Clinical trial NCT04345601: Mesenchymal Stromal Cells for the Treatment of SARS-CoV-2 Induced Acute Respiratory Failure (COVID-19 Disease)
Official title: Single Donor Banked Bone Marrow Mesenchymal Stromal Cells for the Treatment of COVID-19 Induced ARDS: A Non-Blinded Randomized, Controlled Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Sars-CoV2
Acute Respiratory Distress Syndrome
COVID-19
Keywords: Mesenchymal Stromal Cells
Respiratory failure
Lead sponsor: Baylor College of Medicine
Sponsor class: OTHER
Collaborators: name: Center for Cell and Gene Therapy, Baylor College of Medicine
name: The Methodist Hospital Research Institute
First posted: 2020-04-14
Enrollment: 28
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: \*\*\*At this time, we are only enrolling at Houston Methodist Hospital (HMH)/Baylor College of Medicine (BCM) and are not shipping cells outside of BCM/HMH.\*\*\*

This is a study for patients who have respiratory infection caused by SARS-CoV-2 that have not gotten better. Because there is no standard treatment for this infection, patients are being asked to volunteer for a gene transfer research study using mesenchymal stem cells (MSCs).

Stem cells are cells that do not yet have a specific function in the body. Mesenchymal stem cells (MSCs) are a type of stem cell that can be grown from bone marrow (the spongy tissue inside of bones). Stem cells can develop into other types of more mature (specific) cells, such as blood and muscle cells.

The purpose of this study is to see if MSCs versus controls can help to treat respiratory infections caused by SARS-CoV-2.

Detailed description: Earlier, a healthy donor provided blood cells to generate MSCs. These cells were grown and frozen for later use.

Before being treated, the patient will receive a series of standard medical tests: These tests are done to assess the patient's eligibility to receive the cells.

* Physical exam and history
* SARS-CoV-2 test
* Blood tests
* Chest X-ray or chest CT Scan
* A urine pregnancy test, when applicable

The patient will be randomly assigned to a study group. We'll use a computer to put the patient into study group A (study drug) or group B (control) by chance (randomized). Patients randomized to the control group, will receive the standard treatment for their respiratory infection.

On the day that the patient is scheduled to receive the cells they will be pre-medicated with Benadryl and Tylenol. The patient will then receive an intravenous (into the vein) infusion of 1 x 10\^8 cells/kg of MSCs. The patient will be monitored closely for two hours after the infusion. The patient will receive a second infusion at the same dose within 3-5 days of the initial infusion (at the discretion of the investigator) if there is no improvement in respiratory parameters or if there is a worsening of Acute respiratory distress syndrome (ARDS).

The patient will receive standard medical tests when getting the infusion(s) and afterwards. As part of the research study, the patient will be evaluated daily for 7 days and then weekly at weeks 2, 3, and 4. The evaluations that will be done at these visits include:

* Physical exam and history
* SARS-CoV-2 test
* Blood tests
* Chest X-ray or chest CT Scan

Eligibility criteria: Inclusion Criteria:

1. 18 years or older
2. Confirmed SARS-CoV2 infection real-time reverse transcription polymerase chain reaction (RT-PCR) assay
3. Moderate OR severe ARDS, based on the degree of impairment of oxygenation as defined by the ratio of arterial oxygen tension to fraction of inspired oxygen (PaO2/FiO2):

   1. Moderate ARDS: PaO2/FiO2 100-200 mmHg OR
   2. Severe ARDS: PaO2/FiO2 ≤100 mmHg
4. If on invasive or noninvasive (BiPAP) mechanical ventilator, PEEP ≥5 cm H2O
5. Bilateral opacities present on chest radiograph or computed tomographic (CT) scan, that are not fully explained by pleural effusions, lung collapse, or lung nodules.

Exclusion Criteria:

1. Currently receiving extracorporeal membrane oxygenation (ECMO)
2. Severe chronic respiratory disease requiring use of home oxygen
3. Pregnant or lactating
4. Known hypersensitivity to dimethyl sulfoxide (DMSO)
5. Unstable hemodynamics as deemed by the treating physician/investigator including but not limited to unstable, ventricular tachycardia or new cardiac arrythmia requiring cardioversion.
6. Uncontrolled bacterial or fungal co-infection
7. Any end-stage organ disease or condition, which in the opinion of the Investigator, makes the patient an unsuitable candidate for treatment
8. Inability to obtain informed consent (from patient or legally appropriate proxy)
9. Presence of any contraindication to receiving prophylactic low dose unfractionated or low molecular weight heparin.
10. Respiratory failure not fully explained by cardiac failure or fluid overload.

Primary outcomes:
measure: Proportion of Participants With Treatment-related Serious Adverse Events (tSAEs)
timeFrame: 28 days post cell infusion
measure: Number of Participants With Improvement by at Least Two Categories on a Six Category Ordinal Scale at Day 14
timeFrame: 14 days post cell infusion
Secondary outcomes:
measure: Clinical Status Determined by 6-point Ordinal Scale at Day 28
timeFrame: 28 days post cell infusion
measure: Severity of Acute Respiratory Distress Syndrome (ARDS) at Day 14
timeFrame: 14 days post cell infusion
measure: Number of Oxygenation Free Days at Day 28
timeFrame: 28 days post cell infusion
measure: Number of Participants With Progression to Mechanical Ventilation or ECMO
timeFrame: 28 days post cell infusion
measure: Duration of Mechanical Ventilation and/or ECMO
timeFrame: 28 days post cell infusion
measure: Duration of ICU Stay
timeFrame: from the date of admission or data of on study if the patient was admitted to ICU before enrollment to the time of ICU discharge, death, or last follow-up, whichever occurred first. Up to 35 days.
measure: Duration of Hospital Stay
timeFrame: from the date of on study to the time of hospital discharge, death, or last follow-up, whichever occurred first. Up to 35 days.
measure: Overall Survival
timeFrame: 28 days post cell infusion
measure: All-cause Mortality
timeFrame: 28 days post cell infusion
Other outcomes:
Locations:
city: Houston
country: United States
facility: Houston Methodist Hospital
state: Texas
Study officials:
affiliation: Baylor College of Medicine
name: LaQuisa Hill, MD
role: PRINCIPAL_INVESTIGATOR
References: