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/NCT06013839</url>
    </required_header>
    <id_info>
      <org_study_id>TXA127-DMD-002</org_study_id>
      <nct_id>NCT06013839</nct_id>
    </id_info>
    <brief_title>TXA127 in Non-Ambulant Patients With DMD Cardiomyopathy</brief_title>
    <official_title>A Phase 2, Single-Arm, Open-Label, Multi-Center Study to Evaluate the Safety and Efficacy of TXA127/Angiotensin [1-7] in Non-Ambulant Patients With Duchenne Muscular Dystrophy (DMD) Cardiomyopathy Who Are Receiving Systemic Glucocorticoids</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Constant Therapeutics LLC</agency>
        <agency_class>Industry</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Constant Therapeutics LLC</source>
    <oversight_info>
      <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
      <is_us_export>Yes</is_us_export>
    </oversight_info>
    <brief_summary>
      <textblock>
        This open-label, single-arm multi-center study studying the safety and efficacy of TXA127 on&#xD;
        non-ambulant patients with DMD Cardiomyopathy will comprise of two phases:&#xD;
  &#xD;
          1. 6-month open-label treatment phase: Male DMD patients with documented cardiomyopathy,&#xD;
             will receive a daily subcutaneous injection of TXA127 0.5 mg/kg. Treatment will be&#xD;
             provided for 6 months. Treatment safety will be assessed by collection and review of&#xD;
             AEs, vital signs, ECGs, physical examinations, PFTs, and laboratory parameters on Day 1,&#xD;
             Month 1, and Month 6. Ejection Fraction, upper extremity strength and biomarker levels&#xD;
             will be assessed at these study visits as well. In addition, an abbreviated safety visit&#xD;
             will be conducted at Month 3.&#xD;
  &#xD;
          2. 12-month optional extension phase: Patients will continue the same study drug regime for&#xD;
             an additional 12 months. The primary objective of this phase is to obtain long-term&#xD;
             safety data. Efficacy data will also be collected. Safety, efficacy, and exploratory&#xD;
             biomarkers will be assessed at Month 12 and Month 18, using the same methods as in the&#xD;
             treatment phase. In addition, abbreviated safety visits will be conducted at Month 9 and&#xD;
             Month 15.&#xD;
      </textblock>
    </brief_summary>
    <overall_status>Recruiting</overall_status>
    <start_date type="Actual">August 31, 2023</start_date>
    <completion_date type="Anticipated">December 2024</completion_date>
    <primary_completion_date type="Anticipated">August 2024</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>
      <primary_purpose>Treatment</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>To evaluate the safety of TXA127 in patients with DMD</measure>
      <time_frame>6 months plus 12 month extension</time_frame>
      <description>Incidence of adverse events (AEs), their severity and relationship to treatment</description>
    </primary_outcome>
    <primary_outcome>
      <measure>To evaluate the effects of treatment on ejection fraction (EF)</measure>
      <time_frame>6 months plus 12 month extension</time_frame>
      <description>Percent change in EF, as measured by echocardiogram (ECHO); Absolute change in EF, as measured by echocardiogram</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>To evaluate the effects of treatment on upper extremity muscle function</measure>
      <time_frame>6 months plus 12 month extension</time_frame>
      <description>Percent change in upper extremity strength, as measured by grip strength with a dynamometer; Absolute change in upper extremity strength, as measured by grip strength with a dynamometer</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>To evaluate the effects of treatment on fractional shortening (FS)</measure>
      <time_frame>6 months plus 12 month extension</time_frame>
      <description>Percent and absolute change in fractional shortening as measured by echocardiogram</description>
    </secondary_outcome>
    <other_outcome>
      <measure>To evaluate the effects of treatment on exploratory DMD-related clinical signs, FVC</measure>
      <time_frame>6 months plus 12 month extension</time_frame>
      <description>Forced Vital Capacity (FVC) % predicted&#xD;
  Absolute and percent (where applicable) change in the following biomarkers in the blood:&#xD;
  Troponin and Brain Natriuretic Peptide (BNP)&#xD;
  Brain-derived neurotrophic factor (BDNF)</description>
    </other_outcome>
    <other_outcome>
      <measure>To evaluate the effects of treatment on exploratory DMD-related clinical signs, PEF</measure>
      <time_frame>6 months plus 12 month extension</time_frame>
      <description>Peak Expiratory Flow (PEF) % predicted (if available)&#xD;
  Absolute and percent (where applicable) change in the following biomarkers in the blood:&#xD;
  Troponin and Brain Natriuretic Peptide (BNP)&#xD;
  Brain-derived neurotrophic factor (BDNF)</description>
    </other_outcome>
    <other_outcome>
      <measure>To evaluate the effects of treatment on exploratory DMD-related biomarkers, Troponin</measure>
      <time_frame>6 months plus 12 month extension</time_frame>
      <description>Absolute and percent (where applicable) change in Troponin</description>
    </other_outcome>
    <other_outcome>
      <measure>To evaluate the effects of treatment on exploratory DMD-related biomarkers, BNP</measure>
      <time_frame>6 months plus 12 month extension</time_frame>
      <description>Absolute and percent (where applicable) change in Brain Natriuretic Peptide (BNP)</description>
    </other_outcome>
    <other_outcome>
      <measure>To evaluate the effects of treatment on exploratory DMD-related biomarkers, BDNF</measure>
      <time_frame>6 months plus 12 month extension</time_frame>
      <description>Absolute and percent (where applicable) change in Brain-derived neurotrophic factor (BDNF)</description>
    </other_outcome>
    <number_of_arms>1</number_of_arms>
    <enrollment type="Anticipated">10</enrollment>
    <condition>DMD-Associated Dilated Cardiomyopathy</condition>
    <arm_group>
      <arm_group_label>TXA127 SC 0.5mg/kg/day</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>TXA127 (talfirastide) 0.5mg/kg/day given via subcutaneous injection for 6 months</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>talfirastide</intervention_name>
      <description>TXA127 (talfirastide) is a pharmaceutically formulated angiotensin (1-7) heptapeptide, identical to the endogenously produced, non-hypertensive derivative of angiotensin II (Ang II).</description>
      <arm_group_label>TXA127 SC 0.5mg/kg/day</arm_group_label>
      <other_name>TXA127</other_name>
      <other_name>Angiotensin-(1-7)</other_name>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            1. Male subjects 16 years of age or older who provide informed consent and can follow up&#xD;
               with protocol procedures. Parental or guardian consent is required for subjects at&#xD;
               least 16 years of age but younger than 18 years of age.&#xD;
  &#xD;
            2. Documented diagnosis of Duchenne muscular dystrophy by genetic mutation analysis.&#xD;
  &#xD;
            3. Documented cardiomyopathy, as assessed by echocardiogram with EF &gt;35% and &lt;55% and&#xD;
               fractional shortening of ≤ 28% at the time of screening.&#xD;
  &#xD;
            4. Subjects must be taking systemic glucocorticoids for at least six months prior to&#xD;
               screening.&#xD;
  &#xD;
            5. Subjects taking mineralocorticoid receptor antagonists, must be taking the drug for at&#xD;
               least three months prior to screening&#xD;
  &#xD;
            6. Non-ambulant and cared for by a trained caregiver&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            1. Therapy with intravenous inotropic or vasoactive medications at the time of screening&#xD;
  &#xD;
            2. Planned or likelihood of major surgery in the 6 months after planned enrollment.&#xD;
  &#xD;
            3. Patient is using a left ventricular assist device (LVAD) or actively in the process of&#xD;
               acquiring a LVAD.&#xD;
  &#xD;
            4. Estimated glomerular filtration rate (GFR) &lt;50 mL/min, as calculated by the CKD-EPI&#xD;
               Creatinine equation 2021 (https://www.kidney.org/professionals/kdoqi/gfr_calculator)&#xD;
  &#xD;
            5. Reproducible (+/- 10%) difference between screening and baseline, percent predicted&#xD;
               FVC between 45 and 85, inclusive, using best of 3 efforts at each visit&#xD;
  &#xD;
            6. Patients with non-invasive ventilation, such as CPAP and BiPAP&#xD;
  &#xD;
            7. Patient is suffering from unstable systemic allergic reaction(s), connective tissue&#xD;
               disease or autoimmune disorder(s), requiring active intervention&#xD;
  &#xD;
            8. History of cardiac tumor or current cardiac tumor&#xD;
  &#xD;
            9. Known moderate-to-severe aortic stenosis/insufficiency or severe mitral&#xD;
               stenosis/regurgitation&#xD;
  &#xD;
           10. Current alcohol or drug abuse&#xD;
  &#xD;
           11. Known history of chronic viral hepatitis unless considered cured based on hepatitis C&#xD;
               RNA negative results&#xD;
  &#xD;
           12. Hepatic dysfunction upon screening evidenced by bilirubin levels or gamma-GT levels&#xD;
               above normal, deemed as clinically significant by the PI/Sub-I, and/or abnormal&#xD;
               hematology (hematocrit &lt;25%, WBC &lt;3000/μl, platelets &lt;100,000/μl), without a&#xD;
               reversible, identifiable cause. Total bilirubin elevations &gt; 2 times the upper&#xD;
               reference range, consistent with Gilbert's Syndrome, may be enrolled if there is no&#xD;
               other evidence of liver dysfunction&#xD;
  &#xD;
           13. Uncontrolled diabetes (HbA1c &gt;9.0 percent)&#xD;
  &#xD;
           14. Inability to comply with protocol-related procedures, including required study visits&#xD;
  &#xD;
           15. Any condition or other reason that, in the opinion of the investigator or Medical&#xD;
               Monitor, would render the subject unsuitable for the study&#xD;
  &#xD;
           16. Currently receiving or received within 90 days of enrollment (Day 1) an&#xD;
               investigational treatment on another clinical study or expanded access protocol. This&#xD;
               will include patients currently being treated or who have not completed follow-up to&#xD;
               treatment with an investigational cell-based therapy within 6 months prior to&#xD;
               enrollment and patients actively receiving an investigational therapy for&#xD;
               cardiovascular repair/regeneration.&#xD;
        </textblock>
      </criteria>
      <gender>Male</gender>
      <minimum_age>16 Years</minimum_age>
      <maximum_age>N/A</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Richard L Franklin, MD, PhD</last_name>
      <role>Study Chair</role>
      <affiliation>Constant Therapeutics LLC</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Richard L Franklin, MD, PhD</last_name>
      <phone>1-617-245-0289</phone>
      <phone_ext>101</phone_ext>
      <email>rfranklin@constanttherapeutics.com</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Elizabeth Wagner, MS, MBA</last_name>
      <phone>1-617-245-0289</phone>
      <phone_ext>102</phone_ext>
      <email>ewagner@constanttherapeutics.com</email>
    </overall_contact_backup>
    <location>
      <facility>
        <name>Hadassah Medical Center</name>
        <address>
          <city>Jerusalem</city>
          <country>Israel</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Talia Dor, MD</last_name>
      </contact>
      <investigator>
        <last_name>Talia Dor, MD</last_name>
        <role>Principal Investigator</role>
      </investigator>
    </location>
    <location>
      <facility>
        <name>Sheba Medical Center</name>
        <address>
          <city>Ramat Gan</city>
          <country>Israel</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Amir Dori, MD, PhD</last_name>
      </contact>
      <investigator>
        <last_name>Amir Dori, MD, PhD</last_name>
        <role>Principal Investigator</role>
      </investigator>
    </location>
    <location_countries>
      <country>Israel</country>
    </location_countries>
    <verification_date>September 2023</verification_date>
    <study_first_submitted>August 16, 2023</study_first_submitted>
    <study_first_submitted_qc>August 22, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 28, 2023</study_first_posted>
    <last_update_submitted>September 7, 2023</last_update_submitted>
    <last_update_submitted_qc>September 7, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 8, 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>Cardiomyopathies</mesh_term>
      <mesh_term>Cardiomyopathy, Dilated</mesh_term>
    </condition_browse>
    <intervention_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Angiotensin I (1-7)</mesh_term>
    </intervention_browse>
    <patient_data>
      <sharing_ipd>No</sharing_ipd>
    </patient_data>
    <!-- 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/NCT06013839
  org study id: TXA127-DMD-002
  nct id: NCT06013839
  lead sponsor: 
  is fda regulated drug: Yes
  is fda regulated device: No
  is us export: Yes
  This open-label, single-arm multi-center study studying the safety and efficacy of TXA127 on
        non-ambulant patients with DMD Cardiomyopathy will comprise of two phases:
  
          1. 6-month open-label treatment phase: Male DMD patients with documented cardiomyopathy,
             will receive a daily subcutaneous injection of TXA127 0.5 mg/kg. Treatment will be
             provided for 6 months. Treatment safety will be assessed by collection and review of
             AEs, vital signs, ECGs, physical examinations, PFTs, and laboratory parameters on Day 1,
             Month 1, and Month 6. Ejection Fraction, upper extremity strength and biomarker levels
             will be assessed at these study visits as well. In addition, an abbreviated safety visit
             will be conducted at Month 3.
  
          2. 12-month optional extension phase: Patients will continue the same study drug regime for
             an additional 12 months. The primary objective of this phase is to obtain long-term
             safety data. Efficacy data will also be collected. Safety, efficacy, and exploratory
             biomarkers will be assessed at Month 12 and Month 18, using the same methods as in the
             treatment phase. In addition, abbreviated safety visits will be conducted at Month 9 and
             Month 15.
  allocation: N/A
  intervention model: Single Group Assignment
  primary purpose: Treatment
  masking: None (Open Label)
  measure: To evaluate the safety of TXA127 in patients with DMD
  time frame: 6 months plus 12 month extension
  description: Incidence of adverse events (AEs), their severity and relationship to treatment
  measure: To evaluate the effects of treatment on ejection fraction (EF)
  time frame: 6 months plus 12 month extension
  description: Percent change in EF, as measured by echocardiogram (ECHO); Absolute change in EF, as measured by echocardiogram
  measure: To evaluate the effects of treatment on upper extremity muscle function
  time frame: 6 months plus 12 month extension
  description: Percent change in upper extremity strength, as measured by grip strength with a dynamometer; Absolute change in upper extremity strength, as measured by grip strength with a dynamometer
  measure: To evaluate the effects of treatment on fractional shortening (FS)
  time frame: 6 months plus 12 month extension
  description: Percent and absolute change in fractional shortening as measured by echocardiogram
  measure: To evaluate the effects of treatment on exploratory DMD-related clinical signs, FVC
  time frame: 6 months plus 12 month extension
  description: Forced Vital Capacity (FVC) % predicted
  Absolute and percent (where applicable) change in the following biomarkers in the blood:
  Troponin and Brain Natriuretic Peptide (BNP)
  Brain-derived neurotrophic factor (BDNF)
  measure: To evaluate the effects of treatment on exploratory DMD-related clinical signs, PEF
  time frame: 6 months plus 12 month extension
  description: Peak Expiratory Flow (PEF) % predicted (if available)
  Absolute and percent (where applicable) change in the following biomarkers in the blood:
  Troponin and Brain Natriuretic Peptide (BNP)
  Brain-derived neurotrophic factor (BDNF)
  measure: To evaluate the effects of treatment on exploratory DMD-related biomarkers, Troponin
  time frame: 6 months plus 12 month extension
  description: Absolute and percent (where applicable) change in Troponin
  measure: To evaluate the effects of treatment on exploratory DMD-related biomarkers, BNP
  time frame: 6 months plus 12 month extension
  description: Absolute and percent (where applicable) change in Brain Natriuretic Peptide (BNP)
  measure: To evaluate the effects of treatment on exploratory DMD-related biomarkers, BDNF
  time frame: 6 months plus 12 month extension
  description: Absolute and percent (where applicable) change in Brain-derived neurotrophic factor (BDNF)
  arm group label: TXA127 SC 0.5mg/kg/day
  arm group type: Experimental
  description: TXA127 (talfirastide) 0.5mg/kg/day given via subcutaneous injection for 6 months
  intervention type: Drug
  intervention name: talfirastide
  description: TXA127 (talfirastide) is a pharmaceutically formulated angiotensin (1-7) heptapeptide, identical to the endogenously produced, non-hypertensive derivative of angiotensin II (Ang II).
  arm group label: TXA127 SC 0.5mg/kg/day
  other name: TXA127
  other name: Angiotensin-(1-7)
  criteria: 
  gender: Male
  minimum age: 16 Years
  maximum age: N/A
  healthy volunteers: No
  last name: Richard L Franklin, MD, PhD
  role: Study Chair
  affiliation: Constant Therapeutics LLC
  last name: Richard L Franklin, MD, PhD
  phone: 1-617-245-0289
  phone ext: 101
  email: rfranklin@constanttherapeutics.com
  last name: Elizabeth Wagner, MS, MBA
  phone: 1-617-245-0289
  phone ext: 102
  email: ewagner@constanttherapeutics.com
  facility: 
  status: Recruiting
  contact: 
  investigator: 
  facility: 
  status: Recruiting
  contact: 
  investigator: 
  country: Israel
  responsible party type: Sponsor
  mesh term: Cardiomyopathies
  mesh term: Cardiomyopathy, Dilated
  mesh term: Angiotensin I (1-7)
  sharing ipd: No