Back to resultsMesenchymal Stromal Cell Therapy for Severe Covid-19 Infection
Primary Purpose
Coronavirus Infection
Status
Recruiting
Phase
Phase 1
Locations
Belgium
Study Type
Interventional
Intervention
Mesenchymal stromal cells
Sponsored by
About this trial
This is an interventional treatment trial for Coronavirus Infection focused on measuring mesenchymal stromal cells
Eligibility Criteria
COVID-19 patients Inclusion criteria
- Male or female patients aged at least 18 years and up to 70 years
- Diagnosed with microbiologically or radiologically confirmed COVID-19 pneumonia as defined by:
- Extensive interstitial pneumonia on CT scan, consistent with viral pneumonia, within 10 days prior to randomization
- And either positive result of COVID-19 PCR test within 14 days prior to inclusion or positive result of SARS-CoV2 PCR or serology within 14 days after inclusion.
Requiring oxygen administration (SpO2 ≤ 93% on room air):
- Group A: in standard or intensive care unit requiring supplemental oxygen
- Group B: in intensive care unit under mechanical ventilation administered through a tracheal tube, either:
- for less than or equal to 7 days
- for 7 to 14 days, with persisting high inflammation (ferritin > 2,000 µg/L; ferritin > 1,000 µg/L and rising; lymphocytes < 800 with CRP > 70 mg/L and rising or ferritin > 700 µg/L and rising or LDH > 300 UI/L or D-Dimers > 1000 ng/ml), not explained by superinfection. Rising = compared to previous 24H.
- Written consent of the patient, or - if impossible (clinical condition precluding capacity to consent) - of his/her legal representative, or - if impossible - of an impartial witness such as a physician from a non-participating department or member of the Ethics Committee. Any consent obtained this way shall be documented and confirmed by way of normal consent procedures at the earliest opportunity when the patient has recovered
Exclusion criteria
- Ongoing pregnancy. Women of childbearing potential (WOCBP, defined as a premenopausal female capable of becoming pregnant) should use an appropriate method of contraception (oral, injectable, or mechanical contraception; women whose partners have been vasectomized or have received or are utilizing mechanical contraceptive devices).
- Extracorporeal membrane oxygenation
- Limitations to intensity of care
- Life expectancy < 24 hours
- Known allergy to IMP component
- Active secondary infection
- Any malignancy (except non-melanoma skin carcinoma) within 2 years before inclusion
- Pre-existing thrombo-embolic pathology
- Signs of an active drug or alcohol dependence, serious current illness, mental illness or any factors which, in the opinion of the Investigator, may interfere with subject's ability to understand and comply with study requirements
- Patients with any serious medical condition or abnormality of clinical laboratory tests that, in the Investigator's judgment, precludes the patient's safe participation in and completion of the study.
- Participation in another clinical trial(use of anti-viral/supportive drugs for COVID-19 infection on a compassionate use basis is not an exclusion criterion).
MSC donors Inclusion criteria
- Unrelated to the patient
- Male or female
- Age > 18 yrs
- No HLA matching required
- Fulfills generally accepted criteria for allogeneic HSC donation
- Informed consent given by donor
Exclusion criteria
- Any condition not fulfilling inclusion criteria
- Known allergy to lidocaine
- Any risk factor for transmissible infectious diseases, in particular HIV
Sites / Locations
- CHU de LiègeRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
MSC therapy for severe COVID-19 infection
Arm Description
After signed informed consent, patients will receive 3 infusions of (1.5)-3.0 x106/kg BM-MSC (from the same donor) at 3-4 days interval, in addition to the standard of care for COVID-19 disease.
Outcomes
Primary Outcome Measures
To evaluate the safety of intravenous infusion of MSC in patients with severe to critical COVID-19 pneumonia
To assess the infusional toxicity
To evaluate the safety of intravenous infusion of MSC in patients with severe to critical COVID-19 pneumonia
To assess the number of Adverse events of special interest : Incidence of infections (bacterial, viral, fungal, parasitic) and thrombo-embolic events.
To evaluate the efficacy of intravenous infusion of MSC in patients with severe to critical COVID-19 pneumonia
Group A (patients not under mechanical ventilation): to determine the pourcentage of patients requiring mechanical ventilation
To evaluate the efficacy of intravenous infusion of MSC in patients with severe to critical COVID-19 pneumonia
Group B (patients under mechanical ventilation): to determine the vital status (dead/alive)
Secondary Outcome Measures
To evaluate the effect of MSC administration associated with the standard of care (SOC including anti-viral therapy)
To assess the clinical status (on a 7-point WHO ordinal scale)
To evaluate the effect of MSC administration associated with the standard of care (SOC including anti-viral therapy)
To assess the duration of oxygen therapy and/or mechanical ventilation
To evaluate the effect of MSC administration associated with the standard of care (SOC including anti-viral therapy)
To assess the length of stay at the intensive care unit and of hospitalization
To evaluate the effect of MSC administration associated with the standard of care (SOC including anti-viral therapy)
To assess the number of organ failures
To evaluate the effect of MSC administration associated with the standard of care (SOC including anti-viral therapy)
To assess the intensity of the inflammatory response
To evaluate the effect of MSC administration associated with the standard of care (SOC including anti-viral therapy)
To assess the evolution of coagulation parameter
To evaluate the effect of MSC administration associated with the standard of care (SOC including anti-viral therapy)
To assess the presence of Biomarker of lung lesion, repair and scarring
To evaluate the effect of MSC administration associated with the standard of care (SOC including anti-viral therapy)
To assess the v iral load over the 28 days after inclusion and seroconversion to COVID-19 over the 90 days after inclusion
To evaluate the effect of MSC administration associated with the standard of care (SOC including anti-viral therapy)
To assess the pulmonary function
To evaluate the effect of MSC administration associated with the standard of care (SOC including anti-viral therapy)
To assess the number of adverse reactions (ARs), ARs grade > 3, serious adverse events (SAEs), serious ARs (SARs), suspected expected and unexpected SARs (SESARs and SUSARs).
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04445454
Brief Title
Mesenchymal Stromal Cell Therapy for Severe Covid-19 Infection
Official Title
Mesenchymal Stromal Cell Therapy for Severe Covid-19 Infection
Study Type
Interventional
2. Study Status
Record Verification Date
September 2022
Overall Recruitment Status
Recruiting
Study Start Date
June 12, 2020 (Actual)
Primary Completion Date
September 30, 2024 (Anticipated)
Study Completion Date
September 30, 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Liege
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
The overall objective of the study is to evaluate the safety and efficacy of MSC therapy combined with best supportive care in hospitalized patients with COVID-19.
Detailed Description
This study is a monocentric prospective phase I/II clinical trial, aiming at evaluating the safety and efficacy of 3 intravenous administrations of BM-MSC in 20 patients with severe to critical COVID-19 pneumonia.
After signed informed consent, patients will receive 3 infusions of (1.5)-3.0 x106/kg BM-MSC (from the same donor) at 3-4 days interval, in addition to the standard of care for COVID-19 disease.
The trial will be open for inclusion for 2 years after initiation. Each patient will be followed for 90 days after inclusion. The total study duration will thus be 2 years and 90 days.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Coronavirus Infection
Keywords
mesenchymal stromal cells
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Model Description
This study is a monocentric prospective phase I/II clinical trial, aiming at evaluating the safety and efficacy of 3 intravenous administrations of BM-MSC in 20 patients with severe to critical COVID-19 pneumonia.
Masking
None (Open Label)
Allocation
N/A
Enrollment
20 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
MSC therapy for severe COVID-19 infection
Arm Type
Experimental
Arm Description
After signed informed consent, patients will receive 3 infusions of (1.5)-3.0 x106/kg BM-MSC (from the same donor) at 3-4 days interval, in addition to the standard of care for COVID-19 disease.
Intervention Type
Biological
Intervention Name(s)
Mesenchymal stromal cells
Other Intervention Name(s)
MSC
Intervention Description
Bone marrow collection and MSC expansion cultures will be carried out at the Laboratory of Cell and Gene Therapy (LTCG) at the University of Liège as described in IMPD and its SOPs.
Primary Outcome Measure Information:
Title
To evaluate the safety of intravenous infusion of MSC in patients with severe to critical COVID-19 pneumonia
Description
To assess the infusional toxicity
Time Frame
Day 28
Title
To evaluate the safety of intravenous infusion of MSC in patients with severe to critical COVID-19 pneumonia
Description
To assess the number of Adverse events of special interest : Incidence of infections (bacterial, viral, fungal, parasitic) and thrombo-embolic events.
Time Frame
Day 28
Title
To evaluate the efficacy of intravenous infusion of MSC in patients with severe to critical COVID-19 pneumonia
Description
Group A (patients not under mechanical ventilation): to determine the pourcentage of patients requiring mechanical ventilation
Time Frame
Day 28
Title
To evaluate the efficacy of intravenous infusion of MSC in patients with severe to critical COVID-19 pneumonia
Description
Group B (patients under mechanical ventilation): to determine the vital status (dead/alive)
Time Frame
Day 28
Secondary Outcome Measure Information:
Title
To evaluate the effect of MSC administration associated with the standard of care (SOC including anti-viral therapy)
Description
To assess the clinical status (on a 7-point WHO ordinal scale)
Time Frame
Day 28
Title
To evaluate the effect of MSC administration associated with the standard of care (SOC including anti-viral therapy)
Description
To assess the duration of oxygen therapy and/or mechanical ventilation
Time Frame
Day 28
Title
To evaluate the effect of MSC administration associated with the standard of care (SOC including anti-viral therapy)
Description
To assess the length of stay at the intensive care unit and of hospitalization
Time Frame
Day 90
Title
To evaluate the effect of MSC administration associated with the standard of care (SOC including anti-viral therapy)
Description
To assess the number of organ failures
Time Frame
Day 28
Title
To evaluate the effect of MSC administration associated with the standard of care (SOC including anti-viral therapy)
Description
To assess the intensity of the inflammatory response
Time Frame
Day 28
Title
To evaluate the effect of MSC administration associated with the standard of care (SOC including anti-viral therapy)
Description
To assess the evolution of coagulation parameter
Time Frame
Day 28
Title
To evaluate the effect of MSC administration associated with the standard of care (SOC including anti-viral therapy)
Description
To assess the presence of Biomarker of lung lesion, repair and scarring
Time Frame
Day 28
Title
To evaluate the effect of MSC administration associated with the standard of care (SOC including anti-viral therapy)
Description
To assess the v iral load over the 28 days after inclusion and seroconversion to COVID-19 over the 90 days after inclusion
Time Frame
Day 90
Title
To evaluate the effect of MSC administration associated with the standard of care (SOC including anti-viral therapy)
Description
To assess the pulmonary function
Time Frame
Day 90
Title
To evaluate the effect of MSC administration associated with the standard of care (SOC including anti-viral therapy)
Description
To assess the number of adverse reactions (ARs), ARs grade > 3, serious adverse events (SAEs), serious ARs (SARs), suspected expected and unexpected SARs (SESARs and SUSARs).
Time Frame
Day 90
Other Pre-specified Outcome Measures:
Title
To investigate immune modulation
Description
To determine the FACS analysis of regulatory T-cell (Treg) levels and Treg and Tconv sub-populations
Time Frame
Day 28
Title
To compare the cytotoxic activity of PBMCs from healthy control and COVID-19 patients (divided in responders / non-responders to MSC therapy) against MSCs in vitro
Description
To assess the cytotoxic activity by MLR
Time Frame
Day 28
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
COVID-19 patients Inclusion criteria
Male or female patients aged at least 18 years and up to 70 years
Diagnosed with microbiologically or radiologically confirmed COVID-19 pneumonia as defined by:
Extensive interstitial pneumonia on CT scan, consistent with viral pneumonia, within 10 days prior to randomization
And either positive result of COVID-19 PCR test within 14 days prior to inclusion or positive result of SARS-CoV2 PCR or serology within 14 days after inclusion.
Requiring oxygen administration (SpO2 ≤ 93% on room air):
Group A: in standard or intensive care unit requiring supplemental oxygen
Group B: in intensive care unit under mechanical ventilation administered through a tracheal tube, either:
for less than or equal to 7 days
for 7 to 14 days, with persisting high inflammation (ferritin > 2,000 µg/L; ferritin > 1,000 µg/L and rising; lymphocytes < 800 with CRP > 70 mg/L and rising or ferritin > 700 µg/L and rising or LDH > 300 UI/L or D-Dimers > 1000 ng/ml), not explained by superinfection. Rising = compared to previous 24H.
Written consent of the patient, or - if impossible (clinical condition precluding capacity to consent) - of his/her legal representative, or - if impossible - of an impartial witness such as a physician from a non-participating department or member of the Ethics Committee. Any consent obtained this way shall be documented and confirmed by way of normal consent procedures at the earliest opportunity when the patient has recovered
Exclusion criteria
Ongoing pregnancy. Women of childbearing potential (WOCBP, defined as a premenopausal female capable of becoming pregnant) should use an appropriate method of contraception (oral, injectable, or mechanical contraception; women whose partners have been vasectomized or have received or are utilizing mechanical contraceptive devices).
Extracorporeal membrane oxygenation
Limitations to intensity of care
Life expectancy < 24 hours
Known allergy to IMP component
Active secondary infection
Any malignancy (except non-melanoma skin carcinoma) within 2 years before inclusion
Pre-existing thrombo-embolic pathology
Signs of an active drug or alcohol dependence, serious current illness, mental illness or any factors which, in the opinion of the Investigator, may interfere with subject's ability to understand and comply with study requirements
Patients with any serious medical condition or abnormality of clinical laboratory tests that, in the Investigator's judgment, precludes the patient's safe participation in and completion of the study.
Participation in another clinical trial(use of anti-viral/supportive drugs for COVID-19 infection on a compassionate use basis is not an exclusion criterion).
MSC donors Inclusion criteria
Unrelated to the patient
Male or female
Age > 18 yrs
No HLA matching required
Fulfills generally accepted criteria for allogeneic HSC donation
Informed consent given by donor
Exclusion criteria
Any condition not fulfilling inclusion criteria
Known allergy to lidocaine
Any risk factor for transmissible infectious diseases, in particular HIV
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Yves Beguin, MD,PhD
Phone
(0032)43667201
Email
yves.beguin@chuliege.be
First Name & Middle Initial & Last Name or Official Title & Degree
Audrey Janssen
Phone
(0032)43667470
Email
audrey.janssen@chuliege.be
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Yves Beguin, MD,PhD
Organizational Affiliation
CHU de Liège
Official's Role
Principal Investigator
Facility Information:
Facility Name
CHU de Liège
City
Liège
ZIP/Postal Code
4000
Country
Belgium
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Yves Beguin, MD,PhD
Phone
(0032)43667201
Email
yves.beguin@chuliege.be
First Name & Middle Initial & Last Name & Degree
Benoit Misset, MD,PhD
First Name & Middle Initial & Last Name & Degree
Nathalie Layios, MD
First Name & Middle Initial & Last Name & Degree
Bernard Lambermont, MD,PhD
First Name & Middle Initial & Last Name & Degree
Michel Moutschen, MD,PhD
First Name & Middle Initial & Last Name & Degree
Gilles Darcis, MD,PhD
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
35860245
Citation
Gregoire C, Layios N, Lambermont B, Lechanteur C, Briquet A, Bettonville V, Baudoux E, Thys M, Dardenne N, Misset B, Beguin Y. Bone Marrow-Derived Mesenchymal Stromal Cell Therapy in Severe COVID-19: Preliminary Results of a Phase I/II Clinical Trial. Front Immunol. 2022 Jul 4;13:932360. doi: 10.3389/fimmu.2022.932360. eCollection 2022.
Results Reference
derived
Learn more about this trial
Mesenchymal Stromal Cell Therapy for Severe Covid-19 Infection
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