<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/NCT03810508</url>
  </required_header>
  <id_info>
    <org_study_id>CMT4J-100</org_study_id>
    <nct_id>NCT03810508</nct_id>
  </id_info>
  <brief_title>A Natural History Study of Charcot-Marie-Tooth 4J (CMT4J)</brief_title>
  <acronym>CMT4J</acronym>
  <official_title>A Natural History Study of Charcot-Marie-Tooth 4J (CMT4J)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Neurogene Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Neurogene Inc.</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Charcot-Marie-Tooth 4J (CMT4J) is a rare inherited peripheral neuropathy often characterized&#xD;
      by rapidly progressive, asymmetrical upper and lower extremity weakness, muscle atrophy&#xD;
      leading to loss of ambulation, respiratory compromise and premature death with no available&#xD;
      treatment.&#xD;
&#xD;
      The purpose of this study is to investigate the clinical characteristics and natural clinical&#xD;
      progression of symptoms in individuals with CMT4J. This natural history study is important to&#xD;
      better understand disease course to be able to determine clinically meaningful outcome&#xD;
      measures for use in future clinical trials.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Charcot-Marie-Tooth (CMT) diseases are the most common inherited motor and sensory&#xD;
      neuropathies, composed of a group of pathologically and genetically distinct subtypes ranging&#xD;
      from slowly to rapidly progressive disease.&#xD;
&#xD;
      CMT4J is a rare subtype of CMT caused by mutations in the FIG4 gene. Pediatric-onset disease&#xD;
      can often be characterized by rapid progression of muscle weakness and atrophy, culminating&#xD;
      in loss of ambulation and respiratory compromise and premature death. Adult-onset CMT4J can&#xD;
      present with a more variable disease course.&#xD;
&#xD;
      No prospective natural history study for CMT4J has been reported. This study aims to&#xD;
      prospectively investigate the natural history of CMT4J, and concurrently to identify&#xD;
      potential outcome measures that could be used in future clinical trials. No investigational&#xD;
      product will be provided in the study.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Discontinued CMT4J development program&#xD;
  </why_stopped>
  <start_date type="Actual">July 18, 2019</start_date>
  <completion_date type="Actual">February 15, 2022</completion_date>
  <primary_completion_date type="Actual">February 15, 2022</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Charcot Marie-Tooth Pediatric Scale (CMTPedS)</measure>
    <time_frame>Change is being assessed from baseline measures every 6 months for up to five years</time_frame>
    <description>This an 11 item scale is used in patients younger than 18 yrs of age and generates a linear score of disability.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Charcot-Marie-Tooth Neuropathy Score second version (CMTNSv2)</measure>
    <time_frame>Change is being assessed from baseline measures every 6 months for up to five years</time_frame>
    <description>This is a 36 point scale that monitors disease impairment and progression with a higher score signifies increased disability.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Charcot Marie-Tooth Functional Outcome Measure (CMT-FOM)</measure>
    <time_frame>Change is being assessed from baseline measures every 6 months for up to five years</time_frame>
    <description>This is a performance-based outcome assessment which measures limitations in functional abilities in adults.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>CMT Health Index (CMTHI)</measure>
    <time_frame>Change is being assessed from baseline measures every 6 months for up to five years</time_frame>
    <description>The CMTHI is a disease-specific, adult patient reported outcome measure designed to capture the disease burden of inherited neuropathies in the context of a clinical trial.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Magnetic Resonance Imaging (MRI) of the calf muscles without contrast</measure>
    <time_frame>Change is being assessed from baseline measures every 6 months for up to five years</time_frame>
    <description>MRI of bilateral thigh and calf muscles will be performed to characterize the pattern of muscle involvement and evaluate the muscle fat fraction (MFF).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Nerve Conduction Study (NCS)</measure>
    <time_frame>Change is being assessed from baseline measures every 6 months for up to five years</time_frame>
    <description>NCS is an electrophysiological test to evaluate the sensory and motor responses in the upper and lower extremities.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Pulmonary Function Test, sitting and lying (PFT)</measure>
    <time_frame>Change is being assessed from baseline measures every 12 months for up to five years</time_frame>
    <description>The purpose of the PFT is to identify the severity and progression of pulmonary impairment, and will be performed every 12 months.</description>
  </primary_outcome>
  <enrollment type="Actual">21</enrollment>
  <condition>Charcot-Marie-Tooth Disease</condition>
  <condition>Hereditary Motor and Sensory Neuropathy IV</condition>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Patients will also have the opportunity to have biospecimens stored for up to 10 years for&#xD;
      future exploratory analyses.&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Patients with a diagnosis of CMT4J based on clinical presentation and genetic testing&#xD;
        (known or suspected pathogenic mutation in FIG4).&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Subjects must have a prior confirmed molecular (genetic) diagnosis of CMT4J by clinical&#xD;
        presentation and genetic testing.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Elise Beausoleil</last_name>
    <role>Study Director</role>
    <affiliation>Neurogene Inc.</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Iowa</name>
      <address>
        <city>Iowa City</city>
        <state>Iowa</state>
        <zip>52242</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Texas Southwestern</name>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>75390</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>March 2022</verification_date>
  <study_first_submitted>January 17, 2019</study_first_submitted>
  <study_first_submitted_qc>January 17, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 18, 2019</study_first_posted>
  <last_update_submitted>March 16, 2022</last_update_submitted>
  <last_update_submitted_qc>March 16, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">March 31, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>CMT4J</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Tooth Diseases</mesh_term>
    <mesh_term>Charcot-Marie-Tooth Disease</mesh_term>
    <mesh_term>Nerve Compression Syndromes</mesh_term>
    <mesh_term>Hereditary Sensory and Motor Neuropathy</mesh_term>
    <mesh_term>Refsum 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/NCT03810508
org study id: CMT4J-100
nct id: NCT03810508
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Charcot-Marie-Tooth 4J (CMT4J) is a rare inherited peripheral neuropathy often characterized
      by rapidly progressive, asymmetrical upper and lower extremity weakness, muscle atrophy
      leading to loss of ambulation, respiratory compromise and premature death with no available
      treatment.

      The purpose of this study is to investigate the clinical characteristics and natural clinical
      progression of symptoms in individuals with CMT4J. This natural history study is important to
      better understand disease course to be able to determine clinically meaningful outcome
      measures for use in future clinical trials.
Charcot-Marie-Tooth (CMT) diseases are the most common inherited motor and sensory
      neuropathies, composed of a group of pathologically and genetically distinct subtypes ranging
      from slowly to rapidly progressive disease.

      CMT4J is a rare subtype of CMT caused by mutations in the FIG4 gene. Pediatric-onset disease
      can often be characterized by rapid progression of muscle weakness and atrophy, culminating
      in loss of ambulation and respiratory compromise and premature death. Adult-onset CMT4J can
      present with a more variable disease course.

      No prospective natural history study for CMT4J has been reported. This study aims to
      prospectively investigate the natural history of CMT4J, and concurrently to identify
      potential outcome measures that could be used in future clinical trials. No investigational
      product will be provided in the study.
observational model: Cohort
time perspective: Prospective
measure: Charcot Marie-Tooth Pediatric Scale (CMTPedS)
time frame: Change is being assessed from baseline measures every 6 months for up to five years
description: This an 11 item scale is used in patients younger than 18 yrs of age and generates a linear score of disability.
measure: Charcot-Marie-Tooth Neuropathy Score second version (CMTNSv2)
time frame: Change is being assessed from baseline measures every 6 months for up to five years
description: This is a 36 point scale that monitors disease impairment and progression with a higher score signifies increased disability.
measure: Charcot Marie-Tooth Functional Outcome Measure (CMT-FOM)
time frame: Change is being assessed from baseline measures every 6 months for up to five years
description: This is a performance-based outcome assessment which measures limitations in functional abilities in adults.
measure: CMT Health Index (CMTHI)
time frame: Change is being assessed from baseline measures every 6 months for up to five years
description: The CMTHI is a disease-specific, adult patient reported outcome measure designed to capture the disease burden of inherited neuropathies in the context of a clinical trial.
measure: Magnetic Resonance Imaging (MRI) of the calf muscles without contrast
time frame: Change is being assessed from baseline measures every 6 months for up to five years
description: MRI of bilateral thigh and calf muscles will be performed to characterize the pattern of muscle involvement and evaluate the muscle fat fraction (MFF).
measure: Nerve Conduction Study (NCS)
time frame: Change is being assessed from baseline measures every 6 months for up to five years
description: NCS is an electrophysiological test to evaluate the sensory and motor responses in the upper and lower extremities.
measure: Pulmonary Function Test, sitting and lying (PFT)
time frame: Change is being assessed from baseline measures every 12 months for up to five years
description: The purpose of the PFT is to identify the severity and progression of pulmonary impairment, and will be performed every 12 months.
Patients will also have the opportunity to have biospecimens stored for up to 10 years for
      future exploratory analyses.
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: N/A
maximum age: N/A
healthy volunteers: No
last name: Elise Beausoleil
role: Study Director
affiliation: Neurogene Inc.
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Tooth Diseases
mesh term: Charcot-Marie-Tooth Disease
mesh term: Nerve Compression Syndromes
mesh term: Hereditary Sensory and Motor Neuropathy
mesh term: Refsum Disease
sharing ipd: No