Safety and Effectiveness of EV-Pure + WJ-Pure Treatment on Pulmonary Fibrosis Secondary to Covid-19

Study Overview
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Brief Summary
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The COVID-induced fibrotic lung damage continues long after viral infection has subsided and is exhibited by severe respiratory pathology and concomitant symptoms. The long-lasting sequelae in patients who have recovered from severe COVID indicate that there is a 30% chance of developing a persistent respiratory system pathology and a 10% chance of developing a severe pathology. The symptoms of lung fibrosis include a severe disruption of respiration, reduction of exercise tolerance, and concomitant development of persistent fibrotic lung damage. This study intends to evaluate benefits of a combination of WJPure and EVPure in Covid-19 patients exhibiting pulmonary fibrosis.

Detailed Description
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Multiple clinical trials are underway to explore options for treatment of pulmonary fibrosis in patients with history of COVID. Mesenchymal stem cell (MSC)-based therapies have been used worldwide for various pulmonary diseases. A recent review of over 110 reports of clinical trials worldwide with MSC-based therapies in pulmonary diseases found that these therapies have been reported to be safe and effective in the treatment of acute/viral pulmonary disease, community-acquired pneumonia (CAP), chronic obstructive pulmonary disease (COPD), bronchopulmonary dysplasia (BPD), interstitial lung diseases (ILD), chronic pulmonary fibrosis, bronchiolitis obliterans syndrome (BOS) and lung cancer. A phase 2 clinical trial in 101 severe Covid-19 patients with lung damage using human umbilical cord derived MSCs found that the treatment exerted numerical improvement in whole lung lesion volume and the 6-minute walk test from baseline to day 28 compared with the placebo. This proof of concept, double-blind, placebo-controlled trial will evaluate the safety and efficacy of intravenous infusion of EV-Pure™ and WJ-Pure™, versus placebo, for use in the treatment of Covid induced Pulmonary Fibrosis. 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: Saline 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 EV-Pure + WJ-Pure Treatment on Pulmonary Fibrosis Secondary to Covid-19

Conditions
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Pulmonary Fibrosis, COVID-19 Respiratory Infection

Intervention / Treatment
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* Drug: EV-Pure™ and WJ-Pure™ plus standard care
* 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 between 25 years (including) to 90 years old Confirmed and documented COVID-19 infection history with confirmed diagnosis of Pulmonary Fibrosis Negative to current Covid-19 infection as tested by RT-PCR tests Able to perform a 6-minute walk test Blood routine, liver and kidney functions test values are within controllable range Adequate hepatic function as evidenced by ALT, AST and LDH < 2X ULN and bilirubin < 1.5X ULN for the reference lab Adequate renal function as evidenced by a serum creatinine ≤ 1.5 X ULN for the reference laboratory OR a calculated creatinine clearance of ≥ 60 mL/min by the Cockcroft-Gault Equation Adequate hematopoietic function as evidenced by white blood cells ≥ 3x109 / L and platelets ≥ 100x109 / L 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: Clinically relevant heart condition such as, but not limited to, uncontrolled heart failure, severe pulmonary hypertension, atrial fibrillation or significant congenital heart disease Severe asthma on chronic therapy with biologics or steroids Active smokers as defined as individuals who currently smokes at least one cigarette or equivalent product a day. (Ex-smokers who had regularly smoked but who had not smoked the previous month are eligible) Evidence of active malignancy, or prior history of active malignancy not in remission. Life expectancy of < 6 months Patient included in another ongoing interventional therapeutic trial. Pregnant or Lactating. Serious or life-threatening co-morbidities, that in the opinion of the investigators, may compromise the safety or compliance with the study guidelines and tracking.

Ages Eligible for Study
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Minimum Age: 25 Years
Maximum Age: 90 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™ plus standard care<br>* The treatment consists of administration of WJ-Pure™ and EV-Pure™ plus standard care<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Saline plus standard care<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluate incidences of Treatment-Emergent Adverse Events following following EV-Pure™ and WJ-Pure™ administeration to patients exhibiting Covid induced Pulmonary Fibrosis. | Presence of adverse events in less than 10% of the study population, as a measure of safety | 3 months | 
| To evaluate the efficacy of EV-Pure™ and WJ-Pure™ administration in alleviating long term symptoms of Covid induced Pulmonary Fibrosis, compared to placebo | Change in distance walked on the six-minute walk test (6MWT). The 6MWT is a validated endpoint commonly used in clinical trial research. | 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Pulse Oximetry at Rest and During the 6MWT | Oxygen saturation (pulse oximetry) at rest and during the 6-minute walk test (6MWT) | 3 months | 
| Incidence of Re-Hospitalization | Incidence of hospitalization after initial discharge and initiating treatment | 3 months | 
| Quality of Life assessment as collected using the SF-36 | The SF-36 (v2) is a self-administered questionnaire containing 36 items that measures functional status, well-being, and overall evaluation of health in 8 domains. | 3 months |