ExoFlo™ Infusion for Post-Acute COVID-19 and Chronic Post-COVID-19 Syndrome

Bone Marrow Mesenchymal Stem Cell Derived Extracellular Vesicles Infusion Treatment for Post-Acute and Chronic Post-COVID-19 Syndrome: A Phase I/II Clinical Trial

This is a Phase I/II trial to evaluate the safety and efficacy of intravenous (IV) administration of bone marrow mesenchymal stem cell derived extracellular vesicles (EV), ExoFlo, as treatment for Post-Acute COVID-19 and Chronic Post-COVID-19 syndrome.

Study Overview

• Status: Not yet recruiting
• Conditions: Covid19; Dyspnea; Postviral Syndrome
• Intervention / Treatment: Other: Saline; Biological: Bone Marrow Mesenchymal Stem Cell Derived Extracellular Vesicles

Detailed Description

To evaluate the safety and efficacy of intravenous (IV) administration of bone marrow mesenchymal stem cell derived extracellular vesicles (EV), ExoFlo, as treatment for Post-Acute COVID-19 and Chronic Post-COVID-19 syndrome.

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Bill Arana; Phone Number: 1-800-791-1021; Email: clinicalaffairs@directbiologics.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Provision of signed and dated informed consent form (either by the individual or by the individual's healthcare proxy).
2. Stated willingness to comply with all study procedures and availability for the duration of the study
3. Male or female aged 18-85.
4. Discharged from recent hospitalization for severe COVID-19 disease requiring supplemental oxygen but not requiring mechanical ventilation or ECMO or dialysis.
5. Must be between 4 to 20 weeks since onset of acute COVID-19 symptoms onset.
6. No return to baseline health or hiatus between acute COVID-19 and onset of post-acute COVID-19 or chronic post-COVID-19 syndrome.
7. Current SARS-CoV-2 RT PCR must be negative prior to enrollment.
8. At least 2 or more persistent symptoms frequently reported for post-acute COVID-19 or chronic post-COVID-19 syndrome such as fatigue, cough, headache, body aches, fever, chills, loss of taste, loss of smell, diarrhea, congestion, dyspnea, sore throat, chest pain, abdominal pain, confusion, or vomiting must be moderate in severity based on modified CDC Symptoms Questionnaire (See Section 11.1 for severity scoring system).
9. Medical Resource Council Dyspnea Score of < 3 out of 5.
10. Baseline EQ-5D-5L must be higher than 21211. (Of note: EQ-5D-5L has 5 dimensions: mobility, self-care, usual activities, pain/discomfort, anxiety/depression. Each dimension is scored from 1 (full) to 5 (worst), such that a score of 11111 is reflective of full quality-of-life and a score of 55555 is reflective of worst quality-of-life.)
11. Baseline 6-Minute Walk Test (6-MWT) is 500 meters or less.
12. Supplemental oxygen should be ≤5 L O2/min.
13. If the candidate is either male or female of reproductive potential, he or she must agree to use of double barrier method of highly effective birth control contraception such as condoms with oral contraceptive pill or choose to remain abstinent if already practicing abstinence during the screening period. The duration of required usage of double barrier method OR maintenance of abstinence must include the time from the beginning of the screening period until 90 days following the last dose of the study treatment.

Exclusion Criteria:

1. Vulnerable populations such as pregnant patients, children, individuals with severe physical or mental disabilities who cannot provide meaningful consent.
2. Active malignancy requiring treatment within the last five years.
3. Major physical trauma in the last 3 months, including motor vehicle accidents, assaults, mechanical falls with sequelae of significant bleeding or craniofacial bruising, and surgeries.
4. Patients with persistent symptoms due to any of the following chronic comorbidities such as active tuberculosis or cystic fibrosis, chronic respiratory disease including chronic obstructive pulmonary disease or pulmonary fibrosis requiring baseline home oxygen > 5 L O2/min, history of unstable angina or a heart attack during the last 12 months, pulmonary hypertension, hepatic impairment, chronic kidney disease, uncontrolled diabetes, substance abuse, severe osteoarthritis, HIV, migraine disorder, fibromyalgia, dementia, connective tissue disorders, and endocrine disorders.
5. Depression as screened by positive Patient Health Questionnaire (PHQ2) and confirmed as moderate or higher severity on PHQ9 (See Appendix 11.5). Of note, subjects found to have moderate or higher on PHQ-9 will be referred for appropriate outpatient psychiatric evaluation and intervention for their depression.
6. Vital sign abnormalities: temperature ≥ 38 °C, temperature < 35 °C; systolic blood pressure (SBP) < 90 mmHg, SBP ≥ 170 mmHg; diastolic blood pressure (DBP) < 50 mmHg, DBP ≥ 100 mmHg; heart rate (HR) < 50 beats per minute (BPM), HR ≥ 120 BPM.
7. Lab abnormalities: WBC ≥ 12,000 /μL, Creatinine ≥ 1.5 mg/dL, AST ≥ 100 IU/l, and/or ALT ≥ 100 IU/I
8. Patients who require rolling walker or wheelchair or higher level of assistance for ambulation.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Treatment Arm 1; Normal Saline 100 mL	Other: Saline; Placebo Saline
Experimental: Treatment Arm 2; Normal saline 85 mL and ExoFlo 15 mL, which is 10.5 x 10^8 EV	Biological: Bone Marrow Mesenchymal Stem Cell Derived Extracellular Vesicles; Intravenous administration of Bone Marrow Mesenchymal Stem Cell Derived Extracellular Vesicles

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Increased distance on Six Minute Walk Test (6MWT)	Meters walked in a self-paced test in which the subject is instructed to walk as fast as possible during 6 minutes.	61 Days
Incidence of Serious Adverse Events (SAEs)	Rate of SAEs observed over the duration of the study.	61 Days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
EuroQol-5D (EQ-5D)	Five dimensions include mobility, self-care, usual activities, pain/discomfort, and anxiety/depression	61 days
Medical Research Council (MRC) Dyspnea Scale	Degree of breathlessness related to activity, graded 1-5.	61 Days

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
C-Reactive Protein (CRP), D-dimer, Atrial Natriuretic Peptides (ANP)	Acute phase reactants	61 Days

Collaborators and Investigators

• Sponsor: Direct Biologics, LLC
• Investigators: Study Director: Bill Arana, Direct Biologics, LLC

Study record dates

Study Major Dates

• Study Start (Estimated): November 1, 2024
• Primary Completion (Estimated): November 1, 2024
• Study Completion (Estimated): December 1, 2024

Study Registration Dates

• First Submitted: November 9, 2021
• First Submitted That Met QC Criteria: November 9, 2021
• First Posted (Actual): November 11, 2021

Study Record Updates

• Last Update Posted (Actual): February 12, 2024
• Last Update Submitted That Met QC Criteria: February 9, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Respiration Disorders; Pneumonia, Viral; Pneumonia; Lung Diseases; Disease; Signs and Symptoms, Respiratory; COVID-19; Syndrome; Dyspnea
• Other Study ID Numbers: DB-EF-POSTCOVID-0002

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No