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

• ClinicalTrials.gov Identifier: NCT04352803
• Recruitment Status: Not yet recruiting
• First Posted: April 20, 2020
• Last Update Posted: April 21, 2020
• Sponsor: Regeneris Medical
• Information provided by (Responsible Party): Regeneris Medical

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Covid-19 Pneumonia; Cyotokine Storm	Biological: Autologous Adipose MSC's	Phase 1

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 20 participants
• Allocation: Non-Randomized
• Intervention Model: Sequential Assignment
• Intervention Model Description: This is an Interventional, Prospective, Open label (Voluntary Assignment), single to multiple center expansion, unmatched controlled, Sequentially Interim analysis tested Trial
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: IV Infusion of Autologous Adipose Derived Mesenchymal Cells for Abatement of Respiratory Compromise in SARS-CoV-2 Pandemic (COVID-19)
• Estimated Study Start Date: April 2020
• Estimated Primary Completion Date: April 2024
• Estimated Study Completion Date: April 2026

Arms and Interventions

Arm	Intervention/treatment
Experimental: Autologous Adipose Derived Mesenchymal Cells; Conventional treatment plus MSC's IV	Biological: Autologous Adipose MSC's; Autologous Adipose Derived Mesenchymal Cells 500,000/kg IV
No Intervention: Untreated; Conventional treatment only

Outcome Measures

Primary Outcome Measures :

1. Safety - Incidence of unexpected adverse events [ Time Frame: up to 28 days ]
   Incidence of unexpected adverse events within 28 days following IV administration of MSCs.
2. Efficacy - Frequency of progression to mechanical ventilation [ Time Frame: up to 28 days ]
   Changes in progression or rate of subjects progressing to mechanical ventilation
3. Efficacy - Changes in length of mechanical ventilation [ Time Frame: up to 28 days ]
   Changes in time subjects remain on mechanical ventilation
4. Efficacy - Changes in length of weaning of mechanical ventilation [ Time Frame: up to 28 days ]
   Changes in length of time subjects wean off of mechanical ventilation
5. Efficacy - Changes in length of hospital stay [ Time Frame: up to 28 days ]
   Length of Hospital Stay
6. Efficacy - Changes in mortality rate [ Time Frame: up to 28 days ]
   Mortality rate from all causes

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 90 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Contacts

Contact: Ryan Welter, MD PhD; (508) 576-8325; r.welter@regenerismedical.com

Sponsors and Collaborators

Regeneris Medical

More Information

Publications:

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• Responsible Party: Regeneris Medical
• ClinicalTrials.gov Identifier: NCT04352803
• Other Study ID Numbers: COVID-MSCIV
• First Posted: April 20, 2020
• Last Update Posted: April 21, 2020
• Last Verified: April 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Regeneris Medical:

Coronavirus; SARS-CoV-2; ARDS; Pandemic

Additional relevant MeSH terms:

COVID-19; Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases