Mesenchymal Stromal Cell Therapy for Severe Covid-19 Infection

Coronavirus Infection Clinical Trial

Official title:

Mesenchymal Stromal Cell Therapy for Severe Covid-19 Infection

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04445454
• Other study ID #: TJT2012
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: June 12, 2020
• Est. completion date: September 30, 2024

Study information

• Verified date: May 2024
• Source: University of Liege
• Contact: Yves Beguin, MD,PhD
• Phone: (0032)43667201
• Email: yves.beguin[@]chuliege.be
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 20
• Est. completion date: September 30, 2024
• Est. primary completion date: September 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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

Related Conditions & MeSH terms

• Communicable Diseases
• Coronavirus Infection
• Coronavirus Infections
• Infections

Intervention

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.

Locations

Country	Name	City	State
Belgium	CHU de Liège	Liège

Sponsors (1)

Lead Sponsor	Collaborator
University of Liege

Country where clinical trial is conducted

Belgium, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	To investigate immune modulation	To determine the FACS analysis of regulatory T-cell (Treg) levels and Treg and Tconv sub-populations	Day 28
Other	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
Primary	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
Primary	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
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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