Use of UC-MSCs for COVID-19 Patients

• ClinicalTrials.gov Identifier: NCT04355728
• Recruitment Status: Completed
• First Posted: April 21, 2020
• Last Update Posted: November 12, 2020
• Sponsor: Camillo Ricordi
• Information provided by (Responsible Party): Camillo Ricordi, University of Miami

Study Description

Brief Summary:

The purpose of this research study is to learn about the safety and efficacy of human umbilical cord derived Mesenchymal Stem Cells (UC-MSC) for treatment of COVID-19 Patients with Severe Complications of Acute Lung Injury/Acute Respiratory Distress Syndrome (ALI/ARDS).

Condition or disease	Intervention/treatment	Phase
Corona Virus Infection; ARDS; ARDS, Human; Acute Respiratory Distress Syndrome; COVID-19	Biological: Umbilical Cord Mesenchymal Stem Cells + Heparin along with best supportive care.; Other: Vehicle + Heparin along with best supportive care	Phase 1; Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 24 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: The trial has two groups, each with 12 subjects (n=24). All eligible subjects will be randomized to either the treatment group or standard of care, and randomization will be stratified by ARDS severity.
• Masking: Triple (Participant, Care Provider, Investigator)
• Masking Description: Double-Blinding Trial
• Primary Purpose: Treatment
• Official Title: Umbilical Cord-derived Mesenchymal Stem Cells for COVID-19 Patients With Acute Respiratory Distress Syndrome (ARDS)
• Actual Study Start Date: April 25, 2020
• Actual Primary Completion Date: October 31, 2020
• Actual Study Completion Date: October 31, 2020

Arms and Interventions

Arm	Intervention/treatment
Experimental: UC-MSCs Group; Participants in this group will be treated with two infusions of UC-MCSs along with heparin (blood thinner) in addition to standard of care treatment. The first infusion will be administered within 24 hours of study enrollment and the second infusion will be administered within 72 hours of study enrollment.	Biological: Umbilical Cord Mesenchymal Stem Cells + Heparin along with best supportive care.; UC-MSC will be administered at 100x10^6 cells/infusion administered intravenously in addition to the standard of care treatment.
Placebo Comparator: Control Group; Participants in this group will be treated with two infusions of vehicle along with heparin (blood thinner) in addition to standard of care treatment. The first infusion will be administered within 24 hours of study enrollment and the second infusion will be administered within 72 hours of study enrollment.	Other: Vehicle + Heparin along with best supportive care; Best supportive care treatment per the treating hospital protocol.

Outcome Measures

Primary Outcome Measures :

1. Incidence of pre-specified infusion associated adverse events [ Time Frame: Day 5 ]
   Safety will be defined by the incidence of pre-specified infusion associated adverse events as assessed by treating physician
2. Incidence of Severe Adverse Events [ Time Frame: 90 days ]
   Safety will be defined by the incidence of severe adverse events as assessed by treating physician

Secondary Outcome Measures :

1. Survival rate after 90 days post first infusion [ Time Frame: 90 days ]
   Number of participants that are alive at 90 days post first infusion follow up.
2. Ventilator-Free Days [ Time Frame: 28 days or hospital discharge, whichever is earlier ]
   Number of days participants were off ventilators within up to 28 days of hospitalization
3. Change in Oxygenation Index (OI) [ Time Frame: 28 days ]
   Measure the fraction of inspired oxygen (FiO2) and its usage within the body during intensive care, measured using fNIRS (Functional Near Infrared Spectroscopy).
4. Plat-PEEP [ Time Frame: 28 days ]
   Measuring respiratory mechanics in ventilated patients [plateau pressure (Pplat)-positive end-expiratory pressure]
5. Sequential Organ Failure Assessment (SOFA) Scores [ Time Frame: 28 days ]
   The SOFA assessment is used to track a person's risk status during stay in the Intensive Care Unit (ICU). The score is based on six different scores, one each for the respiratory, cardiovascular, hepatic, coagulation, renal, and neurological systems. Each organ system is assigned a point value from 0 (normal) to 4 (high degree of dysfunction/failure)
6. Small Identification Test (SIT) scores [ Time Frame: At baseline, day 18 and day 28. ]
   The SIT is a self-administered 40-item test involving microencapsulated (scratch-and-sniff) odors with a forced-choice design. The test has a total score ranging from 0-40 Follows scoring key for evaluation. The higher score indicates better outcome.
7. Troponin I levels [ Time Frame: Baseline, 28 days ]
   As assessed via serum blood samples.
8. C-Reactive Protein levels [ Time Frame: Baseline, 28 days ]
   As assessed via serum blood samples.
9. Arachidonic Acid (AA)/Eicosapentaenoic Acid (EPA) Ratio [ Time Frame: Baseline, 28 days ]
   As assessed via serum blood samples.
10. D-dimer levels [ Time Frame: Baseline, 28 days ]
    As assessed via serum blood samples.
11. 25-Hydroxy Vitamin D levels [ Time Frame: Baseline, 28 days ]
    As assessed via serum blood samples.
12. Alloantibodies levels [ Time Frame: Baseline, 28 days ]
    As assessed via serum blood samples.
13. Blood white cell count [ Time Frame: Baseline, 28 days ]
    As assessed via serum blood samples.
14. Platelets count [ Time Frame: Baseline, 28 days ]
    As assessed via serum blood samples.

Eligibility Criteria

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

Criteria

Inclusion Criteria:

Patients >/= 18 years old diagnosed with COVID-19 (as evaluated by PCR test confirming infection with SARS-CoV-2) will be eligible for inclusion if they meet all of the below criteria. Inclusion criteria must all be present within a 24-hour time period at the time of enrollment:

1. Patient currently hospitalized
2. Aged ≥ 18 years
3. Willing and able to provide written informed consent, or with a legal representative who can provide informed consent
4. Peripheral capillary oxygen saturation (SpO2) ≤ 94% at room air, or requiring supplemental oxygen at screening
5. PaO2/FiO2 ratio < 300 mmHg
6. Bilateral infiltrates on frontal chest radiograph or bilateral ground glass opacities on a chest CT scan
7. Hypoxemia requiring an increase in the fraction of inspired oxygen (FiO2) of ≥ 20% AND an increase in positive end-expiratory airway pressure (PEEP) level of 5 cm H2O or more to maintain transcutaneous oxygen saturations in the target range of 88-95%, or requirement for escalation from oxygen therapy to invasive mechanical ventilation

Exclusion Criteria:

1. PaO2/FiO2 ≥ 300 at the time of enrollment
2. A previous MSC infusion not related to this trial
3. History of Pulmonary Hypertension (WHO Class III/IV)
4. History of left atrial hypertension or decompensated left heart failure.
5. Pregnant or lactating patient
6. Unstable arrhythmia
7. Patients with previous lung transplant
8. Patients currently receiving chronic dialysis
9. Patients currently receiving Extracorporeal Membrane Oxygenation (ECMO)
10. Presence of any active malignancy (except non-melanoma skin cancer)
11. Any other irreversible disease or condition for which 6-month mortality is estimated to be greater than 50%
12. Moderate to severe liver disease (AST and ALT >5 X ULN)
13. Severe chronic respiratory disease with a PaCO2 > 50 mm Hg or the use of home oxygen
14. Baseline QT prolongation
15. Moribund patient not expected to survive > 24 hours

Contacts and Locations

Locations

United States, Florida

Diabetes Research Institute, University of Miami Miller School of Medicine

Miami, Florida, United States, 33136

Sponsors and Collaborators

Camillo Ricordi

Investigators

• Principal Investigator: Camillo Ricordi, MD; University of Miami

More Information

• Responsible Party: Camillo Ricordi, Professor of Surgery and Chief, Division of Cellular Transplantation, University of Miami
• ClinicalTrials.gov Identifier: NCT04355728
• Other Study ID Numbers: 20200671
• First Posted: April 21, 2020
• Last Update Posted: November 12, 2020
• Last Verified: November 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Camillo Ricordi, University of Miami:

COVID-19

Additional relevant MeSH terms:

Coronavirus Infections; Severe Acute Respiratory Syndrome; Respiratory Distress Syndrome, Newborn; Respiratory Distress Syndrome, Adult; Acute Lung Injury; Syndrome; Disease; Pathologic Processes; Lung Diseases; Respiratory Tract Diseases; Respiration Disorders; Infant, Premature, Diseases; Infant, Newborn, Diseases; Virus Diseases; Lung Injury; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Respiratory Tract Infections; Heparin; Calcium heparin; Anticoagulants; Fibrinolytic Agents; Fibrin Modulating Agents; Molecular Mechanisms of Pharmacological Action