NestaCell® Mesenchymal Stem Cell to Treat Patients With Severe COVID-19 Pneumonia

Study Overview
=================
Brief Summary
-----------------
This is phase II study to assess the efficacy of NestaCell® (mesenchymal stem cell) to treat severe COVID-19 pneumonia.

Detailed Description
-----------------
The number of infections of COVID-19 worldwide has killed thousands and is continually rising. The novel coronavirus attacks the human body by attaching to the angiotensin-converting enzyme-2 (ACE2), a protective enzyme against lung damage. In addition, the cellular serine protease TMPRSS2 for HCoV-19 Spike protein priming is also essential for the host cell entry and spread. Coronaviruses can be deadly, in large part because they cause cytokine storms. These storms result from imbalances between pro-inflammatory and anti-inflammatory proteins called cytokines, which can cause extreme inflammation and respiratory complications. Respiratory distress kills hundreds of thousands of people each year worldwide, and hundreds of clinical trials are testing drugs to treat it. MSCs have been widely used in cell-based therapy, from basic research to clinical trials Safety and effectiveness have been clearly documented in many clinical trials, especially in the immune-mediated inflammatory diseases. NestaCell® is a mesenchymal stem cell therapy produced by Cellavita and proved to be safe in previous clinical trials. The aim of this study is assess the efficacy of NestCell® as an add-on therapy to standard treatment to treat patients with severe COVID-19 pneumonia. . Patients included will be randomized to receive 2x10^7 cells (20 million cells) on days 1, 3, 5 and 7.

Official Title
-----------------
Exploratory Clinical Study to Assess the Efficacy of NestaCell® Mesenchymal Stem Cell to Treat Patients With Severe COVID-19 Pneumonia

Conditions
-----------------
COVID-19 Pneumonia

Intervention / Treatment
-----------------
* Biological: NestaCell®
* Biological: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: 1. Male or female, aged ≥ 18 years 2. Present a confirmed or pending diagnosis of COVID-19, but with tomographic and clinical signs strongly suggestive of SARS-CoV-2 infection (COVID-19), with pulmonary impairment greater than or equal to 50% and: i. Oxygen saturation <95%; ii. CURB-65 rating ≥ a 4; d) Participants with a score on WHO ordinal scale that measures illness severity over time equal to 5 (Hospitalized with non-invasive ventilation or high-flow oxygen). Exclusion Criteria: Patients with autoimmune diseases in the past or screening; Those who have serious basic diseases that affect their survival, including: malignant tumor, hematopathy, malignant fluid, active hemorrhage, severe malnutrition, etc. which have not been controlled and can not be removed due to multiple metastasis; Known or self-reported HIV or syphilis infected persons; Have participated in stem cell clinical research; Pregnant or lactating women or those who have fertility plans in the past year; The estimated life cycle is less than 48 hours; Other conditions that the researcher thinks are not suitable for participating in the experiment. Shock Continuous use of immunosuppressive agents or organ transplants in the past 6 months;

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Patients will be randomized (1:1) to receive NestaCell (n=45) or Placebo (n=45).
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: NestaCell®<br>A dose of 2x10^7 cells (20 million cells) will be administered IV on days 1, 3, 5 and 7 in all subjects. | Biological: NestaCell®<br>* A dose of 2x10^7 cells (20 million cells) will be administered IV on days 1, 3, 5 and 7 in all subjects.<br>* Other names: Mesenchymal Stem Cell;|
| Placebo Comparator: Placebo<br>Matching placebo will be administered IV on days 1, 3, 5 and 7 in all subjects. | Biological: Placebo<br>* Matching Placebo will be administered IV on days 1, 3, 5 and 7 in all subjects.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Clinical Condition | Ordinal scale (WHO ordinal scale that measures illness severity over time) | 10 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of mortality within 10-days | Evaluation of Pneumonia change | 10 days | 
| Change of Clinical symptoms - respiratory rate | Evaluation of Pneumonia change | 10 days | 
| Hypoxia | oxygen saturation | 10 days | 
| PaO2 / FiO2 ratio | oxygen saturation | 10 days | 
| CD4+ and CD8+ T cell count | Marker of Immunological function | Days 1, 2, 4, 6 and 8. | 
| Changes of blood oxygen | PaO2 / FiO2 ratio | 10 days | 
| Side effects in the treatment group | Number of participants with treatment-related adverse events | 10 days | 
| Complete blood count, cardiac, hepatic and renal profiles; | Complete blood count, ALT, AST, GGT, CK, CKmB and creatinine | Days 1, 2, 4, 6 and 8. |