<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/NCT04461925</url>
  </required_header>
  <id_info>
    <org_study_id>#4/24.04.2020</org_study_id>
    <nct_id>NCT04461925</nct_id>
  </id_info>
  <brief_title>Treatment of Coronavirus COVID-19 Pneumonia (Pathogen SARS-CoV-2) With Cryopreserved Allogeneic P_MMSCs and UC-MMSCs</brief_title>
  <official_title>Treatment of Coronavirus COVID-19 Pneumonia (Pathogen SARS-CoV-2) With Cryopreserved Allogeneic Multipotent Mesenchymal Stem Cells of the Placenta and Umbilical Cord</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Institute of Cell Therapy</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Kyiv City Clinical Hospital # 4</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Institute of Cell Therapy</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>
      Assessment of the clinical effects of infusions of cryopreserved allogeneic multipotent&#xD;
      mesenchymal stem cells of the placenta and umbilical cord for COVID-19 patients with acute&#xD;
      respiratory distress syndrome.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Currently, cell-based therapy and especially stem cell therapy has become a promising&#xD;
      therapeutic field, in which many see opportunities to cure incurable diseases. Severe&#xD;
      respiratory consequences of the COVID-19, the disease caused by the novel SARS-CoV-2&#xD;
      coronavirus, have prompted urgent need for novel therapies.&#xD;
&#xD;
      Cell-based approaches, primarily using mesenchymal stem cells (MSCs), have demonstrated&#xD;
      safety and efficacy in patients with the acute respiratory distress syndrome (ARDS) - common&#xD;
      manifestation of cytokine storms, and the cause of death in many COVID-19 patients.&#xD;
&#xD;
      Mesenchymal stem cells are a powerful immunomodulator, they secrete many anti-inflammatory&#xD;
      biologically active substances (cytokines) that reduce the inflammatory process in the lungs.&#xD;
      Also mesenchymal stem cells secrete numerous growth factors that contribute to the recovery&#xD;
      of not only the affected lung tissue but also other organs.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">May 2, 2020</start_date>
  <completion_date type="Anticipated">December 2021</completion_date>
  <primary_completion_date type="Anticipated">May 2, 2021</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>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <intervention_model_description>Experimental: stem cells therapy + treatment in according with approved by Ukrainian Health Ministry COVID-19 clinical protocol Experimental Group 1: Subjects with severe COVID-19 pneumonia shall be received three infusions of cryopreserved allogeneic P-MMSCs (1 million cells/kg body weight) at 2-days intervals: Day &quot;1&quot;, Day &quot;4&quot;, Day &quot;7&quot;.&#xD;
Control Group: treatment in according with approved by Ukrainian MoH COVID-19 clinical protocol.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Changes of oxygenation index PaO2/FiO2, most conveniently the P/F ratio.</measure>
    <time_frame>up to 28 days</time_frame>
    <description>Improvement of pulmonary function. Arterial oxygen tension PaO2 (in mmHg)/fractional inspired oxygen FiO2 (expressed as a fraction, not a percentage), most conveniently the P/F ratio. The normal P/F ratio is ~ 400-500 mmHg (~55-65 kPa). P/F ratio &lt;300mmHg - sign of Acute Respiratory Distress Syndrome (ARDS)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Changes in length of hospital stay</measure>
    <time_frame>up to 28 days</time_frame>
    <description>Length of Hospital Stay</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Changes in mortality rate</measure>
    <time_frame>up to 28 days</time_frame>
    <description>Marker for efficacy of treatment</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Changes of С-reactive protein (CRP, mg/L)</measure>
    <time_frame>At baseline, Day 1, Week 1, Week 2, Week 4, Week 8</time_frame>
    <description>Infection biomarker. Serum CRP levels can be used for early diagnosis of pneumonia, patients with severe pneumonia had high CRP levels.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Evaluation of Pneumonia Improvement</measure>
    <time_frame>At baseline, Day 1, Week 1, Week 2, Week 4, Week 8</time_frame>
    <description>CT assessment of pulmonary lesions and lung tissue changes</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of respiratory symptoms (difficulty breathing, dry cough, fever, etc.)</measure>
    <time_frame>At baseline, Day 1, Week 1, Week 2, Week 4, Week 8</time_frame>
    <description>Indirect response to lung function</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Peripheral blood count recovery time</measure>
    <time_frame>At baseline, Day 1, Week 1, Week 2, Week 4, Week 8</time_frame>
    <description>Degree of infection</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">30</enrollment>
  <condition>COVID-19 Pneumonia</condition>
  <arm_group>
    <arm_group_label>Experimental group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>On the basis conventional symptomatic treatment and supportive therapy, P-MMSCs were given at 1 million cells/kg body weight/ time, once every 3 days for a total of 3 times: Day &quot;1&quot;, Day &quot;4&quot;, Day &quot;7&quot;.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control Group</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Conventional symptomatic treatments such as antibacterial (ceftriaxone, azithromycin), anticoagulants, hormones, oxygen therapy, mechanical ventilation and other supportive therapies</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Placenta-Derived MMSCs; Cryopreserved Placenta-Derived Multipotent Mesenchymal Stromal Cells</intervention_name>
    <description>i/v infusions</description>
    <arm_group_label>Experimental group</arm_group_label>
    <other_name>P-MMSCs</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Antibiotics</intervention_name>
    <description>per os</description>
    <arm_group_label>Control Group</arm_group_label>
    <arm_group_label>Experimental group</arm_group_label>
    <other_name>ceftriaxone and azithromycin capsules</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Hormones</intervention_name>
    <description>a moderate amount of dexamethasone i/v</description>
    <arm_group_label>Control Group</arm_group_label>
    <arm_group_label>Experimental group</arm_group_label>
    <other_name>dexamethasone</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Anticoagulant Therapy</intervention_name>
    <description>Sub-Q</description>
    <arm_group_label>Control Group</arm_group_label>
    <arm_group_label>Experimental group</arm_group_label>
    <other_name>Еnoxaparin</other_name>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Оxygen therapy</intervention_name>
    <description>Оxygen therapy, mechanical ventilation and other supportive therapies</description>
    <arm_group_label>Control Group</arm_group_label>
    <arm_group_label>Experimental group</arm_group_label>
    <other_name>Оxygen insufflation</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Male or female, aged at 18 years (including) - 75 years old.&#xD;
&#xD;
          -  Laboratory confirmation of SARS-CoV-2 infection by reverse-transcription polymerase&#xD;
             chain reaction (RT-PCR) from any diagnostic sampling source.&#xD;
&#xD;
          -  Pneumonia that is judged by X-ray imaging.&#xD;
&#xD;
        In accordance with any one of the following:&#xD;
&#xD;
          -  dyspnea (RR ≥ 30 times / min);&#xD;
&#xD;
          -  finger oxygen saturation ≤ 93% in resting state;&#xD;
&#xD;
          -  arterial oxygen partial pressure (PaO2) / oxygen absorption concentration (FiO2) ≤&#xD;
             300MMHG (if possible);&#xD;
&#xD;
          -  invasive ventilation&lt; 48 h.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Male or female, aged at &lt;18 years and &gt; 75 years old.&#xD;
&#xD;
          -  Pregnancy, lactation and those who are not pregnant but do not take effective&#xD;
             contraceptives measures.&#xD;
&#xD;
          -  Patients with malignant tumor, other serious systemic diseases and psychosis.&#xD;
&#xD;
          -  Patients who are participating in other clinical trials.&#xD;
&#xD;
          -  Inability to provide informed consent or to comply with test requirements.&#xD;
&#xD;
          -  Co-Infection of HIV, syphilis.&#xD;
&#xD;
          -  Invasive ventilation &gt; 48 h.&#xD;
&#xD;
          -  Combined with other organ failure (need organ support).&#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>Peter Nemtinov, MD</last_name>
    <role>Study Director</role>
    <affiliation>Institute of Cell Therapy</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Peter Nemtinov, MD</last_name>
    <phone>+380442079207</phone>
    <email>nemtinov@stemcellclinic.com</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Alina Ustymenko, PhD</last_name>
    <phone>+380442079207</phone>
    <email>ustimenko@stemcellclinic.com</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Institute of Cell Therapy</name>
      <address>
        <city>Kyiv</city>
        <zip>04073</zip>
        <country>Ukraine</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Peter Nemtinov, MD</last_name>
      <phone>+380442079207</phone>
      <email>nemtinov@stemcellclinic.com</email>
    </contact>
    <contact_backup>
      <last_name>Alina Ustymenko, PhD</last_name>
      <phone>+380442079207</phone>
      <email>ustimenko@stemcellclinic.com</email>
    </contact_backup>
    <investigator>
      <last_name>Alexey Chibisov, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>Ukraine</country>
  </location_countries>
  <verification_date>June 2020</verification_date>
  <study_first_submitted>July 1, 2020</study_first_submitted>
  <study_first_submitted_qc>July 7, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 8, 2020</study_first_posted>
  <last_update_submitted>July 7, 2020</last_update_submitted>
  <last_update_submitted_qc>July 7, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">July 8, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Placenta-derived MMSCs</keyword>
  <keyword>i/v infusions</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>COVID-19</mesh_term>
    <mesh_term>Pneumonia</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Anti-Bacterial Agents</mesh_term>
    <mesh_term>Azithromycin</mesh_term>
    <mesh_term>Ceftriaxone</mesh_term>
    <mesh_term>Dexamethasone</mesh_term>
    <mesh_term>Enoxaparin</mesh_term>
    <mesh_term>Anticoagulants</mesh_term>
    <mesh_term>Hormones</mesh_term>
  </intervention_browse>
  <!-- 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/NCT04461925
org study id: #4/24.04.2020
nct id: NCT04461925
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
Assessment of the clinical effects of infusions of cryopreserved allogeneic multipotent
      mesenchymal stem cells of the placenta and umbilical cord for COVID-19 patients with acute
      respiratory distress syndrome.
Currently, cell-based therapy and especially stem cell therapy has become a promising
      therapeutic field, in which many see opportunities to cure incurable diseases. Severe
      respiratory consequences of the COVID-19, the disease caused by the novel SARS-CoV-2
      coronavirus, have prompted urgent need for novel therapies.

      Cell-based approaches, primarily using mesenchymal stem cells (MSCs), have demonstrated
      safety and efficacy in patients with the acute respiratory distress syndrome (ARDS) - common
      manifestation of cytokine storms, and the cause of death in many COVID-19 patients.

      Mesenchymal stem cells are a powerful immunomodulator, they secrete many anti-inflammatory
      biologically active substances (cytokines) that reduce the inflammatory process in the lungs.
      Also mesenchymal stem cells secrete numerous growth factors that contribute to the recovery
      of not only the affected lung tissue but also other organs.
allocation: Non-Randomized
intervention model: Parallel Assignment
intervention model description: Experimental: stem cells therapy + treatment in according with approved by Ukrainian Health Ministry COVID-19 clinical protocol Experimental Group 1: Subjects with severe COVID-19 pneumonia shall be received three infusions of cryopreserved allogeneic P-MMSCs (1 million cells/kg body weight) at 2-days intervals: Day "1", Day "4", Day "7".
Control Group: treatment in according with approved by Ukrainian MoH COVID-19 clinical protocol.
primary purpose: Treatment
masking: None (Open Label)
measure: Changes of oxygenation index PaO2/FiO2, most conveniently the P/F ratio.
time frame: up to 28 days
description: Improvement of pulmonary function. Arterial oxygen tension PaO2 (in mmHg)/fractional inspired oxygen FiO2 (expressed as a fraction, not a percentage), most conveniently the P/F ratio. The normal P/F ratio is ~ 400-500 mmHg (~55-65 kPa). P/F ratio <300mmHg - sign of Acute Respiratory Distress Syndrome (ARDS)
measure: Changes in length of hospital stay
time frame: up to 28 days
description: Length of Hospital Stay
measure: Changes in mortality rate
time frame: up to 28 days
description: Marker for efficacy of treatment
measure: Changes of С-reactive protein (CRP, mg/L)
time frame: At baseline, Day 1, Week 1, Week 2, Week 4, Week 8
description: Infection biomarker. Serum CRP levels can be used for early diagnosis of pneumonia, patients with severe pneumonia had high CRP levels.
measure: Evaluation of Pneumonia Improvement
time frame: At baseline, Day 1, Week 1, Week 2, Week 4, Week 8
description: CT assessment of pulmonary lesions and lung tissue changes
measure: Duration of respiratory symptoms (difficulty breathing, dry cough, fever, etc.)
time frame: At baseline, Day 1, Week 1, Week 2, Week 4, Week 8
description: Indirect response to lung function
measure: Peripheral blood count recovery time
time frame: At baseline, Day 1, Week 1, Week 2, Week 4, Week 8
description: Degree of infection
arm group label: Experimental group
arm group type: Experimental
description: On the basis conventional symptomatic treatment and supportive therapy, P-MMSCs were given at 1 million cells/kg body weight/ time, once every 3 days for a total of 3 times: Day "1", Day "4", Day "7".
arm group label: Control Group
arm group type: Active Comparator
description: Conventional symptomatic treatments such as antibacterial (ceftriaxone, azithromycin), anticoagulants, hormones, oxygen therapy, mechanical ventilation and other supportive therapies
intervention type: Procedure
intervention name: Placenta-Derived MMSCs; Cryopreserved Placenta-Derived Multipotent Mesenchymal Stromal Cells
description: i/v infusions
arm group label: Experimental group
other name: P-MMSCs
intervention type: Drug
intervention name: Antibiotics
description: per os
arm group label: Control Group
arm group label: Experimental group
other name: ceftriaxone and azithromycin capsules
intervention type: Drug
intervention name: Hormones
description: a moderate amount of dexamethasone i/v
arm group label: Control Group
arm group label: Experimental group
other name: dexamethasone
intervention type: Drug
intervention name: Anticoagulant Therapy
description: Sub-Q
arm group label: Control Group
arm group label: Experimental group
other name: Еnoxaparin
intervention type: Device
intervention name: Оxygen therapy
description: Оxygen therapy, mechanical ventilation and other supportive therapies
arm group label: Control Group
arm group label: Experimental group
other name: Оxygen insufflation
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: Peter Nemtinov, MD
role: Study Director
affiliation: Institute of Cell Therapy
last name: Peter Nemtinov, MD
phone: +380442079207
email: nemtinov@stemcellclinic.com
last name: Alina Ustymenko, PhD
phone: +380442079207
email: ustimenko@stemcellclinic.com
facility: 
status: Recruiting
contact: 
contact backup: 
investigator: 
country: Ukraine
responsible party type: Sponsor
mesh term: COVID-19
mesh term: Pneumonia
mesh term: Anti-Bacterial Agents
mesh term: Azithromycin
mesh term: Ceftriaxone
mesh term: Dexamethasone
mesh term: Enoxaparin
mesh term: Anticoagulants
mesh term: Hormones