<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/NCT03822650</url>
  </required_header>
  <id_info>
    <org_study_id>CLN-100</org_study_id>
    <nct_id>NCT03822650</nct_id>
  </id_info>
  <brief_title>A Natural History Study of Neuronal Ceroid Lipofuscinosis Type 5 (CLN5)</brief_title>
  <official_title>A Natural History and Outcome Measure Discovery Study of Neuronal Ceroid Lipofuscinosis Type 5 (CLN5)</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>
      CLN5 is a form of Batten Disease, a neurodegenerative disorder in children causing&#xD;
      psychomotor regression, seizures, blindness, loss of ambulation and premature death, and has&#xD;
      no available treatments.&#xD;
&#xD;
      The purpose of this study is to investigate the clinical characteristics and natural clinical&#xD;
      progression of symptoms in individuals with CLN5. This natural history study is important to&#xD;
      better understand disease course to be able to determine clinically relevant outcome measures&#xD;
      for use in future clinical trials.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Neuronal Ceroid Lipofuscinosis (NCL) are comprised of a group of fatal neurodegenerative&#xD;
      diseases caused by mutations in an enzyme or protein which results in the accumulation of&#xD;
      toxic deposits in the eye, brain, skin, muscle and other cells.&#xD;
&#xD;
      CLN5 is a type of NCL, caused by homozygous or bi-allelic heterozygous variants in the CLN5&#xD;
      gene. Lack of CLN5 protein impairs the breakdown of certain proteins, leads to defective&#xD;
      lysosomal trafficking, resulting in accumulation of toxic material and subsequent cell&#xD;
      damage. CLN5 disease presents in childhood with neurological findings including motor&#xD;
      clumsiness and attention disturbances, followed by progressive visual failure, psychomotor&#xD;
      depression, epilepsy, and premature death.&#xD;
&#xD;
      No investigational product will be provided in the study.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">March 13, 2019</start_date>
  <completion_date type="Anticipated">January 2026</completion_date>
  <primary_completion_date type="Anticipated">January 2026</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>Other</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Unified Batten Disease Rating Scale (UBDRS)</measure>
    <time_frame>3 years</time_frame>
    <description>Disease-specific clinical assessment used to assess physical, seizure, behavioral and functional capabilities. For physical assessments scores range from 0 to 4 with the score of 4 being most severe.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Late Infantile Neuronal Ceroid Lipofuscinosis Rating Scale (Hamburg Scale)</measure>
    <time_frame>3 years</time_frame>
    <description>Disease specific tool used to capture 4 domains including motor function, seizures, visual function and language. Each sub-scale can be scored from 0-3 points in which 0 represents loss of function.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Electroencephalography (EEG)</measure>
    <time_frame>3 years</time_frame>
    <description>EEG records electrical brain activity and Interictal discharges (location, focal/generalized, etc) will be compared to baseline and characterized over time.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Vineland Adaptive Behavior Scale, 2nd Edition (Vineland-II)</measure>
    <time_frame>3 years</time_frame>
    <description>Standard assessment measuring communication, socializing, and daily living skills to assess their overall adaptive functioning for individuals up to 90 years of age. A higher score generally corresponds with higher adaptive function.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Caregiver Global Impression of Change (CaGI-C)</measure>
    <time_frame>3 years</time_frame>
    <description>The CaGI-C is a caregiver reported outcome measure designed to assess any change in the subject's presentation over the preceding 7 days, as compared to the previous visit.</description>
  </secondary_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Anticipated">30</enrollment>
  <condition>Ceroid Lipofuscinosis, Neuronal 5</condition>
  <arm_group>
    <arm_group_label>Prospective</arm_group_label>
    <description>Subjects who meet eligibility criteria and enroll in the prospective arm will be assessed every 6 months ± 4 weeks for a period of up to 3 years, according to the Schedule of Assessments.&#xD;
Subjects in the Prospective arm may also participate in the Retrospective arm.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Retrospective</arm_group_label>
    <description>Upon confirmation of eligibility criteria, the site will obtain an Informed Consent/Assent form and release of medical records from the subject/legally authorized representative to allow review of the medical records from the subject's primary care physician and/or specialists to confirm the CLN5 diagnosis and disease course. To facilitate collection of the medical records, a caregiver interview will be completed at initial enrollment then once yearly for up to 3 years.</description>
  </arm_group>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      whole blood&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Patients with a confirmed genetic diagnosis of CLN5.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Age at disease onset of ≤ 5 years of age.&#xD;
&#xD;
          2. Molecular genetic diagnosis confirming the presence of pathogenic or likely pathogenic&#xD;
             variant(s) on both alleles (biallelic) of the CLN5 gene.&#xD;
&#xD;
        For Prospective Arm only:&#xD;
&#xD;
          1. Subject age of ≤ 9 years.&#xD;
&#xD;
          2. Hamburg motor and vision score of ≥ 1 at time of consent.&#xD;
&#xD;
          3. Subject must have a caregiver available to support the subject and attend visits with&#xD;
             the subject.&#xD;
&#xD;
        Exclusion Criteria - All Subjects:&#xD;
&#xD;
          1. Has another neurologic disease or illness that may have caused cognitive decline&#xD;
             before study entry.&#xD;
&#xD;
          2. Has a known pathogenic or clinically suspected mutation in a seizure associated&#xD;
             genetic mutation besides CLN5.&#xD;
&#xD;
          3. Any prior participation in a study in which a gene therapy vector or stem cell&#xD;
             transplantation was administered.&#xD;
&#xD;
          4. Participation in other investigational studies and non-interventional studies that&#xD;
             have similar study assessments as this protocol while the subject is enrolled in this&#xD;
             study is prohibited.&#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>
  <overall_contact>
    <last_name>Contact Center</last_name>
    <phone>877-237-5020</phone>
    <email>medicalinfo@neurogene.com</email>
  </overall_contact>
  <location>
    <facility>
      <name>University of Rochester Medical Center</name>
      <address>
        <city>Rochester</city>
        <state>New York</state>
        <zip>14642</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Amy Vierhile, RN</last_name>
    </contact>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>March 2023</verification_date>
  <study_first_submitted>January 27, 2019</study_first_submitted>
  <study_first_submitted_qc>January 28, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 30, 2019</study_first_posted>
  <last_update_submitted>March 7, 2023</last_update_submitted>
  <last_update_submitted_qc>March 7, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">March 9, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>CLN</keyword>
  <keyword>NCL</keyword>
  <keyword>Batten</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Neuronal Ceroid-Lipofuscinoses</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/NCT03822650
org study id: CLN-100
nct id: NCT03822650
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
CLN5 is a form of Batten Disease, a neurodegenerative disorder in children causing
      psychomotor regression, seizures, blindness, loss of ambulation and premature death, and has
      no available treatments.

      The purpose of this study is to investigate the clinical characteristics and natural clinical
      progression of symptoms in individuals with CLN5. This natural history study is important to
      better understand disease course to be able to determine clinically relevant outcome measures
      for use in future clinical trials.
Neuronal Ceroid Lipofuscinosis (NCL) are comprised of a group of fatal neurodegenerative
      diseases caused by mutations in an enzyme or protein which results in the accumulation of
      toxic deposits in the eye, brain, skin, muscle and other cells.

      CLN5 is a type of NCL, caused by homozygous or bi-allelic heterozygous variants in the CLN5
      gene. Lack of CLN5 protein impairs the breakdown of certain proteins, leads to defective
      lysosomal trafficking, resulting in accumulation of toxic material and subsequent cell
      damage. CLN5 disease presents in childhood with neurological findings including motor
      clumsiness and attention disturbances, followed by progressive visual failure, psychomotor
      depression, epilepsy, and premature death.

      No investigational product will be provided in the study.
observational model: Cohort
time perspective: Other
measure: Unified Batten Disease Rating Scale (UBDRS)
time frame: 3 years
description: Disease-specific clinical assessment used to assess physical, seizure, behavioral and functional capabilities. For physical assessments scores range from 0 to 4 with the score of 4 being most severe.
measure: Late Infantile Neuronal Ceroid Lipofuscinosis Rating Scale (Hamburg Scale)
time frame: 3 years
description: Disease specific tool used to capture 4 domains including motor function, seizures, visual function and language. Each sub-scale can be scored from 0-3 points in which 0 represents loss of function.
measure: Electroencephalography (EEG)
time frame: 3 years
description: EEG records electrical brain activity and Interictal discharges (location, focal/generalized, etc) will be compared to baseline and characterized over time.
measure: Vineland Adaptive Behavior Scale, 2nd Edition (Vineland-II)
time frame: 3 years
description: Standard assessment measuring communication, socializing, and daily living skills to assess their overall adaptive functioning for individuals up to 90 years of age. A higher score generally corresponds with higher adaptive function.
measure: Caregiver Global Impression of Change (CaGI-C)
time frame: 3 years
description: The CaGI-C is a caregiver reported outcome measure designed to assess any change in the subject's presentation over the preceding 7 days, as compared to the previous visit.
arm group label: Prospective
description: Subjects who meet eligibility criteria and enroll in the prospective arm will be assessed every 6 months ± 4 weeks for a period of up to 3 years, according to the Schedule of Assessments.
Subjects in the Prospective arm may also participate in the Retrospective arm.
arm group label: Retrospective
description: Upon confirmation of eligibility criteria, the site will obtain an Informed Consent/Assent form and release of medical records from the subject/legally authorized representative to allow review of the medical records from the subject's primary care physician and/or specialists to confirm the CLN5 diagnosis and disease course. To facilitate collection of the medical records, a caregiver interview will be completed at initial enrollment then once yearly for up to 3 years.
whole blood
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.
last name: Contact Center
phone: 877-237-5020
email: medicalinfo@neurogene.com
facility: 
status: Recruiting
contact: 
country: United States
responsible party type: Sponsor
mesh term: Neuronal Ceroid-Lipofuscinoses