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Mesenchymal Stromal Cell Therapy For The Treatment Of Acute Respiratory Distress Syndrome (ARDS-MSC-205)

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ClinicalTrials.gov Identifier: NCT04447833
Recruitment Status : Recruiting
First Posted : June 25, 2020
Last Update Posted : June 25, 2020
Sponsor:
Collaborator:
Uppsala University Hospital
Information provided by (Responsible Party):
Uppsala University

Tracking Information
First Submitted Date  ICMJE June 20, 2020
First Posted Date  ICMJE June 25, 2020
Last Update Posted Date June 25, 2020
Actual Study Start Date  ICMJE June 17, 2020
Estimated Primary Completion Date December 30, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 24, 2020)
The incidence of pre-specified treatment related adverse events of interest (TRAEIs). [ Time Frame: From drug administration to day 10 post-infusion ]
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
Original Primary Outcome Measures  ICMJE Same as current
Change History No Changes Posted
Current Secondary Outcome Measures  ICMJE
 (submitted: June 24, 2020)
  • Safety; All-cause mortality [ Time Frame: 60 days post-infusion, 6 months, 1, 2, 3, 4 and 5 years post-infusion ]
    All-cause mortality at 60 days and then annually
  • 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 ]
    Changes from baseline (Day 1; prior to administration of ATIMP) in the leucocyte Count (number/L)
  • 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 ]
    Changes from baseline (Day 1; prior to administration of ATIMP) in the trombocyte Count (number/L)
  • 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 ]
    Changes from baseline (Day 1; prior to administration of ATIMP) in the plasma concentration of CRP (mg/L)
  • 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 ]
    Changes from baseline (Day 1; prior to administration of ATIMP) in the plasma concentration of PK (INR)
  • 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 ]
    Changes from baseline (Day 1; prior to administration of ATIMP) in the plasma concentration of creatinine (μmol/L)
  • 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 ]
    Changes from baseline (Day 1; prior to administration of ATIMP) in the plasma concentration of ASAT (μkat/L)
  • 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 ]
    Changes from baseline (Day 1; prior to administration of ATIMP) in the plasma concentration of ALAT (μkat/L)
  • 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 ]
    Changes from baseline (Day 1; prior to administration of ATIMP) in the plasma concentration of NT-proBNP (ng/L)
  • 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 ]
    Changes from baseline (Day 1; prior to administration of ATIMP) in blood pressure (mmHg)
  • 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 ]
    Changes from baseline (Day 1; prior to administration of ATIMP) in body temperature (°C)
  • Efficacy; Changes in pulmonary compliance [ Time Frame: Baseline (pre-infusion), day 1, 2, 3, 4, 7 and 10 post-infusion ]
    Changes from baseline (Day 1; prior to administration of ATIMP) in pulmonary compliance (dynamic and static) until day 10 post-infusion
  • Efficacy; Changes in driving pressure (Plateau pressure- PEEP) [ Time Frame: Baseline (pre-infusion), day 1, 2, 3, 4, 7 and 10 post-infusion ]
    Changes from baseline (Day 1; prior to administration of ATIMP) in driving pressure (Plateau pressure- PEEP) until day 10 post-infusion
  • Efficacy; Changes in oxygenation (PaO2/FiO2) [ Time Frame: Baseline (pre-infusion), day 1, 2, 3, 4, 7 and 10 post-infusion ]
    Changes from baseline (Day 1; prior to administration of ATIMP) in oxygenation (PaO2/FiO2) until day 10 post-infusion
  • Efficacy; Duration of ventilator support [ Time Frame: Baseline (pre-infusion),day 1, 2, 3, 4, 7, 10 and 60 post-infusion ]
    Number of days with ventilator support
  • 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 ]
    Changes in amount of pulmonary bilateral infiltrates assessed by pulmonary X-ray from baseline (Day 1; prior to administration of ATIMP) until day 60
  • 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 ]
    Changes in Sequential Organ Failure Assessment (SOFA) score from baseline (Day 1; prior to administration of ATIMP) and during the ICU-period
  • Efficacy; Hospital stay [ Time Frame: Day 60 post-infusion ]
    Duration of ICU stay and hospital stay (number of days; whole hospital period + calculated from Day 1)
  • Lung function [ Time Frame: Day 60 post-infusion, 6 months, 1, 2, 3, 4 and 5 years post-infusion ]
    Recovery of lung function assessed by Spirometry (FEV1, Vital Capacity) at day 60 and then annually
  • 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 ]
    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).
  • Six minutes walk test [ Time Frame: 6 months, 1, 2, 3, 4 and 5 years post-infusion ]
    Assessment of the patient's physical capacity by 6-Minute-Walk-Test (6MWT), starting at 6 months post Day 1 and then annually
  • Changes in Quality of life [ Time Frame: 6 months, 1, 2, 3, 4 and 5 years post-infusion ]
    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)
  • 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 ]
    Change in blood biomarkers related to the proposed mechanisms of action of KI-MSC-PL-205 in ARDS
  • Sensitisation test [ Time Frame: Baseline (pre-infusion), day 60 post-infusion ]
    Sensitisation tests (test for donor-specific antibodies) against KI-MSC-PL-205 donor
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Mesenchymal Stromal Cell Therapy For The Treatment Of Acute Respiratory Distress Syndrome
Official Title  ICMJE Mesenchymal Stromal Cell Therapy For The Treatment Of Acute Respiratory Distress Syndrome Validation of Mechanistic Pathways and Clinical Efficacy
Brief Summary 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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE 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).
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • ARDS, Human
  • COVID
Intervention  ICMJE Drug: Mesenchymal Stromal Stem Cells - KI-MSC-PL-205
Allogeneic bone marrow derived mesenchymal stromal stem cells (MSCs).
Other Name: Allogeneic Bone Marrow Derived Mesenchymal Stem Cells
Study Arms  ICMJE Experimental: Mesenchymal Stromal Stem Cell Treatment
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: Drug: Mesenchymal Stromal Stem Cells - KI-MSC-PL-205
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: June 24, 2020)
9
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE June 30, 2025
Estimated Primary Completion Date December 30, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Willing and able to provide written informed consent prior to performing study procedures (and have given written consent)
  • Coronavirus (SARS-CoV-2) infection confirmed by polymerase chain reaction (PCR) test at screening
  • Male or female patient aged 18 to 65 years old
  • Patient must fulfil the Berlin Definition of severe ARDS within 3 weeks to 48 hours prior to enrolment (Will be assessed once the patient has been admitted to the ICU)
  • Patient is on respirator support within 3 weeks to 48 hours prior to enrolment (Will be assessed once the patient has been admitted to the ICU)
  • Pregnancy test in blood confirming negative results before enrolment (for women ≤55 years old)

Exclusion Criteria:

  • History of any clinically significant disease or disorder which, in the opinion of the Investigator, may either put the patient at risk because of participation in the study, or influence the results or the patient's ability to participate in the study
  • Patients with history of treated blood and/or solid organ malignancy with recurrence within five years prior to dosing of the ATIMP are to be excluded. Patients with history of cervix cancer and non-melanoma skin cancer with recurrence within two years prior to dosing of the ATIMP are to be excluded
  • Pregnant or breast feeding female
  • Patient with a history of anti-coagulation therapy for other indications that short-term prophylaxis after surgery
  • Patients with a history and/ or on-going treatment for entity associated with bleeding disorder or potential risk for bleeding (e.g. inflammatory bowel disease, gastro-esophagitis with or without ulcers, haemophilia and other bleeding disorders, inflammatory musculo-skeletal disease with potential bleeding complications)
  • Patients with a history during the latest five years and/or on-going treatment for systemic infection (e.g. Septicaemia due to in vivo foreign body (e.g. stents, catheters, heart valve), tuberculosis, malaria, other opportunistic and parasite infections)
  • Prisoner
  • Any other irreversible disease or condition for which six-month mortality is estimated to be greater than 50%
  • Moderate to severe liver failure (Child-Pugh Score >12)
  • Reduced renal function with a creatinine clearance (Cockcroft-Gault Equation) < 45 mL/min/1.73m2
  • Severe chronic respiratory disease with a PaCO2 >50 mmHg or the use of home oxygen
  • Major trauma in the prior 5 days
  • Lung transplant patient
  • Patients on ECMO-support
  • Patients with a previous history of severe burns
  • Documented deep venous thrombosis or pulmonary embolism within past three months
  • Known hypersensitivity to DMSO
  • Investigator considers the patient unlikely to comply with study procedures, restrictions and requirements
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Oscar Simonsson, MD, PhD +46703366787 oscar.simonsson@surgsci.uu.se
Contact: Karl-Henrik Grinnemo, MD, PhD karl-henrik.grinnemo@surgsci.uu.se
Listed Location Countries  ICMJE Sweden
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04447833
Other Study ID Numbers  ICMJE 2020-02238
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Uppsala University
Study Sponsor  ICMJE Uppsala University
Collaborators  ICMJE Uppsala University Hospital
Investigators  ICMJE
Principal Investigator: Oscar Simonsson, MD, PhD Uppsala University
PRS Account Uppsala University
Verification Date June 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP