Mesenchymal Stromal Cells for the Treatment of SARS-CoV-2 Induced Acute Respiratory Failure (COVID-19 Disease)

Study Overview
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Brief Summary
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***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
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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

Official Title
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Single Donor Banked Bone Marrow Mesenchymal Stromal Cells for the Treatment of COVID-19 Induced ARDS: A Non-Blinded Randomized, Controlled Study

Conditions
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Sars-CoV2, Acute Respiratory Distress Syndrome, COVID-19

Intervention / Treatment
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* Biological: Mesenchymal Stromal Cells
* Other: Supportive Care


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18 years or older Confirmed SARS-CoV2 infection real-time reverse transcription polymerase chain reaction (RT-PCR) assay 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): Moderate ARDS: PaO2/FiO2 100-200 mmHg OR Severe ARDS: PaO2/FiO2 ≤100 mmHg If on invasive or noninvasive (BiPAP) mechanical ventilator, PEEP ≥5 cm H2O 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: Currently receiving extracorporeal membrane oxygenation (ECMO) Severe chronic respiratory disease requiring use of home oxygen Pregnant or lactating Known hypersensitivity to dimethyl sulfoxide (DMSO) Unstable hemodynamics (ventricular tachycardia or fibrillation) Uncontrolled bacterial or fungal co-infection Any end-stage organ disease or condition, which in the opinion of the Investigator, makes the patient an unsuitable candidate for treatment Inability to obtain informed consent (from patient or legally appropriate proxy) Presence of any contraindication to receiving prophylactic low dose unfractionated or low molecular weight heparin.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Mesenchymal stromal cells<br>Patients will receive up to 2 infusions of mesenchymal stem cells. | Biological: Mesenchymal Stromal Cells<br>* Patients will be given the cell product by intravenous injection (into the vein through an IV line). Dose:1 x 10^8 MSCs.<br>* Other names: MSCs;|
| Other: Control Group<br>Patients will receive supportive care or treatment designated by their treating doctor. | Other: Supportive Care<br>* Patients will receive supportive care per their treating physician<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Treatment-related serious adverse events (tSAEs) | Treatment-related serious adverse events (tSAE) will be considered as those directly related to the investigational infusion product per protocol defined criteria. | 28 days post cell infusion | 
| Change in clinical status at day 14 | Change by at least two categories on a six category ordinal scale at day 14 post randomization per protocol defined criteria. The six-category ordinal scale ranges from 6 to 1 with a higher score indicates worse clinical outcome | 14 days post cell infusion | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Mesenchymal Stromal Cells, Respiratory failure