<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/NCT04447833</url>
  </required_header>
  <id_info>
    <org_study_id>2020-02238</org_study_id>
    <nct_id>NCT04447833</nct_id>
  </id_info>
  <brief_title>Mesenchymal Stromal Cell Therapy For The Treatment Of Acute Respiratory Distress Syndrome</brief_title>
  <acronym>ARDS-MSC-205</acronym>
  <official_title>Mesenchymal Stromal Cell Therapy For The Treatment Of Acute Respiratory Distress Syndrome Validation of Mechanistic Pathways and Clinical Efficacy</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Uppsala University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Uppsala University Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Uppsala University</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>
      This is an open label, dose escalating safety study of the advanced therapy investigational&#xD;
      medicinal product (ATIMP) KI-MSC-PL-205, where patients diagnosed with SARS-CoV-2-induced&#xD;
      severe acute respiratory distress syndrome (ARDS), according to the Berlin Definition, and&#xD;
      who are on respirator/ventilator (used synonymously in this protocol) support due to&#xD;
      respiratory insufficiency with or without concomitant circulatory problems, will be included&#xD;
      and treated with a single dose of KI-MSC-PL-205.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">June 17, 2020</start_date>
  <completion_date type="Anticipated">June 30, 2025</completion_date>
  <primary_completion_date type="Actual">January 30, 2021</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>Single Group Assignment</intervention_model>
    <intervention_model_description>This is an open label, dose escalating safety study of the advanced therapy investigational medicinal product (ATIMP) KI-MSC-PL-205, where patients diagnosed with SARS-CoV-2-induced severe acute respiratory distress syndrome (ARDS).</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>The incidence of pre-specified treatment related adverse events of interest (TRAEIs).</measure>
    <time_frame>From drug administration to day 10 post-infusion</time_frame>
    <description>The incidence of pre-specified treatment related adverse events of interest (TRAEIs) occurring during the 10 days interval beginning with the start of the ATIMP infusion:&#xD;
New ventricular tachycardia, ventricular fibrillation or asystole within 10 days after infusion&#xD;
New cardiac arrhythmia requiring cardioversion within 10 days after infusion&#xD;
Clinical scenario consistent with transfusion incompatibility or transfusion-related infection within 10 days after infusion&#xD;
Thromboembolic events (e.g. Pulmonary embolism) within 10 days after infusion&#xD;
Cardiac arrest or death within 10 days after infusion</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Safety; All-cause mortality</measure>
    <time_frame>60 days post-infusion, 6 months, 1, 2, 3, 4 and 5 years post-infusion</time_frame>
    <description>All-cause mortality at 60 days and then annually</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in Leucocytes</measure>
    <time_frame>Baseline (pre-infusion), day 1, 2, 3, 4, 7 and 10 post-infusion, 6 months, 1, 2, 3, 4 and 5 years post-infusion</time_frame>
    <description>Changes from baseline (Day 1; prior to administration of ATIMP) in the leucocyte Count (number/L)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in Trombocytes</measure>
    <time_frame>Baseline (pre-infusion), day 1, 2, 3, 4, 7 and 10 post-infusion, 6 months, 1, 2, 3, 4 and 5 years post-infusion</time_frame>
    <description>Changes from baseline (Day 1; prior to administration of ATIMP) in the trombocyte Count (number/L)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in plasma concentration of C-reactive protein (CRP)</measure>
    <time_frame>Baseline (pre-infusion), day 1, 2, 3, 4, 7 and 10 post-infusion, 6 months, 1, 2, 3, 4 and 5 years post-infusion</time_frame>
    <description>Changes from baseline (Day 1; prior to administration of ATIMP) in the plasma concentration of CRP (mg/L)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in plasma concentration of Prothrombin complex (PK)</measure>
    <time_frame>Baseline (pre-infusion), day 1, 2, 3, 4, 7 and 10 post-infusion, 6 months, 1, 2, 3, 4 and 5 years post-infusion</time_frame>
    <description>Changes from baseline (Day 1; prior to administration of ATIMP) in the plasma concentration of PK (INR)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in plasma concentration of Creatinine</measure>
    <time_frame>Baseline (pre-infusion), day 1, 2, 3, 4, 7 and 10 post-infusion, 6 months, 1, 2, 3, 4 and 5 years post-infusion</time_frame>
    <description>Changes from baseline (Day 1; prior to administration of ATIMP) in the plasma concentration of creatinine (μmol/L)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in plasma concentration of Aspartate amino transferase (ASAT)</measure>
    <time_frame>Baseline (pre-infusion), day 1, 2, 3, 4, 7 and 10 post-infusion, 6 months, 1, 2, 3, 4 and 5 years post-infusion</time_frame>
    <description>Changes from baseline (Day 1; prior to administration of ATIMP) in the plasma concentration of ASAT (μkat/L)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in plasma concentration of Alanine amino transferase (ALAT)</measure>
    <time_frame>Baseline (pre-infusion), day 1, 2, 3, 4, 7 and 10 post-infusion, 6 months, 1, 2, 3, 4 and 5 years post-infusion</time_frame>
    <description>Changes from baseline (Day 1; prior to administration of ATIMP) in the plasma concentration of ALAT (μkat/L)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in plasma concentration of N-terminal pro-brain natriuretic peptide (NT-proBNP)</measure>
    <time_frame>Baseline (pre-infusion), day 1, 2, 3, 4, 7 and 10 post-infusion, 6 months, 1, 2, 3, 4 and 5 years post-infusion</time_frame>
    <description>Changes from baseline (Day 1; prior to administration of ATIMP) in the plasma concentration of NT-proBNP (ng/L)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in Blood pressure</measure>
    <time_frame>Baseline (pre-infusion), day 1, 2, 3, 4, 7 and 10 post-infusion, 6 months, 1, 2, 3, 4 and 5 years post-infusion</time_frame>
    <description>Changes from baseline (Day 1; prior to administration of ATIMP) in blood pressure (mmHg)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in Body temperature</measure>
    <time_frame>Baseline (pre-infusion), day 1, 2, 3, 4, 7 and 10 post-infusion, 6 months, 1, 2, 3, 4 and 5 years post-infusion</time_frame>
    <description>Changes from baseline (Day 1; prior to administration of ATIMP) in body temperature (°C)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Efficacy; Changes in pulmonary compliance</measure>
    <time_frame>Baseline (pre-infusion), day 1, 2, 3, 4, 7 and 10 post-infusion</time_frame>
    <description>Changes from baseline (Day 1; prior to administration of ATIMP) in pulmonary compliance (dynamic and static) until day 10 post-infusion</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Efficacy; Changes in driving pressure (Plateau pressure- PEEP)</measure>
    <time_frame>Baseline (pre-infusion), day 1, 2, 3, 4, 7 and 10 post-infusion</time_frame>
    <description>Changes from baseline (Day 1; prior to administration of ATIMP) in driving pressure (Plateau pressure- PEEP) until day 10 post-infusion</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Efficacy; Changes in oxygenation (PaO2/FiO2)</measure>
    <time_frame>Baseline (pre-infusion), day 1, 2, 3, 4, 7 and 10 post-infusion</time_frame>
    <description>Changes from baseline (Day 1; prior to administration of ATIMP) in oxygenation (PaO2/FiO2) until day 10 post-infusion</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Efficacy; Duration of ventilator support</measure>
    <time_frame>Baseline (pre-infusion),day 1, 2, 3, 4, 7, 10 and 60 post-infusion</time_frame>
    <description>Number of days with ventilator support</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Efficacy; Pulmonary bilateral infiltrates</measure>
    <time_frame>Baseline (pre-infusion), day 1, 2, 3, 4, 7 and 10 post-infusion, 6 months, 1, 2, 3, 4 and 5 years post-infusion</time_frame>
    <description>Changes in amount of pulmonary bilateral infiltrates assessed by pulmonary X-ray from baseline (Day 1; prior to administration of ATIMP) until day 60</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Efficacy; Sequential Organ Failure Assessment (SOFA) score</measure>
    <time_frame>Baseline (pre-infusion), day 1, 2, 3, 4, 7 and 10 post-infusion, end of ICU</time_frame>
    <description>Changes in Sequential Organ Failure Assessment (SOFA) score from baseline (Day 1; prior to administration of ATIMP) and during the ICU-period</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Efficacy; Hospital stay</measure>
    <time_frame>Day 60 post-infusion</time_frame>
    <description>Duration of ICU stay and hospital stay (number of days; whole hospital period + calculated from Day 1)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Lung function</measure>
    <time_frame>Day 60 post-infusion, 6 months, 1, 2, 3, 4 and 5 years post-infusion</time_frame>
    <description>Recovery of lung function assessed by Spirometry (FEV1, Vital Capacity) at day 60 and then annually</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Lung fibrosis</measure>
    <time_frame>Baseline (pre-infusion), day 1, 3, 7 and 10 post-infusion, 6 months, 1, 2, 3, 4 and 5 years post-infusion</time_frame>
    <description>To assess development of lung fibrosis using the HRCT Fibrosis Score using Computed tomography (CT) at baseline and on day 1, 3, 7, 10, end of ICU-residence, end of hospital stay, day 60, 6 month and 12 month and end of study (if possible during the infectious stage depending on hospital safety regimen during the pandemic).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Six minutes walk test</measure>
    <time_frame>6 months, 1, 2, 3, 4 and 5 years post-infusion</time_frame>
    <description>Assessment of the patient's physical capacity by 6-Minute-Walk-Test (6MWT), starting at 6 months post Day 1 and then annually</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in Quality of life</measure>
    <time_frame>6 months, 1, 2, 3, 4 and 5 years post-infusion</time_frame>
    <description>Changes in Quality of Life by assessing the Short Form Health Survey (SF-36) score (starting at 6 months post Day 1 and then annually; patient reported outcome)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Blood biomarkers</measure>
    <time_frame>Baseline (pre-infusion), day 1, 2, 3, 4, 7 and 10 post-infusion, 6 months, 1, 2, 3, 4 and 5 years post-infusion</time_frame>
    <description>Change in blood biomarkers related to the proposed mechanisms of action of KI-MSC-PL-205 in ARDS</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Sensitisation test</measure>
    <time_frame>Baseline (pre-infusion), day 60 post-infusion</time_frame>
    <description>Sensitisation tests (test for donor-specific antibodies) against KI-MSC-PL-205 donor</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">7</enrollment>
  <condition>ARDS, Human</condition>
  <condition>COVID</condition>
  <arm_group>
    <arm_group_label>Mesenchymal Stromal Stem Cell Treatment</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Infusion of allogeneic bone marrow derived mesenchymal stromal stem cells (MSC). First three patients receive a singe dose of 1x10^6 MSC/kg dose, next six patients receive a single dose of 2x10^6 MSC/kg.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Mesenchymal Stromal Stem Cells - KI-MSC-PL-205</intervention_name>
    <description>Allogeneic bone marrow derived mesenchymal stromal stem cells (MSCs).</description>
    <arm_group_label>Mesenchymal Stromal Stem Cell Treatment</arm_group_label>
    <other_name>Allogeneic Bone Marrow Derived Mesenchymal Stem Cells</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Willing and able to provide written informed consent prior to performing study&#xD;
             procedures (and have given written consent)&#xD;
&#xD;
          -  Coronavirus (SARS-CoV-2) infection confirmed by polymerase chain reaction (PCR) test&#xD;
             at screening&#xD;
&#xD;
          -  Male or female patient aged 18 to 65 years old&#xD;
&#xD;
          -  Patient must fulfil the Berlin Definition of severe ARDS within 3 weeks to 48 hours&#xD;
             prior to enrolment (Will be assessed once the patient has been admitted to the ICU)&#xD;
&#xD;
          -  Patient is on respirator support within 3 weeks to 48 hours prior to enrolment (Will&#xD;
             be assessed once the patient has been admitted to the ICU)&#xD;
&#xD;
          -  Pregnancy test in blood confirming negative results before enrolment (for women ≤55&#xD;
             years old)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  History of any clinically significant disease or disorder which, in the opinion of the&#xD;
             Investigator, may either put the patient at risk because of participation in the&#xD;
             study, or influence the results or the patient's ability to participate in the study&#xD;
&#xD;
          -  Patients with history of treated blood and/or solid organ malignancy with recurrence&#xD;
             within five years prior to dosing of the ATIMP are to be excluded. Patients with&#xD;
             history of cervix cancer and non-melanoma skin cancer with recurrence within two years&#xD;
             prior to dosing of the ATIMP are to be excluded&#xD;
&#xD;
          -  Pregnant or breast feeding female&#xD;
&#xD;
          -  Patient with a history of anti-coagulation therapy for other indications that&#xD;
             short-term prophylaxis after surgery&#xD;
&#xD;
          -  Patients with a history and/ or on-going treatment for entity associated with bleeding&#xD;
             disorder or potential risk for bleeding (e.g. inflammatory bowel disease,&#xD;
             gastro-esophagitis with or without ulcers, haemophilia and other bleeding disorders,&#xD;
             inflammatory musculo-skeletal disease with potential bleeding complications)&#xD;
&#xD;
          -  Patients with a history during the latest five years and/or on-going treatment for&#xD;
             systemic infection (e.g. Septicaemia due to in vivo foreign body (e.g. stents,&#xD;
             catheters, heart valve), tuberculosis, malaria, other opportunistic and parasite&#xD;
             infections)&#xD;
&#xD;
          -  Prisoner&#xD;
&#xD;
          -  Any other irreversible disease or condition for which six-month mortality is estimated&#xD;
             to be greater than 50%&#xD;
&#xD;
          -  Moderate to severe liver failure (Child-Pugh Score &gt;12)&#xD;
&#xD;
          -  Reduced renal function with a creatinine clearance (Cockcroft-Gault Equation) &lt; 45&#xD;
             mL/min/1.73m2&#xD;
&#xD;
          -  Severe chronic respiratory disease with a PaCO2 &gt;50 mmHg or the use of home oxygen&#xD;
&#xD;
          -  Major trauma in the prior 5 days&#xD;
&#xD;
          -  Lung transplant patient&#xD;
&#xD;
          -  Patients on ECMO-support&#xD;
&#xD;
          -  Patients with a previous history of severe burns&#xD;
&#xD;
          -  Documented deep venous thrombosis or pulmonary embolism within past three months&#xD;
&#xD;
          -  Known hypersensitivity to DMSO&#xD;
&#xD;
          -  Investigator considers the patient unlikely to comply with study procedures,&#xD;
             restrictions and requirements&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Oscar Simonsson, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Uppsala University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Uppsala University Hospital</name>
      <address>
        <city>Uppsala</city>
        <zip>75185</zip>
        <country>Sweden</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Sweden</country>
  </location_countries>
  <verification_date>December 2022</verification_date>
  <study_first_submitted>June 20, 2020</study_first_submitted>
  <study_first_submitted_qc>June 24, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 25, 2020</study_first_posted>
  <last_update_submitted>December 21, 2022</last_update_submitted>
  <last_update_submitted_qc>December 21, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">December 22, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Mesenchymal Stromal Stem Cells</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>
  </condition_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/NCT04447833
org study id: 2020-02238
nct id: NCT04447833
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
This is an open label, dose escalating safety study of the advanced therapy investigational
      medicinal product (ATIMP) KI-MSC-PL-205, where patients diagnosed with SARS-CoV-2-induced
      severe acute respiratory distress syndrome (ARDS), according to the Berlin Definition, and
      who are on respirator/ventilator (used synonymously in this protocol) support due to
      respiratory insufficiency with or without concomitant circulatory problems, will be included
      and treated with a single dose of KI-MSC-PL-205.
allocation: N/A
intervention model: Single Group Assignment
intervention model description: This is an open label, dose escalating safety study of the advanced therapy investigational medicinal product (ATIMP) KI-MSC-PL-205, where patients diagnosed with SARS-CoV-2-induced severe acute respiratory distress syndrome (ARDS).
primary purpose: Treatment
masking: None (Open Label)
measure: The incidence of pre-specified treatment related adverse events of interest (TRAEIs).
time frame: From drug administration to day 10 post-infusion
description: The incidence of pre-specified treatment related adverse events of interest (TRAEIs) occurring during the 10 days interval beginning with the start of the ATIMP infusion:
New ventricular tachycardia, ventricular fibrillation or asystole within 10 days after infusion
New cardiac arrhythmia requiring cardioversion within 10 days after infusion
Clinical scenario consistent with transfusion incompatibility or transfusion-related infection within 10 days after infusion
Thromboembolic events (e.g. Pulmonary embolism) within 10 days after infusion
Cardiac arrest or death within 10 days after infusion
measure: Safety; All-cause mortality
time frame: 60 days post-infusion, 6 months, 1, 2, 3, 4 and 5 years post-infusion
description: All-cause mortality at 60 days and then annually
measure: Changes in Leucocytes
time frame: Baseline (pre-infusion), day 1, 2, 3, 4, 7 and 10 post-infusion, 6 months, 1, 2, 3, 4 and 5 years post-infusion
description: Changes from baseline (Day 1; prior to administration of ATIMP) in the leucocyte Count (number/L)
measure: Changes in Trombocytes
time frame: Baseline (pre-infusion), day 1, 2, 3, 4, 7 and 10 post-infusion, 6 months, 1, 2, 3, 4 and 5 years post-infusion
description: Changes from baseline (Day 1; prior to administration of ATIMP) in the trombocyte Count (number/L)
measure: Changes in plasma concentration of C-reactive protein (CRP)
time frame: Baseline (pre-infusion), day 1, 2, 3, 4, 7 and 10 post-infusion, 6 months, 1, 2, 3, 4 and 5 years post-infusion
description: Changes from baseline (Day 1; prior to administration of ATIMP) in the plasma concentration of CRP (mg/L)
measure: Changes in plasma concentration of Prothrombin complex (PK)
time frame: Baseline (pre-infusion), day 1, 2, 3, 4, 7 and 10 post-infusion, 6 months, 1, 2, 3, 4 and 5 years post-infusion
description: Changes from baseline (Day 1; prior to administration of ATIMP) in the plasma concentration of PK (INR)
measure: Changes in plasma concentration of Creatinine
time frame: Baseline (pre-infusion), day 1, 2, 3, 4, 7 and 10 post-infusion, 6 months, 1, 2, 3, 4 and 5 years post-infusion
description: Changes from baseline (Day 1; prior to administration of ATIMP) in the plasma concentration of creatinine (μmol/L)
measure: Changes in plasma concentration of Aspartate amino transferase (ASAT)
time frame: Baseline (pre-infusion), day 1, 2, 3, 4, 7 and 10 post-infusion, 6 months, 1, 2, 3, 4 and 5 years post-infusion
description: Changes from baseline (Day 1; prior to administration of ATIMP) in the plasma concentration of ASAT (μkat/L)
measure: Changes in plasma concentration of Alanine amino transferase (ALAT)
time frame: Baseline (pre-infusion), day 1, 2, 3, 4, 7 and 10 post-infusion, 6 months, 1, 2, 3, 4 and 5 years post-infusion
description: Changes from baseline (Day 1; prior to administration of ATIMP) in the plasma concentration of ALAT (μkat/L)
measure: Changes in plasma concentration of N-terminal pro-brain natriuretic peptide (NT-proBNP)
time frame: Baseline (pre-infusion), day 1, 2, 3, 4, 7 and 10 post-infusion, 6 months, 1, 2, 3, 4 and 5 years post-infusion
description: Changes from baseline (Day 1; prior to administration of ATIMP) in the plasma concentration of NT-proBNP (ng/L)
measure: Changes in Blood pressure
time frame: Baseline (pre-infusion), day 1, 2, 3, 4, 7 and 10 post-infusion, 6 months, 1, 2, 3, 4 and 5 years post-infusion
description: Changes from baseline (Day 1; prior to administration of ATIMP) in blood pressure (mmHg)
measure: Changes in Body temperature
time frame: Baseline (pre-infusion), day 1, 2, 3, 4, 7 and 10 post-infusion, 6 months, 1, 2, 3, 4 and 5 years post-infusion
description: Changes from baseline (Day 1; prior to administration of ATIMP) in body temperature (°C)
measure: Efficacy; Changes in pulmonary compliance
time frame: Baseline (pre-infusion), day 1, 2, 3, 4, 7 and 10 post-infusion
description: Changes from baseline (Day 1; prior to administration of ATIMP) in pulmonary compliance (dynamic and static) until day 10 post-infusion
measure: Efficacy; Changes in driving pressure (Plateau pressure- PEEP)
time frame: Baseline (pre-infusion), day 1, 2, 3, 4, 7 and 10 post-infusion
description: Changes from baseline (Day 1; prior to administration of ATIMP) in driving pressure (Plateau pressure- PEEP) until day 10 post-infusion
measure: Efficacy; Changes in oxygenation (PaO2/FiO2)
time frame: Baseline (pre-infusion), day 1, 2, 3, 4, 7 and 10 post-infusion
description: Changes from baseline (Day 1; prior to administration of ATIMP) in oxygenation (PaO2/FiO2) until day 10 post-infusion
measure: Efficacy; Duration of ventilator support
time frame: Baseline (pre-infusion),day 1, 2, 3, 4, 7, 10 and 60 post-infusion
description: Number of days with ventilator support
measure: Efficacy; Pulmonary bilateral infiltrates
time frame: Baseline (pre-infusion), day 1, 2, 3, 4, 7 and 10 post-infusion, 6 months, 1, 2, 3, 4 and 5 years post-infusion
description: Changes in amount of pulmonary bilateral infiltrates assessed by pulmonary X-ray from baseline (Day 1; prior to administration of ATIMP) until day 60
measure: Efficacy; Sequential Organ Failure Assessment (SOFA) score
time frame: Baseline (pre-infusion), day 1, 2, 3, 4, 7 and 10 post-infusion, end of ICU
description: Changes in Sequential Organ Failure Assessment (SOFA) score from baseline (Day 1; prior to administration of ATIMP) and during the ICU-period
measure: Efficacy; Hospital stay
time frame: Day 60 post-infusion
description: Duration of ICU stay and hospital stay (number of days; whole hospital period + calculated from Day 1)
measure: Lung function
time frame: Day 60 post-infusion, 6 months, 1, 2, 3, 4 and 5 years post-infusion
description: Recovery of lung function assessed by Spirometry (FEV1, Vital Capacity) at day 60 and then annually
measure: Lung fibrosis
time frame: Baseline (pre-infusion), day 1, 3, 7 and 10 post-infusion, 6 months, 1, 2, 3, 4 and 5 years post-infusion
description: To assess development of lung fibrosis using the HRCT Fibrosis Score using Computed tomography (CT) at baseline and on day 1, 3, 7, 10, end of ICU-residence, end of hospital stay, day 60, 6 month and 12 month and end of study (if possible during the infectious stage depending on hospital safety regimen during the pandemic).
measure: Six minutes walk test
time frame: 6 months, 1, 2, 3, 4 and 5 years post-infusion
description: Assessment of the patient's physical capacity by 6-Minute-Walk-Test (6MWT), starting at 6 months post Day 1 and then annually
measure: Changes in Quality of life
time frame: 6 months, 1, 2, 3, 4 and 5 years post-infusion
description: Changes in Quality of Life by assessing the Short Form Health Survey (SF-36) score (starting at 6 months post Day 1 and then annually; patient reported outcome)
measure: Blood biomarkers
time frame: Baseline (pre-infusion), day 1, 2, 3, 4, 7 and 10 post-infusion, 6 months, 1, 2, 3, 4 and 5 years post-infusion
description: Change in blood biomarkers related to the proposed mechanisms of action of KI-MSC-PL-205 in ARDS
measure: Sensitisation test
time frame: Baseline (pre-infusion), day 60 post-infusion
description: Sensitisation tests (test for donor-specific antibodies) against KI-MSC-PL-205 donor
arm group label: Mesenchymal Stromal Stem Cell Treatment
arm group type: Experimental
description: Infusion of allogeneic bone marrow derived mesenchymal stromal stem cells (MSC). First three patients receive a singe dose of 1x10^6 MSC/kg dose, next six patients receive a single dose of 2x10^6 MSC/kg.
intervention type: Drug
intervention name: Mesenchymal Stromal Stem Cells - KI-MSC-PL-205
description: Allogeneic bone marrow derived mesenchymal stromal stem cells (MSCs).
arm group label: Mesenchymal Stromal Stem Cell Treatment
other name: Allogeneic Bone Marrow Derived Mesenchymal Stem Cells
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
last name: Oscar Simonsson, MD, PhD
role: Principal Investigator
affiliation: Uppsala University
facility: 
country: Sweden
responsible party type: Sponsor
mesh term: Respiratory Distress Syndrome
mesh term: Respiratory Distress Syndrome, Newborn
mesh term: Acute Lung Injury