Safety and Effectiveness of Placental Derived Exosomes and Umbilical Cord Mesenchymal Stem Cells in Moderate to Severe Acute Respiratory Distress Syndrome (ARDS) Associated With the Novel Corona Virus Infection (COVID-19)

Study Overview
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Brief Summary
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Recent advances have been made in prevention of the viral infection via vaccines but there is still need for effective treatment options for patients. Novel therapies need to be developed to further improve clinical outcomes. The biggest medical challenge in the response to COVID-19 is ARDS requiring hospitalization in an intensive care setting and ventilator dependence. Intravenously administered umbilical cord derived exosomes and stem cells have been reported in literature to alleviate pulmonary distress in such patients. The purpose of this study is to explore the safety and benefits of intravenous administration of WJPure and EVPure in the treatment of COVID-19 patients with moderate to severe ARDS. .

Detailed Description
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One of the hallmark features of the progression of COVID-19 is lung injury from the viral infection leading to potentially acute respiratory distress syndrome (ARDS) and respiratory failure requiring ventilator support. In patients who survive ARDS, regardless of the pathology, there is evidence that their long-term quality of life is adversely affected. The rationale for the dose and dosing regimen proposed in this study is based on the safe administration and benefits of this treatment regimen reported to us last year by physicians trying to treat moderate to severe COVID-19 patients. In those reports, the intravenous route of administration was used. It has been reported that dosing every 2 days amplified the benefit of the combination of exosomes and mesenchymal stem cells. It has been suggested based on clinical experience that the exosomes and MSCs are complementary to one another as well as enhancing the innate abilities of both. During the early days of the pandemic, intravenous infusion of a mixture of EV-Pure™ and WJ-Pure™ was reported to benefit hospitalized patients with moderate to severe COVID-19 related ARDS. This study is designed to systematically explore the risk and benefits of intravenous infusion of EV-Pure™ and WJ-Pure™ in the treatment of hospitalized COVID-19 patients with moderate to severe ARDS. This is a proof of concept, double-blind, placebo-controlled trial to evaluate the safety and efficacy of intravenous infusion of EV-Pure™ and WJ-Pure™, versus placebo, for use in the treatment of moderate to severe ARDS related to COVID-19. This is an add-on treatment study; subjects will be allowed to take standard of care treatments available. The study will have two arms (n=10 each): Experimental/treatment arm: EV-Pure™ and WJ-Pure™ plus standard care Placebo: Cryopreservation media plus standard care The study duration would be 5 days of treatment plus 12 weeks follow up.

Official Title
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Safety and Effectiveness of Placental Derived Exosomes and Umbilical Cord Mesenchymal Stem Cells in Moderate to Severe Acute Respiratory Distress Syndrome (ARDS) Associated With the Novel Corona Virus Infection (COVID-19)

Conditions
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COVID-19 Acute Respiratory Distress Syndrome, Respiratory Distress Syndrome

Intervention / Treatment
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* Drug: EV-Pure™ and WJ-Pure™
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects will be eligible for enrollment in the study only if they meet the following criteria: Male or female, aged at 18 years (including) to 75 years old. Patient with a confirmed SARS-CoV-2 infection (by positive reverse-transcription polymerase chain reaction (RT-PCR) from nasopharyngeal sample or any other sample) Hospitalized with moderate to severe ARDS. Have ARDS or acute lung injury, comply with any of the following: i. Respiratory distress, Respiratory rate (RR) ≥ 30 times/min ii. Pulse oxygen saturation (SpO2) at rest ≤ 93% iii. Partial pressure of oxygen/fraction of inspired oxygen (PaO2/FiO2) ≤ 300mmHg If childbearing age: agree to practice effective birth control from screening until 12 weeks after the last study treatment. Exclusion Criteria: Subjects will be ineligible for enrollment in the study if they meet any of the following criteria: Patient under invasive mechanical ventilation for more than 48 hours Allergic or hypersensitive to any of the ingredients. Pneumonia caused by bacteria, mycoplasma, chlamydia, legionella, fungi or other viruses. Obstructive HABP/VABP induced by lung cancer or other known causes. Carcinoid syndrome. History of long-term use of immunosuppressive agents. History of Class III or IV pulmonary arterial hypertension. Patient with chronic respiratory disease under oxygen therapy. Undergoing hemodialysis or peritoneal dialysis. Estimated or actual rate of creatinine clearance < 15 mL/min. History of moderate and severe liver disease (Child-Pugh score >12). History of deep venous thrombosis or pulmonary embolism within the last 3 years. Undergoing extracorporeal membrane oxygenation (ECMO) or high-frequency oscillatory ventilation support. Patient included in another ongoing interventional therapeutic trial. Pregnant or Lactating. Any condition of unsuitable for the study determined by Principal Investigator (PI).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental/treatment arm<br> | Drug: EV-Pure™ and WJ-Pure™<br>* The treatment consists of administration of WJ-Pure™ and EV-Pure™ plus standard care<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Cryopreservation media plus standard care<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To Assess the safety of EV-Pure™ and WJ-Pure™ administration in patients exhibiting moderate to severe ARDS associated with COVID-19, compared to placebo. | Evaluate incidences of Treatment-Emergent Adverse Events following EV-Pure™ and WJ-Pure™ administeration in patients exhibiting moderate to severe ARDS associated with COVID-19 compared to placebo. Presence of adverse events in less than 10% of the study population, as a measure of safety | 3 months | 
| To assess the efficacy of EV-Pure™ and WJ-Pure™ compared to placebo, in patients with moderate to severe ARDS assoociated with COVID-19 | Clinical data will be evaluated to determine if there were any significant changes in the COVID-19 symptoms in patients in the treated versus placebo groups. The following information will be collected to evaluate the effectiveness of the treatment at 4 weeks post- treatment: Discharged home on no supplemental oxygen Discharged home on supplemental oxygen Continued hospitalization on no oxygen Continued hospitalization on oxygen but not in ICU Continued hospitalization on oxygen in ICU (invasive and noninvasive ventilatory support) Death | 3 Months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to clinical improvement | The following information will be collected from the subjects during the follow-up visits or calls: Medical history review Physical exam and vital signs Assessment for delayed adverse reactions | 3 months | 
| Overall Survival | Survival of the subjects in the 2 arms of the study | 3 months | 
| COVID-19 polymerase chain reaction (PCR) test result as negative | COVID-19 polymerase chain reaction (PCR) test result as negative in the subjects in the 2 arms of the study | 3 months |