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/NCT05984134</url>
    </required_header>
    <id_info>
      <org_study_id>NL005-AMI-IIb</org_study_id>
      <nct_id>NCT05984134</nct_id>
    </id_info>
    <brief_title>Efficacy and Safety Study of Thymosin Beta 4 in Patients With Acute Myocardial Infarction</brief_title>
    <official_title>Efficacy and Safety of Recombinant Human Thymosin β4(NL005) for Injection in Patients With Acute Myocardial Infarction: a Phase IIb Clinical Study</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Beijing Northland Biotech. Co., Ltd.</agency>
        <agency_class>Industry</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Beijing Northland Biotech. Co., Ltd.</source>
    <oversight_info>
      <is_fda_regulated_drug>No</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
    </oversight_info>
    <brief_summary>
      <textblock>
        A multicenter randomized double-blind placebo parallel control design was used in this study.&#xD;
        The 90 participants were randomly assigned to placebo, 0.5μg/kg dose group, and 1.0μg/kg dose&#xD;
        group in a ratio of 1:1:1. After randomization, subjects received the trial drug or placebo&#xD;
        intravenously within 12 hours and on days 2 to 7 after PCI. The patients were observed 90&#xD;
        days after PCI.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        Cardiovascular magnetic resonance imaging (CMR) was performed on day 5 and day 90 after PCI&#xD;
        to evaluate myocardial infarction size, microvascular obstruction area, left ventricular&#xD;
        ejection fraction (LVEF), left ventricular end-systolic volume (LVESV), and left ventricular&#xD;
        end-diastolic volume (LVEDV). Physical examination, blood routine examination, and&#xD;
        coagulation function examination were performed before the first dose, on the 7th, 30th, and&#xD;
        90th day after PCI. The examination before the first dose was conducted to accept the&#xD;
        examination results from the current onset to the first dose.Electrocardiogram (ECG) was&#xD;
        performed before the first dose, day 2, day 7, day 30, and day 90 after PCI, and the test&#xD;
        results from the period after PCI to the first dose were received. Vital signs were examined&#xD;
        before the first dose, day 1 to day 7, day 30, and day 90 after PCI, and the results of the&#xD;
        examination from the first onset to the first dose were accepted during the examination&#xD;
        before the first dose. Blood biochemical tests were performed before the first dose, from day&#xD;
        2 to day 4, day 7, day 30, and day 90 after PCI. The results of the examinations from the&#xD;
        first onset to the first dose were accepted during the examination before the first dose.&#xD;
        High-sensitivity troponin I(hs-cTnI) or troponin I(cTnI) and amino-terminal B-type&#xD;
        natriuretic peptide precursor (NT-proBNP) or B-type natriuretic peptide (BNP) were tested&#xD;
        before first administration and on days 2, 3, 4, and 7 after PCI. Examination results from&#xD;
        the time after PCI to the time before initial administration; Creatine kinase isoenzyme&#xD;
        (CK-MB) tests were performed before the first dose, 12 hours after the first dose, day 2 (if&#xD;
        it coincided with 12 hours after the first dose, no repeat blood collection was required),&#xD;
        day 3, and day 4. The test results from the period after PCI to the period before the first&#xD;
        dose were accepted. Tumor markers were detected and immunogenic blood samples were collected&#xD;
        before the first dose and on the 30th day after PCI. The tumor markers were examined before&#xD;
        the first dose. Urine routine examination was performed before the first dose and on the 90th&#xD;
        day after PCI. The examination before the first dose accepted the examination results from&#xD;
        the onset of the disease to the first dose. Drug combinations, adverse events, and&#xD;
        cardiovascular events were recorded during the trial.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Completed</overall_status>
    <start_date type="Actual">July 15, 2022</start_date>
    <completion_date type="Actual">May 29, 2023</completion_date>
    <primary_completion_date type="Actual">May 26, 2023</primary_completion_date>
    <phase>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>Basic Science</primary_purpose>
      <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Percentage change of myocardial infarction area</measure>
      <time_frame>Day 5、Day 90</time_frame>
      <description>The percentage of myocardial infarction area was defined as the percentage of CMR delayed enhancement area in the entire left ventricular myocardium as measured by plane geometry of computer-assisted enhanced myocardium.Percentage change of myocardial infarction size =D5 percentage of myocardial infarction size -D90 percentage of myocardial infarction size</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Myocardial mass (g)</measure>
      <time_frame>Day 5、Day 90</time_frame>
      <description>Myocardial infarction area was defined as CMR delayed enhancement area, and myocardial mass (g) were calculated , and determined by plane geometry method of computer-aided enhanced myocardium. Myocardial infarction size change =D5 myocardial infarction size -D90 myocardial infarction size.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Myocardial volume (ml)</measure>
      <time_frame>Day 5、Day 90</time_frame>
      <description>Myocardial infarction area was defined as CMR delayed enhancement area, and volume (ml) were calculated, and determined by plane geometry method of computer-aided enhanced myocardium.Myocardial infarction size change =D5 myocardial infarction size -D90 myocardial infarction size.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Myocardial microvessel obstruction area change value</measure>
      <time_frame>Day 5、Day 90</time_frame>
      <description>Myocardial microvessel obstruction area change value =D5 microvessel obstruction area -D90 microvessel obstruction area</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>The change of CK-MB before and after administration</measure>
      <time_frame>Before the first dose, 12 hours after the first dose, day 2, day 3, day 4</time_frame>
      <description>CK-MB change value = CK-MB value before administration - CK-MB value after administration</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>The area under the CK-MB curve within 4 days</measure>
      <time_frame>Before the first dose, 12 hours after the first dose, day 2, day 3, day 4</time_frame>
      <description>CK-MB change value = CK-MB value before administration - CK-MB value after administration</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Changes of left ventricular ejection fraction (LVEF)</measure>
      <time_frame>Day 5、Day 90</time_frame>
      <description>Left ventricular ejection fraction (LVEF) change =D90 LVEF-D5 LVEF</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Changes of left ventricular end-systolic volume (LVESV)</measure>
      <time_frame>Day 5、Day 90</time_frame>
      <description>Left ventricular end-systolic volume (LVESV) change =D90 LVESV-D5 LVESV</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Changes of left ventricular end-diastolic volume (LVEDV)</measure>
      <time_frame>Day 5、Day 90</time_frame>
      <description>Left ventricular end-diastolic volume (LVEDV) change = D90 LVEDV-D5 LVEDV</description>
    </secondary_outcome>
    <number_of_arms>3</number_of_arms>
    <enrollment type="Actual">90</enrollment>
    <condition>Acute Myocardial Infarction</condition>
    <arm_group>
      <arm_group_label>Middle Dose</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>12 hours after PCI: 0.5 ug/kg Recombinant Human Thymosin β4 （intravenous injection），Day2-Day7 after PCI：0.5 ug/kg Recombinant Human Thymosin β4 （intravenous injection）</description>
    </arm_group>
    <arm_group>
      <arm_group_label>High Dose</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>12 hours after PCI: 1.0 ug/kg Recombinant Human Thymosin β4 （intravenous injection），Day2-Day7 after PCI：1.0 ug/kg Recombinant Human Thymosin β4 （intravenous injection）</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Placebo</arm_group_label>
      <arm_group_type>Placebo Comparator</arm_group_type>
      <description>Patients in this treatment group will receive placebo respective. Continuous administration for 7 days.</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Middle Dose</intervention_name>
      <description>Patients in this treatment group will receive NL005 for 0.5 ug/kg respective.Continuous administration for 7 days.</description>
      <arm_group_label>Middle Dose</arm_group_label>
      <other_name>NL005（ Middle Dose）</other_name>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>High Dose</intervention_name>
      <description>Patients in this treatment group will receive NL005 for 1.5 ug/kg respective.Continuous administration for 7 days.</description>
      <arm_group_label>High Dose</arm_group_label>
      <other_name>NL005（ High Dose）</other_name>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Placebo</intervention_name>
      <description>30 subjects will be randomly assigned to the placebo for 7 days</description>
      <arm_group_label>Placebo</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            1. The subjects or their guardians voluntarily participate in the experiment and sign the&#xD;
               informed consent;&#xD;
  &#xD;
            2. Age ≥18 years old and ≤75 years old, gender is not limited;&#xD;
  &#xD;
            3. STEMI patients with proximal or/and middle occlusion of a single left anterior&#xD;
               descending artery (TIMI grade 0-1) and PCI;&#xD;
  &#xD;
            4. No coronary collateral (Rentrop grade 0);&#xD;
  &#xD;
            5. meet one of the following conditions:&#xD;
  &#xD;
                 -  The total myocardial ischemia time before PCI was &lt; 6 hours, and the TIMI grade&#xD;
                    after PCI was &lt; 3&#xD;
  &#xD;
                 -  6 hours ≤ Total myocardial ischemia time before PCI ≤24 hours Note: Total&#xD;
                    myocardial ischemia time =PCI wire passage time - start time of chest pain&#xD;
  &#xD;
            6. All subjects (male and female) must agree to use appropriate contraceptive methods&#xD;
               (hormonal or barrier methods, abstinence) during study participation and up to 6&#xD;
               months of the last dosing, and women of childbearing age must test negative for&#xD;
               pregnancy before dosing.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            1. Patients with a history of myocardial infarction who have received acute coronary&#xD;
               thrombolysis, interventional therapy, or bypass surgery; A clear diagnosis of acute&#xD;
               heart failure (Killip grade ≥III);&#xD;
  &#xD;
            2. Severe arrhythmias that cannot be corrected;&#xD;
  &#xD;
            3. Aortic dissection;&#xD;
  &#xD;
            4. Severe liver and kidney dysfunction or severe consumption;&#xD;
  &#xD;
            5. History of major surgery or hemorrhagic stroke within six months;&#xD;
  &#xD;
            6. Previous history of malignant tumors;&#xD;
  &#xD;
            7. Hypertensive patients with systolic blood pressure ≥180 mmHg and/or diastolic blood&#xD;
               pressure ≥110 mmHg after active antihypertensive treatment;&#xD;
  &#xD;
            8. Clinically significant allergic reaction history, especially mannitol, drugs, protein&#xD;
               preparations, biological products;&#xD;
  &#xD;
            9. Patients who participated in other clinical studies within 3 months prior to&#xD;
               screening;&#xD;
  &#xD;
           10. Can not perform CMR examination;&#xD;
  &#xD;
           11. Other conditions deemed unsuitable for inclusion by the investigators (for example,&#xD;
               those whose coronary arteries other than the left anterior descending branch were&#xD;
               judged by the investigators to require elective revascularization therapy at the same&#xD;
               time or within 1 month).&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>75 Years</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>KeFei Dou</last_name>
      <role>Principal Investigator</role>
      <affiliation>Chinese Academy of Medical Sciences, Fuwai Hospital</affiliation>
    </overall_official>
    <location>
      <facility>
        <name>Fuwai Hospital, Chinese Academy of Medical Sciences</name>
        <address>
          <city>Beijing</city>
          <country>China</country>
        </address>
      </facility>
    </location>
    <location_countries>
      <country>China</country>
    </location_countries>
    <verification_date>July 2023</verification_date>
    <study_first_submitted>July 20, 2023</study_first_submitted>
    <study_first_submitted_qc>July 31, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 9, 2023</study_first_posted>
    <last_update_submitted>July 31, 2023</last_update_submitted>
    <last_update_submitted_qc>July 31, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 9, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <keyword>CMR</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Myocardial Infarction</mesh_term>
      <mesh_term>Infarction</mesh_term>
    </condition_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/NCT05984134
  org study id: NL005-AMI-IIb
  nct id: NCT05984134
  lead sponsor: 
  is fda regulated drug: No
  is fda regulated device: No
  A multicenter randomized double-blind placebo parallel control design was used in this study.
        The 90 participants were randomly assigned to placebo, 0.5μg/kg dose group, and 1.0μg/kg dose
        group in a ratio of 1:1:1. After randomization, subjects received the trial drug or placebo
        intravenously within 12 hours and on days 2 to 7 after PCI. The patients were observed 90
        days after PCI.
  Cardiovascular magnetic resonance imaging (CMR) was performed on day 5 and day 90 after PCI
        to evaluate myocardial infarction size, microvascular obstruction area, left ventricular
        ejection fraction (LVEF), left ventricular end-systolic volume (LVESV), and left ventricular
        end-diastolic volume (LVEDV). Physical examination, blood routine examination, and
        coagulation function examination were performed before the first dose, on the 7th, 30th, and
        90th day after PCI. The examination before the first dose was conducted to accept the
        examination results from the current onset to the first dose.Electrocardiogram (ECG) was
        performed before the first dose, day 2, day 7, day 30, and day 90 after PCI, and the test
        results from the period after PCI to the first dose were received. Vital signs were examined
        before the first dose, day 1 to day 7, day 30, and day 90 after PCI, and the results of the
        examination from the first onset to the first dose were accepted during the examination
        before the first dose. Blood biochemical tests were performed before the first dose, from day
        2 to day 4, day 7, day 30, and day 90 after PCI. The results of the examinations from the
        first onset to the first dose were accepted during the examination before the first dose.
        High-sensitivity troponin I(hs-cTnI) or troponin I(cTnI) and amino-terminal B-type
        natriuretic peptide precursor (NT-proBNP) or B-type natriuretic peptide (BNP) were tested
        before first administration and on days 2, 3, 4, and 7 after PCI. Examination results from
        the time after PCI to the time before initial administration; Creatine kinase isoenzyme
        (CK-MB) tests were performed before the first dose, 12 hours after the first dose, day 2 (if
        it coincided with 12 hours after the first dose, no repeat blood collection was required),
        day 3, and day 4. The test results from the period after PCI to the period before the first
        dose were accepted. Tumor markers were detected and immunogenic blood samples were collected
        before the first dose and on the 30th day after PCI. The tumor markers were examined before
        the first dose. Urine routine examination was performed before the first dose and on the 90th
        day after PCI. The examination before the first dose accepted the examination results from
        the onset of the disease to the first dose. Drug combinations, adverse events, and
        cardiovascular events were recorded during the trial.
  allocation: Randomized
  intervention model: Parallel Assignment
  primary purpose: Basic Science
  masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
  measure: Percentage change of myocardial infarction area
  time frame: Day 5、Day 90
  description: The percentage of myocardial infarction area was defined as the percentage of CMR delayed enhancement area in the entire left ventricular myocardium as measured by plane geometry of computer-assisted enhanced myocardium.Percentage change of myocardial infarction size =D5 percentage of myocardial infarction size -D90 percentage of myocardial infarction size
  measure: Myocardial mass (g)
  time frame: Day 5、Day 90
  description: Myocardial infarction area was defined as CMR delayed enhancement area, and myocardial mass (g) were calculated , and determined by plane geometry method of computer-aided enhanced myocardium. Myocardial infarction size change =D5 myocardial infarction size -D90 myocardial infarction size.
  measure: Myocardial volume (ml)
  time frame: Day 5、Day 90
  description: Myocardial infarction area was defined as CMR delayed enhancement area, and volume (ml) were calculated, and determined by plane geometry method of computer-aided enhanced myocardium.Myocardial infarction size change =D5 myocardial infarction size -D90 myocardial infarction size.
  measure: Myocardial microvessel obstruction area change value
  time frame: Day 5、Day 90
  description: Myocardial microvessel obstruction area change value =D5 microvessel obstruction area -D90 microvessel obstruction area
  measure: The change of CK-MB before and after administration
  time frame: Before the first dose, 12 hours after the first dose, day 2, day 3, day 4
  description: CK-MB change value = CK-MB value before administration - CK-MB value after administration
  measure: The area under the CK-MB curve within 4 days
  time frame: Before the first dose, 12 hours after the first dose, day 2, day 3, day 4
  description: CK-MB change value = CK-MB value before administration - CK-MB value after administration
  measure: Changes of left ventricular ejection fraction (LVEF)
  time frame: Day 5、Day 90
  description: Left ventricular ejection fraction (LVEF) change =D90 LVEF-D5 LVEF
  measure: Changes of left ventricular end-systolic volume (LVESV)
  time frame: Day 5、Day 90
  description: Left ventricular end-systolic volume (LVESV) change =D90 LVESV-D5 LVESV
  measure: Changes of left ventricular end-diastolic volume (LVEDV)
  time frame: Day 5、Day 90
  description: Left ventricular end-diastolic volume (LVEDV) change = D90 LVEDV-D5 LVEDV
  arm group label: Middle Dose
  arm group type: Experimental
  description: 12 hours after PCI: 0.5 ug/kg Recombinant Human Thymosin β4 （intravenous injection），Day2-Day7 after PCI：0.5 ug/kg Recombinant Human Thymosin β4 （intravenous injection）
  arm group label: High Dose
  arm group type: Experimental
  description: 12 hours after PCI: 1.0 ug/kg Recombinant Human Thymosin β4 （intravenous injection），Day2-Day7 after PCI：1.0 ug/kg Recombinant Human Thymosin β4 （intravenous injection）
  arm group label: Placebo
  arm group type: Placebo Comparator
  description: Patients in this treatment group will receive placebo respective. Continuous administration for 7 days.
  intervention type: Drug
  intervention name: Middle Dose
  description: Patients in this treatment group will receive NL005 for 0.5 ug/kg respective.Continuous administration for 7 days.
  arm group label: Middle Dose
  other name: NL005（ Middle Dose）
  intervention type: Drug
  intervention name: High Dose
  description: Patients in this treatment group will receive NL005 for 1.5 ug/kg respective.Continuous administration for 7 days.
  arm group label: High Dose
  other name: NL005（ High Dose）
  intervention type: Drug
  intervention name: Placebo
  description: 30 subjects will be randomly assigned to the placebo for 7 days
  arm group label: Placebo
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 75 Years
  healthy volunteers: No
  last name: KeFei Dou
  role: Principal Investigator
  affiliation: Chinese Academy of Medical Sciences, Fuwai Hospital
  facility: 
  country: China
  responsible party type: Sponsor
  mesh term: Myocardial Infarction
  mesh term: Infarction
  sharing ipd: No