Table 6 EVs-based therapeutics in clinical trials

Not Applicable

n = 20

Human amniotic mesenchymal stem cells

Hair Loss; Alopecia

Exosome (100e10 particle) injections with an interval of 14 days during two months

Change in mean total hair density (hair/cm²)

NCT05658094

Phase 1

Phase2

n = 80

Human Placenta Mesenchymal Stem Cells

Fistula Perianal

In 3 weekly episodes

Safety of injected exosomes

NCT05402748

Phase 2

Phase3

n = 60

MSCs

SARS-CoV2 Infection

Intravenous injection twice, in day 1 and day 7 of 14 days

Time to clinical improvement (days)

NCT05216562

Phase 1

Phase2

n = 80

Human Placenta Mesenchymal Stem Cells

Perianal Fistula in Patients With Crohn’s Disease

5 mL of exosome solution

Safety of injected exosomes

NCT05499156

Phase 1

n = 24

Allogenic Adipose Mesenchymal Stem Cells

Coronavirus

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)

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

NCT04276987

Phase 1

n = 30

Platelet rich plasma

Chronic Low Back Pain; Degenerativ-e Disc Disease

2 mL of exosomes

Visual analog scale (VAS)

NCT04849429

Phase 2

n = 30

MSCs

Knee; Injury; Meniscus (Lateral) (Medial)

1 million cells/kg Exosome

Evaluation of Knee Functions

NCT05261360

Not Applicable

n = 30

 N/A

Exosome Post-stroke Dementia; Acupunctur-e

N/A

concentration of Exosome

NCT05326724

Phase 1

Phase 2

n = 30

MSCs

COVID-19

Twice a day for 10 days inhalation of 3 mL special solution contained 0.5 ~ 2 × 10¹⁰ of nanoparticles (exosomes)

Number of Participants With Non-serious and Serious Adverse Events During Trial

NCT04491240

Phase 2

n = 41

Tumor Antigen-loaded Dendritic Cell

Non-Small Cell Lung Cancer

Intradermal injections once a week during 4 consecutive weeks

Progression free survival

NCT01159288

Early Phase 1

n = 9

Dendritic cells, macrophages, Tumor cells

Recurrent or Metastatic Bladder Cancer

N/A

Clinical response rate

NCT05559177

Phase 1

n = 13

Tumor cells

Malignant Glioma of Brain

10 to 20 million IGF-1R/AS ODN treated tumor cells, encapsulated in diffusion chambers (maximum of 10), and re-implanted in the patient’s abdomen within 24 h after the surgery for a 24-hour period

To establish the safety profile of a combination product with an optimized Good Manufacturing Practices AS ODN in the treatment of patients with recurrent malignant glioma with concomitant assessment of any therapeutic impact

NCT01550523

Phase 1

n = 38

Wharton’s Jelly Mesenchymal Stem Cells

Chronic Ulcer

Conditioned Medium gel for 2 weeks

Knowing the success rate of chronic ulcer healing in patients undergoing wound care with conditioned medium

NCT04134676

Phase 2

n = 102

Bone marrow

COVID-19, Acute respiratory distress syndrome (ARDS)

10 mL, which is 800 billion EVs. 15 mL, which is 1.2 trillion EVs

Evaluation of 60 day mortality rate

NCT04493242

Phase 1

n = 28

MSCs

Metastatic Pancreatic Adenocarci-noma ;

Pancreatic Ductal Adenocarci-noma;

Stage IV Pancreatic Cancer

over 15 ~ 20 min on days 1, 4, and 10. Treatment repeats every 14 days for up to 3 courses in the absence of disease progression or unacceptable toxicity. Participants who respond may continue 3 additional courses

Maximum Tolerated Dose Determined by Dose Limiting Toxicity

NCT03608631

Phase 1

Phase 2

n = 20

MSCs

Segmental; Fracture - Bone Loss

N/A

Adverse effects associated with the therapy

NCT05520125

Phase 1

Phase 2

n = 81

BMSCs

ARDS; Human

10 mL, 15 mL

The incidence of serious adverse events

NCT05127122

Not Applicable

n = 25

Autologous blood

Otitis Media Chronic; Temporal Bone

N/A

Change in Inflammation Surface Area

NCT04281901

n = 300

Explore the source of extracellular vesicles

Traumatic Brain Injury

N/A

The type and content of circulating extracellular vesicles

NCT05279599

Phase 2

Phase 3

n = 100

Autologous blood

Otitis Media Chronic

N/A

Change of tympanic membrane perforation size

NCT04761562

Phase 1

n = 10

MSCs

Burns

1 × 10⁴ MSCs for each cm²

Primary Objective

NCT05078385

N/A

BMSCs

Covid19; ARDS; Hypoxia Cytokine Storm

Intravenous Infusion over 60 min

N/A

NCT04657458

Phase 1

Phase 2

n = 60

BMSCs

Covid19; Postviral Syndrome; Dyspnea

ExoFlo 15 mL (10.5 × 10⁸ EVs)

Increased distance on Six Minute Walk Test (6MWT)

NCT05116761

n = 50

Peripheral blood samples

ARDS Human

N/A

28 day mortality

NCT05061212

Not Applicable

n = 10

Autologous serum

Ulcer Venous

3 weeks once a week

Changes in the ulcer area from baseline to eight weeks

NCT04652531

Phase 1

n = 10

Adult allogeneic bone marrow mesenchymal stem cell

Ulcerative Colitis

15mL of ExoFlo at Day 0, 2, 4 Week 2, 6, and every 8 weeks after that to week 46

Safety of intravenous ExoFlo in subjects with moderately to severely active Ulcerative colitis who have failed, or are intolerant, or have a contraindication to one or more monoclonal antibodies

NCT05176366

Phase 1

n = 10

Adult allogeneic bone marrow mesenchymal stem cell

Crohn Disease

15mL of ExoFlo at Day 0, 2, 4, Week 2, Week 6, and every 8 weeks after that to week 46

Safety of intravenous ExoFlo in subjects with moderately to severely active Crohn’s disease who have failed, or are intolerant, or have a contraindication to one or more monoclonal antibodies

NCT05130983

Phase 3

n = 400

BMSCs

COVID-19; ARDS

15mL, which is approximately 1.2 trillion EVs

The primary efficacy endpoint is overall 60 day mortality (due to any cause)

NCT05354141

Not Applicable

n = 5

Adipose tissue

Wounds and Injuries

N/A

Percentage of wound healing in each group at 4 weeks

NCT05475418

Early Phase 1

n = 20

BMSCs

Solid Organ Transplant Rejection

Intravenous Infusion over 60 min

Number of participants with adverse/serious adverse events

NCT05215288

Early Phase 1

n = 10

Adipose stem cells

Periodontiti-s

N/A

change in gingival inflammation

NCT04270006

Not Applicable

n = 30

MSCs

Foot; Diabetic

N/A

Ulcer evaluation

NCT05243368

Phase 1

n = 13

Autologous dendritic cell

Non-small cell lung cancer

Weekly, Four weeks

Survival of patients after the first DEX dose was 52 ~ 665 days. DTH reactivity against MAGE peptides was detected in 3/9 patients. Immune responses were detected in patients as follows: MAGE-specific T cell responses in 1/3, increased NK lytic activity in 2/4

[259]

Phase 1

n = 15

Autologous dendritic cell

Metastatic melanoma

Weekly, Four weeks

There was no grade II toxicity and the maximal tolerated dose, MAGE3 specific CD4 + and CD8 + T cell responses could not be detected in peripheral blood

[260]

Phase 1

n = 40

Ascites- derived exosomes (Aex)

Autologous Ascites

100, 200, 300, and 500 µg doses

the therapies were safe and well tolerated, the exosomes alone had no effect. After addition of colony stimulating factor, 1 case was stable and 1 case was mild

[261]

Phase 2

n = 22

Dendritic cell

Non-small cell lung cancer

Intradermal injections were given four times every other week interval

One patient exhibited a grade three hepatotoxicity. The median time to progression was 2.2 mo and median overall survival (OS) was 15 mo

[262]

Phase 1

n = 20

HL-60 cells

Biliary obstruction

20 mL MTX–TMPs containing 6 × 10⁷ tumour-cell-derived microparticles and 120 µg Methotrexate

Most patients (about 70%) had a transient fever (1–4 h) but no other uncomfortable symptoms and relieved biliary obstruction in 25% of the patients

[263]

Phase 2

n = 90

MSCs

SARS-CoV-2 PNEUMONIA

Twice a day during 10 days inhalation of 3 mL special solution contained 0.5 ~ 2 × 10¹⁰ of nanoparticles (exosomes)

Primary Outcome Measures: Number of participants with non-serious and serious adverse events during trial

NCT04602442

Phase 1

Phase 2

n = 30

MSCs

SARS-CoV-2 PNEUMON-IA

Twice a day during 10 days inhalation of 3 ml special solution contained 0.5 ~ 2 × 10¹⁰ of nanoparticles (exosomes)

Number of Participants With Non-serious and Serious Adverse Events During Trial

NCT04491240

n = 24

Allogeneic bone marrow mesenchymal stem cells

COVID-19

Single 15mL intravenous dose of ExoFlo and were evaluated for both safety and efficacy from days 1 to 14 post-treatment

N/A

[227]

Phase 2

n = 90

MSCs

SARS-CoV-2 PNEUMON-IA

Twice a day during 10 days inhalation of 3 mL special solution contained 0.5 ~ 2 × 10¹⁰ of nanoparticles (exosomes)

Number of participants with non-serious and serious adverse events during trial

NCT04384445

Phase 1

n = 24

MSCs

Coronavirus

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)

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

NCT04276987

Phase 1

n = 35

T-REx™-293 cells engineered to express CD24 at high levels

SARS-CoV-2

1 × 10⁸ ~ 1 × 10¹⁰ exosome particles per 2 mL saline

Primary safety endpoint: Adverse events

NCT04747574

Phase 1

Phase 2

n = 55

MSCs

Covid19;

Novel Coronavirus Pneumonia;

ARDS

2 × 10⁹, 4 × 10⁹, 8 × 10⁹ exosomes

Measure and report the number of participants with treatment-related-adverse events as assessed by CTCAE v4.0; for patients receiving ARDOXSO™, perinatal MSC-derived exosome therapy

NCT04798716