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

NCT04345601 | Completed Phase 1 Results DMC FDA Drug

• 1 other identifier: H-47561 MSC for COVID-19
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 1

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.

Conditions

Sars-CoV2; Acute Respiratory Distress Syndrome; COVID-19

Keywords

Mesenchymal Stromal Cells; Respiratory failure

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (9)

• Clinical Status Determined by 6-point Ordinal Scale at Day 28

  28 days post cell infusion

• Severity of Acute Respiratory Distress Syndrome (ARDS) at Day 14

  14 days post cell infusion

• Number of Oxygenation Free Days at Day 28

  28 days post cell infusion

• Number of Participants With Progression to Mechanical Ventilation or ECMO

  28 days post cell infusion

• Duration of Mechanical Ventilation and/or ECMO

  28 days post cell infusion

Study Arms (3)

Safety Run In

EXPERIMENTAL

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

Mesenchymal stromal cells

EXPERIMENTAL

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

Control Group

OTHER

Patients randomized to the control arm will receive supportive care or treatment designated by their treating physicians.

Other: Supportive Care

Interventions

Mesenchymal Stromal Cells BIOLOGICAL

Patients will be given the cell product by intravenous injection (into the vein through an IV line). Dose:1 x 10\^8 MSCs.

Also known as: MSCs

Mesenchymal stromal cells; Safety Run In

Supportive Care OTHER

Patients will receive supportive care per their treating physician

Control Group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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 as deemed by the treating physician/investigator including but not limited to unstable, ventricular tachycardia or new cardiac arrythmia requiring cardioversion.
• 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.
• Respiratory failure not fully explained by cardiac failure or fluid overload.

Sponsors & Collaborators

• Baylor College of Medicine: lead
• Center for Cell and Gene Therapy, Baylor College of Medicine: collaborator
• The Methodist Hospital Research Institute: collaborator

Study Sites (1)

Houston Methodist Hospital

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Respiratory Distress Syndrome; COVID-19; Respiratory Insufficiency

Interventions

Palliative Care

Condition Hierarchy (Ancestors)

Lung Diseases; Respiratory Tract Diseases; Respiration Disorders; Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections

Intervention Hierarchy (Ancestors)

Patient Care; Therapeutics; Health Services; Health Care Facilities Workforce and Services

Results Point of Contact

• Title: Dr. Laquisa Hill
• Organization: Baylor College of Medicine

LaQuisa.Hill@bcm.edu

713-441-1450

Study Officials

• LaQuisa Hill, MD

  Baylor College of Medicine

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: April 10, 2020
• First Posted: April 14, 2020
• Study Start: February 12, 2021
• Primary Completion: January 10, 2023
• Study Completion: January 10, 2023
• Last Updated: October 9, 2024
• Results First Posted: April 1, 2024

Record last verified: 2024-10

Locations

US (1)