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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04276987
Recruitment Status : Not yet recruiting
First Posted : February 19, 2020
Last Update Posted : February 25, 2020
Sponsor:
Collaborators:
Shanghai Public Health Clinical Center
Wuhan Jinyintan Hospital, Wuhan, China
Cellular Biomedicine Group Ltd.
Information provided by (Responsible Party):
Ruijin Hospital

Tracking Information
First Submitted Date  ICMJE February 16, 2020
First Posted Date  ICMJE February 19, 2020
Last Update Posted Date February 25, 2020
Estimated Study Start Date  ICMJE February 15, 2020
Estimated Primary Completion Date May 31, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 18, 2020)
  • Adverse reaction (AE) and severe adverse reaction (SAE) [ Time Frame: Up to 28 days ]
    Safety evaluation within 28 days after first treatment, including frequency of adverse reaction (AE) and severe adverse reaction (SAE)
  • Time to clinical improvement (TTIC) [ Time Frame: Up to 28 days ]
    Efficiency evaluation within 28 days, including time to clinical improvement (TTIC)
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: February 18, 2020)
  • Number of patients weaning from mechanical ventilation [ Time Frame: Up to 28 days ]
    Number of patients weaning from mechanical ventilation within 28 days
  • Duration (days) of ICU monitoring [ Time Frame: Up to 28 days ]
    Duration (days) of ICU monitoring within 28 days
  • Duration (days) of vasoactive agents usage [ Time Frame: Up to 28 days ]
    Duration (days) of vasoactive agents using within 28 days
  • Duration (days) of mechanical ventilation supply [ Time Frame: Up to 28 days ]
    Duration (days) of mechanical ventilation supply among survivors
  • Number of patients with improved organ failure [ Time Frame: 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
  • Rate of mortality [ Time Frame: Up to 28 days ]
    Rate of mortality within 28 days
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures
 (submitted: February 21, 2020)
  • Sequential organ failure assessment (SOFA) score [ Time Frame: Every day for 28 days ]
    Records of daily sequential organ failure assessment (SOFA) score (From 0 to 24 points, higher scores mean a worse outcome)
  • Lymphocyte Count (10E9/L) [ Time Frame: Day0, Day3, Day7, Day14, Day21, Day28, indicated time points can be added if available ]
    Records of Blood routine test
  • C-reactive protein (CRP) (mg/L) [ Time Frame: Day0, Day3, Day7, Day14, Day21, Day28, indicated time points can be added if available ]
  • Lactate dehydrogenase (U/L) [ Time Frame: Day0, Day3, Day7, Day14, Day21, Day28, indicated time points can be added if available ]
  • D-dimer (mg/L) [ Time Frame: Day0, Day3, Day7, Day14, Day21, Day28, indicated time points can be added if available ]
    Coagulation function
  • pro-type B natriuretic peptide (pro-BNP) (pg/ml) [ Time Frame: Day0, Day3, Day7, Day14, Day21, Day28, indicated time points can be added if available ]
    Records of heart failure
  • IL-1β (pg/ml) [ Time Frame: Day0, Day3, Day7, Day14, Day21, Day28, indicated time points can be added if available ]
    Record of serum cytokine
  • IL-2R (ng/L) [ Time Frame: Day0, Day3, Day7, Day14, Day21, Day28, indicated time points can be added if available ]
    Record of serum cytokine
  • IL-6 (ng/L) [ Time Frame: Day0, Day3, Day7, Day14, Day21, Day28, indicated time points can be added if available ]
    Record of serum cytokine
  • IL-8 (ng/L) [ Time Frame: Day0, Day3, Day7, Day14, Day21, Day28, indicated time points can be added if available ]
    Record of serum cytokine
  • Chest imaging [ Time Frame: Day0, Day3, Day7, Day14, Day21, Day28, indicated time points can be added if available ]
    Computed tomography or X-ray
  • Time to SARS-CoV-2 RT-PCR negativity [ Time Frame: Up to 28 days ]
    Time to SARS-CoV-2 RT-PCR negativity in respiratory tract specimens
Original Other Pre-specified Outcome Measures
 (submitted: February 18, 2020)
  • Sequential organ failure assessment (SOFA) score [ Time Frame: Every day for 28 days ]
    Records of daily sequential organ failure assessment (SOFA) score
  • Lymphocyte Count (10E9/L) [ Time Frame: Day0, Day3, Day7, Day14, Day21, Day28, indicated time points can be added if available ]
    Records of Blood routine test
  • C-reactive protein (CRP) (mg/L) [ Time Frame: Day0, Day3, Day7, Day14, Day21, Day28, indicated time points can be added if available ]
  • Lactate dehydrogenase (U/L) [ Time Frame: Day0, Day3, Day7, Day14, Day21, Day28, indicated time points can be added if available ]
  • D-dimer (mg/L) [ Time Frame: Day0, Day3, Day7, Day14, Day21, Day28, indicated time points can be added if available ]
    Coagulation function
  • pro-type B natriuretic peptide (pro-BNP) (pg/ml) [ Time Frame: Day0, Day3, Day7, Day14, Day21, Day28, indicated time points can be added if available ]
    Records of heart failure
  • IL-1β (pg/ml) [ Time Frame: Day0, Day3, Day7, Day14, Day21, Day28, indicated time points can be added if available ]
    Record of serum cytokine
  • IL-2R (ng/L) [ Time Frame: Day0, Day3, Day7, Day14, Day21, Day28, indicated time points can be added if available ]
    Record of serum cytokine
  • IL-6 (ng/L) [ Time Frame: Day0, Day3, Day7, Day14, Day21, Day28, indicated time points can be added if available ]
    Record of serum cytokine
  • IL-8 (ng/L) [ Time Frame: Day0, Day3, Day7, Day14, Day21, Day28, indicated time points can be added if available ]
    Record of serum cytokine
  • Chest imaging [ Time Frame: Day0, Day3, Day7, Day14, Day21, Day28, indicated time points can be added if available ]
    Computed tomography or X-ray
  • Time to SARS-CoV-2 RT-PCR negativity [ Time Frame: Up to 28 days ]
    Time to SARS-CoV-2 RT-PCR negativity in respiratory tract specimens
 
Descriptive Information
Brief Title  ICMJE A Pilot Clinical Study on Inhalation of Mesenchymal Stem Cells Exosomes Treating Severe Novel Coronavirus Pneumonia
Official Title  ICMJE A Pilot Clinical Study on Aerosol Inhalation of the Exosomes Derived From Allogenic Adipose Mesenchymal Stem Cells in the Treatment of Severe Patients With Novel Coronavirus Pneumonia
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 Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Coronavirus
Intervention  ICMJE Biological: MSCs-derived exosomes
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).
Study Arms  ICMJE Experimental: MSCs-derived Exosomes Treatment Group
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).
Intervention: Biological: MSCs-derived exosomes
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Not yet recruiting
Estimated Enrollment  ICMJE
 (submitted: February 18, 2020)
30
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE July 31, 2020
Estimated Primary Completion Date May 31, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Jie-ming Qu, MD.,PhD. +86-21-64370045 jmqu0906@163.com
Listed Location Countries  ICMJE Not Provided
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04276987
Other Study ID Numbers  ICMJE MEXCOVID
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: all IPD that underlie results in a publication
Supporting Materials: Study Protocol
Supporting Materials: Statistical Analysis Plan (SAP)
Supporting Materials: Informed Consent Form (ICF)
Supporting Materials: Clinical Study Report (CSR)
Supporting Materials: Analytic Code
Time Frame: Starting 6 months after publication
Responsible Party Ruijin Hospital
Study Sponsor  ICMJE Ruijin Hospital
Collaborators  ICMJE
  • Shanghai Public Health Clinical Center
  • Wuhan Jinyintan Hospital, Wuhan, China
  • Cellular Biomedicine Group Ltd.
Investigators  ICMJE
Principal Investigator: Jie-ming Qu, MD.,PhD. Ruijin Hospital, Medical School of Shanghai Jiaotong University Shanghai, China
PRS Account Ruijin Hospital
Verification Date February 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP