<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/NCT04475549</url>
  </required_header>
  <id_info>
    <org_study_id>C6463-201</org_study_id>
    <secondary_id>CY6463</secondary_id>
    <nct_id>NCT04475549</nct_id>
  </id_info>
  <brief_title>Phase 2a Study of IW-6463 in Adults Diagnosed With Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-like Episodes (MELAS)</brief_title>
  <official_title>A Phase 2a Safety, Tolerability, Pharmacokinetic, and Pharmacodynamic Study in Individuals With Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-like Episodes (MELAS)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Cyclerion Therapeutics</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Cyclerion Therapeutics</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>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a single-arm study to evaluate safety and tolerability of oral IW-6463 in adults&#xD;
      diagnosed with MELAS.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      IW-6463 tablets will be orally administered once-daily (QD) for up to 29 days&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Study terminated due to enrollment challenges.&#xD;
  </why_stopped>
  <start_date type="Actual">November 13, 2020</start_date>
  <completion_date type="Actual">January 23, 2022</completion_date>
  <primary_completion_date type="Actual">January 23, 2022</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <intervention_model_description>Open-label, single-arm study with daily dosing for up to 29 days.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number (or %) of participants who discontinue or dose reduced the study drug due to a treatment-emergent adverse event (TEAE)</measure>
    <time_frame>From first dose date to Day 43 (±4)</time_frame>
    <description>TEAE is defined as an adverse event with an onset that occurs after receiving the study drug, until the end of study period</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number (or %) of participants who experience at least one treatment-emergent adverse event (TEAE)</measure>
    <time_frame>From first dose date to Day 43 (±4)</time_frame>
    <description>TEAE is defined as an adverse event with an onset that occurs after receiving the study drug, until the end of study period</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number (or %) of participants who experience at least one treatment-emergent adverse event (TEAE) by severity</measure>
    <time_frame>From first dose date to Day 43 (±4)</time_frame>
    <description>TEAE is defined as an adverse event with an onset that occurs after receiving the study drug, until the end of study period</description>
  </primary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">8</enrollment>
  <condition>MELAS</condition>
  <arm_group>
    <arm_group_label>IW-6463</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Open-label IW-6463 15 mg once daily (QD), with possibility to dose reduce to 10 mg.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>IW-6463 Tablets</intervention_name>
    <description>IW-6463 tablets administered orally (daily)</description>
    <arm_group_label>IW-6463</arm_group_label>
    <other_name>CY6463</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Prior genetic confirmation of a known mitochondrial disease mutation&#xD;
&#xD;
          2. Neurological features of MELAS (can be based on medical history)&#xD;
&#xD;
          3. Elevated plasma lactate levels at Screening Visit (≥1.0 mmol/L)&#xD;
&#xD;
          4. Women of childbearing potential must have a negative pregnancy test prior to&#xD;
             randomization and must agree to use protocol-specified contraception from the&#xD;
             Screening Visit through 90 days after the final dose of study drug.&#xD;
&#xD;
          5. Male participants must be surgically sterile by vasectomy (conducted ≥60 days before&#xD;
             the Screening Visit or confirmed via sperm analysis) or must agree to use&#xD;
             protocol-specified contraception and agree to refrain from sperm donation from the&#xD;
             Screening Visit through 90 days after the final dose of study drug.&#xD;
&#xD;
          6. Other inclusion criteria per protocol&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Positive pregnancy test at Screening or on Day 1&#xD;
&#xD;
          2. Hypotension defined as systolic blood pressure (BP) ≤90 mmHg or diastolic BP ≤60 mmHg&#xD;
             at Screening or predose at Day 1&#xD;
&#xD;
          3. Hypertension defined as systolic BP &gt;160 mmHg or diastolic BP &gt;100 mmHg, at Screening&#xD;
             or predose at Day 1&#xD;
&#xD;
          4. Uncontrolled diabetes&#xD;
&#xD;
          5. Severe gastrointestinal dysmotility as determined by the investigator that may impact&#xD;
             compliance and/or oral drug administration, absorption and exposure.&#xD;
&#xD;
          6. Unable to fast for 3-4 hours after a meal&#xD;
&#xD;
          7. Unable or unwilling to adhere to the study schedule, lifestyle restrictions,&#xD;
             assessment requirements or, in the clinical judgment of the investigator, is otherwise&#xD;
             not suitable for study participation.&#xD;
&#xD;
          8. Current or past history of clinically significant cardiomyopathy and/or cardiac&#xD;
             conduction abnormality&#xD;
&#xD;
          9. Used any nicotine-containing products (eg, cigarettes, e-cigarettes, vape pens,&#xD;
             cigars) within 1 month of enrollment&#xD;
&#xD;
         10. Other exclusion criteria per protocol&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Chad Glasser, PharmD</last_name>
    <role>Study Director</role>
    <affiliation>Cyclerion Therapeutics, Inc.</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Children's National Hospital of DC</name>
      <address>
        <city>Washington</city>
        <state>District of Columbia</state>
        <zip>20010</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Johns Hopkins University</name>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <zip>21205</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Massachusetts General Hospital</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02114</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Columbia University</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10032</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Children's Hospital of Philadelphia</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>January 2023</verification_date>
  <study_first_submitted>July 14, 2020</study_first_submitted>
  <study_first_submitted_qc>July 14, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 17, 2020</study_first_posted>
  <disposition_first_submitted>January 20, 2023</disposition_first_submitted>
  <disposition_first_submitted_qc>January 20, 2023</disposition_first_submitted_qc>
  <disposition_first_posted type="Actual">January 25, 2023</disposition_first_posted>
  <last_update_submitted>January 20, 2023</last_update_submitted>
  <last_update_submitted_qc>January 20, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">January 25, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>mitochondrial disease</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>MELAS Syndrome</mesh_term>
    <mesh_term>Mitochondrial Encephalomyopathies</mesh_term>
    <mesh_term>Acidosis</mesh_term>
    <mesh_term>Acidosis, Lactic</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted, but a results disposition has been submitted           -->
</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/NCT04475549
org study id: C6463-201
secondary id: CY6463
nct id: NCT04475549
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
This is a single-arm study to evaluate safety and tolerability of oral IW-6463 in adults
      diagnosed with MELAS.
IW-6463 tablets will be orally administered once-daily (QD) for up to 29 days
allocation: N/A
intervention model: Single Group Assignment
intervention model description: Open-label, single-arm study with daily dosing for up to 29 days.
primary purpose: Treatment
masking: None (Open Label)
measure: Number (or %) of participants who discontinue or dose reduced the study drug due to a treatment-emergent adverse event (TEAE)
time frame: From first dose date to Day 43 (±4)
description: TEAE is defined as an adverse event with an onset that occurs after receiving the study drug, until the end of study period
measure: Number (or %) of participants who experience at least one treatment-emergent adverse event (TEAE)
time frame: From first dose date to Day 43 (±4)
description: TEAE is defined as an adverse event with an onset that occurs after receiving the study drug, until the end of study period
measure: Number (or %) of participants who experience at least one treatment-emergent adverse event (TEAE) by severity
time frame: From first dose date to Day 43 (±4)
description: TEAE is defined as an adverse event with an onset that occurs after receiving the study drug, until the end of study period
arm group label: IW-6463
arm group type: Experimental
description: Open-label IW-6463 15 mg once daily (QD), with possibility to dose reduce to 10 mg.
intervention type: Drug
intervention name: IW-6463 Tablets
description: IW-6463 tablets administered orally (daily)
arm group label: IW-6463
other name: CY6463
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Chad Glasser, PharmD
role: Study Director
affiliation: Cyclerion Therapeutics, Inc.
facility: 
facility: 
facility: 
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: MELAS Syndrome
mesh term: Mitochondrial Encephalomyopathies
mesh term: Acidosis
mesh term: Acidosis, Lactic
sharing ipd: No