<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/NCT04428476</url>
  </required_header>
  <id_info>
    <org_study_id>CAP-1002-DMD-02-OLE</org_study_id>
    <nct_id>NCT04428476</nct_id>
  </id_info>
  <brief_title>Open-label Extension of the HOPE-2 Trial</brief_title>
  <acronym>HOPE-2-OLE</acronym>
  <official_title>Open-Label Extension of the HOPE-2 Duchenne Muscular Dystrophy Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Capricor Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Capricor 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 Phase 2, multi-center, open-label extension trial will provide CAP-1002 to subjects that&#xD;
      were enrolled in the HOPE-2 trial and completed 12 months of follow-up. The trial will&#xD;
      explore the safety and efficacy of twelve intravenous administrations of CAP-1002, each&#xD;
      separated by three months. Subjects will undergo a targeted screening during a 30-day&#xD;
      screening period, eligible subjects will then undergo baseline safety and efficacy&#xD;
      assessments on Day 1 prior to their first infusion of CAP-1002.&#xD;
&#xD;
      Subjects will complete trial assessments at Screening; Day 1; Months 3, 6, 9, 12, 15, 18, 21,&#xD;
      24, 27, 30, 33, and 36. Safety and efficacy assessments will be conducted prior to CAP-1002&#xD;
      administration at the Day 1, Months 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33 trial visits,&#xD;
      unless otherwise indicated.&#xD;
&#xD;
      All CAP-1002 infusions will be conducted in an outpatient setting at the investigative site&#xD;
      on Day 1 and Months 3, 6, 9, 12, 15, 18, 21, 24, 27, 30 and 33. Subjects will be observed in&#xD;
      the outpatient setting for at least two hours post infusion and then discharged the same day,&#xD;
      if medically cleared by the site Investigator.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This Phase 2, multi-center, open-label extension trial will provide CAP-1002 to subjects that&#xD;
      were enrolled in the HOPE-2 trial and completed 12 months of follow-up. The trial will&#xD;
      explore the safety and efficacy of twelve intravenous administrations of CAP-1002, each&#xD;
      separated by three months. Subjects will undergo a targeted screening during a 30-day&#xD;
      screening period to determine eligibility based on protocol inclusion and exclusion criteria.&#xD;
&#xD;
      Eligible subjects will undergo baseline safety and efficacy assessments on Day 1 prior to&#xD;
      their first infusion of CAP-1002. Administration of CAP-1002 (Day 1) should occur within a&#xD;
      maximum of 30 days following confirmation of eligibility.&#xD;
&#xD;
      Subjects will complete trial assessments at Screening; Day 1; Months 3, 6, 9, 12 (± 14 days,&#xD;
      each), 15, 18, 21, 24, 27, 30, 30, 33, and 36 (± 21 days, each). Safety and efficacy&#xD;
      assessments will be conducted prior to CAP-1002 administration at the Day 1, Months 3, 6, 9,&#xD;
      12, 15, 18, 21, 24, 27, 30, and 33 trial visits, unless otherwise indicated.&#xD;
&#xD;
      All CAP-1002 infusions will be conducted in an outpatient setting at the investigative site&#xD;
      on Day 1 and Months 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, and 33. Prior to each CAP-1002&#xD;
      administration, medications will be administered to the subject as determined by the&#xD;
      Investigator based on the pre-treatment guidelines as outlined in the protocol and/or&#xD;
      institutional protocols to minimize the risk of potential severe allergic reactions such as&#xD;
      anaphylaxis. Subjects will be observed in the outpatient setting for at least two hours post&#xD;
      infusion and then discharged the same day if medically cleared by the site Investigator. If&#xD;
      clinically indicated, an unscheduled in-person visit will be performed at the investigative&#xD;
      site with targeted assessments based on presentation of signs and symptoms following any&#xD;
      infusion.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">July 20, 2020</start_date>
  <completion_date type="Anticipated">March 2024</completion_date>
  <primary_completion_date type="Actual">February 16, 2022</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>Single Group Assignment</intervention_model>
    <intervention_model_description>Open Label Extension of the HOPE-2 Trial</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>The primary safety endpoint is the incidence and severity of all treatment-emergent adverse events</measure>
    <time_frame>At Month 12 timepoint</time_frame>
    <description>Change from baseline in the incidence and severity of all treatment-emergent adverse events</description>
  </primary_outcome>
  <primary_outcome>
    <measure>The primary efficacy endpoint is change in upper limb function</measure>
    <time_frame>At Month 12 timepoint</time_frame>
    <description>Mean change from baseline in upper limb function assessed by full Performance of the Upper Limb test, version 2 (PUL 2.0). Items are scored on a three-point scale: 0=unable to perform the item, 1=impaired or performs with compensation, 2=performs task without compensation.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Incidence and severity of all treatment-emergent adverse events</measure>
    <time_frame>At Month 24, Month 36 timepoint</time_frame>
    <description>Change from baseline in the incidence and severity of all treatment-emergent adverse events</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline in upper limb function</measure>
    <time_frame>At Month 24 and Month 36 timepoint</time_frame>
    <description>Mean change from baseline in upper limb function assessed by full Performance of the Upper Limb test, version 2 (PUL 2.0). Items are scored on a three-point scale: 0=unable to perform the item, 1=impaired or performs with compensation, 2=performs task without compensation.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from from baseline in distal-level (wrist and hand) upper limb function</measure>
    <time_frame>At Month 12, Month 24, Month 36 timepoint</time_frame>
    <description>Mean change from baseline in distal-level (wrist and hand) function assessed by Performance of the Upper Limb test, version 2 (PUL 2.0) for a subgroup of subjects with entry level scores of 2 and 3. Items are scored on a three-point scale: 0=unable to perform the item, 1=impaired or performs with compensation, 2=performs task without compensation.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from from baseline in mid-level (elbow) upper limb function</measure>
    <time_frame>At Month 12, Month 24, Month 36 timepoint</time_frame>
    <description>Mean change from baseline in mid-level (elbow) function assessed by Performance of the Upper Limb test, version 2 (PUL 2.0) for a subgroup of subjects with entry level scores of 4 and 5. Items are scored on a three-point scale: 0=unable to perform the item, 1=impaired or performs with compensation, 2=performs task without compensation.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in cardiac muscle function and structure by assessment of Left Ventricular Ejection Fraction (LVEF)</measure>
    <time_frame>At Month 24, Month 36 timepoint</time_frame>
    <description>Mean change from baseline in LVEF as assessed by Cardiac Magnetic Resonance (cMRI)</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">13</enrollment>
  <condition>Duchenne Muscular Dystrophy</condition>
  <arm_group>
    <arm_group_label>Open-label arm</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Open-label CAP-1002 will be administered to all subjects enrolled in the trial</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>CAP-1002</intervention_name>
    <description>Peripheral infusion of 150 million allogeneic cardiosphere-derived cells administered every three months</description>
    <arm_group_label>Open-label arm</arm_group_label>
    <other_name>Allogeneic Cardiosphere-Derived Cells</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Documented enrollment in the HOPE-2 trial and completion of trial follow-up through&#xD;
             Month 12&#xD;
&#xD;
          2. Willing and able to provide informed consent to participate in the trial if ≥ 18 years&#xD;
             of age, and assent with parental or guardian informed consent if &lt; 18 years of age&#xD;
&#xD;
          3. Adequate venous access for intravenous CAP-1002 infusions in the judgement of the&#xD;
             Investigator&#xD;
&#xD;
          4. Assessed by the Investigator as willing and able to comply with the requirements of&#xD;
             the trial&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Planned or likely major surgery in the next 12 months after planned first infusion&#xD;
&#xD;
          2. Risk of near-term respiratory decompensation in the judgment of the investigator, or&#xD;
             the need for initiation of non-invasive ventilator support as defined by serum&#xD;
             bicarbonate ≥ 29 mmol/L&#xD;
&#xD;
          3. History of non DMD-related chronic respiratory disease including, but not limited to,&#xD;
             asthma, bronchitis, and tuberculosis&#xD;
&#xD;
          4. Acute respiratory illness within 60 days prior to first infusion&#xD;
&#xD;
          5. Known hypersensitivity to dimethyl sulfoxide (DMSO) or bovine products&#xD;
&#xD;
          6. Treatment with an investigational product ≤ 6 months prior to first infusion&#xD;
&#xD;
          7. History, or current use, of drugs or alcohol that could impair ability to comply with&#xD;
             participation in the trial&#xD;
&#xD;
          8. Inability to comply with the investigational plan and follow-up visit schedule for any&#xD;
             reason, in the judgment of the investigator&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>10 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Craig McDonald, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>UC Davis</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Mark Awadalla</last_name>
    <role>Study Director</role>
    <affiliation>Capricor Inc.</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of California, Davis</name>
      <address>
        <city>Sacramento</city>
        <state>California</state>
        <zip>95817</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>Washington University</name>
      <address>
        <city>Saint Louis</city>
        <state>Missouri</state>
        <zip>63110</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cincinnati Children's Hospital Medical Center</name>
      <address>
        <city>Cincinnati</city>
        <state>Ohio</state>
        <zip>45229</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Children's Hospital Wisconsin</name>
      <address>
        <city>Milwaukee</city>
        <state>Wisconsin</state>
        <zip>53226</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>April 2023</verification_date>
  <study_first_submitted>June 9, 2020</study_first_submitted>
  <study_first_submitted_qc>June 9, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 11, 2020</study_first_posted>
  <disposition_first_submitted>February 3, 2023</disposition_first_submitted>
  <disposition_first_submitted_qc>February 3, 2023</disposition_first_submitted_qc>
  <disposition_first_posted type="Actual">February 13, 2023</disposition_first_posted>
  <last_update_submitted>April 28, 2023</last_update_submitted>
  <last_update_submitted_qc>April 28, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">May 3, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>DMD, Muscular dystrophy, Duchenne</keyword>
  <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, 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/NCT04428476
org study id: CAP-1002-DMD-02-OLE
nct id: NCT04428476
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This Phase 2, multi-center, open-label extension trial will provide CAP-1002 to subjects that
      were enrolled in the HOPE-2 trial and completed 12 months of follow-up. The trial will
      explore the safety and efficacy of twelve intravenous administrations of CAP-1002, each
      separated by three months. Subjects will undergo a targeted screening during a 30-day
      screening period, eligible subjects will then undergo baseline safety and efficacy
      assessments on Day 1 prior to their first infusion of CAP-1002.

      Subjects will complete trial assessments at Screening; Day 1; Months 3, 6, 9, 12, 15, 18, 21,
      24, 27, 30, 33, and 36. Safety and efficacy assessments will be conducted prior to CAP-1002
      administration at the Day 1, Months 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33 trial visits,
      unless otherwise indicated.

      All CAP-1002 infusions will be conducted in an outpatient setting at the investigative site
      on Day 1 and Months 3, 6, 9, 12, 15, 18, 21, 24, 27, 30 and 33. Subjects will be observed in
      the outpatient setting for at least two hours post infusion and then discharged the same day,
      if medically cleared by the site Investigator.
This Phase 2, multi-center, open-label extension trial will provide CAP-1002 to subjects that
      were enrolled in the HOPE-2 trial and completed 12 months of follow-up. The trial will
      explore the safety and efficacy of twelve intravenous administrations of CAP-1002, each
      separated by three months. Subjects will undergo a targeted screening during a 30-day
      screening period to determine eligibility based on protocol inclusion and exclusion criteria.

      Eligible subjects will undergo baseline safety and efficacy assessments on Day 1 prior to
      their first infusion of CAP-1002. Administration of CAP-1002 (Day 1) should occur within a
      maximum of 30 days following confirmation of eligibility.

      Subjects will complete trial assessments at Screening; Day 1; Months 3, 6, 9, 12 (± 14 days,
      each), 15, 18, 21, 24, 27, 30, 30, 33, and 36 (± 21 days, each). Safety and efficacy
      assessments will be conducted prior to CAP-1002 administration at the Day 1, Months 3, 6, 9,
      12, 15, 18, 21, 24, 27, 30, and 33 trial visits, unless otherwise indicated.

      All CAP-1002 infusions will be conducted in an outpatient setting at the investigative site
      on Day 1 and Months 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, and 33. Prior to each CAP-1002
      administration, medications will be administered to the subject as determined by the
      Investigator based on the pre-treatment guidelines as outlined in the protocol and/or
      institutional protocols to minimize the risk of potential severe allergic reactions such as
      anaphylaxis. Subjects will be observed in the outpatient setting for at least two hours post
      infusion and then discharged the same day if medically cleared by the site Investigator. If
      clinically indicated, an unscheduled in-person visit will be performed at the investigative
      site with targeted assessments based on presentation of signs and symptoms following any
      infusion.
allocation: N/A
intervention model: Single Group Assignment
intervention model description: Open Label Extension of the HOPE-2 Trial
primary purpose: Treatment
masking: None (Open Label)
measure: The primary safety endpoint is the incidence and severity of all treatment-emergent adverse events
time frame: At Month 12 timepoint
description: Change from baseline in the incidence and severity of all treatment-emergent adverse events
measure: The primary efficacy endpoint is change in upper limb function
time frame: At Month 12 timepoint
description: Mean change from baseline in upper limb function assessed by full Performance of the Upper Limb test, version 2 (PUL 2.0). Items are scored on a three-point scale: 0=unable to perform the item, 1=impaired or performs with compensation, 2=performs task without compensation.
measure: Incidence and severity of all treatment-emergent adverse events
time frame: At Month 24, Month 36 timepoint
description: Change from baseline in the incidence and severity of all treatment-emergent adverse events
measure: Change from baseline in upper limb function
time frame: At Month 24 and Month 36 timepoint
description: Mean change from baseline in upper limb function assessed by full Performance of the Upper Limb test, version 2 (PUL 2.0). Items are scored on a three-point scale: 0=unable to perform the item, 1=impaired or performs with compensation, 2=performs task without compensation.
measure: Change from from baseline in distal-level (wrist and hand) upper limb function
time frame: At Month 12, Month 24, Month 36 timepoint
description: Mean change from baseline in distal-level (wrist and hand) function assessed by Performance of the Upper Limb test, version 2 (PUL 2.0) for a subgroup of subjects with entry level scores of 2 and 3. Items are scored on a three-point scale: 0=unable to perform the item, 1=impaired or performs with compensation, 2=performs task without compensation.
measure: Change from from baseline in mid-level (elbow) upper limb function
time frame: At Month 12, Month 24, Month 36 timepoint
description: Mean change from baseline in mid-level (elbow) function assessed by Performance of the Upper Limb test, version 2 (PUL 2.0) for a subgroup of subjects with entry level scores of 4 and 5. Items are scored on a three-point scale: 0=unable to perform the item, 1=impaired or performs with compensation, 2=performs task without compensation.
measure: Change in cardiac muscle function and structure by assessment of Left Ventricular Ejection Fraction (LVEF)
time frame: At Month 24, Month 36 timepoint
description: Mean change from baseline in LVEF as assessed by Cardiac Magnetic Resonance (cMRI)
arm group label: Open-label arm
arm group type: Other
description: Open-label CAP-1002 will be administered to all subjects enrolled in the trial
intervention type: Biological
intervention name: CAP-1002
description: Peripheral infusion of 150 million allogeneic cardiosphere-derived cells administered every three months
arm group label: Open-label arm
other name: Allogeneic Cardiosphere-Derived Cells
criteria: 
gender: All
minimum age: 10 Years
maximum age: N/A
healthy volunteers: No
last name: Craig McDonald, MD
role: Principal Investigator
affiliation: UC Davis
last name: Mark Awadalla
role: Study Director
affiliation: Capricor Inc.
facility: 
facility: 
facility: 
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Muscular Dystrophies
mesh term: Muscular Dystrophy, Duchenne