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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04490486
Recruitment Status : Not yet recruiting
First Posted : July 29, 2020
Last Update Posted : September 9, 2020
Sponsor:
Information provided by (Responsible Party):
Joshua M Hare, University of Miami

Brief Summary:
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

Condition or disease Intervention/treatment Phase
COVID-19 Acute Respiratory Distress Syndrome Corona Virus Infection Biological: UCMSCs Other: Placebo Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 21 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: 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
Estimated Study Start Date : March 1, 2021
Estimated Primary Completion Date : June 1, 2024
Estimated Study Completion Date : June 1, 2024


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




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


Secondary Outcome Measures :
  1. Change in inflammatory marker levels [ Time Frame: Baseline, Day 30 ]
    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.

  2. Change in systemic inflammatory marker levels [ Time Frame: Baseline, Day 30 ]
    Change in serum systemic inflammatory marker levels including D-dimer, high sensitivity C-reactive protein (hsCRP) and ferritin will be evaluated in mg/L.

  3. COVID-19 Viral Load [ Time Frame: Up to 30 Days ]
    Assessed using blood samples or nose/throat swabs.

  4. Change in SOFA score [ Time Frame: Baseline, Up to 30 Days ]
    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.

  5. Change in electrolytes levels [ Time Frame: Baseline, Up to 30 Days ]
    Sodium, Potassium, Chloride and Carbon Dioxide (CO2) will be evaluated in mmol/L. Changes from baseline to Day 30 will be compared between groups.

  6. Change in LDH levels [ Time Frame: Baseline, Up to 30 Days ]
    Serum Lactate Dehydrogenase (LDH) levels assessed in U/L. Changes in LDH from baseline to Day 30 will be compared between groups.

  7. Number of subjects discharged from the ICU [ Time Frame: Up to 7 Days ]
    ICU monitoring status will be reported as the number of subjects discharged from the ICU within 7 days.

  8. Percentage of participants with less requirement for vasoactive agents [ Time Frame: Up to 30 Days ]
    Percentage of participants requiring less use of vasoactive agents will be reported.

  9. Rate of Mortality [ Time Frame: Up to 30 Days ]
    Percentage of participant deaths throughout the study period.

  10. Percentage of participants with changes in immune marker expression [ Time Frame: Up to 30 Days ]
    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.

  11. Percentage of participants with changes in radiologic findings [ Time Frame: Up to 30 Days ]
    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).

  12. Percentage of participants with less pneumonia symptoms [ Time Frame: Up to 30 Days ]
    Percentage of participants showing less pneumonia symptoms will be reported as evaluated by treating physician using chest radiography or chest CT.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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

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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04490486


Contacts
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Contact: Joshua M Hare, MD 305-243-5579 Jhare@med.miami.edu
Contact: Yvenie Desire, BS 305-243-7273 Ydesire@miami.edu

Locations
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United States, Florida
University of Miami
Miami, Florida, United States, 33136
Contact: Joshua M Hare, MD    305-243-5579    jhare@miami.edu   
Sponsors and Collaborators
Joshua M Hare
Investigators
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Principal Investigator: Joshua M Hare, MD ISCI/University of Miami Miller School of Medicine
Additional Information:
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Responsible Party: Joshua M Hare, Director of ISCI, Louis Lemberg Professor of Medicine, University of Miami
ClinicalTrials.gov Identifier: NCT04490486    
Other Study ID Numbers: 20200575
First Posted: July 29, 2020    Key Record Dates
Last Update Posted: September 9, 2020
Last Verified: September 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Joshua M Hare, University of Miami:
Acute Pulmonary Inflammation
Additional relevant MeSH terms:
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Coronavirus Infections
Severe Acute Respiratory Syndrome
Respiratory Distress Syndrome, Newborn
Respiratory Distress Syndrome, Adult
Acute Lung Injury
Pneumonia
Inflammation
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