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Mesenchymal Stromal Cell Therapy for Severe Covid-19 Infection

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ClinicalTrials.gov Identifier: NCT04445454
Recruitment Status : Recruiting
First Posted : June 24, 2020
Last Update Posted : June 24, 2020
Sponsor:
Information provided by (Responsible Party):
Yves Beguin, University of Liege

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.

Condition or disease Intervention/treatment Phase
Coronavirus Infection Biological: Mesenchymal stromal cells Phase 1 Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Intervention 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)
Primary Purpose: Treatment
Official Title: Mesenchymal Stromal Cell Therapy for Severe Covid-19 Infection
Actual Study Start Date : June 12, 2020
Estimated Primary Completion Date : September 30, 2022
Estimated Study Completion Date : September 30, 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: MSC therapy for severe COVID-19 infection
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.
Biological: Mesenchymal stromal cells
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.
Other Name: MSC




Primary Outcome Measures :
  1. To evaluate the safety of intravenous infusion of MSC in patients with severe to critical COVID-19 pneumonia [ Time Frame: Day 28 ]
    To assess the infusional toxicity

  2. To evaluate the safety of intravenous infusion of MSC in patients with severe to critical COVID-19 pneumonia [ Time Frame: Day 28 ]
    To assess the number of Adverse events of special interest : Incidence of infections (bacterial, viral, fungal, parasitic) and thrombo-embolic events.

  3. To evaluate the efficacy of intravenous infusion of MSC in patients with severe to critical COVID-19 pneumonia [ Time Frame: Day 28 ]
    Group A (patients not under mechanical ventilation): to determine the pourcentage of patients requiring mechanical ventilation

  4. To evaluate the efficacy of intravenous infusion of MSC in patients with severe to critical COVID-19 pneumonia [ Time Frame: Day 28 ]
    Group B (patients under mechanical ventilation): to determine the vital status (dead/alive)


Secondary Outcome Measures :
  1. To evaluate the effect of MSC administration associated with the standard of care (SOC including anti-viral therapy) [ Time Frame: Day 28 ]
    To assess the clinical status (on a 7-point WHO ordinal scale)

  2. To evaluate the effect of MSC administration associated with the standard of care (SOC including anti-viral therapy) [ Time Frame: Day 28 ]
    To assess the duration of oxygen therapy and/or mechanical ventilation

  3. To evaluate the effect of MSC administration associated with the standard of care (SOC including anti-viral therapy) [ Time Frame: Day 90 ]
    To assess the length of stay at the intensive care unit and of hospitalization

  4. To evaluate the effect of MSC administration associated with the standard of care (SOC including anti-viral therapy) [ Time Frame: Day 28 ]
    To assess the number of organ failures

  5. To evaluate the effect of MSC administration associated with the standard of care (SOC including anti-viral therapy) [ Time Frame: Day 28 ]
    To assess the intensity of the inflammatory response

  6. To evaluate the effect of MSC administration associated with the standard of care (SOC including anti-viral therapy) [ Time Frame: Day 28 ]
    To assess the evolution of coagulation parameter

  7. To evaluate the effect of MSC administration associated with the standard of care (SOC including anti-viral therapy) [ Time Frame: Day 28 ]
    To assess the presence of Biomarker of lung lesion, repair and scarring

  8. To evaluate the effect of MSC administration associated with the standard of care (SOC including anti-viral therapy) [ Time Frame: Day 90 ]
    To assess the v iral load over the 28 days after inclusion and seroconversion to COVID-19 over the 90 days after inclusion

  9. To evaluate the effect of MSC administration associated with the standard of care (SOC including anti-viral therapy) [ Time Frame: Day 90 ]
    To assess the pulmonary function

  10. To evaluate the effect of MSC administration associated with the standard of care (SOC including anti-viral therapy) [ Time Frame: Day 90 ]
    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).


Other Outcome Measures:
  1. To investigate immune modulation [ Time Frame: Day 28 ]
    To determine the FACS analysis of regulatory T-cell (Treg) levels and Treg and Tconv sub-populations

  2. 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 [ Time Frame: Day 28 ]
    To assess the cytotoxic activity by MLR



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
  • Pre-existing bone marrow transplant or immunosuppressive therapy
  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04445454


Contacts
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Contact: Yves Beguin, MD,PhD (0032)43667201 yves.beguin@chuliege.be
Contact: Audrey Janssen (0032)43667470 audrey.janssen@chuliege.be

Locations
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Belgium
CHU de Liège Recruiting
Liège, Belgium, 4000
Contact: Yves Beguin, MD,PhD    (0032)43667201    yves.beguin@chuliege.be   
Sub-Investigator: Benoit Misset, MD,PhD         
Sub-Investigator: Nathalie Layios, MD         
Sub-Investigator: Bernard Lambermont, MD,PhD         
Sub-Investigator: Michel Moutschen, MD,PhD         
Sub-Investigator: Gilles Darcis, MD,PhD         
Sponsors and Collaborators
University of Liege
Investigators
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Principal Investigator: Yves Beguin, MD,PhD CHU de Liège
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Responsible Party: Yves Beguin, MD,PhD, University of Liege
ClinicalTrials.gov Identifier: NCT04445454    
Other Study ID Numbers: TJT2012
First Posted: June 24, 2020    Key Record Dates
Last Update Posted: June 24, 2020
Last Verified: June 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Yves Beguin, University of Liege:
mesenchymal stromal cells
Additional relevant MeSH terms:
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Infection
Communicable Diseases
Coronavirus Infections
Severe Acute Respiratory Syndrome
Coronaviridae Infections
Nidovirales Infections
RNA Virus Infections
Virus Diseases
Respiratory Tract Infections
Respiratory Tract Diseases