Table 1.

Clinical trials in Exosomes Therapy In Respiratory Diseases

No	Title and sponsor	Trial ID	Location	Design	Primary outcome	Recruitment status	Phase
1.	The use of exosomes for the treatment of acute respiratory distress syndrome or novel coronavirus pneumonia caused by COVID-19 (ARDOXSO) Sponsor: AVEM HealthCare	NCT04798716	United States, California	Open label, interventional, mesenchymal stem cell exosomes for the treatment of COVID-19 positive patients with acute respiratory distress syndrome and/or novel coronavirus pneumonia N:55	Measure and report the number of participants with treatment-related-adverse events Tabulate and report the number of IMV days for patients receiving ARDOXSO™ perinatal MSC-derived exosome therapy	Not yet recruiting July 21, 2021	Phase 1 Phase 2
2.	Safety and efficiency of method of exosome inhalation in COVID-19 associated pneumonia (COVID-19EXO2) Sponsor: Olga Tyumina	NCT04602442	Russian, Samara	Randomized, interventional, the extended protocol of evaluation of safety and efficiency of method of exosome inhalation in COVID-19 associated two-sided pneumonia N: 90	Number of participants with non-serious and serious adverse events during trial Number of participants with non-serious and serious adverse during inhalation procedure	Enrolling by invitation October 26, 2020	Phase 2
3.	Evaluation of safety and efficiency of method of exosome inhalation in SARS-CoV-2 associated pneumonia. (COVID-19EXO) Sponsor: State-Financed Health Facility “Samara Regional Medical Center Dinasty”	NCT04491240	Russian, Samara	Randomized, interventional, the protocol of evaluation of safety and efficiency of method of exosome inhalation in SARS-CoV-2 associated two-sided pneumonia N: 30	Number of participants with non-serious and serious adverse events during trial Number of participants with non-serious and serious adverse during inhalation procedure	Completed November 4, 2020	Phase 1 Phase 2
4.	A safety study of IV stem cell-derived extracellular vesicles (UNEX-42) in preterm neonates at high risk for BPD Sponsor: United Therapeutics	NCT03857841	United States, Colorado, Massachusetts, Mississippi, Missouri	Randomized, interventional, a safety study of intravenous infusion of bone marrow mesenchymal stem cell-derived extracellular vesicles (UNEX-42) in preterm neonates at high risk for bronchopulmonary dysplasia N: 3	Number of subjects with treatment-emergent adverse events during the post-treatment phase	Terminated October 12, 2021	Phase 1
5.	A clinical study of mesenchymal stem cell exosomes nebulizer for the treatment of ARDS Sponsor: Ruijin Hospital	NCT04602104	China, Shanghai	Randomized, double-blinded, controlled clinical study of allogeneic human mesenchymal stem cell exosomes (hMSC-Exos) nebulized inhalation in the treatment of acute respiratory distress syndrome N:169	Incidence of adverse reaction Time to clinical improvement 28-day mortality	Recruiting November 2, 2021	Phase 1 Phase 2
6.	A tolerance clinical study on aerosol inhalation of mesenchymal stem cells exosomes in healthy volunteers Sponsor: Ruijin Hospital	NCT04313647	China, Shanghai	Open label, non randomized, interventional, a tolerance clinical study on aerosol inhalation of mesenchymal stem cells exosomes in healthy volunteers N: 24	Number of Participants With Adverse Reaction (AE) and severe adverse reaction (SAE)	Completed August 4, 2021	Phase 1
7.	Omics sequencing of exosomes in body fluids of patients with acute lung injury Sponsor: Nanfang Hospital of Southern Medical University	NCT05058768	China, Guangdong	Observational, case–control, exosomes in urine, blood, and alveolar lavage fluid from patients with acute respiratory distress syndrome (ADRS) were sequenced by omics N:180	Compare the omics differences of blood samples between the experimental and control groups Compare the omics differences of urine samples between the experimental and control groups	Recruiting September 28, 2021	Case–Control
8.	Exosomes derived from placental mesenchymal stem cells as treatment for severe COVID-19: Phase 1 and 2 clinical trials Sponsor: Omid Cell and Tissue center	IRCT20200413047063N2	Tehran, Iran	Participants were randomly divided into two equal groups using a randomized double AB blocking method based on a random number table. Patients allocated randomly to two groups: (1) Intervention 1, Patients will receive Six doses of Exosomes. (2) Control, Patients will receive conventional therapy N:50	Adverse events assessment	Recruiting July 8, 2021	Phase 1 Phase 2
9.	Molecular profiling of exosomes in tumor-draining vein of early-staged lung cancer (ExOnSite-Pro) Sponsor: University Hospital, Limoges	NCT04939324	France, Limoges	Open label, single group assignment, Analyse du Profil moléculaire Des Exosomes de la Veine Pulmonaire Dans le Cancer Bronchique de Stade précoce N:30	Evaluate size distribution, concentration and molecular profiling of pulmonary vein exosomes at inclusion	Recruiting November 11, 2021	Not applicable
10.	A pilot clinical study on inhalation of mesenchymal stem cells exosomes treating severe novel coronavirus pneumonia Sponsor: Ruijin Hospital	NCT04276987	China, Shanghai	Open label, single group assignment, 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 N:24	Adverse reaction (AE) and severe adverse reaction (SAE) Time to clinical improvement (TTIC)	Completed September 7, 2020	Phase 1
11.	Extracellular vesicle infusion treatment for COVID-19 Associated ARDS (EXIT-COVID19) Sponsor: Direct Biologics, LLC	NCT04493242	United States, Alabama, California, Pennsylvania, Texas	Randomized, double-blinded, bone marrow mesenchymal stem cell derived extracellular vesicles infusion treatment for COVID-19 associated acute respiratory distress syndrome (ARDS): a phase II clinical trial N: 120	7 day change in partial pressure of arterial oxygen to fraction of inspired oxygen ratio	Completed December 6, 2021	Phase 2
12.	Safety and efficacy of exosomes overexpressing CD24 in two doses for patients with moderate or severe COVID-19 Sponsor: Athens Medical Society	NCT04902183	Greece, Athens, Attica	Randomized, single, a Phase II randomized, single-blind dose study to evaluate the safety and efficacy of exosomes overexpressing CD24 in 10^9 dose versus 10^10 dose, for the prevention of clinical deterioration in patients with moderate or severe COVID-19 N:90	Collection of serious adverse events Proportion of patients related with Respiratory rate and SpO2 saturation	Recruiting June 15, 2021	Phase 2