Clinical Study for Subjects With COVID-19 Using Allogeneic Adipose Tissue-Derived Mesenchymal Stem Cells

Study Overview
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Brief Summary
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This is an interventional new drug clinical trial for a Phase 2 randomized, double-blind, and placebo control study using intravenous injection of allogeneic adipose stem cells (Celltex AdMSCs) for subjects with severe COVID-19.

Official Title
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Clinical Study for Subjects With Coronavirus 2019 (COVID-19) Using Multiple Dose Intravenous Infusions of Allogeneic Adipose Tissue-Derived Mesenchymal Stem Cells (AdMSCs)

Conditions
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Corona Virus Infection, Covid19

Intervention / Treatment
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* Biological: Allogeneic adipose-derived stem cells


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age above 18 years. Male and female Must understand and voluntarily sign an Informed Consent for study participation obtained prior to undergoing any study-specific procedures Diagnosed as COVID-19 based upon SARS-CoV-2 RT-PCR test positive Clinical diagnosis meets severe and/or critical parameters Male participants must be willing to ensure their partners do not become pregnant either by practicing abstinence or the use of condoms during sexual activity Exclusion Criteria: Participation in another clinical study (with use of another Investigational Medical Product) within 3 months prior to study treatment start Unwillingness or inability to comply with study procedures Patients with serious basic diseases that affect survival, including blood diseases, cachexia, active bleeding, severe malnutrition, etc. Clinically active malignant disease Subjects who are receiving ECMO and CRRT currently History of known pulmonary embolism or known secondary anti-phospholipid syndrome Known or suspected hypersensitivity to any components used to culture the AdMSCs, e.g. BSA and sulfur containing products (e.g., DMSO) Known or suspected allergic to diphenhydramine. Major trauma or surgery within 14 days of study treatment start Mental condition rendering the subject (or the subject's legally acceptable representative[s]) unable to understand the nature, scope and possible consequences of the study Alcohol, drug, or medication abuse within one year prior to study treatment start Any condition that, in the Investigator's opinion, is likely to interfere with evaluation of the AdMSC therapy or satisfactory conduct of the study Irreversible severe end organ failure, such as heart failure/attack, stroke, liver and renal failure due to other disease conditions Patients or family history with hypercoagulable status, such as protein C/protein S deficiency, factor V Leiden, prothrombin gene mutation, dysfibrinogenemia, etc. History of long-term use of immunosuppressive agents Organ transplants in the past 6 months Pregnant, breastfeeding, or desire to become pregnant or unwilling to practice birth control during participation in the study duration, unless surgically sterilized or postmenopausal during the study. Patients with previous pulmonary obstructive pneumonia, severe pulmonary interstitial fibrosis, alveolar proteinosis, allergic alveolitis, and other known viral pneumonia or bacterial pneumonia before COVID-19 infection. The pulmonary imaging revealed the interstitial damage of lungs before the COVID-19 confirmed. QT interval shows greater than 450 ms in males and 470 ms in females in the medical histories or during screen EKG test. Subjects are not medically unstable at time of infusion including but not limiting unstable hypertension, pulse, oximetry, etc.

Ages Eligible for Study
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Minimum Age: 18 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
Interventional Model Description: The Phase 2 study is a randomized, double blind and placebo control study conducted initially in a single clinic facility.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Study Group<br>Each subject receives three separate doses of 200 million allogeneic adipose-derived mesenchymal stem cells via intravenously infusion on days 0, 3, and 6 with a total of 600 million AdMSCs during 7 days in addition to their standard of care. | Biological: Allogeneic adipose-derived stem cells<br>* Culture expanded mesenchymal stem cells isolated from a patient's own abdominal fat tissue<br>* Other names: Celltex-AdMSCs;|
| Placebo Comparator: Control Group<br>The control group will receive placebo infusion on day 0, 3 and 6 along with standard of care. | Biological: Allogeneic adipose-derived stem cells<br>* Culture expanded mesenchymal stem cells isolated from a patient's own abdominal fat tissue<br>* Other names: Celltex-AdMSCs;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety of AdMSC injection will be evaluated by assessment of the frequency and nature of adverse events occurring during the study based on the rate of all AdMSC-associated adverse events (AEs) in all subjects. | Incidence of treatment-related adverse events and severe adverse events during the study period | 6 months | 
| Safety for AdMSCs based upon incidence of all AEs | Grouped by Medical Dictionary for Regulatory Activities (MedDRA) | 6 months | 
| Compare the mortality rate | AdMSC treating group vs. control group | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Recognized immune measurements evaluating patients' symptom changes and overall function | To evaluate change of sequential organ failure assessment (SOFA) score as compare to the baseline | 6 months | 
| Organ functional tests including blood specific enzymes and proteins | To evaluate the efficacy of allogeneic AdMSCs for COVID-19 | 6 months | 
| Duration (days) of weaning from mechanical ventilation | Compared to control group | 6 months | 
| Duration (days) of ICU monitoring | Compared to control group | 6 months | 
| Duration (days) of vasoactive agent's usage | Compared to control group | 6 months | 
| Duration of hospitalization (days) | Compared to control group | 6 months | 
| Proportions of SARS-CoV-2 RT-PCR change to negative from respiratory tract specimens (oropharyngeal swabs) using CDC standard method | Compared to control group | 6 months | 
| Proportions of quantifying viral RNA in stool change to negative in final follow-up using CDC standard method | Compared to control group | 6 months | 
| Proportions of blood SARS-CoV-2 antibodies IgM/IgG show positive | Compared to control group | 6 months |