Umbilical Cord Tissue (UC) Derived Mesenchymal Stem Cells (MSCs) Versus Placebo to Treat Acute Pulmonary Inflammation Due to COVID-19 (COVID-19)

Phase I, Randomized, Double Blinded, Placebo Control Study to Evaluate the Safety and Potential Efficacy of Intravenous Infusion of Umbilical Cord Tissue (UC) Derived Mesenchymal Stem Cells (MSCs) Versus Placebo to Treat Acute Pulmonary Inflammation Due to COVID-19 With Moderate to Severe Symptoms

The purpose of this study is to demonstrate the safety of Umbilical Cord Tissue Derived Mesenchymal Stem Cells (UCMSCs) administered intravenously in patients with acute pulmonary inflammation due to COVID-19 with moderately severe symptoms

Study Overview

• Status: Withdrawn
• Conditions: COVID-19; Acute Respiratory Distress Syndrome; Corona Virus Infection
• Intervention / Treatment: Biological: UCMSCs; Other: Placebo

• Study Type: Interventional
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Provide written informed consent
2. Male or female subjects age > 18 years at the time of signing the Informed Consent Form.
3. COVID-19 positive according to diagnosis (evaluated by reverse transcription (RT)-polymerase chain reaction (PCR) test confirming infection with severe acute respiratory syndrome coronavirus and clinical management of COVID-19 criteria (refer to appendix B)

4. Individuals with moderate to severe COVID-19 symptoms.

   • Moderate:
   • Patients with moderate disease are symptomatic (e.g. fever, cough, headache, myalgia, sore throat, nasal congestion, nausea, vomiting, diarrhea, fatigue, anosmia, or dysgeusia) and have abnormal chest imaging or some degree of hypoxia requiring supplemental oxygen but not intubation.
   • Moderate-severe:
   • The Moderately Severe disease category includes patients who are symptomatic (as described above), have abnormal chest imaging, but also have worsening hypoxia compatible with mild acute respiratory distress syndrome (ARDS) (Partial Pressure of Oxygen (PaO2)/Fraction of Inspired Oxygen (FiO2) </= 300 but > 200) - Berlin criteria; but do not yet require intubation .
5. Adequate venous access
6. For female patients only, willingness to use FDA-recommended birth control until 6 months post treatment.
7. Must agree to comply with all study requirements and be willing to complete all study visits.
8. Need in-patient admission

Exclusion Criteria:

1. PaO2/FiO2 </= 200
2. Anticipated intubation within 24h
3. Be a female who is pregnant, nursing, or of childbearing potential while not practicing effective contraceptive methods. Female subjects must undergo a blood pregnancy test at screening and prior to infusion.
4. Inability to perform any of the assessments required for endpoint analysis.
5. Subjects that are unsuitable with the study requirements .
6. Active listing (or expected future listing) for transplant of any organ.
7. Have known allergies to penicillin or streptomycin.
8. Be a solid organ transplant recipient. This does not include prior cell-based therapy (>12 months prior to enrollment), bone, skin, ligament, tendon or corneal grafting.
9. Have a history of organ or cell transplant rejection
10. Has a history of an adverse response to cell-based therapy
11. Have presence of any active malignancy (other than non-melanoma skin cancer) that required treatment within the last 1 year.
12. History of active drug abuse (illegal "street" drugs except marijuana, or prescription medications not being used appropriately for a pre-existing medical condition) or alcohol abuse (≥ 5 drinks/day for ˃ 3 months), or documented medical, occupational, or legal problems arising from the use of alcohol or drugs within the past 24 months
13. Be serum positive for HIV, Surface antigen of Hepatitis B virus (HBsAg) or Viremic hepatitis C.
14. Severe hepatic impairment (defined as liver cirrhosis Child stage B or C);
15. Stage 4 chronic kidney disease or currently receiving chronic dialysis;
16. Advanced cardiac (eg, severe heart failure [New York Heart Association (NYHA) III-IV]) or pulmonary diseases;
17. Has uncontrolled hypertension as defined by BP systolic above 180 and diastolic above 110 which, in the Investigator's judgment, would not make participation appropriate;
18. Known allergy or hypersensitivity to stem cell infusions or its components;
19. Current enrollment in an investigational drug or participation in such a study within 15 days of entry into this study;
20. Moderate to severe liver failure (Childs-Pugh Score > 10) Alanine Aminotransferase (ALT)/Aspartate Aminotransferase (AST) > 5 times the upper limit of normal;
21. Congenital prolonged QT syndrome;
22. Current QT corrected (QTc) above 490 msec. If patient has Q, R and S waves (QRS) interval greater or equal to 120 msec, then the QT/QTc will be normalized to a QRS interval of 110 msec. (For instance, if the patient has a bundle branch block with QRS of 140 msec and QT/QTc of 470 msec, the normalized QTc will be 470;
23. Subjects taking drugs that could affect the QT interval (e.g. procainamide, disopyramide, mexiletine, flecainide, propafenone, amiodarone, sotalol, cimetidine, dronedarone, dofetilide, levofloxacin, ciprofloxacin, moxifloxacin);
24. Anticipated transfer to another hospital which is not a study site within 72 hours;
25. Coagulopathy (Platelets less than 80,000, or Prothrombin Time (PT)/Partial Thromboplastin time (PTT) twice normal range without systemic anticoagulation;
26. Greater than 24h since first meeting ARDS criteria (Berlin definition) or 72h of ICU admission;
27. Subjects who are legally detained in an official institution;
28. A previous MSC infusion in last 30 days not related to this trial;
29. History of Pulmonary Hypertension (WHO Class III/IV);
30. Unstable arrhythmia or uncontrolled hypertension not responding to best ICU treatment;
31. Patients currently receiving Extracorporeal Membrane Oxygenation (ECMO);
32. Any other irreversible disease or condition for which 6-month mortality is estimated to be greater than 50%;
33. Moribund patient not expected to survive > 24 hours;
34. The investigator believes that participating in the trial is not in the best interest of the patient, or the investigator considers patient unsuitable for enrollment (such as unpredictable risks or subject compliance issues)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group 1: (UCMSCs); Participants in this group will receive the 2 intravenous (IV) UCMSCs intervention on day 0 and day 3.	Biological: UCMSCs; 100 x 106 (100 million) UCMSCs delivered via peripheral intravenous infusion.
Placebo Comparator: Group 2: (Placebo); Participants in this group will receive the placebo, a solution of 1% human serum albumin in Plasmalyte A, on day 0 and day 3.	Other: Placebo; Placebo, a solution of 1% human serum albumin in Plasmalyte A, delivered via peripheral intravenous infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent of participants with treatment related Serious Adverse Events (SAE)	Safety of UCMSCs will be reported as the percentage of participants in each treatment group that experienced a treatment related SAEs.	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in inflammatory marker levels	Change in serum inflammatory marker levels including Interleukin (IL) IL-6, IL-2, Tumor Necrosis Factor Alpha (TNF-a) and procalcitonin will be evaluated in ng/L.	Baseline, Day 30
Change in systemic inflammatory marker levels	Change in serum systemic inflammatory marker levels including D-dimer, high sensitivity C-reactive protein (hsCRP) and ferritin will be evaluated in mg/L.	Baseline, Day 30
COVID-19 Viral Load	Assessed using blood samples or nose/throat swabs.	Up to 30 Days
Change in SOFA score	Sequential Organ Failure Assessment (SOFA) will be used to assess organ failure including the cardiovascular system, coagulation system, liver, kidney and other extra-pulmonary organs. SOFA score ranges from 0-24 with the higher score indicating worse outcomes.	Baseline, Up to 30 Days
Change in electrolytes levels	Sodium, Potassium, Chloride and Carbon Dioxide (CO2) will be evaluated in mmol/L. Changes from baseline to Day 30 will be compared between groups.	Baseline, Up to 30 Days
Change in LDH levels	Serum Lactate Dehydrogenase (LDH) levels assessed in U/L. Changes in LDH from baseline to Day 30 will be compared between groups.	Baseline, Up to 30 Days
Number of subjects discharged from the ICU	ICU monitoring status will be reported as the number of subjects discharged from the ICU within 7 days.	Up to 7 Days
Percentage of participants with less requirement for vasoactive agents	Percentage of participants requiring less use of vasoactive agents will be reported.	Up to 30 Days
Rate of Mortality	Percentage of participant deaths throughout the study period.	Up to 30 Days
Percentage of participants with changes in immune marker expression	The percentage of participants with changes in serum immune marker levels including Cluster of Differentiation (CD) CD 4+ and CD 8+, as evaluated by treating physician will be reported.	Up to 30 Days
Percentage of participants with changes in radiologic findings	Percentage of participants with changes in their chest imaging such as ground-glass opacity, local patch shadowing, bilateral patch shadowing and interstitial abnormalities will be reported. Imaging will be assessed by treating physician using chest radiography or chest Computed Tomography (CT).	Up to 30 Days
Percentage of participants with less pneumonia symptoms	Percentage of participants showing less pneumonia symptoms will be reported as evaluated by treating physician using chest radiography or chest CT.	Up to 30 Days

Collaborators and Investigators

• Sponsor: Joshua M Hare
• Investigators: Principal Investigator: Joshua M Hare, MD, ISCI/University of Miami Miller School of Medicine

Publications and helpful links

Helpful Links

• Interdisciplinary Stem Cell Institute at the University of Miami Miller School website

Study record dates

Study Major Dates

• Study Start (Anticipated): October 1, 2022
• Primary Completion (Anticipated): June 1, 2024
• Study Completion (Anticipated): June 1, 2024

Study Registration Dates

• First Submitted: July 27, 2020
• First Submitted That Met QC Criteria: July 28, 2020
• First Posted (Actual): July 29, 2020

Study Record Updates

• Last Update Posted (Actual): May 12, 2022
• Last Update Submitted That Met QC Criteria: May 6, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Keywords: Acute Pulmonary Inflammation
• Additional Relevant MeSH Terms: Pathologic Processes; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Respiration Disorders; Pneumonia, Viral; Lung Diseases; Infant, Newborn, Diseases; Lung Injury; Infant, Premature, Diseases; COVID-19; Coronavirus Infections; Inflammation; Pneumonia; Respiratory Distress Syndrome; Respiratory Distress Syndrome, Newborn; Acute Lung Injury
• Other Study ID Numbers: 20200575

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No