<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/NCT04442295</url>
  </required_header>
  <id_info>
    <org_study_id>STK-001-DS-101</org_study_id>
    <nct_id>NCT04442295</nct_id>
  </id_info>
  <brief_title>An Open-Label Study to Investigate the Safety of Single and Multiple Ascending Doses in Children and Adolescents With Dravet Syndrome</brief_title>
  <official_title>An Open-Label Study to Investigate the Safety and Pharmacokinetics of Single and Multiple Ascending Doses of Antisense Oligonucleotide STK-001 in Children and Adolescents With Dravet Syndrome</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Stoke Therapeutics, Inc</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Stoke Therapeutics, Inc</source>
  <oversight_info>
    <has_dmc>Yes</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>
      Stoke Therapeutics is evaluating the safety and tolerability of single and multiple ascending&#xD;
      doses of STK-001 in patients with Dravet syndrome. Change in seizure frequency, overall&#xD;
      clinical status, and quality of life will be measured as secondary endpoints in this&#xD;
      open-label study.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      STK-001 is an investigational new medicine for the treatment of Dravet syndrome. STK-001 is&#xD;
      an antisense oligonucleotide (ASO) that is intended to increase the level of productive SCN1A&#xD;
      messenger RNA (mRNA) and consequently increase the expression of the sodium channel Nav1.1&#xD;
      protein. This RNA-based approach is not gene therapy, but rather RNA modulation, as it does&#xD;
      not manipulate nor insert genetic deoxyribonucleic acid (DNA).&#xD;
&#xD;
      STK-001 is designed to upregulate Nav1.1 protein expression from the nonmutant (wild-type)&#xD;
      copy of the SCN1A gene to restore physiological Nav1.1 levels. Nav1.1 levels are reduced in&#xD;
      people with Dravet syndrome. Stoke has generated preclinical data demonstrating&#xD;
      proof-of-mechanism for STK-001.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">June 3, 2020</start_date>
  <completion_date type="Anticipated">May 4, 2025</completion_date>
  <primary_completion_date type="Anticipated">September 22, 2024</primary_completion_date>
  <phase>Phase 1/Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Sequential Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Safety and Tolerability of single and multiple doses of STK-001 with respect to:</measure>
    <time_frame>Screening (Day -28) until 6 months after single and multiple drug dosing</time_frame>
    <description>Incidence of adverse events&#xD;
incidence of abnormal vital signs&#xD;
Abnormal physical examination findings&#xD;
Abnormal 12-lead electrocardiogram (ECG)&#xD;
Abnormal laboratory parameters</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Pharmacokinetic (PK) Parameters</measure>
    <time_frame>Day 1 (Dosing) until 6 months after single and multiple drug dosing</time_frame>
    <description>Analysis of plasma concentrations of STK-001</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Exposure of STK-001 in Cerebrospinal Fluid (CSF)</measure>
    <time_frame>Day 1 (Dosing) until 6 months after single and multiple drug dosing</time_frame>
    <description>Measurement of STK-001 concentrations</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Measurement of seizure frequency</measure>
    <time_frame>Screening (Day -28) until 6 months after single and multiple drug dosing</time_frame>
    <description>Measured by paper diary</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Caregiver Global Impression of Change Scale</measure>
    <time_frame>Baseline (Day -1) until 6 months after single and multiple drug dosing</time_frame>
    <description>Change from baseline in overall clinical status as measured by the Clinical Global Impression of Change (CGIC).&#xD;
Values of scales:&#xD;
Very much improved&#xD;
Much improved&#xD;
Minimally improved&#xD;
No change&#xD;
Minimally worse&#xD;
Much worse&#xD;
Very much worse</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Clinician-assessed Global Impression of Change Scale</measure>
    <time_frame>Baseline (Day -1) until 6 months after single and multiple drug dosing</time_frame>
    <description>Change from baseline in overall clinical status as measured by the Caregiver Global Impression of Change (CaGIC)&#xD;
Values of scales:&#xD;
Very much improved&#xD;
Much improved&#xD;
Minimally improved&#xD;
No change&#xD;
Minimally worse&#xD;
Much worse&#xD;
Very much worse</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Measurement of Quality of Life</measure>
    <time_frame>Baseline (Day -1) until 6 months after single and multiple drug dosing</time_frame>
    <description>Change in quality of life as measured by the EuroQoL-five dimensions, youth version (EQ-5D-Y) instrument. The scale is scored from 0-100. The reference to a high score indicates a better outcome of quality of life.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">78</enrollment>
  <condition>Dravet Syndrome</condition>
  <arm_group>
    <arm_group_label>Single Ascending Doses</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Enrollment of patients in two age groups. A Sentinel group of 2 patients aged 13 to 18 years of age, inclusive, and an expanded group of 2 patients 2 to 12 years of age to receive single doses. There will be an option to dose up to 6 additional patients at each dose level and an option to expand the maximum tolerated dose level with 5 additional patients.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Multiple Ascending Doses</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Enrollment of patients in two age groups. A Sentinel group of 2 patients aged 13 to 18 years of age, inclusive, and an expanded group of 2 patients 2 to 12 years of age to receive multiple doses. There will be an option to dose up to 6 additional patients at each dose level and an option to expand the maximum tolerated dose level with 10 additional patients.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>STK-001 - Single Ascending Doses</intervention_name>
    <description>Experimental : Single Ascending Doses - STK-001 drug product is an antisense oligonucleotide administered as an intrathecal injection. Four dose levels will be evaluated ( 10mg, 20mg,30mg, 45mg and 70mg ).</description>
    <arm_group_label>Single Ascending Doses</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>STK-001 - Multiple Ascending Doses</intervention_name>
    <description>Experimental : Multiple Ascending Doses - STK-001 drug product is an antisense oligonucleotide administered as an intrathecal injection. Three dose levels will be evaluated ( 20mg,30mg and 45mg ).</description>
    <arm_group_label>Multiple Ascending Doses</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Diagnosis of Dravet Syndrome (DS) with onset of recurrent focal motor or&#xD;
             hemiconvulsive or generalized tonic-clonic seizures prior to 12 months of age, which&#xD;
             are often prolonged and triggered by hyperthermia.&#xD;
&#xD;
               -  No history of causal MRI lesion&#xD;
&#xD;
               -  No other known etiology&#xD;
&#xD;
               -  Normal development at seizure onset.&#xD;
&#xD;
          -  Documented pathogenic, likely pathogenic variant, or variant of uncertain significance&#xD;
             in the SCN1A gene associated with DS.&#xD;
&#xD;
          -  Use of at least 2 prior treatments for epilepsy that either had lack of adequate&#xD;
             seizure control (requiring an additional AED) or had to be discontinued due to an&#xD;
             AE(s).&#xD;
&#xD;
          -  Currently taking at least one AED at a dose which has been stable for at least 4 weeks&#xD;
             prior to Screening.&#xD;
&#xD;
          -  Stable epilepsy medications or interventions for epilepsy (including ketogenic diet or&#xD;
             vagal nerve stimulator) for at least 4 weeks prior to Screening.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Known pathogenic mutation in another gene that causes epilepsy&#xD;
&#xD;
          -  Currently treated with an AED acting primarily as a sodium channel blocker, as&#xD;
             maintenance treatment, including: phenytoin, carbamazepine, oxcarbazepine,&#xD;
             lamotrigine, lacosamide, or rufinamide.&#xD;
&#xD;
          -  Clinically significant unstable medical conditions other than epilepsy.&#xD;
&#xD;
          -  Clinically relevant symptoms or a clinically significant illness in the 4 weeks prior&#xD;
             to Screening or prior to dosing on Day 1, other than epilepsy.&#xD;
&#xD;
          -  History of brain or spinal cord disease (other than epilepsy or DS), or history of&#xD;
             bacterial meningitis or brain malformation&#xD;
&#xD;
          -  Spinal deformity or other condition that may alter the free flow of cerebrospinal&#xD;
             fluid (CSF) or has an implanted CSF drainage shunt.&#xD;
&#xD;
          -  Any other significant disease or disorder which, in the opinion of the Investigator,&#xD;
             may either put the patient at risk because of participation in the study, may&#xD;
             influence the results of the study, or may affect the patient's ability to participate&#xD;
             in the study.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>2 Years</minimum_age>
    <maximum_age>18 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Javier Avendaño, MD</last_name>
    <role>Study Director</role>
    <affiliation>Medical Director</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>UCSF Benioff Children's Hospital</name>
      <address>
        <city>San Francisco</city>
        <state>California</state>
        <zip>94158</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Children's Hospital Colorado</name>
      <address>
        <city>Aurora</city>
        <state>Colorado</state>
        <zip>80045</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Children's National Medical Center</name>
      <address>
        <city>Washington</city>
        <state>District of Columbia</state>
        <zip>20010</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Nicklaus Children's Hospital</name>
      <address>
        <city>Miami</city>
        <state>Florida</state>
        <zip>33155</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>AdventHealth Orlando</name>
      <address>
        <city>Orlando</city>
        <state>Florida</state>
        <zip>32803</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ann &amp; Robert H. Lurie Children's Hospital of Chicago</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60611</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Iowa Hospitals and Clinics; Pediatric Specialty Clinic</name>
      <address>
        <city>Iowa City</city>
        <state>Iowa</state>
        <zip>52242</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Massachusetts General Hospital - Pediatric Epilepsy Program</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02114</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Michigan - Mott Children's Hospital</name>
      <address>
        <city>Ann Arbor</city>
        <state>Michigan</state>
        <zip>48109</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mayo Clinic</name>
      <address>
        <city>Rochester</city>
        <state>Minnesota</state>
        <zip>55905</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>NYU Comprehensive Epilepsy Center</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10016</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Oregon Health &amp; Science University</name>
      <address>
        <city>Portland</city>
        <state>Oregon</state>
        <zip>97239</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>
    <facility>
      <name>Le Bonheur Children's Hospital</name>
      <address>
        <city>Memphis</city>
        <state>Tennessee</state>
        <zip>38105</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cook Children's Health Care System</name>
      <address>
        <city>Fort Worth</city>
        <state>Texas</state>
        <zip>76104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Primary Children's Hospital</name>
      <address>
        <city>Salt Lake City</city>
        <state>Utah</state>
        <zip>84108</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Seattle Children's Hospital</name>
      <address>
        <city>Seattle</city>
        <state>Washington</state>
        <zip>98105</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Multicare Institute for Research and Innovation</name>
      <address>
        <city>Tacoma</city>
        <state>Washington</state>
        <zip>98405</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>June 2023</verification_date>
  <study_first_submitted>June 8, 2020</study_first_submitted>
  <study_first_submitted_qc>June 19, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 22, 2020</study_first_posted>
  <last_update_submitted>June 26, 2023</last_update_submitted>
  <last_update_submitted_qc>June 26, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">June 27, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Pediatric epilepsy</keyword>
  <keyword>Epileptic Encephalopathies</keyword>
  <keyword>Refractory Myoclonic Epilepsy</keyword>
  <keyword>Severe Myoclonic Epilepsy in Infancy</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Epilepsies, Myoclonic</mesh_term>
    <mesh_term>Syndrome</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/NCT04442295
org study id: STK-001-DS-101
nct id: NCT04442295
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
Stoke Therapeutics is evaluating the safety and tolerability of single and multiple ascending
      doses of STK-001 in patients with Dravet syndrome. Change in seizure frequency, overall
      clinical status, and quality of life will be measured as secondary endpoints in this
      open-label study.
STK-001 is an investigational new medicine for the treatment of Dravet syndrome. STK-001 is
      an antisense oligonucleotide (ASO) that is intended to increase the level of productive SCN1A
      messenger RNA (mRNA) and consequently increase the expression of the sodium channel Nav1.1
      protein. This RNA-based approach is not gene therapy, but rather RNA modulation, as it does
      not manipulate nor insert genetic deoxyribonucleic acid (DNA).

      STK-001 is designed to upregulate Nav1.1 protein expression from the nonmutant (wild-type)
      copy of the SCN1A gene to restore physiological Nav1.1 levels. Nav1.1 levels are reduced in
      people with Dravet syndrome. Stoke has generated preclinical data demonstrating
      proof-of-mechanism for STK-001.
allocation: Non-Randomized
intervention model: Sequential Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Safety and Tolerability of single and multiple doses of STK-001 with respect to:
time frame: Screening (Day -28) until 6 months after single and multiple drug dosing
description: Incidence of adverse events
incidence of abnormal vital signs
Abnormal physical examination findings
Abnormal 12-lead electrocardiogram (ECG)
Abnormal laboratory parameters
measure: Pharmacokinetic (PK) Parameters
time frame: Day 1 (Dosing) until 6 months after single and multiple drug dosing
description: Analysis of plasma concentrations of STK-001
measure: Exposure of STK-001 in Cerebrospinal Fluid (CSF)
time frame: Day 1 (Dosing) until 6 months after single and multiple drug dosing
description: Measurement of STK-001 concentrations
measure: Measurement of seizure frequency
time frame: Screening (Day -28) until 6 months after single and multiple drug dosing
description: Measured by paper diary
measure: Change in Caregiver Global Impression of Change Scale
time frame: Baseline (Day -1) until 6 months after single and multiple drug dosing
description: Change from baseline in overall clinical status as measured by the Clinical Global Impression of Change (CGIC).
Values of scales:
Very much improved
Much improved
Minimally improved
No change
Minimally worse
Much worse
Very much worse
measure: Change in Clinician-assessed Global Impression of Change Scale
time frame: Baseline (Day -1) until 6 months after single and multiple drug dosing
description: Change from baseline in overall clinical status as measured by the Caregiver Global Impression of Change (CaGIC)
Values of scales:
Very much improved
Much improved
Minimally improved
No change
Minimally worse
Much worse
Very much worse
measure: Measurement of Quality of Life
time frame: Baseline (Day -1) until 6 months after single and multiple drug dosing
description: Change in quality of life as measured by the EuroQoL-five dimensions, youth version (EQ-5D-Y) instrument. The scale is scored from 0-100. The reference to a high score indicates a better outcome of quality of life.
arm group label: Single Ascending Doses
arm group type: Experimental
description: Enrollment of patients in two age groups. A Sentinel group of 2 patients aged 13 to 18 years of age, inclusive, and an expanded group of 2 patients 2 to 12 years of age to receive single doses. There will be an option to dose up to 6 additional patients at each dose level and an option to expand the maximum tolerated dose level with 5 additional patients.
arm group label: Multiple Ascending Doses
arm group type: Experimental
description: Enrollment of patients in two age groups. A Sentinel group of 2 patients aged 13 to 18 years of age, inclusive, and an expanded group of 2 patients 2 to 12 years of age to receive multiple doses. There will be an option to dose up to 6 additional patients at each dose level and an option to expand the maximum tolerated dose level with 10 additional patients.
intervention type: Drug
intervention name: STK-001 - Single Ascending Doses
description: Experimental : Single Ascending Doses - STK-001 drug product is an antisense oligonucleotide administered as an intrathecal injection. Four dose levels will be evaluated ( 10mg, 20mg,30mg, 45mg and 70mg ).
arm group label: Single Ascending Doses
intervention type: Drug
intervention name: STK-001 - Multiple Ascending Doses
description: Experimental : Multiple Ascending Doses - STK-001 drug product is an antisense oligonucleotide administered as an intrathecal injection. Three dose levels will be evaluated ( 20mg,30mg and 45mg ).
arm group label: Multiple Ascending Doses
criteria: 
gender: All
minimum age: 2 Years
maximum age: 18 Years
healthy volunteers: No
last name: Javier Avendaño, MD
role: Study Director
affiliation: Medical Director
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Epilepsies, Myoclonic
mesh term: Syndrome