Back to resultsMesenchymal Stromal Cell Therapy For The Treatment Of Acute Respiratory Distress Syndrome (ARDS-MSC-205)
Primary Purpose
ARDS, Human, COVID
Status
Active
Phase
Phase 1
Locations
Sweden
Study Type
Interventional
Intervention
Mesenchymal Stromal Stem Cells - KI-MSC-PL-205
Sponsored by
About this trial
This is an interventional treatment trial for ARDS, Human focused on measuring Mesenchymal Stromal Stem Cells
Eligibility Criteria
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
Sites / Locations
- Uppsala University Hospital
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Mesenchymal Stromal Stem Cell Treatment
Arm 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.
Outcomes
Primary Outcome Measures
The incidence of pre-specified treatment related adverse events of interest (TRAEIs).
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
Secondary Outcome Measures
Safety; All-cause mortality
All-cause mortality at 60 days and then annually
Changes in Leucocytes
Changes from baseline (Day 1; prior to administration of ATIMP) in the leucocyte Count (number/L)
Changes in Trombocytes
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)
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)
Changes from baseline (Day 1; prior to administration of ATIMP) in the plasma concentration of PK (INR)
Changes in plasma concentration of Creatinine
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)
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)
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)
Changes from baseline (Day 1; prior to administration of ATIMP) in the plasma concentration of NT-proBNP (ng/L)
Changes in Blood pressure
Changes from baseline (Day 1; prior to administration of ATIMP) in blood pressure (mmHg)
Changes in Body temperature
Changes from baseline (Day 1; prior to administration of ATIMP) in body temperature (°C)
Efficacy; Changes in pulmonary compliance
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)
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)
Changes from baseline (Day 1; prior to administration of ATIMP) in oxygenation (PaO2/FiO2) until day 10 post-infusion
Efficacy; Duration of ventilator support
Number of days with ventilator support
Efficacy; Pulmonary bilateral infiltrates
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
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
Duration of ICU stay and hospital stay (number of days; whole hospital period + calculated from Day 1)
Lung function
Recovery of lung function assessed by Spirometry (FEV1, Vital Capacity) at day 60 and then annually
Lung fibrosis
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
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
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
Change in blood biomarkers related to the proposed mechanisms of action of KI-MSC-PL-205 in ARDS
Sensitisation test
Sensitisation tests (test for donor-specific antibodies) against KI-MSC-PL-205 donor
Full Information
NCT ID
NCT04447833
First Posted
June 20, 2020
Last Updated
December 21, 2022
Sponsor
Uppsala University
Collaborators
Uppsala University Hospital
1. Study Identification
Unique Protocol Identification Number
NCT04447833
Brief Title
Mesenchymal Stromal Cell Therapy For The Treatment Of Acute Respiratory Distress Syndrome
Acronym
ARDS-MSC-205
Official Title
Mesenchymal Stromal Cell Therapy For The Treatment Of Acute Respiratory Distress Syndrome Validation of Mechanistic Pathways and Clinical Efficacy
Study Type
Interventional
2. Study Status
Record Verification Date
December 2022
Overall Recruitment Status
Active, not recruiting
Study Start Date
June 17, 2020 (Actual)
Primary Completion Date
January 30, 2021 (Actual)
Study Completion Date
June 30, 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Uppsala University
Collaborators
Uppsala University Hospital
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
ARDS, Human, COVID
Keywords
Mesenchymal Stromal Stem Cells
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
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)
Allocation
N/A
Enrollment
7 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Mesenchymal Stromal Stem Cell Treatment
Arm Type
Experimental
Arm 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(s)
Mesenchymal Stromal Stem Cells - KI-MSC-PL-205
Other Intervention Name(s)
Allogeneic Bone Marrow Derived Mesenchymal Stem Cells
Intervention Description
Allogeneic bone marrow derived mesenchymal stromal stem cells (MSCs).
Primary Outcome Measure Information:
Title
The incidence of pre-specified treatment related adverse events of interest (TRAEIs).
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
Time Frame
From drug administration to day 10 post-infusion
Secondary Outcome Measure Information:
Title
Safety; All-cause mortality
Description
All-cause mortality at 60 days and then annually
Time Frame
60 days post-infusion, 6 months, 1, 2, 3, 4 and 5 years post-infusion
Title
Changes in Leucocytes
Description
Changes from baseline (Day 1; prior to administration of ATIMP) in the leucocyte Count (number/L)
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
Title
Changes in Trombocytes
Description
Changes from baseline (Day 1; prior to administration of ATIMP) in the trombocyte Count (number/L)
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
Title
Changes in plasma concentration of C-reactive protein (CRP)
Description
Changes from baseline (Day 1; prior to administration of ATIMP) in the plasma concentration of CRP (mg/L)
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
Title
Changes in plasma concentration of Prothrombin complex (PK)
Description
Changes from baseline (Day 1; prior to administration of ATIMP) in the plasma concentration of PK (INR)
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
Title
Changes in plasma concentration of Creatinine
Description
Changes from baseline (Day 1; prior to administration of ATIMP) in the plasma concentration of creatinine (μmol/L)
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
Title
Changes in plasma concentration of Aspartate amino transferase (ASAT)
Description
Changes from baseline (Day 1; prior to administration of ATIMP) in the plasma concentration of ASAT (μkat/L)
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
Title
Changes in plasma concentration of Alanine amino transferase (ALAT)
Description
Changes from baseline (Day 1; prior to administration of ATIMP) in the plasma concentration of ALAT (μkat/L)
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
Title
Changes in plasma concentration of N-terminal pro-brain natriuretic peptide (NT-proBNP)
Description
Changes from baseline (Day 1; prior to administration of ATIMP) in the plasma concentration of NT-proBNP (ng/L)
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
Title
Changes in Blood pressure
Description
Changes from baseline (Day 1; prior to administration of ATIMP) in blood pressure (mmHg)
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
Title
Changes in Body temperature
Description
Changes from baseline (Day 1; prior to administration of ATIMP) in body temperature (°C)
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
Title
Efficacy; Changes in pulmonary compliance
Description
Changes from baseline (Day 1; prior to administration of ATIMP) in pulmonary compliance (dynamic and static) until day 10 post-infusion
Time Frame
Baseline (pre-infusion), day 1, 2, 3, 4, 7 and 10 post-infusion
Title
Efficacy; Changes in driving pressure (Plateau pressure- PEEP)
Description
Changes from baseline (Day 1; prior to administration of ATIMP) in driving pressure (Plateau pressure- PEEP) until day 10 post-infusion
Time Frame
Baseline (pre-infusion), day 1, 2, 3, 4, 7 and 10 post-infusion
Title
Efficacy; Changes in oxygenation (PaO2/FiO2)
Description
Changes from baseline (Day 1; prior to administration of ATIMP) in oxygenation (PaO2/FiO2) until day 10 post-infusion
Time Frame
Baseline (pre-infusion), day 1, 2, 3, 4, 7 and 10 post-infusion
Title
Efficacy; Duration of ventilator support
Description
Number of days with ventilator support
Time Frame
Baseline (pre-infusion),day 1, 2, 3, 4, 7, 10 and 60 post-infusion
Title
Efficacy; Pulmonary bilateral infiltrates
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
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
Title
Efficacy; Sequential Organ Failure Assessment (SOFA) score
Description
Changes in Sequential Organ Failure Assessment (SOFA) score from baseline (Day 1; prior to administration of ATIMP) and during the ICU-period
Time Frame
Baseline (pre-infusion), day 1, 2, 3, 4, 7 and 10 post-infusion, end of ICU
Title
Efficacy; Hospital stay
Description
Duration of ICU stay and hospital stay (number of days; whole hospital period + calculated from Day 1)
Time Frame
Day 60 post-infusion
Title
Lung function
Description
Recovery of lung function assessed by Spirometry (FEV1, Vital Capacity) at day 60 and then annually
Time Frame
Day 60 post-infusion, 6 months, 1, 2, 3, 4 and 5 years post-infusion
Title
Lung fibrosis
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).
Time Frame
Baseline (pre-infusion), day 1, 3, 7 and 10 post-infusion, 6 months, 1, 2, 3, 4 and 5 years post-infusion
Title
Six minutes walk test
Description
Assessment of the patient's physical capacity by 6-Minute-Walk-Test (6MWT), starting at 6 months post Day 1 and then annually
Time Frame
6 months, 1, 2, 3, 4 and 5 years post-infusion
Title
Changes in Quality of life
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)
Time Frame
6 months, 1, 2, 3, 4 and 5 years post-infusion
Title
Blood biomarkers
Description
Change in blood biomarkers related to the proposed mechanisms of action of KI-MSC-PL-205 in ARDS
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
Title
Sensitisation test
Description
Sensitisation tests (test for donor-specific antibodies) against KI-MSC-PL-205 donor
Time Frame
Baseline (pre-infusion), day 60 post-infusion
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Oscar Simonsson, MD, PhD
Organizational Affiliation
Uppsala University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Uppsala University Hospital
City
Uppsala
ZIP/Postal Code
75185
Country
Sweden
12. IPD Sharing Statement
Learn more about this trial
Mesenchymal Stromal Cell Therapy For The Treatment Of Acute Respiratory Distress Syndrome
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