A Pilot Clinical Study on Inhalation of Mesenchymal Stem Cells Exosomes Treating Severe Novel Coronavirus Pneumonia

Phase 1

Completed

• Conditions: Coronavirus
• Interventions: Biological: MSCs-derived exosomes

• Registration Number: NCT04276987
• Lead Sponsor: Ruijin Hospital

Brief Summary

In December 2019, a novel coronavirus infectious disease characterized by acute respiratory impairment due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) broke out in Wuhan city of Hubei province in China. So far no specific antiviral therapy can be available for patients with SARS-CoV-2 infection. Although symptomatic and supportive care, even with mechanical ventilation or extracorporeal membrane oxygenation (ECMO), are strongly recommended for severe infected individuals, those with advancing age and co-morbidities such as diabetes and heart disease remain to be at high risk for adverse outcomes. This pilot clinical trial will be performed to explore the safety and efficiency of aerosol inhalation of the exosomes derived from allogenic adipose mesenchymal stem cells (MSCs-Exo) in severe patients with novel coronavirus pneumonia (NCP).

Detailed Description

Since December 2019, SARS-CoV-2 infection has become a worldwide urgent public health event, especially in China. As of February 13, 2020, over 63,000 cases have been confirmed with over 10,200 severe cases in mainland of China. There is currently no vaccine or specific antiviral treatment existing for SARS-CoV-2 infection. Although symptomatic and supportive care are recommended for severe infected individuals, those with advancing age and co-morbidities such as diabetes and heart disease remain to be at high risk for adverse outcomes, with mortality of \~10%. Therefore, it is urgent to find a safe and effective therapeutic approach to patients with severe coronavirus disease-19(COVID-19) characterized by an severe acute respiratory impairment.

Experimental studies have demonstrated that mesenchymal stem cells (MSCs) or their exosomes (MSCs-Exo) significantly reduced lung inflammation and pathological impairment resulting from different types of lung injury. In addition, macrophage phagocytosis, bacterial killing and outcome are improved. It is highly likely that MSCs-Exo have the same therapeutic effect on inoculation pneumonia as MSCs themselves.

Although human bone marrow MSCs have been safely administered in patients with ARDS and septic shock (phase I/II trials), it seems safer to deliver MSCs-Exo rather than live MSCs. The intravenous administration of MSCs may result in aggregating or clumping in the injured microcirculation and carries the risk of mutagenicity and oncogenicity, which do not exist by treating with nebulized MSCs-Exo. Another advantage of MSCs-Exo over MSCs is the possibility of storing them for several weeks/months allowing their safe transportation and delayed therapeutic use.

The purpose of this single-arm design, open label, combined interventional clinical trial, therefore, is to explore the safety and efficiency of aerosol inhalation of the exosomes derived from allogenic adipose mesenchymal stem cells (MSCs-Exo) in the treatment of severe patients hospitalized with novel coronavirus pneumonia (NCP).

Study Timeline

• Study Start: 2020-02-15
• Study First Submitted: 2020-02-16
• Study First Submitted QC: 2020-02-18
• Study First Posted: 2020-02-19
• Primary Completion: 2020-05-31
• Study Completion: 2020-07-31
• Status Verified: 2020-09
• Last Update Submitted: 2020-09-03
• Last Update Posted: 2020-09-07

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 24

Inclusion Criteria

1.Willingness of study participant to accept this treatment arm, and signed informed consent; 2.Male or female, aged at 18 years (including) to 75 years old; 3.Patients with confirmed novel coronavirus pneumonia; 4.Confirmation of SARS-CoV-2 infection by reverse-transcription polymerase chain reaction (RT-PCR) from respiratory tract or blood specimens; 5.Diagnostic criteria of "Severe" or " Critical":

1. Severe, comply with any of the following:

   1. Respiratory distress, Respiratory rate (RR) ≥ 30 times/min
   2. Pulse oxygen saturation (SpO2) at rest ≤ 93%
   3. Partial pressure of oxygen/fraction of inspired oxygen (PaO2/FiO2) ≤ 300mmHg

2. Critical, comply with any of the following:

   1. Respiratory failure, and requirement for mechanical ventilation
   2. Shock
   3. Other organ failure and requirement for ICU monitoring

Exclusion Criteria

1. Allergic or hypersensitive to any of the ingredients;

2. Pneumonia caused by bacteria, mycoplasma, chlamydia, legionella, fungi or other viruses;

3. Obstructive HABP/VABP induced by lung cancer or other known causes;

4. Carcinoid syndrome;

5. History of long-term use of immunosuppressive agents;

6. History of epilepsy and requirement for continuous anticonvulsant treatment or anticonvulsant treatment received within the last 3 years;

7. History of severe chronic respiratory disease and requirement for long-term oxygen therapy;

8. Undergoing hemodialysis or peritoneal dialysis;

9. Estimated or actual rate of creatinine clearance < 15 ml/min;

10. History of moderate and severe liver disease (Child-Pugh score >12);

11. Expectation of receiving any of following medications during the study:

    1. Receiving continuous valproic acid or sodium valproate within the first 2 weeks prior to screening
    2. Receiving 5-transtryptamine reuptake inhibitors, tricyclic antidepressants, 5-HT1 receptor agonists or monoamine oxidase inhibitors within the first 2 weeks prior to screening

12. Incapable of understanding study protocol;

13. History of deep venous thrombosis or pulmonary embolism within the last 3 years;

14. Undergoing ECMO or high-frequency oscillatory ventilation support;

15. HIV, hepatitis virus, or syphilis infection;

16. Period of pregnancy or lactation, or planned pregnancy within 6 months;

17. Any condition of unsuitable for the study determined by investigators.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
MSCs-derived Exosomes Treatment Group	MSCs-derived exosomes	Conventional treatment and aerosol inhalation of MSCs-derived exosomes treatment participants will receive conventional treatment and 5 times aerosol inhalation of MSCs-derived exosomes (2.0\*10E8 nano vesicles/3 ml at Day 1, Day 2, Day 3, Day 4, Day 5).

Primary Outcome Measures

Name	Time	Method
Time to clinical improvement (TTIC)	Up to 28 days	Efficiency evaluation within 28 days, including time to clinical improvement (TTIC)
Adverse reaction (AE) and severe adverse reaction (SAE)	Up to 28 days	Safety evaluation within 28 days after first treatment, including frequency of adverse reaction (AE) and severe adverse reaction (SAE)

Secondary Outcome Measures

Name	Time	Method
Duration (days) of vasoactive agents usage	Up to 28 days	Duration (days) of vasoactive agents using within 28 days
Number of patients weaning from mechanical ventilation	Up to 28 days	Number of patients weaning from mechanical ventilation within 28 days
Duration (days) of mechanical ventilation supply	Up to 28 days	Duration (days) of mechanical ventilation supply among survivors
Rate of mortality	Up to 28 days	Rate of mortality within 28 days
Duration (days) of ICU monitoring	Up to 28 days	Duration (days) of ICU monitoring within 28 days
Number of patients with improved organ failure	Up to 28 days	Number of patients with improved organ failure within 28 days, including cardiovascular system, coagulation system, liver, kidney and other extra-pulmonary organs

Trial Locations

Locations (1)

Ruijin Hospital Shanghai Jiao Tong University School of Medicine; 🇨🇳 Shanghai, Shanghai, China