Mesenchymal Stromal Cell Therapy for Severe Covid-19 Infection

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.

Study Overview

• Status: Recruiting
• Conditions: Coronavirus Infection
• Intervention / Treatment: Biological: Mesenchymal stromal cells

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.

• Study Type: Interventional
• Enrollment (Anticipated): 20
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Yves Beguin, MD,PhD; Phone Number: (0032)43667201; Email: yves.beguin@chuliege.be
• Study Contact Backup: Name: Audrey Janssen; Phone Number: (0032)43667470; Email: audrey.janssen@chuliege.be

Study Locations

• Belgium
  • Liège, Belgium, 4000
    • Recruiting
    • CHU de Liège
    • Contact: Yves Beguin, MD,PhD; Phone Number: (0032)43667201; Email: 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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / 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 Names: MSC

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To evaluate the safety of intravenous infusion of MSC in patients with severe to critical COVID-19 pneumonia	To assess the infusional toxicity	Day 28
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.	Day 28
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	Day 28
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)	Day 28

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)	Day 28
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	Day 28
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	Day 90
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	Day 28
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	Day 28
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	Day 28
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	Day 28
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	Day 90
To evaluate the effect of MSC administration associated with the standard of care (SOC including anti-viral therapy)	To assess the pulmonary function	Day 90
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).	Day 90

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
To investigate immune modulation	To determine the FACS analysis of regulatory T-cell (Treg) levels and Treg and Tconv sub-populations	Day 28
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	To assess the cytotoxic activity by MLR	Day 28

Collaborators and Investigators

• Sponsor: University of Liege
• Investigators: Principal Investigator: Yves Beguin, MD,PhD, CHU de Liège

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (ACTUAL): June 12, 2020
• Primary Completion (ANTICIPATED): September 30, 2024
• Study Completion (ANTICIPATED): September 30, 2024

Study Registration Dates

• First Submitted: June 19, 2020
• First Submitted That Met QC Criteria: June 22, 2020
• First Posted (ACTUAL): June 24, 2020

Study Record Updates

• Last Update Posted (ACTUAL): September 21, 2022
• Last Update Submitted That Met QC Criteria: September 19, 2022
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Keywords: mesenchymal stromal cells
• Additional Relevant MeSH Terms: Pathologic Processes; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Disease Attributes; Coronavirus Infections; Infections; Communicable Diseases
• Other Study ID Numbers: TJT2012

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No