<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/NCT03796637</url>
  </required_header>
  <id_info>
    <org_study_id>PTC124-GD-046-DMD</org_study_id>
    <secondary_id>2019-001691-11</secondary_id>
    <nct_id>NCT03796637</nct_id>
  </id_info>
  <brief_title>A Study to Assess Dystrophin Levels in Participants With Nonsense Mutation Duchenne Muscular Dystrophy (nmDMD) Who Have Been Treated With Ataluren</brief_title>
  <official_title>Phase 2, Non-Interventional, Clinical Study to Assess Dystrophin Levels in Subjects With Nonsense Mutation Duchenne Muscular Dystrophy Who Have Been Treated With Ataluren for ≥9 Months</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>PTC Therapeutics</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>PTC 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 study is designed to generate additional data on the effect of ataluren for producing&#xD;
      dystrophin protein in nonsense mutation nmDMD participants. This study will evaluate&#xD;
      dystrophin levels from participants with nmDMD who currently have been receiving ataluren for&#xD;
      ≥9 months.&#xD;
&#xD;
      The study will have a single visit (Visit 1).&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">April 11, 2019</start_date>
  <completion_date type="Actual">June 3, 2019</completion_date>
  <primary_completion_date type="Actual">June 3, 2019</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>
    <primary_purpose>Other</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Mean Dystrophin Levels as Measured by Electrochemiluminescence (ECL)</measure>
    <time_frame>Day 1 of biopsy</time_frame>
    <description>The mean dystrophin protein levels were measured by ECL. Dystrophin levels are reported by muscle group (gastrocnemius, tibialis anterior, and across muscle locations). Results below the limit of quantitation were imputed as half of lower limit of quantitation (LLOQ). LLOQ = 0.5 micrograms (μg)/milliliter (mL)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Dystrophin Protein Levels as Determined by Immunohistochemistry</measure>
    <time_frame>Day 1 of biopsy</time_frame>
    <description>Dystrophin levels by IHC mean membrane stain density are reported by muscle group (gastrocnemius, tibialis anterior, and across muscle locations).</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">6</enrollment>
  <condition>Duchenne Muscular Dystrophy</condition>
  <arm_group>
    <arm_group_label>nmDMD Participants</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants who have been receiving ataluren, will be dosed daily 10 milligrams per kilogram (mg/kg) in the morning, 10 mg/kg at midday, and 20 mg/kg in the evening, for &gt;=9 months from ongoing PTC-sponsored nmDMD clinical trials.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ataluren</intervention_name>
    <description>Ataluren will be administered as per the dose and schedule specified in the arm.</description>
    <arm_group_label>nmDMD Participants</arm_group_label>
    <other_name>PTC124</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Evidence of signed and dated informed consent/assent document(s) indicating that the&#xD;
             participant (and/or his parent/legal guardian) has been informed of all pertinent&#xD;
             aspects of the trial.&#xD;
&#xD;
          -  Ambulatory (10 meters walk/run in less than [&lt;] 30 seconds) and functional grade on&#xD;
             the Brooke Upper Extremity Scale of a 1 or a 2.&#xD;
&#xD;
          -  Currently being treated with ataluren 10, 10, 20 mg/kg for &gt;=9 months, with no gap in&#xD;
             treatment of greater than (&gt;) 1 month, in an ongoing PTC-sponsored nmDMD clinical&#xD;
             trial prior to study entry.&#xD;
&#xD;
          -  Phenotypic evidence of duchenne muscular dystrophy (DMD) based on the onset of&#xD;
             characteristic clinical symptoms or signs (for example, proximal muscle weakness,&#xD;
             waddling gait, and Gowers' maneuver) by 6 years of age and an elevated serum creatine&#xD;
             kinase (CK). Medical documentation of phenotypic evidence of DMD needs to be provided&#xD;
             upon request by the medical monitor.&#xD;
&#xD;
          -  Willing to undergo muscle biopsy.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Known contra-indication to muscle biopsy (such as bleeding or clotting disorders).&#xD;
&#xD;
          -  Exposure to another investigational drug within 2 months prior to study enrollment or&#xD;
             ongoing participation in any non-ataluren interventional clinical trial.&#xD;
&#xD;
          -  Requirement for daytime ventilator assistance or any use of invasive mechanical&#xD;
             ventilation via tracheostomy. Note: Evening non-invasive mechanical ventilation such&#xD;
             as use of bilevel positive airway pressure (Bi-PAP) therapy is allowed.&#xD;
&#xD;
          -  Prior or ongoing medical condition (for example, concomitant illness, psychiatric&#xD;
             condition, behavioral disorder), medical history, physical findings or laboratory&#xD;
             abnormality that, in the investigator's opinion, could adversely affect the safety of&#xD;
             the participant, makes it unlikely that the course of treatment or follow-up would be&#xD;
             completed, or could impair the assessment of study results.&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <gender_based>Yes</gender_based>
    <minimum_age>N/A</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Francesco Bibbiani, MD</last_name>
    <role>Study Director</role>
    <affiliation>PTC Therapeutics, Inc.</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of California, Los Angeles (UCLA)</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90025</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>February 2022</verification_date>
  <study_first_submitted>January 4, 2019</study_first_submitted>
  <study_first_submitted_qc>January 4, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 8, 2019</study_first_posted>
  <results_first_submitted>March 9, 2022</results_first_submitted>
  <results_first_submitted_qc>March 9, 2022</results_first_submitted_qc>
  <results_first_posted type="Actual">April 5, 2022</results_first_posted>
  <disposition_first_submitted>April 6, 2020</disposition_first_submitted>
  <disposition_first_submitted_qc>April 6, 2020</disposition_first_submitted_qc>
  <disposition_first_posted type="Actual">April 10, 2020</disposition_first_posted>
  <last_update_submitted>March 9, 2022</last_update_submitted>
  <last_update_submitted_qc>March 9, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">April 5, 2022</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>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>March 20, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/37/NCT03796637/Prot_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Statistical Analysis Plan</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>February 12, 2020</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/37/NCT03796637/SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Ataluren</title>
          <description>Participants who had been receiving ataluren, were dosed daily 10 milligrams (mg)/kilogram (kg) in the morning, 10 mg/kg at midday, and 20 mg/kg in the evening, for ≥9 months from ongoing PTC-sponsored nmDMD clinical trials.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>Intent-to-treat (ITT) population included all enrolled participants with a valid assessment of dystrophin level, as measured by electrochemiluminescence (ECL).</population>
      <group_list>
        <group group_id="B1">
          <title>Ataluren</title>
          <description>Participants who had been receiving ataluren, were dosed daily 10 mg/kg in the morning, 10 mg/kg at midday, and 20 mg/kg in the evening, for ≥9 months from ongoing PTC-sponsored nmDMD clinical trials.</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="6"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="10.2" spread="2.04"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Mean Dystrophin Levels as Measured by Electrochemiluminescence (ECL)</title>
        <description>The mean dystrophin protein levels were measured by ECL. Dystrophin levels are reported by muscle group (gastrocnemius, tibialis anterior, and across muscle locations). Results below the limit of quantitation were imputed as half of lower limit of quantitation (LLOQ). LLOQ = 0.5 micrograms (μg)/milliliter (mL)</description>
        <time_frame>Day 1 of biopsy</time_frame>
        <population>ITT population included all enrolled participants with a valid assessment of dystrophin level, as measured by ECL.</population>
        <group_list>
          <group group_id="O1">
            <title>Ataluren</title>
            <description>Participants who had been receiving ataluren, were dosed daily 10 mg/kg in the morning, 10 mg/kg at midday, and 20 mg/kg in the evening, for ≥9 months from ongoing PTC-sponsored nmDMD clinical trials.</description>
          </group>
        </group_list>
        <measure>
          <title>Mean Dystrophin Levels as Measured by Electrochemiluminescence (ECL)</title>
          <description>The mean dystrophin protein levels were measured by ECL. Dystrophin levels are reported by muscle group (gastrocnemius, tibialis anterior, and across muscle locations). Results below the limit of quantitation were imputed as half of lower limit of quantitation (LLOQ). LLOQ = 0.5 micrograms (μg)/milliliter (mL)</description>
          <population>ITT population included all enrolled participants with a valid assessment of dystrophin level, as measured by ECL.</population>
          <units>nanograms (ng)/mg</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Gastrocnemius</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0844" spread="0.05874"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Tibialis Anterior</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.1002" spread="0.08060"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Across Muscle Locations</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.1054" spread="0.08300"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Dystrophin Protein Levels as Determined by Immunohistochemistry</title>
        <description>Dystrophin levels by IHC mean membrane stain density are reported by muscle group (gastrocnemius, tibialis anterior, and across muscle locations).</description>
        <time_frame>Day 1 of biopsy</time_frame>
        <population>ITT population included all enrolled participants with a valid assessment of dystrophin level, as measured by ECL.</population>
        <group_list>
          <group group_id="O1">
            <title>Ataluren</title>
            <description>Participants who had been receiving ataluren, were dosed daily 10 mg/kg in the morning, 10 mg/kg at midday, and 20 mg/kg in the evening, for ≥9 months from ongoing PTC-sponsored nmDMD clinical trials.</description>
          </group>
        </group_list>
        <measure>
          <title>Dystrophin Protein Levels as Determined by Immunohistochemistry</title>
          <description>Dystrophin levels by IHC mean membrane stain density are reported by muscle group (gastrocnemius, tibialis anterior, and across muscle locations).</description>
          <population>ITT population included all enrolled participants with a valid assessment of dystrophin level, as measured by ECL.</population>
          <units>ng/mg</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Gastrocnemius</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.28817" spread="0.220547"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Tibialis Anterior</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.26578" spread="0.226510"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Across Muscle Locations</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.30483" spread="0.218600"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Baseline (Day 1) up to Week 1</time_frame>
      <desc>Safety population included all participants who received at least 1 dose of ataluren.</desc>
      <group_list>
        <group group_id="E1">
          <title>Ataluren</title>
          <description>Participants who had been receiving ataluren, were dosed daily 10 mg/kg in the morning, 10 mg/kg at midday, and 20 mg/kg in the evening, for ≥9 months from ongoing PTC-sponsored nmDMD clinical trials.</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA 22.1</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Puncture site discharge</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Procedural pain</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>The Sponsor can review results and/or communications prior to public release and can embargo communications regarding trial results for a period that is up to 180 days from the time submitted to the sponsor for review. The sponsor may consult with the PI to require changes to the communication or extend the embargo.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Medical Information</name_or_title>
      <organization>PTC Therapeutics, Inc.</organization>
      <phone>1-866-562-4620</phone>
      <email>medinfo@ptcbio.com</email>
    </point_of_contact>
  </clinical_results>
</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/NCT03796637
org study id: PTC124-GD-046-DMD
secondary id: 2019-001691-11
nct id: NCT03796637
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
This study is designed to generate additional data on the effect of ataluren for producing
      dystrophin protein in nonsense mutation nmDMD participants. This study will evaluate
      dystrophin levels from participants with nmDMD who currently have been receiving ataluren for
      ≥9 months.

      The study will have a single visit (Visit 1).
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Other
masking: None (Open Label)
measure: Mean Dystrophin Levels as Measured by Electrochemiluminescence (ECL)
time frame: Day 1 of biopsy
description: The mean dystrophin protein levels were measured by ECL. Dystrophin levels are reported by muscle group (gastrocnemius, tibialis anterior, and across muscle locations). Results below the limit of quantitation were imputed as half of lower limit of quantitation (LLOQ). LLOQ = 0.5 micrograms (μg)/milliliter (mL)
measure: Dystrophin Protein Levels as Determined by Immunohistochemistry
time frame: Day 1 of biopsy
description: Dystrophin levels by IHC mean membrane stain density are reported by muscle group (gastrocnemius, tibialis anterior, and across muscle locations).
arm group label: nmDMD Participants
arm group type: Experimental
description: Participants who have been receiving ataluren, will be dosed daily 10 milligrams per kilogram (mg/kg) in the morning, 10 mg/kg at midday, and 20 mg/kg in the evening, for >=9 months from ongoing PTC-sponsored nmDMD clinical trials.
intervention type: Drug
intervention name: Ataluren
description: Ataluren will be administered as per the dose and schedule specified in the arm.
arm group label: nmDMD Participants
other name: PTC124
criteria: 
gender: Male
gender based: Yes
minimum age: N/A
maximum age: N/A
healthy volunteers: No
last name: Francesco Bibbiani, MD
role: Study Director
affiliation: PTC Therapeutics, Inc.
facility: 
country: United States
responsible party type: Sponsor
mesh term: Muscular Dystrophies
mesh term: Muscular Dystrophy, Duchenne
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 