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

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

***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.

Study Overview

• Status: Completed
• Conditions: COVID-19; Acute Respiratory Distress Syndrome; Sars-CoV2
• Intervention / Treatment: Biological: Mesenchymal Stromal Cells; Other: Supportive Care

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

• Study Type: Interventional
• Enrollment (Actual): 28
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: LaQuisa Hill, MD; Phone Number: (713) 441-1450; Email: LaQuisa.Hill@bcm.edu

Study Locations

• United States
  • Texas
    • Houston, Texas, United States, 77030
      • Houston Methodist Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 (ventricular tachycardia or fibrillation)
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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Safety Run In; The study will first enroll and treat six patients with MSCs for safety run in. If no more than 2 treatment-related severe adverse events (tSAEs) are observed, the study will enroll and randomize additional patients in a ratio of 1:1 to receive either MSCs or routine/supportive care.	Biological: Mesenchymal Stromal Cells; Patients will be given the cell product by intravenous injection (into the vein through an IV line). Dose:1 x 10^8 MSCs.; Other Names: MSCs
Experimental: Mesenchymal stromal cells; Patients randomized to the MSC arm will be administered an intravenous infusion of MSCs at a dose of 1 x 10^8. A second infusion will be allowed if the patient does not have improvement in respiratory parameters per discretion of the investigator, or ARDS clinically worsens, within 3-5 days following the initial infusion.	Biological: Mesenchymal Stromal Cells; Patients will be given the cell product by intravenous injection (into the vein through an IV line). Dose:1 x 10^8 MSCs.; Other Names: MSCs
Other: Control Group; Patients randomized to the control arm will receive supportive care or treatment designated by their treating physicians.	Other: Supportive Care; Patients will receive supportive care per their treating physician

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of Participants With Treatment-related Serious Adverse Events (tSAEs)	Treatment-related serious adverse events (tSAE) are those directly related to the investigational infusion product. Adverse event grading will be per NCI Common Terminology Criteria for Adverse Events(CTCAE), vs 5. Rate of tSAEs in patients treated with MSCs will be reported as proportion and its 95% confidence interval.	28 days post cell infusion
Number of Participants With Improvement by at Least Two Categories on a Six Category Ordinal Scale at Day 14	Change by at least two categories on a six-category ordinal scale as improvement at day 14 post-randomization per protocol defined criteria. The six-category ordinal scale ranges from 6 to 1 with a higher score indicating a worse clinical outcome as follows: 6 ꞊ death; 5 ꞊ hospitalization, requiring extracorporeal membrane oxygenation (ECMO) and/or invasive mechanical ventilation (IMV); 4 ꞊ hospitalization, requiring non-invasive mechanical ventilation (NIV) and/or High-flow nasal cannula (HFNC) therapy; 3 = hospitalization, requiring supplemental oxygen (but not NIV/HFNC); 2 = hospitalization, not requiring supplemental oxygen; 1 = hospital discharge.	14 days post cell infusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical Status Determined by 6-point Ordinal Scale at Day 28	Clinical status at day 28 as determined by 6-point ordinal scale as follows: 6 ꞊ death; 5 ꞊ hospitalization, requiring extracorporeal membrane oxygenation (ECMO) and/or invasive mechanical ventilation (IMV); 4 ꞊ hospitalization, requiring non-invasive mechanical ventilation (NIV) and/or High-flow nasal cannula (HFNC) therapy; 3 = hospitalization, requiring supplemental oxygen (but not NIV/HFNC); 2 = hospitalization, not requiring supplemental oxygen; 1 = hospital discharge. The six-category ordinal scale ranges from 6 to 1 with a higher score indicating a worse clinical outcome.	28 days post cell infusion
Severity of Acute Respiratory Distress Syndrome (ARDS) at Day 14	ARDS is divided into 3 groups based on the degree of hypoxemia: mild (partial pressure of oxygen in the arterial blood(PaO2)/fraction of inspired oxygen(FIO2) 201-300 mm Hg), moderate (PaO2/FIO2: 101-200 mm Hg), and severe (PaO2/FIO2 ≤ 100 mm Hg) and ventilator settings with a positive end-expiratory pressure (PEEP) or continuous positive airway pressure (CPAP) ≥5 cm water (H2O).	14 days post cell infusion
Number of Oxygenation Free Days at Day 28	Number of oxygen support-free days through Day 28	28 days post cell infusion
Number of Participants With Progression to Mechanical Ventilation or ECMO	Participants not receiving mechanical ventilation at baseline who progress to requiring mechanical ventilation.	28 days post cell infusion
Duration of Mechanical Ventilation and/or ECMO	Number of days requiring invasive mechanical ventilation and/or ECMO (ventilation/ECMO free days at day 28)	28 days post cell infusion
Duration of ICU Stay	The number of days a participant spent in ICU. Duration of ICU stay is calculated 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.	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.
Duration of Hospital Stay	Duration of hospital stay is calculated from the date of on study to the time of hospital discharge, death, or last follow-up, whichever occurred first. It does not reflect the entire hospitalization time.	from the date of on study to the time of hospital discharge, death, or last follow-up, whichever occurred first. Up to 35 days.
Overall Survival	Probability of overall survival is calculated using Kaplan-Meier survival curves per protocol. Overall survival time is defined as days from the date of randomization or date of infusion if received MSCs to the date of death or the date of the last follow-up for censoring.	28 days post cell infusion
All-cause Mortality	Number and percentage of deaths (all-cause) until Day 28	28 days post cell infusion

Collaborators and Investigators

• Sponsor: Baylor College of Medicine
• Collaborators: The Methodist Hospital Research Institute; Center for Cell and Gene Therapy, Baylor College of Medicine
• Investigators: Principal Investigator: LaQuisa Hill, MD, Baylor College of Medicine

Study record dates

Study Major Dates

• Study Start (Actual): February 12, 2021
• Primary Completion (Actual): January 10, 2023
• Study Completion (Actual): January 10, 2023

Study Registration Dates

• First Submitted: April 10, 2020
• First Submitted That Met QC Criteria: April 13, 2020
• First Posted (Actual): April 14, 2020

Study Record Updates

• Last Update Posted (Actual): April 1, 2024
• Last Update Submitted That Met QC Criteria: March 29, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Respiratory failure; Mesenchymal Stromal Cells
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Respiration Disorders; Pneumonia, Viral; Pneumonia; Lung Diseases; Infant, Newborn, Diseases; Lung Injury; Infant, Premature, Diseases; COVID-19; Respiratory Distress Syndrome; Respiratory Distress Syndrome, Newborn; Acute Lung Injury
• Other Study ID Numbers: H-47561 MSC for COVID-19

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No