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

Joshua M Hare

Status and phase

Withdrawn

Phase 1

Conditions

COVID-19

Corona Virus Infection

Acute Respiratory Distress Syndrome

Treatments

Other: Placebo

Biological: UCMSCs

Study type

Interventional

Funder types

Other

Identifiers

NCT04490486

20200575

Details and patient eligibility

About

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

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Provide written informed consent
Male or female subjects age > 18 years at the time of signing the Informed Consent Form.
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)
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 .
Adequate venous access
For female patients only, willingness to use FDA-recommended birth control until 6 months post treatment.
Must agree to comply with all study requirements and be willing to complete all study visits.
Need in-patient admission

Exclusion criteria

PaO2/FiO2 </= 200
Anticipated intubation within 24h
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.
Inability to perform any of the assessments required for endpoint analysis.
Subjects that are unsuitable with the study requirements .
Active listing (or expected future listing) for transplant of any organ.
Have known allergies to penicillin or streptomycin.
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.
Have a history of organ or cell transplant rejection
Has a history of an adverse response to cell-based therapy
Have presence of any active malignancy (other than non-melanoma skin cancer) that required treatment within the last 1 year.
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
Be serum positive for HIV, Surface antigen of Hepatitis B virus (HBsAg) or Viremic hepatitis C.
Severe hepatic impairment (defined as liver cirrhosis Child stage B or C);
Stage 4 chronic kidney disease or currently receiving chronic dialysis;
Advanced cardiac (eg, severe heart failure [New York Heart Association (NYHA) III-IV]) or pulmonary diseases;
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;
Known allergy or hypersensitivity to stem cell infusions or its components;
Current enrollment in an investigational drug or participation in such a study within 15 days of entry into this study;
Moderate to severe liver failure (Childs-Pugh Score > 10) Alanine Aminotransferase (ALT)/Aspartate Aminotransferase (AST) > 5 times the upper limit of normal;
Congenital prolonged QT syndrome;
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;
Subjects taking drugs that could affect the QT interval (e.g. procainamide, disopyramide, mexiletine, flecainide, propafenone, amiodarone, sotalol, cimetidine, dronedarone, dofetilide, levofloxacin, ciprofloxacin, moxifloxacin);
Anticipated transfer to another hospital which is not a study site within 72 hours;
Coagulopathy (Platelets less than 80,000, or Prothrombin Time (PT)/Partial Thromboplastin time (PTT) twice normal range without systemic anticoagulation;
Greater than 24h since first meeting ARDS criteria (Berlin definition) or 72h of ICU admission;
Subjects who are legally detained in an official institution;
A previous MSC infusion in last 30 days not related to this trial;
History of Pulmonary Hypertension (WHO Class III/IV);
Unstable arrhythmia or uncontrolled hypertension not responding to best ICU treatment;
Patients currently receiving Extracorporeal Membrane Oxygenation (ECMO);
Any other irreversible disease or condition for which 6-month mortality is estimated to be greater than 50%;
Moribund patient not expected to survive > 24 hours;
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)