Adipose Mesenchymal Cells for Abatement of SARS-CoV-2 Respiratory Compromise in COVID-19 Disease

Phase 1

Not yet recruiting

• Conditions: Cyotokine Storm; Covid-19 Pneumonia
• Interventions: Biological: Autologous Adipose MSC's

• Registration Number: NCT04352803
• Lead Sponsor: Regeneris Medical

Brief Summary

The aim of this study is to evaluate the safety and efficacy of autologous adipose-derived mesenchymal cells for treating confirmed or suspected patients with SARS-CoV-2 and compromised respiratory function requiring hospitalization.

The hypothesis of the Study is autologous adipose-derived mesenchymal cells given IV to eligible patients will improve clinical outcomes of COVID 19 positive patients with severe pneumonia or ARDS by reducing or avoiding cytokine storm.

Detailed Description

While most patients with SARS-CoV-2 present with mild respiratory disease with the most common symptoms of fever and cough, approximately 14 % progress to severe pneumonia and ARDS.

The overall mortality rate is 2% but varies by country and age of the patient.

In COVID-19 ARDS standard supportive care and treatment for underlying illnesses remain the mainstay with limited success.

Numerous antiviral medications including remdesivir, lopinavir-ritonavir or lopinavir-ritonavir and interferon Beta-1a are in clinical trials but safety and efficacy remain unclear.

Inflammation associated with a cytokine storm begins at a local site and spreads throughout the body via systemic circulation. The lungs and other organs are damaged with progressive inflammation.

Mesenchymal cells offer the potential to treat viral infection both directly and through reducing the immune response. MSCs play a role as an immunomodulator, which is safe and effective as demonstrated in numerous clinical trials.

Mesenchymal cells are a potential privileged cell-based therapy in SARS-CoV-2. MSCs derived extracellular vesicles have demonstrated comparable and sometimes more effective effects in ameliorating lung inflammation and injury.

Study Timeline

• Status Verified: 2020-04
• Study Start: 2020-04
• Study First Submitted: 2020-04-16
• Study First Submitted QC: 2020-04-17
• Last Update Submitted: 2020-04-17
• Study First Posted: 2020-04-20
• Last Update Posted: 2020-04-21
• Primary Completion: 2024-04
• Study Completion: 2026-04

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 20

Inclusion Criteria

1. Male or female patients ≥ 18 years of and less than 90
2. COVID 19 diagnosis confirmed
3. Ability to give informed consent
4. Hospitalized

Exclusion Criteria

1. Mild Illness

   1. Patients with uncomplicated upper respiratory tract viral infection, may have non-specific symptoms such as fever, fatigue, cough (with or without sputum production), anorexia, malaise, muscle pain, sore throat, dyspnea, nasal congestion, or headache. Rarely, patients may also present with diarrhea, nausea and vomiting.
   2. The elderly and immunosuppressed candidates may present with atypical symptoms. Symptoms due to physiologic adaptations of pregnancy or adverse pregnancy events, such as e.g. dyspnea, fever, GI-symptoms or fatigue, may overlap with COVID-19 symptoms. Still, they will be excluded, unless they progress to Inclusion Criteria within 72 hours from recruitment.

2. Pneumonia (uncomplicated):

   a. Adults with pneumonia but no signs of severe pneumonia AND NO need for supplemental oxygen

3. Reported pregnant or positive pregnancy test

4. Other chronic respiratory disorders such as COPD, emphysema, lung cancer, or cystic fibrosis

5. BMI lower than 21

6. Skinfold test < 3 cm at harvest area

7. Patients with Do-Not-Resuscitate orders that limit mechanical ventilation assistance in place at hospital admission

8. Males and females < 18 years of age

9. Patients who are currently breastfeeding

10. Co-Infection of HIV, tuberculosis, influenza virus, adenovirus and other respiratory infection viruses.

11. History of systemic malignant neoplasms within the last 5 years.

12. Subject is in the opinion of the Investigator or designee, unable to comply with the requirements of the study protocol or is unsuitable for the study for any reason

13. Participating in another clinical research study

14. History of Bleeding disorder which in PI's opinion would render the patient unsuitable for the study

15. PT (plasma) < 9 or >11.6 seconds and in the opinion of the PI and attending physician that lipoaspiration would be contraindicated. May be eligible for re-screening if coagulopathy improves within 72 hours of consent

16. PTT < 23 or >32 seconds and in the opinion of the PI and attending physician that lipoaspiration would be contraindicated. May be eligible for re-screening if coagulopathy improves within 72 hours of consent

17. Platelets count less than 70,0000

18. History of DVT

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Autologous Adipose Derived Mesenchymal Cells	Autologous Adipose MSC's	Conventional treatment plus MSC's IV

Primary Outcome Measures

Name	Time	Method
Efficacy - Changes in mortality rate	up to 28 days	Mortality rate from all causes
Efficacy - Changes in length of mechanical ventilation	up to 28 days	Changes in time subjects remain on mechanical ventilation
Efficacy - Frequency of progression to mechanical ventilation	up to 28 days	Changes in progression or rate of subjects progressing to mechanical ventilation
Safety - Incidence of unexpected adverse events	up to 28 days	Incidence of unexpected adverse events within 28 days following IV administration of MSCs.
Efficacy - Changes in length of weaning of mechanical ventilation	up to 28 days	Changes in length of time subjects wean off of mechanical ventilation
Efficacy - Changes in length of hospital stay	up to 28 days	Length of Hospital Stay