Bone Marrow Mesenchymal Stem Cell Derived EVs for COVID-19 Moderate-to-Severe Acute Respiratory Distress Syndrome (ARDS): A Phase III Clinical Trial

Sponsor

Direct Biologics, LLC (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05354141

Collaborator

(none)

400

Enrollment

Location

Arms

12.1

Anticipated Duration (Months)

33.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Extracellular Vesicle Infusion as Early Goal Directed Therapy for COVID-19 related ARDS (EXTINGuish COVID-19) is a multicenter, double-blinded, placebo-controlled, randomized clinical trial to evaluate the efficacy of ExoFlo in treating moderate to severe ARDS caused by COVID-19.

Condition or Disease	Intervention/Treatment	Phase
COVID-19 Acute Respiratory Distress Syndrome	Drug: EXOFLO	Phase 3

Detailed Description

The purpose of the trial is to evaluate the safety and efficacy of intravenous (IV) administration of bone marrow mesenchymal stem cell derived extracellular vesicles (EVs), ExoFlo, versus placebo as treatment for COVID-19 associated moderate-to-severe Acute Respiratory Distress Syndrome (ARDS).

The study population includes 574 male and female patients between 18 and 85 years of age hospitalized with COVID-19 associated ARDS.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

400 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

Triple (Participant, Care Provider, Investigator)

Primary Purpose:

Treatment

Official Title:

Bone Marrow Mesenchymal Stem Cell Derived Extracellular Vesicles as Early Goal Directed Therapy for COVID-19 Moderate-to-Severe Acute Respiratory Distress Syndrome (ARDS):

Actual Study Start Date :

Jul 1, 2022

Anticipated Primary Completion Date :

Apr 3, 2023

Anticipated Study Completion Date :

Jul 3, 2023

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Treatment Arm 1 PLACEBO Normal saline 100 mL	Drug: EXOFLO The intervention will be infused over 60 minutes on Day 1 and repeated on Day 4 provided that the patient has not recovered as defined by WHO ordinal scale category 4 or less. The intervention will be infused over 60 minutes on Day 1 and repeated on Day 4 provided that the patient has not recovered as defined by WHO ordinal scale category 4 or less.
Experimental: Treatment Arm 2 IP (ExoFlo) 15ml dose in Normal saline 85 mL, which is approximately 1.2 trillion EVs.	Drug: EXOFLO The intervention will be infused over 60 minutes on Day 1 and repeated on Day 4 provided that the patient has not recovered as defined by WHO ordinal scale category 4 or less. The intervention will be infused over 60 minutes on Day 1 and repeated on Day 4 provided that the patient has not recovered as defined by WHO ordinal scale category 4 or less.

Arm

Intervention/Treatment

Placebo Comparator: Treatment Arm 1

PLACEBO Normal saline 100 mL

Drug: EXOFLO

The intervention will be infused over 60 minutes on Day 1 and repeated on Day 4 provided that the patient has not recovered as defined by WHO ordinal scale category 4 or less. The intervention will be infused over 60 minutes on Day 1 and repeated on Day 4 provided that the patient has not recovered as defined by WHO ordinal scale category 4 or less.

Experimental: Treatment Arm 2

IP (ExoFlo) 15ml dose in Normal saline 85 mL, which is approximately 1.2 trillion EVs.

Drug: EXOFLO

Outcome Measures

Primary Outcome Measures

The primary efficacy endpoint is overall 60-day mortality (due to any cause). [60 days]
The primary efficacy endpoint is overall 60-day mortality (due to any cause).

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 85 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Admitted to hospital with symptoms suggestive of COVID-19 infection.
Subject (or legally authorized representative) provides informed consent prior to the initiation of any study procedures.
Subject (or legally authorized representative) understands and agrees to comply with planned study procedures.
Male or nonpregnant female aged 18-85 of age at time of enrollment.
Has laboratory-confirmed SARS-CoV-2 infection as determined by PCR as documented by either of the following:
PCR positive in sample collected < 72 hours prior to randomization; OR
PCR positive in sample collected ≥ 72 hours prior to randomization, documented inability to obtain a repeat sample (e.g. due to lack of testing supplies, limited testing capacity, results taking > 24 hours, etc.). AND progressive disease suggestive of ongoing SARS-CoV-2 infection.
Presence of moderate-to-severe ARDS as defined by Berlin criteria (i-iv).
Onset within one week of known clinical insult or new or worsening respiratory symptoms
Bilateral opacities consistent with pulmonary edema on chest imaging
PaO2/FiO2 (P/F ratio) ≤ 200 mm Hg
Minimum 5 cm H2O PEEP on mechanical ventilation or acceptable equivalent*.
Must not be fully explained by cardiac failure or fluid overload.
*Minimum 5 cm H2O PEEP on BiPAP, minimum 5 cm H2O CPAP, or minimum 30 L/min on HFNC.
Women of childbearing potential must agree to either abstinence or use at least one primary form of contraception not including hormonal contraception from time of screening through Day 29.

Exclusion Criteria:

Active malignancy requiring treatment within the last five years.
Major physical trauma in the last 5 days, including accidents, assaults, and falls.
Any chronic respiratory disease, such as tuberculosis, cystic fibrosis, or pulmonary hypertension.
Use of extracorporeal membrane oxygenation (ECMO) during the current hospitalization.
ALT or AST > 5 x Upper Limit of Normal (ULN)
Estimated Glomerular Filtration Rate (eGFR) < 30 ml/min
Overt Disseminated Intravascular Coagulopathy (DIC) as evidenced by a total score of ≥ 5 on the following DIC score from International Society of Thrombosis & Hemostasis:
INR ≤ 1.3 (0 Points); 1.3- 1.7 (1 Point); > 1.7 (2 Points)
Fibrinogen > 100 mg/dL (0 Points); < 100 mg/dL (1 Point)
D-dimer < 400 ng/dL (0 Points); 400-4000 ng/mL (2 Points); >4,000 ng/ml (3 Points)
Platelets > 100,000/uL (0 Points); 50,000-100,000/uL (1 Point); < 50,000/uL (2 Points)
Pneumonia clearly attributable to a non-COVID-19 related process, including aspiration pneumonia or pneumonia that is exclusively bacterial, or originating from a diagnosed alternative virus (e.g., influenza).
DNR order, as in electing not to receive chest compressions, cardiac defibrillation, cardiac drugs, or intubation.
Endotracheal intubation duration > 48 hours.
Moribund-expected survival < 24 hours.
Severe metabolic disturbances on presentation (e.g., ketoacidosis, pH < 7.3)