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/NCT05983627</url>
    </required_header>
    <id_info>
      <org_study_id>QS-ARDS-S1</org_study_id>
      <nct_id>NCT05983627</nct_id>
    </id_info>
    <brief_title>Safety and Tolerance of Umbilical Cord Mesenchymal Stem Cells in Patients With Acute Respiratory Distress Syndrome</brief_title>
    <official_title>A Clinical Trial to Evaluate the Safety, Tolerance and Efficacy of aCell Inj. of Allogeneic UC-MSCs in Patients With Mild to Moderate Acute Respiratory Distress Syndrome</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Asia Cell Therapeutics (Shanghai) Co., Ltd.</agency>
        <agency_class>Industry</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Asia Cell Therapeutics (Shanghai) Co., Ltd.</source>
    <oversight_info>
      <has_dmc>No</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>
        The goal of this clinical trial is to evaluate the safety and tolerability of multiple doses&#xD;
        of human umbilical cord mesenchymal stem cell injection in patients with Mild to Moderate&#xD;
        Acute Respiratory Distress Syndrome (ARDS), and to further explore the efficacy,&#xD;
        pharmacodynamic profile and appropriate dose of administration to provide a basis for the use&#xD;
        of safer and more effective treatments for patients with Mild to Moderate Acute Respiratory&#xD;
        Distress Syndrome (ARDS).&#xD;
  &#xD;
        Participants are required to sign an informed consent form and, after undergoing a series of&#xD;
        tests and meeting the protocol's entry and exclusion criteria, are assigned to a dose group&#xD;
        for intravenous infusion of human umbilical cord mesenchymal stem cells. Each subject will&#xD;
        receive three infusions.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        Acute respiratory distress syndrome (ARDS) refers to various pathogenic factors that lead to&#xD;
        excessive activation of the lung or even the whole body inflammatory response, which is&#xD;
        manifested by the destruction of the lung epithelium and vascular endothelium, the decrease&#xD;
        of alveolar clearance, and the occurrence of non-cardiogenic pulmonary edema. According to an&#xD;
        international study involving 29144 patients, 10% of patients in ICU are ARDS patients, 23%&#xD;
        of patients with mechanical ventilation suffer from ARDS, and the case fatality rate of ARDS&#xD;
        ranges from 35% to 46%. At present, the treatment of ARDS includes primary disease treatment,&#xD;
        protective mechanical ventilation and drug therapy, such as systemic infection, trauma,&#xD;
        shock, burn, acute severe pancreatitis and other common causes of ARDS.&#xD;
  &#xD;
        It is necessary to control the primary disease and control the systemic uncontrolled&#xD;
        inflammatory response induced by it to prevent and treat ARDS. In the treatment of ARDS, in&#xD;
        addition to actively treating the primary disease, respiratory support technology is the main&#xD;
        treatment mode, which aims to correct intractable hypoxemia, prevent alveolar collapse,&#xD;
        reduce the degree of pulmonary edema, improve the oxygenation index, and reduce respiratory&#xD;
        muscle fatigue. In addition to the above treatment means, effective drug therapeutic&#xD;
        intervention should be carried out early. Reducing ventilator dependence is the key to&#xD;
        improve survival rate. Pharmacotherapy for ARDS includes anti-inflammatory drug therapy (such&#xD;
        as glucocorticoids), antioxidant therapy for N-acetylcysteine, and alveolar surfactant&#xD;
        replacement therapy.&#xD;
  &#xD;
        Stem cells are a kind of undifferentiated cells that exist in embryonic or adult tissues and&#xD;
        have the potential of self-renewal replication and multidirectional differentiation.&#xD;
        mesenchymal stem cells (MSCs) are the most widely used stem cells in basic and clinical&#xD;
        research. According to literature reports, MSCs have the ability to migrate to damaged&#xD;
        tissues and repair damaged tissues through their multidirectional differentiation potential&#xD;
        in vivo. Through its paracrine mechanism, MSCs can also improve the local microenvironment,&#xD;
        support and promote the regeneration and differentiation of endogenous stem cells, play an&#xD;
        anti-inflammatory role and regulate immunity. Human umbilical cord is considered medical&#xD;
        waste and the collection of human umbilical cord mesenchymal stem cells is non-invasive, so&#xD;
        there are no medical ethical issues with obtaining hUC-MSCs. Similar to other tissue-derived&#xD;
        MSCs, hUC-MSCs have unique self-renewal ability and multi-differentiation potential, such as&#xD;
        the ability to differentiate into adipose, bone, cartilage, nerve, and liver cells. Clinical&#xD;
        trials of MSCs in the treatment of ARDS have been reported. A single-center, randomized,&#xD;
        double-blind Phase I clinical trial reported the safety of intravenous injection of&#xD;
        allogeneic adipose derived MSCs in the treatment of ARDS, and the results showed that MSCs&#xD;
        were safe and non-tumorigenic. Another multi-center Phase I clinical trial reported the&#xD;
        safety of different doses of MSCs derived from bone marrow in the treatment of ARDS. Based on&#xD;
        this, the Phase II a clinical trial showed that MSCs improved the oxygenation index of ARDS&#xD;
        patients. A case report reported that 2 patients with severe refractory ARDS showed&#xD;
        improvement in respiratory distress, hemodynamic disturbance, and multiple organ failure&#xD;
        after receiving MSCs treatment, which may be related to the reduction of inflammatory markers&#xD;
        in the blood. The development of hUC-MSCs stem cell drugs has important clinical application&#xD;
        value. At present, the human umbilical cord mesenchymal stem cell injection has completed the&#xD;
        pharmacodynamics test of lung injury, the 4-week repeated administration in rats for 8 weeks,&#xD;
        the 4-week repeated administration in rats for 8 weeks, the 4-week repeated administration in&#xD;
        rhesus monkeys for 8 weeks, and the 4-week repeated administration in rhesus monkeys for 8&#xD;
        weeks Week recovery toxicity test, transfer and validation of toxic bioassay method (qPCR&#xD;
        method), in vitro tumorigenesis test (soft AGAR cloning method), in vivo tumorigenesis test&#xD;
        in naked mice (non-GLP), in vitro hemolysis test (rabbit blood), tissue distribution study in&#xD;
        rats, safety pharmacological test of central nervous system in rats. In summary, the&#xD;
        treatment of human umbilical cord mesenchymal stem cells has a wide safety window, and&#xD;
        preclinical studies have shown that this product is safe and effective; The sponsors and&#xD;
        investigators believe that MSC transplantation may improve the clinical symptoms of ARDS.&#xD;
  &#xD;
        The clinical trial design of multi-center, single-arm, single administration, dose increment&#xD;
        + dose extension was mainly adopted in this study. The &quot;3+3&quot; dose increment design was&#xD;
        adopted in 3 preset dose groups, from low-dose group to high-dose group, and 3-6 subjects&#xD;
        were included in each dose group Receive a corresponding dose. After all subjects in each&#xD;
        dose group have completed the 2-week (14-day) DLT safety observation period, it will be up to&#xD;
        the investigator and sponsor to discuss whether to proceed to the next dose group based on&#xD;
        relevant safety data.&#xD;
  &#xD;
        Adverse Events (AE) : All adverse medical events that occur after a clinical trial subject&#xD;
        receives the investigational drug, but a clear causal relationship with the investigational&#xD;
        drug may not be inferred. Adverse events can be symptoms, signs, diseases, or abnormalities&#xD;
        in laboratory tests and include the following:&#xD;
  &#xD;
          1. An aggravation of the pre-existing (prior to entry into the clinical trial) medical&#xD;
             condition/disease (including an aggravation of symptoms, signs, laboratory&#xD;
             abnormalities).&#xD;
  &#xD;
          2. Any newly occurring adverse event: Any newly occurring adverse medical condition&#xD;
             (including symptoms, signs, and newly diagnosed diseases).&#xD;
  &#xD;
          3. Abnormal clinically significant laboratory test values or results that are not caused by&#xD;
             concomitant disease.&#xD;
  &#xD;
        Adverse reaction (ADR) : Any harmful or unintended reaction that may be associated with the&#xD;
        investigational drug during a clinical trial. There is at least one reasonable possibility of&#xD;
        a causal relationship between the investigational drug product and the adverse reaction, that&#xD;
        is, an association cannot be ruled out.&#xD;
  &#xD;
        Adverse events are monitored throughout the trial and it is the responsibility of the&#xD;
        investigator to record all aes observed during the trial. The trial should record any adverse&#xD;
        medical events, regardless of severity and causal relationship with the investigational drug,&#xD;
        from the time of initial dosing until the end of follow-up, and the investigator should&#xD;
        record them on the appropriate AE page in the CRF&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">August 30, 2023</start_date>
    <completion_date type="Anticipated">December 31, 2026</completion_date>
    <primary_completion_date type="Anticipated">June 30, 2025</primary_completion_date>
    <phase>Phase 1</phase>
    <study_type>Interventional</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <allocation>N/A</allocation>
      <intervention_model>Sequential Assignment</intervention_model>
      <primary_purpose>Treatment</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Adverse Event (AE)</measure>
      <time_frame>Day 1 to Day 28</time_frame>
      <description>Adverse events that occurred during the trials</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Serious Adverse Event (SAE)</measure>
      <time_frame>Day 1 to Day 28</time_frame>
      <description>Serious adverse events that occurred during the trial</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Maximum Tolerated Dose (MTD)</measure>
      <time_frame>Day 1 to Day 28</time_frame>
      <description>Maximum Tolerated Dose</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Oxygenation index</measure>
      <time_frame>Day 1(Before infusion)、Day 2、Day 3、Day 4、Day 7、Day 14、Day 28</time_frame>
      <description>To observe the improvement in oxygenation index (P/F) from baseline</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Chest routine scan</measure>
      <time_frame>Baseline、Day 4、Day 14、Day 28</time_frame>
      <description>To explore the improvement in lung imaging (calculation of lung exudate area)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Intubation rate</measure>
      <time_frame>Day 1 to Day 28</time_frame>
      <description>To explore the rate of intubation in subjects within 28 days after infusion</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Length of hospitalisation</measure>
      <time_frame>Day 1 to Day 28</time_frame>
      <description>Length of stay in hospital within 28 days</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Time out of ICU</measure>
      <time_frame>Day 1 to Day 28</time_frame>
      <description>Observe the time that subjects are not in the ICU for 28 days after infusion</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Rate of Mortality</measure>
      <time_frame>Day 1 to Day 28</time_frame>
      <description>Rate of Mortality within 28 days after infusion</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Murray lung injury score</measure>
      <time_frame>Day 1(Before infusion)、Day 2、Day 3、Day 4、Day 7、Day 14、Day 28</time_frame>
      <description>Improvement in assessment scores from baseline. The higher the score is, the more severe the lung damage is.</description>
    </secondary_outcome>
    <other_outcome>
      <measure>Interferon-γ (IFN-γ）</measure>
      <time_frame>Baseline (1h before infusion)、Day 2、Day 3、Day 7、Day 14、Day 28</time_frame>
      <description>The concentration of IFN-γ in blood</description>
    </other_outcome>
    <other_outcome>
      <measure>Interleukin-1β （IL-1β）</measure>
      <time_frame>Baseline (1h before infusion)、Day 2、Day 3、Day 7、Day 14、Day 28</time_frame>
      <description>The concentration of IL-1β in blood</description>
    </other_outcome>
    <other_outcome>
      <measure>Interleukin-6 （IL-6）</measure>
      <time_frame>Baseline (1h before infusion)、Day 2、Day 3、Day 7、Day 14、Day 28</time_frame>
      <description>The concentration of IL-6 in blood</description>
    </other_outcome>
    <other_outcome>
      <measure>Interleukin-8 （IL-8）</measure>
      <time_frame>Baseline (1h before infusion)、Day 2、Day 3、Day 7、Day 14、D28</time_frame>
      <description>The concentration of IL-8 in blood</description>
    </other_outcome>
    <other_outcome>
      <measure>Interleukin-10 （IL-10）</measure>
      <time_frame>Baseline (1h before infusion)、Day 2、Day 3、Day 7、Day 14、D28</time_frame>
      <description>The concentration of IL-10 in blood</description>
    </other_outcome>
    <other_outcome>
      <measure>Tumor necrosis factor-α （TNF-α）</measure>
      <time_frame>Baseline (1h before infusion)、Day 2、Day 3、Day 7、Day 14、D28</time_frame>
      <description>The concentration of TNF-α in blood</description>
    </other_outcome>
    <other_outcome>
      <measure>C-reaction protein (CRP)</measure>
      <time_frame>Baseline (1h before infusion)、Day 2、Day 3、Day 7、Day 14、D28</time_frame>
      <description>The concentration of CRP in blood</description>
    </other_outcome>
    <other_outcome>
      <measure>Procalcitonin (PCT)</measure>
      <time_frame>Baseline (1h before infusion)、Day 2、Day 3、Day 7、Day 14、Day 28</time_frame>
      <description>The concentration of PCT in blood</description>
    </other_outcome>
    <number_of_arms>1</number_of_arms>
    <enrollment type="Anticipated">9</enrollment>
    <condition>Acute Respiratory Distress Syndrome</condition>
    <arm_group>
      <arm_group_label>Human Umbilical Cord Mesenchymal Stem Cells</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>The trial was divided into three dose groups： Low-dose group: 1000000 cells/kg Medium-dose group: 2000000 cells/kg High-does group: 4000000 cells/kg</description>
    </arm_group>
    <intervention>
      <intervention_type>Biological</intervention_type>
      <intervention_name>Human Umbilical Cord Mesenchymal Stem Cells</intervention_name>
      <description>The stem cell infusion route is peripheral intravenous infusion. All subjects received experimental drugs and conventional treatment during the study period.</description>
      <arm_group_label>Human Umbilical Cord Mesenchymal Stem Cells</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  18-75 years old (including the threshold), male or female&#xD;
  &#xD;
            -  A definite diagnosis of mild to moderate acute respiratory distress syndrome (ARDS)&#xD;
               (according to the ARDS Berlin definition and diagnostic criteria)&#xD;
  &#xD;
            -  ARDS onset ≤ 5 days&#xD;
  &#xD;
            -  100 mmHg &lt; PaO2/FiO2 ≤ 300 mmHg&#xD;
  &#xD;
            -  Bilateral pulmonary infiltrates on chest radiograph or chest CT&#xD;
  &#xD;
            -  Rule out other causes of pulmonary oedema, such as cardiogenic pulmonary oedema and&#xD;
               pulmonary oedema due to fluid overload&#xD;
  &#xD;
            -  Have no plans to have children within 2 weeks before screening and 3 months after the&#xD;
               end of the trial, and agree to use effective non-pharmacological contraception during&#xD;
               the trial&#xD;
  &#xD;
            -  Patients voluntarily signed an informed consent form and were willing to co-operate&#xD;
               with the trial process&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Hypersensitivity to known components of the drug (the main component of this product&#xD;
               is human umbilical cord mesenchymal stem cells, excipients include dimethyl sulfoxide,&#xD;
               human albumin, compound electrolyte injection), the presence of a history of allergy&#xD;
               to gentamicin or other history of severe allergy&#xD;
  &#xD;
            -  Patients requiring treatment for any malignancy within 2 years prior to administration&#xD;
               (except non-melanoma skin cancer)&#xD;
  &#xD;
            -  Lung transplant patients&#xD;
  &#xD;
            -  Patients with malignant haematological diseases&#xD;
  &#xD;
            -  Persons who have had a cardiovascular event within 3 months prior to dosing (e.g.,&#xD;
               unstable angina, congestive heart failure, myocardial infarction within the last 12&#xD;
               months, haemodynamic instability or known left ventricular ejection fraction (LVEF)&#xD;
               &lt;40% or clinically significant rhythm or conduction abnormalities)&#xD;
  &#xD;
            -  A history of deep vein thrombosis or pulmonary embolism during the Screening Period&#xD;
               that, in the judgement of the Investigator, may be triggered or increase risk by&#xD;
               receiving MSC transplantation therapy&#xD;
  &#xD;
            -  A breastfeeding female or a female with a positive blood pregnancy test result during&#xD;
               the Screening Period&#xD;
  &#xD;
            -  History of immunodeficiency and/or autoimmune disease such as systemic lupus&#xD;
               erythematosus (SLE), or other congenital immunodeficiency disease, idiopathic IgA&#xD;
               deficiency. Laboratory tests at screening meet any of the following: Albuminous&#xD;
               transaminase (AST) or albuminous transaminase (ALT) &gt; 5 x ULN (non-hepatic sources are&#xD;
               excluded; Serum creatinine &gt; 1.5 x ULN or glomerular filtration rate &lt; 60 mL/min/1.74&#xD;
               m2; Activated partial thromboplastin time (APTT) &gt; 2.5 x ULN or prothrombin time; (PT)&#xD;
               &gt; 2.5 x ULN (not receiving anticoagulation)&#xD;
  &#xD;
            -  Positive infectious diseases (HBsAg, HCV, HIV-1, syphilis, active tuberculosis)&#xD;
  &#xD;
            -  Currently receiving extracorporeal life support (ECLS) such as continuous&#xD;
               haemodialysis (CRRT) and carbon dioxide removal (ECCO2R), or high frequency&#xD;
               oscillatory ventilation (HFOV)&#xD;
  &#xD;
            -  Presence of any other irreversible condition or symptom for which the subject has an&#xD;
               expected survival of &lt;3 months&#xD;
  &#xD;
            -  Combined WHO Class III or IV pulmonary hypertension&#xD;
  &#xD;
            -  Patients who refuse lung protective ventilation and fluid management&#xD;
  &#xD;
            -  Participation in other clinical trials or studies within 3 months prior to&#xD;
               administration&#xD;
  &#xD;
            -  Persons with prior stem cell therapy&#xD;
  &#xD;
            -  Any other condition that, in the judgement of the investigator, makes participation in&#xD;
               this trial inappropriate, such as a condition in which the study is not in the&#xD;
               subject's current best interest (e.g., detrimental to health)&#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>Jieming Qu</last_name>
      <role>Principal Investigator</role>
      <affiliation>SHANGHAI JIAOTONG UNIVERSITY SCHOOL OF MEDICINE RUIJIN HOSPITAL</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Wenli Liu</last_name>
      <phone>+86 13402137712</phone>
      <email>liuwenli@xibaozhiliao.cn</email>
    </overall_contact>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>July 26, 2023</study_first_submitted>
    <study_first_submitted_qc>August 7, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 9, 2023</study_first_posted>
    <last_update_submitted>August 7, 2023</last_update_submitted>
    <last_update_submitted_qc>August 7, 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>Human Umbilical Cord Mesenchymal Stem Cells</keyword>
    <keyword>Acute Respiratory Distress Syndrome</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Respiratory Distress Syndrome</mesh_term>
      <mesh_term>Respiratory Distress Syndrome, Newborn</mesh_term>
      <mesh_term>Acute Lung Injury</mesh_term>
      <mesh_term>Syndrome</mesh_term>
    </condition_browse>
    <!-- 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/NCT05983627
  org study id: QS-ARDS-S1
  nct id: NCT05983627
  lead sponsor: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  The goal of this clinical trial is to evaluate the safety and tolerability of multiple doses
        of human umbilical cord mesenchymal stem cell injection in patients with Mild to Moderate
        Acute Respiratory Distress Syndrome (ARDS), and to further explore the efficacy,
        pharmacodynamic profile and appropriate dose of administration to provide a basis for the use
        of safer and more effective treatments for patients with Mild to Moderate Acute Respiratory
        Distress Syndrome (ARDS).
  
        Participants are required to sign an informed consent form and, after undergoing a series of
        tests and meeting the protocol's entry and exclusion criteria, are assigned to a dose group
        for intravenous infusion of human umbilical cord mesenchymal stem cells. Each subject will
        receive three infusions.
  Acute respiratory distress syndrome (ARDS) refers to various pathogenic factors that lead to
        excessive activation of the lung or even the whole body inflammatory response, which is
        manifested by the destruction of the lung epithelium and vascular endothelium, the decrease
        of alveolar clearance, and the occurrence of non-cardiogenic pulmonary edema. According to an
        international study involving 29144 patients, 10% of patients in ICU are ARDS patients, 23%
        of patients with mechanical ventilation suffer from ARDS, and the case fatality rate of ARDS
        ranges from 35% to 46%. At present, the treatment of ARDS includes primary disease treatment,
        protective mechanical ventilation and drug therapy, such as systemic infection, trauma,
        shock, burn, acute severe pancreatitis and other common causes of ARDS.
  
        It is necessary to control the primary disease and control the systemic uncontrolled
        inflammatory response induced by it to prevent and treat ARDS. In the treatment of ARDS, in
        addition to actively treating the primary disease, respiratory support technology is the main
        treatment mode, which aims to correct intractable hypoxemia, prevent alveolar collapse,
        reduce the degree of pulmonary edema, improve the oxygenation index, and reduce respiratory
        muscle fatigue. In addition to the above treatment means, effective drug therapeutic
        intervention should be carried out early. Reducing ventilator dependence is the key to
        improve survival rate. Pharmacotherapy for ARDS includes anti-inflammatory drug therapy (such
        as glucocorticoids), antioxidant therapy for N-acetylcysteine, and alveolar surfactant
        replacement therapy.
  
        Stem cells are a kind of undifferentiated cells that exist in embryonic or adult tissues and
        have the potential of self-renewal replication and multidirectional differentiation.
        mesenchymal stem cells (MSCs) are the most widely used stem cells in basic and clinical
        research. According to literature reports, MSCs have the ability to migrate to damaged
        tissues and repair damaged tissues through their multidirectional differentiation potential
        in vivo. Through its paracrine mechanism, MSCs can also improve the local microenvironment,
        support and promote the regeneration and differentiation of endogenous stem cells, play an
        anti-inflammatory role and regulate immunity. Human umbilical cord is considered medical
        waste and the collection of human umbilical cord mesenchymal stem cells is non-invasive, so
        there are no medical ethical issues with obtaining hUC-MSCs. Similar to other tissue-derived
        MSCs, hUC-MSCs have unique self-renewal ability and multi-differentiation potential, such as
        the ability to differentiate into adipose, bone, cartilage, nerve, and liver cells. Clinical
        trials of MSCs in the treatment of ARDS have been reported. A single-center, randomized,
        double-blind Phase I clinical trial reported the safety of intravenous injection of
        allogeneic adipose derived MSCs in the treatment of ARDS, and the results showed that MSCs
        were safe and non-tumorigenic. Another multi-center Phase I clinical trial reported the
        safety of different doses of MSCs derived from bone marrow in the treatment of ARDS. Based on
        this, the Phase II a clinical trial showed that MSCs improved the oxygenation index of ARDS
        patients. A case report reported that 2 patients with severe refractory ARDS showed
        improvement in respiratory distress, hemodynamic disturbance, and multiple organ failure
        after receiving MSCs treatment, which may be related to the reduction of inflammatory markers
        in the blood. The development of hUC-MSCs stem cell drugs has important clinical application
        value. At present, the human umbilical cord mesenchymal stem cell injection has completed the
        pharmacodynamics test of lung injury, the 4-week repeated administration in rats for 8 weeks,
        the 4-week repeated administration in rats for 8 weeks, the 4-week repeated administration in
        rhesus monkeys for 8 weeks, and the 4-week repeated administration in rhesus monkeys for 8
        weeks Week recovery toxicity test, transfer and validation of toxic bioassay method (qPCR
        method), in vitro tumorigenesis test (soft AGAR cloning method), in vivo tumorigenesis test
        in naked mice (non-GLP), in vitro hemolysis test (rabbit blood), tissue distribution study in
        rats, safety pharmacological test of central nervous system in rats. In summary, the
        treatment of human umbilical cord mesenchymal stem cells has a wide safety window, and
        preclinical studies have shown that this product is safe and effective; The sponsors and
        investigators believe that MSC transplantation may improve the clinical symptoms of ARDS.
  
        The clinical trial design of multi-center, single-arm, single administration, dose increment
        + dose extension was mainly adopted in this study. The "3+3" dose increment design was
        adopted in 3 preset dose groups, from low-dose group to high-dose group, and 3-6 subjects
        were included in each dose group Receive a corresponding dose. After all subjects in each
        dose group have completed the 2-week (14-day) DLT safety observation period, it will be up to
        the investigator and sponsor to discuss whether to proceed to the next dose group based on
        relevant safety data.
  
        Adverse Events (AE) : All adverse medical events that occur after a clinical trial subject
        receives the investigational drug, but a clear causal relationship with the investigational
        drug may not be inferred. Adverse events can be symptoms, signs, diseases, or abnormalities
        in laboratory tests and include the following:
  
          1. An aggravation of the pre-existing (prior to entry into the clinical trial) medical
             condition/disease (including an aggravation of symptoms, signs, laboratory
             abnormalities).
  
          2. Any newly occurring adverse event: Any newly occurring adverse medical condition
             (including symptoms, signs, and newly diagnosed diseases).
  
          3. Abnormal clinically significant laboratory test values or results that are not caused by
             concomitant disease.
  
        Adverse reaction (ADR) : Any harmful or unintended reaction that may be associated with the
        investigational drug during a clinical trial. There is at least one reasonable possibility of
        a causal relationship between the investigational drug product and the adverse reaction, that
        is, an association cannot be ruled out.
  
        Adverse events are monitored throughout the trial and it is the responsibility of the
        investigator to record all aes observed during the trial. The trial should record any adverse
        medical events, regardless of severity and causal relationship with the investigational drug,
        from the time of initial dosing until the end of follow-up, and the investigator should
        record them on the appropriate AE page in the CRF
  allocation: N/A
  intervention model: Sequential Assignment
  primary purpose: Treatment
  masking: None (Open Label)
  measure: Adverse Event (AE)
  time frame: Day 1 to Day 28
  description: Adverse events that occurred during the trials
  measure: Serious Adverse Event (SAE)
  time frame: Day 1 to Day 28
  description: Serious adverse events that occurred during the trial
  measure: Maximum Tolerated Dose (MTD)
  time frame: Day 1 to Day 28
  description: Maximum Tolerated Dose
  measure: Oxygenation index
  time frame: Day 1(Before infusion)、Day 2、Day 3、Day 4、Day 7、Day 14、Day 28
  description: To observe the improvement in oxygenation index (P/F) from baseline
  measure: Chest routine scan
  time frame: Baseline、Day 4、Day 14、Day 28
  description: To explore the improvement in lung imaging (calculation of lung exudate area)
  measure: Intubation rate
  time frame: Day 1 to Day 28
  description: To explore the rate of intubation in subjects within 28 days after infusion
  measure: Length of hospitalisation
  time frame: Day 1 to Day 28
  description: Length of stay in hospital within 28 days
  measure: Time out of ICU
  time frame: Day 1 to Day 28
  description: Observe the time that subjects are not in the ICU for 28 days after infusion
  measure: Rate of Mortality
  time frame: Day 1 to Day 28
  description: Rate of Mortality within 28 days after infusion
  measure: Murray lung injury score
  time frame: Day 1(Before infusion)、Day 2、Day 3、Day 4、Day 7、Day 14、Day 28
  description: Improvement in assessment scores from baseline. The higher the score is, the more severe the lung damage is.
  measure: Interferon-γ (IFN-γ）
  time frame: Baseline (1h before infusion)、Day 2、Day 3、Day 7、Day 14、Day 28
  description: The concentration of IFN-γ in blood
  measure: Interleukin-1β （IL-1β）
  time frame: Baseline (1h before infusion)、Day 2、Day 3、Day 7、Day 14、Day 28
  description: The concentration of IL-1β in blood
  measure: Interleukin-6 （IL-6）
  time frame: Baseline (1h before infusion)、Day 2、Day 3、Day 7、Day 14、Day 28
  description: The concentration of IL-6 in blood
  measure: Interleukin-8 （IL-8）
  time frame: Baseline (1h before infusion)、Day 2、Day 3、Day 7、Day 14、D28
  description: The concentration of IL-8 in blood
  measure: Interleukin-10 （IL-10）
  time frame: Baseline (1h before infusion)、Day 2、Day 3、Day 7、Day 14、D28
  description: The concentration of IL-10 in blood
  measure: Tumor necrosis factor-α （TNF-α）
  time frame: Baseline (1h before infusion)、Day 2、Day 3、Day 7、Day 14、D28
  description: The concentration of TNF-α in blood
  measure: C-reaction protein (CRP)
  time frame: Baseline (1h before infusion)、Day 2、Day 3、Day 7、Day 14、D28
  description: The concentration of CRP in blood
  measure: Procalcitonin (PCT)
  time frame: Baseline (1h before infusion)、Day 2、Day 3、Day 7、Day 14、Day 28
  description: The concentration of PCT in blood
  arm group label: Human Umbilical Cord Mesenchymal Stem Cells
  arm group type: Experimental
  description: The trial was divided into three dose groups： Low-dose group: 1000000 cells/kg Medium-dose group: 2000000 cells/kg High-does group: 4000000 cells/kg
  intervention type: Biological
  intervention name: Human Umbilical Cord Mesenchymal Stem Cells
  description: The stem cell infusion route is peripheral intravenous infusion. All subjects received experimental drugs and conventional treatment during the study period.
  arm group label: Human Umbilical Cord Mesenchymal Stem Cells
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 75 Years
  healthy volunteers: No
  last name: Jieming Qu
  role: Principal Investigator
  affiliation: SHANGHAI JIAOTONG UNIVERSITY SCHOOL OF MEDICINE RUIJIN HOSPITAL
  last name: Wenli Liu
  phone: +86 13402137712
  email: liuwenli@xibaozhiliao.cn
  responsible party type: Sponsor
  mesh term: Respiratory Distress Syndrome
  mesh term: Respiratory Distress Syndrome, Newborn
  mesh term: Acute Lung Injury
  mesh term: Syndrome