX 250</intervention_name>
    <description>Chimeric fusion of recombinant human alpha-N-acetylglucosaminidase and truncated human insulin-like growth factor 2 (rhNAGLU-IGF2)</description>
    <arm_group_label>AX 250</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Must have completed 48 weeks in Part 2 of Study 250-201 and enter 250-202 within 8&#xD;
             weeks of study completion&#xD;
&#xD;
          -  Written informed consent from parent or legal guardian and assent from subject, if&#xD;
             required&#xD;
&#xD;
          -  Has the ability to comply with protocol requirements, in the opinion of the&#xD;
             investigator&#xD;
&#xD;
          -  Males and females who are of reproductive age should practice true abstinence, defined&#xD;
             as no sexual activity, during the study and for 6 months after the study has been&#xD;
             completed (or withdrawal from the study). If sexually active and not practicing true&#xD;
             abstinence, males and females of reproductive age must use a highly effective method&#xD;
             of contraception while participating in the study.&#xD;
&#xD;
          -  If female with childbearing potential, must have a negative pregnancy test at the&#xD;
             Screening visit and be willing to have additional pregnancy tests during the study.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Has both (1) a cognitive AEq score ≤ 18 months, and (2) a DQ score ≤ 20&#xD;
&#xD;
          -  Would not benefit from enrolling in the study in the opinion of the investigator&#xD;
&#xD;
          -  Has received stem cell, gene therapy or ERT (other than AX 250) for MPS IIIB&#xD;
&#xD;
          -  Has contraindications for neurosurgery (eg, congenital heart disease, severe&#xD;
             respiratory impairment, or clotting abnormalities)&#xD;
&#xD;
          -  Has contraindications for MRI scans (eg, cardiac pacemaker, metal fragment or chip in&#xD;
             the eye, or aneurysm clip in the brain)&#xD;
&#xD;
          -  Has a history of poorly controlled seizure disorder&#xD;
&#xD;
          -  Is prone to complications from intraventricular drug administration, including&#xD;
             patients with hydrocephalus or ventricular shunts&#xD;
&#xD;
          -  Has received any investigational medication other than AX 250 within 30 days prior to&#xD;
             the Baseline visit or is scheduled to receive any investigational drug during the&#xD;
             course of the study&#xD;
&#xD;
          -  Has a medical condition or extenuating circumstance that, in the opinion of the&#xD;
             investigator, might compromise the subject's ability to comply with protocol&#xD;
             requirements, the subject's well-being or safety, or the interpretability of the&#xD;
             subject's clinical data.&#xD;
&#xD;
          -  Is pregnant at any time during the study&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>0 Years</minimum_age>
    <maximum_age>18 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Medical Monitor, MD</last_name>
    <role>Study Director</role>
    <affiliation>Allievex Corporation</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Children's Hospital and Research Center Oakland</name>
      <address>
        <city>Oakland</city>
        <state>California</state>
        <zip>94609</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UPMC Children's Hospital Pittburgh</name>
      <address>
        <city>Pittsburgh</city>
        <state>Pennsylvania</state>
        <zip>15224</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Fundación Cardio Infantil - Instituto de Cardiología</name>
      <address>
        <city>Bogotá,</city>
        <country>Colombia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Medical Center Hamburg-Eppendorf</name>
      <address>
        <city>Hamburg</city>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Complexo Hospitalario Universitario de Santiago (CHUS) - Hospital Clínico Universitario</name>
      <address>
        <city>Santiago de Compostela</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>MacKay Memorial Children's Hospital</name>
      <address>
        <city>Taipei</city>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Gazi University Faculty of Medicine</name>
      <address>
        <city>Ankara</city>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Great Ormond Street Hospital For Children, NHS Foundation Trust</name>
      <address>
        <city>London</city>
        <zip>WC1N 3JH</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Colombia</country>
    <country>Germany</country>
    <country>Spain</country>
    <country>Taiwan</country>
    <country>Turkey</country>
    <country>United Kingdom</country>
    <country>United States</country>
  </location_countries>
  <verification_date>October 2022</verification_date>
  <study_first_submitted>March 30, 2018</study_first_submitted>
  <study_first_submitted_qc>December 19, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 21, 2018</study_first_posted>
  <last_update_submitted>January 16, 2023</last_update_submitted>
  <last_update_submitted_qc>January 16, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">January 18, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Sanfilippo Syndrome Type B</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Mucopolysaccharidoses</mesh_term>
    <mesh_term>Mucopolysaccharidosis III</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/NCT03784287
org study id: AX 250-202
nct id: NCT03784287
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
is us export: Yes
The primary objectives of this study are to evaluate the long-term safety and tolerability of
      AX 250 administered to subjects with MPS IIIB by an implanted ICV reservoir and catheter and
      to evaluate the impact of long-term AX 250 treatment on cognitive function in patients with
      MPS IIIB as assessed by developmental quotient (DQ).
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Evaluate the Long-term safety and tolerability of AX 250 administered in up to 33 subjects with MPS IIIB by assessing the number of participants with abnormal clinical laboratory values and/or Adverse Events related to the treatment
time frame: Entire study period, up to 240 weeks
measure: Evaluating the impact of long-term AX 250 treatment on cognitive function in up to 33 patients with MPS IIIB as assessed by developmental quotient (DQ)
time frame: Entire study period, up to 240 weeks
measure: Evaluate the impact of long-term AX 250 treatment on cognitive function in up to 33 patients with MPS IIIB as assessed by age equivalent score (AEq)
time frame: Entire study period, up to 240 weeks
description: Age equivalent score is derived from neurocognitive tests (Bayley Scales of Infant Development, 3rd edition OR Kaufman Assessment battery for Children, 2nd edition)
measure: Characterize immunogenicity as measured by IgE levels, formation of anti-AX 250, IGF1 and IGF2 antibodies in Cerebrospinal fluid (CSF) and serum.
time frame: Entire study period, up to 240 weeks
measure: Evaluate the impact of long-term AX 250 treatment on Heparan sulfate (HS) levels in cerebrospinal fluid (CSF), serum and urine.
time frame: Entire study period, up to 240 weeks
measure: Evaluate the impact of long-term AX 250 treatment on brain structure assessed by magnetic resonance imaging (MRI)
time frame: Entire study period, up to 240 weeks
measure: Evaluate the impact of long-term AX 250 treatment on adaptive function derived from the Vineland Adaptive Behavior Scales, 2nd edition (VABS-II)
time frame: Entire study period, up to 240 weeks
description: VABS-II is a measure of adaptive behavior and can be used to assess the level of subjects' functioning at various ages. Scale ranges from 0-4 (0 meaning never performs the behavior, and 4 meaning almost always performs the behavior independently)
arm group label: AX 250
arm group type: Experimental
description: All subjects will receive AX 250 at the MTTD established in 250-201, 300mg administered weekly by ICV infusion that will continue for up to 240 weeks.
intervention type: Drug
intervention name: AX 250
description: Chimeric fusion of recombinant human alpha-N-acetylglucosaminidase and truncated human insulin-like growth factor 2 (rhNAGLU-IGF2)
arm group label: AX 250
criteria: 
gender: All
minimum age: 0 Years
maximum age: 18 Years
healthy volunteers: No
last name: Medical Monitor, MD
role: Study Director
affiliation: Allievex Corporation
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Colombia
country: Germany
country: Spain
country: Taiwan
country: Turkey
country: United Kingdom
country: United States
responsible party type: Sponsor
mesh term: Mucopolysaccharidoses
mesh term: Mucopolysaccharidosis III