<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/NCT03763136</url>
  </required_header>
  <id_info>
    <org_study_id>JWang</org_study_id>
    <nct_id>NCT03763136</nct_id>
  </id_info>
  <brief_title>Treating Heart Failure With hPSC-CMs</brief_title>
  <acronym>HEAL-CHF</acronym>
  <official_title>Epicardial Injection of Allogeneic Human Pluripotent Stem Cell-derived Cardiomyocytes to Treat Severe Chronic Heart Failure</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Help Therapeutics</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Help Therapeutics</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Heart failure has a high morbidity and mortality because the heart is one of the least&#xD;
      regenerative organs in the human body. Drug treatments for heart failure manage symptoms but&#xD;
      do not restore lost myocytes. Cellular replacement therapy is a potential approach to repair&#xD;
      damaged myocardial tissue, restore cardiac function, which has become a new strategy for the&#xD;
      treatment of heart failure. The purpose of this study is to assess the safety, feasibility&#xD;
      and efficacy of intramyocardial delivery of cardiomyocytes at the time of coronary artery&#xD;
      bypass grafting in patients with chronic heart failure.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Patients with heart failure will be treated with allogenic human pluripotent stem&#xD;
      cell-derived cardiomyocytes ( hPSC-CM ) from healthy donors. The cells will be injected&#xD;
      directly into the myocardium at time of coronary artery bypass grafting. Patients will be&#xD;
      assessed at 1, 3, 6 and 12 months after cell transplantation for safety, feasibility and&#xD;
      efficacy.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">October 8, 2021</start_date>
  <completion_date type="Anticipated">July 31, 2023</completion_date>
  <primary_completion_date type="Anticipated">December 31, 2022</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>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Outcomes Assessor)</masking>
    <masking_description>The study adopts a &quot;single-blind design plus double-blind management&quot; principle. To ensure the study results are evaluated without bias, participants and outcomes assessors will not be informed the randomization details.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Incidence of sustained ventricular arrhythmias</measure>
    <time_frame>1~6 Month Post-operation</time_frame>
    <description>defined as the proportion of patients experiencing ventricular arrhythmias lasting more than 30 seconds</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Incidence of newly formed tumors</measure>
    <time_frame>1~6 Month Post-operation</time_frame>
    <description>by comparing chest, abdominal and pelvic CT scan and PET-CT scan</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Overall Left Ventricular systolic performance as assessed by MRI</measure>
    <time_frame>Baseline, 1, 3, 6 and 12 Months Post-operation</time_frame>
    <description>Size of infracted myocardium, left ventricular side wall thickness at diastolic, interventricular septum thickness, left ventricular ejection fraction, left ventricular end-systolic volume and end-diastolic volume, stroke volume, cardiac output, myocardium density and left ventricular mass at diastolic will be evaluated and compared to baseline values.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Left Ventricular systolic performance as assessed by Echocardiogram</measure>
    <time_frame>Baseline, 1, 3, 6 and 12 Months Post-operation</time_frame>
    <description>Interventricular septum thickness at diastolic, left ventricular end-systolic diameter and end-diastolic diameter, left ventricular posterior wall thickness at diastolic, left atrial diameter, left ventricular ejection fraction, mitral flow pattern (E/A) will be evaluated and compared to baseline values.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Left Ventricular systolic performance as assessed by PET/ECT Scan</measure>
    <time_frame>Baseline, 6 and 12 Months Post-operation</time_frame>
    <description>Myocardium perfusion</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Functional status by 6 minute walk test</measure>
    <time_frame>Baseline, 1, 3, 6 and 12 Months Post-operation</time_frame>
    <description>Evaluate Functional Capacity via the Six Minute Walk Test</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Functional status by New York Heart Association (NYHA) Classification</measure>
    <time_frame>Baseline, 1, 3, 6 and 12 Months Post-operation</time_frame>
    <description>Evaluate Functional Capacity via New York Heart Association (NYHA) Class Determination</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Minnesota Living With Heart Failure Questionnaire (MLHFQ)</measure>
    <time_frame>Baseline, 1, 3, 6 and 12 Months Post-operation</time_frame>
    <description>Evaluate Quality Of Life Changes via Minnesota Living with Heart Failure (MLHF). The Maximum possible scores being 105 and the minimum 0. Higher scores indicate a worse or worsening quality of life, while lower scores or decreasing scores indicate a better quality of life.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of Major Adverse Cardiac Events (MACE)</measure>
    <time_frame>Baseline, 1~12 Months Post-operation</time_frame>
    <description>Major Adverse Cardiac Events (MACE), defined as the composite incidence of (1) death, (2) non-lethal myocardial infraction, and (3) hospitalization for worsening HF</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of Serious Adverse Events (SAE)</measure>
    <time_frame>Baseline, 1~12 Months Post-operation</time_frame>
    <description>SAE justified (all undesirable or unintended diseases or laboratory and imaging disorders and symptoms that occur in subjects after CABG surgery and 12 months postoperative follow-up, or until the subject withdrawals from the study. AE grading will be based on Common Terminology Criteria for Adverse Events (CTCAE) V5.0.)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in penal reactive antibodies (PRA)</measure>
    <time_frame>Baseline, 1, 3, 6 and 12 Months Post-operation</time_frame>
    <description>Changes in penal reactive antibodies (PRA) as assessed via blooddraw</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in donor specific antibodies (DSA)</measure>
    <time_frame>Baseline, 1, 3, 6 and 12 Months Post-operation</time_frame>
    <description>Changes in donor specific antibodies (DSA) as assessed via blooddraw</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of severe arrhythmia</measure>
    <time_frame>First month post-operatively</time_frame>
    <description>Clinically significant arrhythmias will be recorded by Electrocardiogram monitoring</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in cytokines</measure>
    <time_frame>Baseline,1, 3, 6 and 12 Months Post-operation</time_frame>
    <description>Change in NT-proBNP as assessed via blooddraw</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">20</enrollment>
  <condition>Heart Failure</condition>
  <arm_group>
    <arm_group_label>hPSC-CM Therapy</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Procedure: Injection of allogenic human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) during coronary artery bypass grafting surgery. 200 million hPSC-CMs in 2.5-5 mL medium suspension will be injected into the myocardium.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control</arm_group_label>
    <arm_group_type>Sham Comparator</arm_group_type>
    <description>Procedure: Coronary artery bypass grafting surgery only.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>hPSC-CM Therapy</intervention_name>
    <description>Injection of allogenic human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) during coronary artery bypass grafting surgery. 200 million hPSC-CMs in 2.5-5 mL medium suspension will be injected into the myocardium.</description>
    <arm_group_label>Control</arm_group_label>
    <arm_group_label>hPSC-CM Therapy</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion criteria&#xD;
&#xD;
          1. Aged 35-75 (including 35 and 75).&#xD;
&#xD;
          2. Have signed the Informed Consent Form (ICF).&#xD;
&#xD;
          3. Patients have chronic left ventricular dysfunction.&#xD;
&#xD;
          4. Patients have NYHA Class III-IV cardiac function even after improved medication for&#xD;
             the treatment of advanced chronic heart failure.&#xD;
&#xD;
          5. Patients have indications for Coronary Artery Bypass Grafting.&#xD;
&#xD;
          6. 20% ≤ LVEF ≤ 45% as determined by echocardiogram (data collected up to 6 months prior&#xD;
             to inclusion evaluation are valid; data collected within 1 month since a myocardial&#xD;
             infarction are invalid).&#xD;
&#xD;
          7. Weakening or absence of segmental regional wall motion as determined by standard&#xD;
             imaging.&#xD;
&#xD;
        Exclusion criteria&#xD;
&#xD;
          1. PRA ≥ 20% or DSA-positive.&#xD;
&#xD;
          2. Patient received ICD transplantation, CRT or similar treatment.&#xD;
&#xD;
          3. Patients with valvular heart disease or received heart valvular disease&#xD;
&#xD;
          4. Patients received treatment of percutaneous transluminal coronary intervention (PCI)&#xD;
&#xD;
          5. Patients with atrial fibrillation&#xD;
&#xD;
          6. Patients previously suffered sustained ventricular tachycardia or sudden cardiac&#xD;
             death.&#xD;
&#xD;
          7. Baseline glomerular filtration rate &lt;30ml/min/1.73m2.&#xD;
&#xD;
          8. Liver dysfunction, as evidenced by enzymes (AST and ALT) greater than three times the&#xD;
             ULN.&#xD;
&#xD;
          9. Hematological abnormality: A hematocrit &lt;25% as determined by HCT, white blood&#xD;
             cell&lt;2500/ul or platelet values &lt;100000/ul without another explanation.&#xD;
&#xD;
         10. Known, serious radiographic contrast allergy, penicillin allergy, streptomycin&#xD;
             allergy.&#xD;
&#xD;
         11. Coagulopathy (INR&gt;1.3) not due to a reversible cause.&#xD;
&#xD;
         12. Contra-indication to performance of a MRI scan.&#xD;
&#xD;
         13. Recipients of organ transplant.&#xD;
&#xD;
         14. Clinical history of malignancy within 5 years (patients with prior malignancy must be&#xD;
             disease free for 5 years).&#xD;
&#xD;
         15. Non-cardiac condition that limits lifespan &lt;1 year.&#xD;
&#xD;
         16. On chronic therapy with immunosuppressant medication, such as glucocorticoid and TNFα&#xD;
             antagonist.&#xD;
&#xD;
         17. Patients allergy to or cannot use immunosuppressant.&#xD;
&#xD;
         18. Serum positive for HIV, HBV, HCV, TP.&#xD;
&#xD;
         19. Currently enrolled other investigational therapeutic or device study.&#xD;
&#xD;
         20. Patients who are pregnant or breast feeding.&#xD;
&#xD;
         21. Other conditions that researchers consider not suitable to participate in this study.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>35 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Dongjin Wang, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Jiaxian Wang, MD, PhD</last_name>
    <phone>+86-18565616060</phone>
    <email>wangjx@helpsci.com.cn</email>
  </overall_contact>
  <location>
    <facility>
      <name>HelpThera</name>
      <address>
        <city>Nanjing</city>
        <state>Jiangsu</state>
        <zip>210000</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Jiaxian Wang, Phd</last_name>
      <phone>+86-18565616060</phone>
      <email>wangjx@helpsci.com.cn</email>
    </contact>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>March 2022</verification_date>
  <study_first_submitted>November 9, 2018</study_first_submitted>
  <study_first_submitted_qc>December 1, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 4, 2018</study_first_posted>
  <last_update_submitted>March 24, 2022</last_update_submitted>
  <last_update_submitted_qc>March 24, 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>Heart Failure</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>Results of the trial will be disseminated to study participants through direct consultation with a trial clinician at completion of the trial, as well as through the publication of results.</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Clinical Study Report (CSR)</ipd_info_type>
    <ipd_time_frame>One year after study completed</ipd_time_frame>
    <ipd_access_criteria>Results of the trial will be disseminated to study participants through direct consultation with a trial clinician at completion of the trial, as well as through the publication of results.</ipd_access_criteria>
  </patient_data>
  <!-- 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/NCT03763136
org study id: JWang
nct id: NCT03763136
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
Heart failure has a high morbidity and mortality because the heart is one of the least
      regenerative organs in the human body. Drug treatments for heart failure manage symptoms but
      do not restore lost myocytes. Cellular replacement therapy is a potential approach to repair
      damaged myocardial tissue, restore cardiac function, which has become a new strategy for the
      treatment of heart failure. The purpose of this study is to assess the safety, feasibility
      and efficacy of intramyocardial delivery of cardiomyocytes at the time of coronary artery
      bypass grafting in patients with chronic heart failure.
Patients with heart failure will be treated with allogenic human pluripotent stem
      cell-derived cardiomyocytes ( hPSC-CM ) from healthy donors. The cells will be injected
      directly into the myocardium at time of coronary artery bypass grafting. Patients will be
      assessed at 1, 3, 6 and 12 months after cell transplantation for safety, feasibility and
      efficacy.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Outcomes Assessor)
masking description: The study adopts a "single-blind design plus double-blind management" principle. To ensure the study results are evaluated without bias, participants and outcomes assessors will not be informed the randomization details.
measure: Incidence of sustained ventricular arrhythmias
time frame: 1~6 Month Post-operation
description: defined as the proportion of patients experiencing ventricular arrhythmias lasting more than 30 seconds
measure: Incidence of newly formed tumors
time frame: 1~6 Month Post-operation
description: by comparing chest, abdominal and pelvic CT scan and PET-CT scan
measure: Overall Left Ventricular systolic performance as assessed by MRI
time frame: Baseline, 1, 3, 6 and 12 Months Post-operation
description: Size of infracted myocardium, left ventricular side wall thickness at diastolic, interventricular septum thickness, left ventricular ejection fraction, left ventricular end-systolic volume and end-diastolic volume, stroke volume, cardiac output, myocardium density and left ventricular mass at diastolic will be evaluated and compared to baseline values.
measure: Overall Left Ventricular systolic performance as assessed by Echocardiogram
time frame: Baseline, 1, 3, 6 and 12 Months Post-operation
description: Interventricular septum thickness at diastolic, left ventricular end-systolic diameter and end-diastolic diameter, left ventricular posterior wall thickness at diastolic, left atrial diameter, left ventricular ejection fraction, mitral flow pattern (E/A) will be evaluated and compared to baseline values.
measure: Overall Left Ventricular systolic performance as assessed by PET/ECT Scan
time frame: Baseline, 6 and 12 Months Post-operation
description: Myocardium perfusion
measure: Functional status by 6 minute walk test
time frame: Baseline, 1, 3, 6 and 12 Months Post-operation
description: Evaluate Functional Capacity via the Six Minute Walk Test
measure: Functional status by New York Heart Association (NYHA) Classification
time frame: Baseline, 1, 3, 6 and 12 Months Post-operation
description: Evaluate Functional Capacity via New York Heart Association (NYHA) Class Determination
measure: Minnesota Living With Heart Failure Questionnaire (MLHFQ)
time frame: Baseline, 1, 3, 6 and 12 Months Post-operation
description: Evaluate Quality Of Life Changes via Minnesota Living with Heart Failure (MLHF). The Maximum possible scores being 105 and the minimum 0. Higher scores indicate a worse or worsening quality of life, while lower scores or decreasing scores indicate a better quality of life.
measure: Incidence of Major Adverse Cardiac Events (MACE)
time frame: Baseline, 1~12 Months Post-operation
description: Major Adverse Cardiac Events (MACE), defined as the composite incidence of (1) death, (2) non-lethal myocardial infraction, and (3) hospitalization for worsening HF
measure: Incidence of Serious Adverse Events (SAE)
time frame: Baseline, 1~12 Months Post-operation
description: SAE justified (all undesirable or unintended diseases or laboratory and imaging disorders and symptoms that occur in subjects after CABG surgery and 12 months postoperative follow-up, or until the subject withdrawals from the study. AE grading will be based on Common Terminology Criteria for Adverse Events (CTCAE) V5.0.)
measure: Changes in penal reactive antibodies (PRA)
time frame: Baseline, 1, 3, 6 and 12 Months Post-operation
description: Changes in penal reactive antibodies (PRA) as assessed via blooddraw
measure: Changes in donor specific antibodies (DSA)
time frame: Baseline, 1, 3, 6 and 12 Months Post-operation
description: Changes in donor specific antibodies (DSA) as assessed via blooddraw
measure: Incidence of severe arrhythmia
time frame: First month post-operatively
description: Clinically significant arrhythmias will be recorded by Electrocardiogram monitoring
measure: Changes in cytokines
time frame: Baseline,1, 3, 6 and 12 Months Post-operation
description: Change in NT-proBNP as assessed via blooddraw
arm group label: hPSC-CM Therapy
arm group type: Experimental
description: Procedure: Injection of allogenic human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) during coronary artery bypass grafting surgery. 200 million hPSC-CMs in 2.5-5 mL medium suspension will be injected into the myocardium.
arm group label: Control
arm group type: Sham Comparator
description: Procedure: Coronary artery bypass grafting surgery only.
intervention type: Biological
intervention name: hPSC-CM Therapy
description: Injection of allogenic human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) during coronary artery bypass grafting surgery. 200 million hPSC-CMs in 2.5-5 mL medium suspension will be injected into the myocardium.
arm group label: Control
arm group label: hPSC-CM Therapy
criteria: 
gender: All
minimum age: 35 Years
maximum age: 75 Years
healthy volunteers: No
last name: Dongjin Wang, MD
role: Principal Investigator
affiliation: The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
last name: Jiaxian Wang, MD, PhD
phone: +86-18565616060
email: wangjx@helpsci.com.cn
facility: 
status: Recruiting
contact: 
country: China
responsible party type: Sponsor
mesh term: Heart Failure
sharing ipd: Yes
ipd description: Results of the trial will be disseminated to study participants through direct consultation with a trial clinician at completion of the trial, as well as through the publication of results.
ipd info type: Study Protocol
ipd info type: Clinical Study Report (CSR)
ipd time frame: One year after study completed
ipd access criteria: Results of the trial will be disseminated to study participants through direct consultation with a trial clinician at completion of the trial, as well as through the publication of results.