ASC Therapy for Patients With Severe Respiratory COVID-19

Study Overview
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Brief Summary
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The emerging field of stem cell therapy holds promise of treating a variety of diseases. Especially the mesenchymal stromal cells from bone marrow or adipose tissue (ASCs) have proven their potential for regenerative therapy in patients with ischemic heart disease. Both of these cell types have putative immunomodulatory properties, as they have demonstrated their ability to evade recognition and actively suppress the immune system. This knowledge is transferred into studies with COVID-19 patients having severe pulmonary dysfunction, to modify the virus induced immunological and inflammatory activity involved in the progression of disease often leading to prolonged ICU stay and in some occasion's death. We will conduct a clinical trial in which patients with COVID-19 and severe pulmonary symptoms will be randomized to either placebo or treatment with allogeneic CSCC_ASCs from adipose tissue. The aim is to assess the impact of CSCC_ASCs on the activated immune system and clinical efficacy on pulmonary function. The perspective is that this new information can be of pivotal importance and potentially be a paradigm shift for the clinical problems and severe outcome seen in some patients with severe COVID-19 and other severe diseases with Acute Respiratory Distress Syndrome.

Official Title
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Allogeneic Adipose Tissue Derived Mesenchymal Stromal Cell Therapy for Treating Patients With Severe Respiratory COVID-19. A Danish, Double-blind, Randomized Placebo-controlled Study

Conditions
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Respiratory Tract Diseases

Intervention / Treatment
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* Drug: Stem Cell Product


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients between 18-80 years Confirmed HCoV-19 infection Temperature above 38.0o C Pulmonary symptoms and signs, at least one of the following before clinical decision for intubation and respirator treatment: Respiratory distress, RR ≥ 30/min; Oxygen saturation ≤ 93% at rest state; Arterial partial pressure of oxygen (PaO2) / Fraction of inspiration O2 (FiO2) ≤ 300mmHg, 1mmHg=0.133kPa Pneumonia that is judged by chest radiograph or computed tomography In respirator and possible for treatment within the first 24 hours Exclusion Criteria: Patients that have need for additional immunosuppressive treatment Patients with any past (within the past 3-5 years) or present malignancy (other than excised basal cell carcinoma). Co-Infection with other infectious agent. Females capable of becoming pregnant must have a negative pregnancy test prior to treatment. After inclusion, they must use contraceptives for 2 months following the given stem cell treatment. The pill, spiral, depot injection of progesterone, sub-dermal implantation, hormonal vaginal ring and transdermal patch regarded as safe contraceptives. Patients who are participating in other clinical trials.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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: Double-blind placebo-controlled
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: ASC<br>100 million allogeneic adipose-derived mesenchymal stromal cell | Drug: Stem Cell Product<br>* 100 million allogeneic adipose-derived mesenchymal stromal cells diluted in 100 ml saline<br>|
| Placebo Comparator: Placebo<br>Saline | Drug: Stem Cell Product<br>* 100 million allogeneic adipose-derived mesenchymal stromal cells diluted in 100 ml saline<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in clinical critical treatment index |  | day 7 from randomization | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Days of respirator treatment |  | 3 months | 
| Improvement of clinical symptoms including duration of fever and respiratory need |  | 3 months | 
| Mortality |  | 3 months | 
| Marker of Immunological function -CD4+ and CD8+ T cell count |  | 3 months | 
| C-reactive protein and leucocyte |  | 3 months | 
| Cytokine profile |  | 3 months | 
| Glomerular Filtration Rate |  | 3 months | 
| Duration of hospitalization |  | 3 months |