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/NCT05996003</url>
    </required_header>
    <id_info>
      <org_study_id>NS-089/NCNP-02-201</org_study_id>
      <nct_id>NCT05996003</nct_id>
    </id_info>
    <brief_title>NS-089/NCNP-02-201 in Boys With Duchenne Muscular Dystrophy (DMD)</brief_title>
    <official_title>A Phase 2 Study to Assess the Efficacy, Safety, Tolerability, and Pharmacokinetics of NS-089/NCNP-02 in Boys With Duchenne Muscular Dystrophy (DMD)</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>NS Pharma, Inc.</agency>
        <agency_class>Industry</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>NS Pharma, 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>
        This is a Phase 2, open-label, multi-center, 2-part study of NS-089/NCNP-02 administered by&#xD;
        weekly IV infusion to ambulant boys aged ≥4 to &lt;15 years with DMD due to mutations amenable&#xD;
        to exon 44 skipping. Participants will receive a selected dose of NS-089/NCNP-02 administered&#xD;
        once weekly.&#xD;
  &#xD;
        The study consists of 2 parts: Part 1 and Part 2. Six participants (Cohort 1) will&#xD;
        participate in both Part 1 and Part 2, and 14 participants (Cohort 2) will be added for Part&#xD;
        2.&#xD;
      </textblock>
    </brief_summary>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">August 10, 2023</start_date>
    <completion_date type="Anticipated">May 28, 2025</completion_date>
    <primary_completion_date type="Anticipated">May 28, 2025</primary_completion_date>
    <phase>Phase 2</phase>
    <study_type>Interventional</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <allocation>N/A</allocation>
      <intervention_model>Sequential Assignment</intervention_model>
      <primary_purpose>Treatment</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Adverse Event and Adverse Drug Reaction</measure>
      <time_frame>through study completion, up to follow-up phone call for Part 2</time_frame>
    </primary_outcome>
    <primary_outcome>
      <measure>Plasma pharmacokinetic (PK) parameters</measure>
      <time_frame>Day1, Week4 for each dose for Part 1, Day1 and Week24 for Part 2] Maximum plasma concentration (Cmax) of NS-089/NCNP-02</time_frame>
    </primary_outcome>
    <primary_outcome>
      <measure>Plasma pharmacokinetic (PK) parameters</measure>
      <time_frame>Day1, Week4 for each dose for Part 1, Day1 and Week24 for Part 2] Time of the maximum plasma concentration （Tmax） of NS-089/NCNP-02</time_frame>
    </primary_outcome>
    <primary_outcome>
      <measure>Plasma pharmacokinetic (PK) parameters</measure>
      <time_frame>Day1, Week4 for each dose for Part 1, Day1 and Week24 for Part 2] Terminal half-life (T1/2) of NS-089/NCNP-02</time_frame>
    </primary_outcome>
    <primary_outcome>
      <measure>Plasma pharmacokinetic (PK) parameters</measure>
      <time_frame>Day1, Week4 for each dose for Part 1, Day1 and Week24 for Part 2] Area under the concentration-time curve from time 0 to the last time point (AUC0-t) of NS-089/NCNP-02</time_frame>
    </primary_outcome>
    <primary_outcome>
      <measure>Plasma pharmacokinetic (PK) parameters</measure>
      <time_frame>Day1, Week4 for each dose for Part 1, Day1 and Week24 for Part 2] Area under the concentration-time curve from time 0 to infinity (AUC0-∞) of NS-089/NCNP-02</time_frame>
    </primary_outcome>
    <primary_outcome>
      <measure>Plasma pharmacokinetic (PK) parameters</measure>
      <time_frame>[Time Frame: Day1, Week4 for each dose for Part 1, Day1 and Week24 for Part 2] Total body clearance (CLtot) of NS-089/NCNP-02</time_frame>
    </primary_outcome>
    <primary_outcome>
      <measure>Plasma pharmacokinetic (PK) parameters</measure>
      <time_frame>Day1, Week4 for each dose for Part 1, Day1 and Week24 for Part 2] The steady-state volume of distribution (Vdss) of NS-089/NCNP-02</time_frame>
    </primary_outcome>
    <primary_outcome>
      <measure>Urine pharmacokinetic parameters</measure>
      <time_frame>Day1, Week4 for each dose for Part 1, Day1 and Week24 for Part 2] Urinary excretion of NS-089/NCNP-02</time_frame>
    </primary_outcome>
    <primary_outcome>
      <measure>Change from baseline in skeletal muscle dystrophin protein by immunoblot (Western blot).</measure>
      <time_frame>Baseline, Week25</time_frame>
    </primary_outcome>
    <secondary_outcome>
      <measure>Change from baseline in skeletal muscle dystrophin protein by mass spectrometry.</measure>
      <time_frame>Baseline, Week25</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change from baseline in skeletal muscle dystrophin protein levels by immunofluorescence staining.</measure>
      <time_frame>Baseline, Week25</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change from baseline in percentage of exon 44-skipped mRNA of skeletal muscle dystrophin</measure>
      <time_frame>Baseline, Week25</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>North Star Ambulatory Assessment (NSAA) score</measure>
      <time_frame>Baseline, Week13, Week25</time_frame>
      <description>The NSAA is a functional scale devised for use in ambulant children with Duchenne muscular dystrophy (DMD). It consists of 17 activities graded 0 (unable to perform), 1 (performs with modifications), 2 (normal movement). It assesses abilities necessary to remain ambulant that have been found to progressively deteriorate in untreated DMD patients, as well as in other muscular dystrophies such as Becker Muscular Dystrophy. NSAA Total Score ranges from 0 to 34, with a score of 34 implying normal function.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Time to Run/Walk 10 Meters (TTRW)</measure>
      <time_frame>Baseline, Week13, Week25</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Time to Stand (TTSTAND)</measure>
      <time_frame>Baseline, Week13, Week25</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Total distance of 6 Minute Walk Test (6MWT)</measure>
      <time_frame>Baseline, Week13, Week25</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Time to Climb 4 Stairs (TTCLIMB)</measure>
      <time_frame>Baseline, Week13, Week25</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Muscle strength measured by Quantitative Muscle Testing (QMT)</measure>
      <time_frame>Baseline, Week13, Week25</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Grip and pinch strength</measure>
      <time_frame>Baseline, Week13, Week25</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Performance of Upper Limb (PUL) 2.0. score</measure>
      <time_frame>Baseline, Week13, Week25</time_frame>
      <description>The PUL 2.0 provides both a total score and sub-scores for the 3 domains (shoulder, middle, and distal) that in DMD are progressively involved with a proximal to distal gradient. The PUL includes 22 items with an entry item to define the starting functional level. The 22 items are subdivided into the high-level shoulder dimension (6 items), middle level elbow dimension (9 items), and distal wrist and hand dimension (7 items). For weaker patients, a low score on the entry item (0-2) means high level items do not need to be performed. Scoring options vary across the scale between 0-1 and 0-2 according to performance. Each dimension can be scored separately with a maximum score of 12 for the high-level shoulder dimension, 17 for the middle level elbow dimension, and 13 for the distal wrist and hand dimension. A total score can be achieved by adding the 3 level scores (maximum total score of 42).</description>
    </secondary_outcome>
    <number_of_arms>1</number_of_arms>
    <enrollment type="Anticipated">20</enrollment>
    <condition>Duchenne Muscular Dystrophy</condition>
    <arm_group>
      <arm_group_label>NS-089/NCNP-02</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Experimental: NS-089/NCNP-02&#xD;
  NS-089/NCNP-02 solution for infusion (Cohort 1)&#xD;
  NS-089/NCNP-02 solution for infusion (Cohort 2)</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>NS-089/NCNP-02</intervention_name>
      <description>Cohort 1:&#xD;
  Part 1 Dose Level 1-3: a 4-week Treatment Phase at each treatment dose level&#xD;
  Part 2 Single Dose Level: a 24-week Treatment Phase at the MTD of Part 1&#xD;
  Cohort 2:&#xD;
  Part 2 Single Dose Level: a 24-week Treatment Phase at the MTD of Part 1</description>
      <arm_group_label>NS-089/NCNP-02</arm_group_label>
      <other_name>Brogidirsen</other_name>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Male ≥ 4 years and &lt;15 years of age&#xD;
  &#xD;
            -  Confirmed DMD mutation(s) in the dystrophin gene that is amenable to skipping of exon&#xD;
               44 to restore the dystrophin mRNA reading frame&#xD;
  &#xD;
            -  Able to walk independently without assistive devices&#xD;
  &#xD;
            -  Ability to complete the TTSTAND without assistance in &lt;7 seconds&#xD;
  &#xD;
            -  Stable dose of glucocorticoid for at least 3 months and the dose is expected to remain&#xD;
               on a stable dose for the duration of the study.&#xD;
  &#xD;
            -  Other inclusion criteria may apply.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Evidence of symptomatic cardiomyopathy&#xD;
  &#xD;
            -  Current or previous treatment with anabolic steroids (e.g., oxandrolone) or products&#xD;
               containing resveratrol or adenosine triphosphate within 3 months prior to first dose&#xD;
               of study drug&#xD;
  &#xD;
            -  Current or previous treatment with any other investigational drug within 3 months&#xD;
               prior to the first dose of study drug or within 5 times the half-life of a medication,&#xD;
               whichever is longer&#xD;
  &#xD;
            -  Surgery within the 3 months prior to the first dose of study drug or planned during&#xD;
               the study duration&#xD;
  &#xD;
            -  Previously treated in an interventional study of NS-089/NCNP-02&#xD;
  &#xD;
            -  Having taken any gene therapy or other exon-skipping oligonucleotide&#xD;
  &#xD;
            -  Other exclusion criteria may apply.&#xD;
        </textblock>
      </criteria>
      <gender>Male</gender>
      <minimum_age>4 Years</minimum_age>
      <maximum_age>14 Years</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_contact>
      <last_name>Trial info</last_name>
      <phone>1-866-677-4276</phone>
      <email>trialinfo@nspharma.com</email>
    </overall_contact>
    <location>
      <facility>
        <name>Shriners Hospital for Children</name>
        <address>
          <city>Portland</city>
          <state>Oregon</state>
          <zip>97239</zip>
          <country>United States</country>
        </address>
      </facility>
    </location>
    <location_countries>
      <country>United States</country>
    </location_countries>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>July 18, 2023</study_first_submitted>
    <study_first_submitted_qc>August 10, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 16, 2023</study_first_posted>
    <last_update_submitted>August 16, 2023</last_update_submitted>
    <last_update_submitted_qc>August 16, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 21, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Muscular Dystrophies</mesh_term>
      <mesh_term>Muscular Dystrophy, Duchenne</mesh_term>
    </condition_browse>
    <!-- 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/NCT05996003
  org study id: NS-089/NCNP-02-201
  nct id: NCT05996003
  lead sponsor: 
  has dmc: Yes
  is fda regulated drug: Yes
  is fda regulated device: No
  This is a Phase 2, open-label, multi-center, 2-part study of NS-089/NCNP-02 administered by
        weekly IV infusion to ambulant boys aged ≥4 to <15 years with DMD due to mutations amenable
        to exon 44 skipping. Participants will receive a selected dose of NS-089/NCNP-02 administered
        once weekly.
  
        The study consists of 2 parts: Part 1 and Part 2. Six participants (Cohort 1) will
        participate in both Part 1 and Part 2, and 14 participants (Cohort 2) will be added for Part
        2.
  allocation: N/A
  intervention model: Sequential Assignment
  primary purpose: Treatment
  masking: None (Open Label)
  measure: Adverse Event and Adverse Drug Reaction
  time frame: through study completion, up to follow-up phone call for Part 2
  measure: Plasma pharmacokinetic (PK) parameters
  time frame: Day1, Week4 for each dose for Part 1, Day1 and Week24 for Part 2] Maximum plasma concentration (Cmax) of NS-089/NCNP-02
  measure: Plasma pharmacokinetic (PK) parameters
  time frame: Day1, Week4 for each dose for Part 1, Day1 and Week24 for Part 2] Time of the maximum plasma concentration （Tmax） of NS-089/NCNP-02
  measure: Plasma pharmacokinetic (PK) parameters
  time frame: Day1, Week4 for each dose for Part 1, Day1 and Week24 for Part 2] Terminal half-life (T1/2) of NS-089/NCNP-02
  measure: Plasma pharmacokinetic (PK) parameters
  time frame: Day1, Week4 for each dose for Part 1, Day1 and Week24 for Part 2] Area under the concentration-time curve from time 0 to the last time point (AUC0-t) of NS-089/NCNP-02
  measure: Plasma pharmacokinetic (PK) parameters
  time frame: Day1, Week4 for each dose for Part 1, Day1 and Week24 for Part 2] Area under the concentration-time curve from time 0 to infinity (AUC0-∞) of NS-089/NCNP-02
  measure: Plasma pharmacokinetic (PK) parameters
  time frame: [Time Frame: Day1, Week4 for each dose for Part 1, Day1 and Week24 for Part 2] Total body clearance (CLtot) of NS-089/NCNP-02
  measure: Plasma pharmacokinetic (PK) parameters
  time frame: Day1, Week4 for each dose for Part 1, Day1 and Week24 for Part 2] The steady-state volume of distribution (Vdss) of NS-089/NCNP-02
  measure: Urine pharmacokinetic parameters
  time frame: Day1, Week4 for each dose for Part 1, Day1 and Week24 for Part 2] Urinary excretion of NS-089/NCNP-02
  measure: Change from baseline in skeletal muscle dystrophin protein by immunoblot (Western blot).
  time frame: Baseline, Week25
  measure: Change from baseline in skeletal muscle dystrophin protein by mass spectrometry.
  time frame: Baseline, Week25
  measure: Change from baseline in skeletal muscle dystrophin protein levels by immunofluorescence staining.
  time frame: Baseline, Week25
  measure: Change from baseline in percentage of exon 44-skipped mRNA of skeletal muscle dystrophin
  time frame: Baseline, Week25
  measure: North Star Ambulatory Assessment (NSAA) score
  time frame: Baseline, Week13, Week25
  description: The NSAA is a functional scale devised for use in ambulant children with Duchenne muscular dystrophy (DMD). It consists of 17 activities graded 0 (unable to perform), 1 (performs with modifications), 2 (normal movement). It assesses abilities necessary to remain ambulant that have been found to progressively deteriorate in untreated DMD patients, as well as in other muscular dystrophies such as Becker Muscular Dystrophy. NSAA Total Score ranges from 0 to 34, with a score of 34 implying normal function.
  measure: Time to Run/Walk 10 Meters (TTRW)
  time frame: Baseline, Week13, Week25
  measure: Time to Stand (TTSTAND)
  time frame: Baseline, Week13, Week25
  measure: Total distance of 6 Minute Walk Test (6MWT)
  time frame: Baseline, Week13, Week25
  measure: Time to Climb 4 Stairs (TTCLIMB)
  time frame: Baseline, Week13, Week25
  measure: Muscle strength measured by Quantitative Muscle Testing (QMT)
  time frame: Baseline, Week13, Week25
  measure: Grip and pinch strength
  time frame: Baseline, Week13, Week25
  measure: Performance of Upper Limb (PUL) 2.0. score
  time frame: Baseline, Week13, Week25
  description: The PUL 2.0 provides both a total score and sub-scores for the 3 domains (shoulder, middle, and distal) that in DMD are progressively involved with a proximal to distal gradient. The PUL includes 22 items with an entry item to define the starting functional level. The 22 items are subdivided into the high-level shoulder dimension (6 items), middle level elbow dimension (9 items), and distal wrist and hand dimension (7 items). For weaker patients, a low score on the entry item (0-2) means high level items do not need to be performed. Scoring options vary across the scale between 0-1 and 0-2 according to performance. Each dimension can be scored separately with a maximum score of 12 for the high-level shoulder dimension, 17 for the middle level elbow dimension, and 13 for the distal wrist and hand dimension. A total score can be achieved by adding the 3 level scores (maximum total score of 42).
  arm group label: NS-089/NCNP-02
  arm group type: Experimental
  description: Experimental: NS-089/NCNP-02
  NS-089/NCNP-02 solution for infusion (Cohort 1)
  NS-089/NCNP-02 solution for infusion (Cohort 2)
  intervention type: Drug
  intervention name: NS-089/NCNP-02
  description: Cohort 1:
  Part 1 Dose Level 1-3: a 4-week Treatment Phase at each treatment dose level
  Part 2 Single Dose Level: a 24-week Treatment Phase at the MTD of Part 1
  Cohort 2:
  Part 2 Single Dose Level: a 24-week Treatment Phase at the MTD of Part 1
  arm group label: NS-089/NCNP-02
  other name: Brogidirsen
  criteria: 
  gender: Male
  minimum age: 4 Years
  maximum age: 14 Years
  healthy volunteers: No
  last name: Trial info
  phone: 1-866-677-4276
  email: trialinfo@nspharma.com
  facility: 
  country: United States
  responsible party type: Sponsor
  mesh term: Muscular Dystrophies
  mesh term: Muscular Dystrophy, Duchenne