xml: <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/NCT06014541</url>
    </required_header>
    <id_info>
      <org_study_id>NH00006</org_study_id>
      <nct_id>NCT06014541</nct_id>
    </id_info>
    <brief_title>Observational Study to Characterize Biomarkers and Disease Progression in Participants With Methyl CpG Binding Protein 2 (MECP2) Duplication Syndrome</brief_title>
    <official_title>A Prospective and Retrospective Observational/Non-interventional Study to Characterize Biomarkers and Disease Progression in Patients With MECP2 Duplication Syndrome</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Ionis Pharmaceuticals, Inc.</agency>
        <agency_class>Industry</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Ionis Pharmaceuticals, 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>
        The purpose of the study is to prospectively assess longitudinal changes in biomarkers&#xD;
        (MECP2, potential biomarkers of target engagement and disease activity) in cerebrospinal&#xD;
        fluid (CSF) and blood; characterize longitudinal changes in performance on clinical scales&#xD;
        (clinician-reported measures of neurodevelopment and functioning) and caregiver-reported&#xD;
        outcome assessments (communication, gastrointestinal, social-emotional-adaptive behavioral&#xD;
        measures); evaluate longitudinal changes in caregiver-reported health-related quality-of-life&#xD;
        measures; and assess the frequency, type, and severity of seizures over time.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        This is a multi-center, non-randomized, non-interventional prospective and retrospective&#xD;
        study in up to 40 participants with MECP2 duplication syndrome (MDS) who can undergo general&#xD;
        anesthesia or conscious sedation to collect fluid biomarkers (CSF and blood), undergo&#xD;
        electrophysiological assessments (electroencephalogram [EEG], evoked potentials [EP],&#xD;
        pupillometry), clinical assessments and caregiver reported outcomes measures, to be used in&#xD;
        support of the development of therapies for MDS. The study duration for each participant will&#xD;
        be approximately 110 weeks.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">August 2023</start_date>
    <completion_date type="Anticipated">June 2026</completion_date>
    <primary_completion_date type="Anticipated">June 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>Change From Baseline in MeCP2 in the CSF</measure>
      <time_frame>Baseline and on Weeks 13, 26, 39, 52</time_frame>
    </primary_outcome>
    <primary_outcome>
      <measure>Laboratory biomarkers for MECP2 Duplication</measure>
      <time_frame>Baseline and on Weeks 13, 26, 39, 52</time_frame>
      <description>Proteomic analysis of plasma samples to determine biomarkers of disease progression.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Change From Baseline in MECP2 Duplication Syndrome Severity Scale Across All Domains</measure>
      <time_frame>Baseline and on Weeks 13, 26, 39, 52, 78, 104</time_frame>
    </primary_outcome>
    <primary_outcome>
      <measure>Change From Baseline in the Revised Motor Behavioral Assessment</measure>
      <time_frame>Baseline and on Weeks 13, 26, 39, 52, 78, 104</time_frame>
    </primary_outcome>
    <primary_outcome>
      <measure>Change From Baseline in the Bayley Scales of Infant and Toddler Development, 3rd Edition</measure>
      <time_frame>Baseline and on Weeks 13, 26, 39, 52, 78, 104</time_frame>
    </primary_outcome>
    <primary_outcome>
      <measure>Change From Baseline in Vineland Adaptive Behavior Scales 3rd Edition</measure>
      <time_frame>Baseline and on Weeks 13, 26, 39, 52, 78, 104</time_frame>
    </primary_outcome>
    <primary_outcome>
      <measure>Change From Baseline in Observer Reported Communication Ability Measure</measure>
      <time_frame>Baseline and on Weeks 13, 26, 39, 52, 78, 104</time_frame>
    </primary_outcome>
    <primary_outcome>
      <measure>Change From Baseline in Quality-of-Life Inventory-Disability Score</measure>
      <time_frame>Baseline and on Weeks 13, 26, 39, 52, 78, 104</time_frame>
    </primary_outcome>
    <primary_outcome>
      <measure>Change From Baseline in the Frequency of Seizures</measure>
      <time_frame>Baseline and on Weeks 13, 26, 39, 52, 78, 104</time_frame>
    </primary_outcome>
    <primary_outcome>
      <measure>Change From Baseline in Global Assessment of Severity of Epilepsy Scale Score</measure>
      <time_frame>Baseline and on Weeks 13, 26, 39, 52, 78, 104</time_frame>
    </primary_outcome>
    <secondary_outcome>
      <measure>Change From Baseline in Auditory Evoked Potential</measure>
      <time_frame>Baseline and on Weeks 13, 26, 39, 52, 78, 104</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change From Baseline in Visual Evoked Potentials</measure>
      <time_frame>Baseline and on Weeks 13, 26, 39, 52, 78, 104</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Perform a retrospective chart review of the participant's medical history and family history to characterize the natural history of MDS</measure>
      <time_frame>Baseline and on Weeks 13, 26, 39, 52, 78, 104</time_frame>
    </secondary_outcome>
    <number_of_groups>1</number_of_groups>
    <enrollment type="Anticipated">40</enrollment>
    <condition>Methyl CpG Binding Protein 2 (MECP2) Duplication Syndrome</condition>
    <arm_group>
      <arm_group_label>MECP2 Duplication Syndrome Disease Participants</arm_group_label>
      <description>Participants with a diagnosis of MDS with genetic confirmation of MECP2 duplication (or triplication) will undergo CSF and blood collection, electrophysiological and clinical assessments, up to Week 104 as a part of prospective study. Each participant's medical and family history data will be collected retrospectively from available medical notes and charts, from birth up to the end of the study (up to 110 weeks). Participants will have an option to participate in an optional sub-study that will capture pre-defined list of activities at home video.</description>
    </arm_group>
    <biospec_retention>Samples With DNA</biospec_retention>
    <biospec_descr>
      <textblock>
        CSF and blood samples will be collected.&#xD;
      </textblock>
    </biospec_descr>
    <eligibility>
      <study_pop>
        <textblock>
          Participants who have a diagnosis of MDS with genetic confirmation of MECP2 duplication or&#xD;
          triplication will be enrolled into this study.&#xD;
        </textblock>
      </study_pop>
      <sampling_method>Non-Probability Sample</sampling_method>
      <criteria>
        <textblock>
          Key Inclusion Criteria&#xD;
  &#xD;
            -  Participant has a diagnosis of MDS with genetic confirmation of MECP2 duplication (or&#xD;
               triplication)&#xD;
  &#xD;
            -  Participant has a parent or caregiver (CG) ≥ 18 years old capable of providing&#xD;
               informed consent (signed and dated), and able to attend all scheduled study visits and&#xD;
               provide feedback regarding the participant's symptoms and performance as described in&#xD;
               the protocol and be able to comply with all study requirements and activities&#xD;
  &#xD;
            -  Male ≥ 1 month and ≤ 65 years of age&#xD;
  &#xD;
            -  No contraindications for lumbar puncture (LP)'s, blood draws, sedation (if necessary)&#xD;
               or other study activities&#xD;
  &#xD;
            -  Medically stable to complete the study and will tolerate sedation or general&#xD;
               anesthesia and other study activities&#xD;
  &#xD;
          Key Exclusion Criteria&#xD;
  &#xD;
            -  Clinically significant abnormalities in medical history (e.g., clinically significant&#xD;
               renal, hepatic, or cardiac abnormalities; major surgery within 3 months of screening)&#xD;
               or upon physical examination that could potentially impact the NH of MDS&#xD;
  &#xD;
            -  Unwillingness or inability to comply with study procedures, including follow up, as&#xD;
               specified by this protocol, or unwillingness to cooperate fully with the Investigator&#xD;
  &#xD;
            -  Treatment with an investigational drug, gene therapy, stem cell therapy, biological&#xD;
               agent, or device within 30 days of screening, or 5 half-lives of investigational&#xD;
               agent, whichever is longer&#xD;
        </textblock>
      </criteria>
      <gender>Male</gender>
      <gender_based>Yes</gender_based>
      <gender_description>Male participants who have a diagnosis of MDS, with genetic confirmation of MECP2 duplication (or triplication) will be enrolled.</gender_description>
      <minimum_age>1 Month</minimum_age>
      <maximum_age>65 Years</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_contact>
      <last_name>Ionis Pharmaceuticals, Inc.</last_name>
      <phone>(844) 662-0293</phone>
      <email>ionisMDSNaturalHistorystudy@clinicaltrialmedia.com</email>
    </overall_contact>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>August 9, 2023</study_first_submitted>
    <study_first_submitted_qc>August 23, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 28, 2023</study_first_posted>
    <last_update_submitted>August 23, 2023</last_update_submitted>
    <last_update_submitted_qc>August 23, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 28, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <keyword>MDS</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Rett Syndrome</mesh_term>
      <mesh_term>Syndrome</mesh_term>
      <mesh_term>Disease Progression</mesh_term>
    </condition_browse>
    <patient_data>
      <sharing_ipd>No</sharing_ipd>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT06014541
  org study id: NH00006
  nct id: NCT06014541
  lead sponsor: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  The purpose of the study is to prospectively assess longitudinal changes in biomarkers
        (MECP2, potential biomarkers of target engagement and disease activity) in cerebrospinal
        fluid (CSF) and blood; characterize longitudinal changes in performance on clinical scales
        (clinician-reported measures of neurodevelopment and functioning) and caregiver-reported
        outcome assessments (communication, gastrointestinal, social-emotional-adaptive behavioral
        measures); evaluate longitudinal changes in caregiver-reported health-related quality-of-life
        measures; and assess the frequency, type, and severity of seizures over time.
  This is a multi-center, non-randomized, non-interventional prospective and retrospective
        study in up to 40 participants with MECP2 duplication syndrome (MDS) who can undergo general
        anesthesia or conscious sedation to collect fluid biomarkers (CSF and blood), undergo
        electrophysiological assessments (electroencephalogram [EEG], evoked potentials [EP],
        pupillometry), clinical assessments and caregiver reported outcomes measures, to be used in
        support of the development of therapies for MDS. The study duration for each participant will
        be approximately 110 weeks.
  observational model: Cohort
  time perspective: Other
  measure: Change From Baseline in MeCP2 in the CSF
  time frame: Baseline and on Weeks 13, 26, 39, 52
  measure: Laboratory biomarkers for MECP2 Duplication
  time frame: Baseline and on Weeks 13, 26, 39, 52
  description: Proteomic analysis of plasma samples to determine biomarkers of disease progression.
  measure: Change From Baseline in MECP2 Duplication Syndrome Severity Scale Across All Domains
  time frame: Baseline and on Weeks 13, 26, 39, 52, 78, 104
  measure: Change From Baseline in the Revised Motor Behavioral Assessment
  time frame: Baseline and on Weeks 13, 26, 39, 52, 78, 104
  measure: Change From Baseline in the Bayley Scales of Infant and Toddler Development, 3rd Edition
  time frame: Baseline and on Weeks 13, 26, 39, 52, 78, 104
  measure: Change From Baseline in Vineland Adaptive Behavior Scales 3rd Edition
  time frame: Baseline and on Weeks 13, 26, 39, 52, 78, 104
  measure: Change From Baseline in Observer Reported Communication Ability Measure
  time frame: Baseline and on Weeks 13, 26, 39, 52, 78, 104
  measure: Change From Baseline in Quality-of-Life Inventory-Disability Score
  time frame: Baseline and on Weeks 13, 26, 39, 52, 78, 104
  measure: Change From Baseline in the Frequency of Seizures
  time frame: Baseline and on Weeks 13, 26, 39, 52, 78, 104
  measure: Change From Baseline in Global Assessment of Severity of Epilepsy Scale Score
  time frame: Baseline and on Weeks 13, 26, 39, 52, 78, 104
  measure: Change From Baseline in Auditory Evoked Potential
  time frame: Baseline and on Weeks 13, 26, 39, 52, 78, 104
  measure: Change From Baseline in Visual Evoked Potentials
  time frame: Baseline and on Weeks 13, 26, 39, 52, 78, 104
  measure: Perform a retrospective chart review of the participant's medical history and family history to characterize the natural history of MDS
  time frame: Baseline and on Weeks 13, 26, 39, 52, 78, 104
  arm group label: MECP2 Duplication Syndrome Disease Participants
  description: Participants with a diagnosis of MDS with genetic confirmation of MECP2 duplication (or triplication) will undergo CSF and blood collection, electrophysiological and clinical assessments, up to Week 104 as a part of prospective study. Each participant's medical and family history data will be collected retrospectively from available medical notes and charts, from birth up to the end of the study (up to 110 weeks). Participants will have an option to participate in an optional sub-study that will capture pre-defined list of activities at home video.
  CSF and blood samples will be collected.
  study pop: 
  sampling method: Non-Probability Sample
  criteria: 
  gender: Male
  gender based: Yes
  gender description: Male participants who have a diagnosis of MDS, with genetic confirmation of MECP2 duplication (or triplication) will be enrolled.
  minimum age: 1 Month
  maximum age: 65 Years
  healthy volunteers: No
  last name: Ionis Pharmaceuticals, Inc.
  phone: (844) 662-0293
  email: ionisMDSNaturalHistorystudy@clinicaltrialmedia.com
  responsible party type: Sponsor
  mesh term: Rett Syndrome
  mesh term: Syndrome
  mesh term: Disease Progression
  sharing ipd: No