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

NCT04276987 | Completed Phase 1

• 1 other identifier: MEXCOVID
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

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).

Conditions

Coronavirus

Keywords

mesenchymal stem cells; exosome; nebulization; SARS-CoV-2; novel coronavirus pneumonia

Outcome Measures

Primary Outcomes (2)

• Adverse reaction (AE) and severe adverse reaction (SAE)

  Safety evaluation within 28 days after first treatment, including frequency of adverse reaction (AE) and severe adverse reaction (SAE)

  Up to 28 days

• Time to clinical improvement (TTIC)

  Efficiency evaluation within 28 days, including time to clinical improvement (TTIC)

  Up to 28 days

Secondary Outcomes (6)

• Number of patients weaning from mechanical ventilation

  Up to 28 days

• Duration (days) of ICU monitoring

  Up to 28 days

• Duration (days) of vasoactive agents usage

  Up to 28 days

• Duration (days) of mechanical ventilation supply

  Up to 28 days

• Number of patients with improved organ failure

  Up to 28 days

Other Outcomes (12)

• Sequential organ failure assessment (SOFA) score

  Every day for 28 days

• Lymphocyte Count (10E9/L)

  Day0, Day3, Day7, Day14, Day21, Day28, indicated time points can be added if available

• C-reactive protein (CRP) (mg/L)

  Day0, Day3, Day7, Day14, Day21, Day28, indicated time points can be added if available

Study Arms (1)

MSCs-derived Exosomes Treatment Group

EXPERIMENTAL

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).

Biological: MSCs-derived exosomes

Interventions

MSCs-derived exosomes BIOLOGICAL

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).

MSCs-derived Exosomes Treatment Group

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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":
• Severe, comply with any of the following:
• Respiratory distress, Respiratory rate (RR) ≥ 30 times/min
• Pulse oxygen saturation (SpO2) at rest ≤ 93%
• Partial pressure of oxygen/fraction of inspired oxygen (PaO2/FiO2) ≤ 300mmHg
• Critical, comply with any of the following:
• Respiratory failure, and requirement for mechanical ventilation
• Shock
• Other organ failure and requirement for ICU monitoring

You may not qualify if:

• Allergic or hypersensitive to any of the ingredients;
• Pneumonia caused by bacteria, mycoplasma, chlamydia, legionella, fungi or other viruses;
• Obstructive HABP/VABP induced by lung cancer or other known causes;
• Carcinoid syndrome;
• History of long-term use of immunosuppressive agents;
• History of epilepsy and requirement for continuous anticonvulsant treatment or anticonvulsant treatment received within the last 3 years;
• History of severe chronic respiratory disease and requirement for long-term oxygen therapy;
• Undergoing hemodialysis or peritoneal dialysis;
• Estimated or actual rate of creatinine clearance \< 15 ml/min;
• History of moderate and severe liver disease (Child-Pugh score \>12);
• Expectation of receiving any of following medications during the study:
• Receiving continuous valproic acid or sodium valproate within the first 2 weeks prior to screening
• Receiving 5-transtryptamine reuptake inhibitors, tricyclic antidepressants, 5-HT1 receptor agonists or monoamine oxidase inhibitors within the first 2 weeks prior to screening
• Incapable of understanding study protocol;
• History of deep venous thrombosis or pulmonary embolism within the last 3 years;

Sponsors & Collaborators

• Ruijin Hospital: lead
• Shanghai Public Health Clinical Center: collaborator
• Wuhan Jinyintan Hospital, Wuhan, China: collaborator
• Shanghai AbelZeta Ltd.: collaborator

Study Sites (1)

Ruijin Hospital Shanghai Jiao Tong University School of Medicine

Shanghai, Shanghai Municipality, 200025, China

Location

Related Publications (1)

• Zhu YG, Shi MM, Monsel A, Dai CX, Dong X, Shen H, Li SK, Chang J, Xu CL, Li P, Wang J, Shen MP, Ren CJ, Chen DC, Qu JM. Nebulized exosomes derived from allogenic adipose tissue mesenchymal stromal cells in patients with severe COVID-19: a pilot study. Stem Cell Res Ther. 2022 May 26;13(1):220. doi: 10.1186/s13287-022-02900-5.

  PMID: 35619189 DERIVED

MeSH Terms

Conditions

Coronavirus Infections

Condition Hierarchy (Ancestors)

Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections

Study Officials

• Jie-ming Qu, MD.,PhD.

  Ruijin Hospital, Medical School of Shanghai Jiaotong University Shanghai, China

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 16, 2020
• First Posted: February 19, 2020
• Study Start: February 15, 2020
• Primary Completion: May 31, 2020
• Study Completion: July 31, 2020
• Last Updated: September 7, 2020

Record last verified: 2020-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: Starting 6 months after publication

Locations

CN (1)