ExoFlo™ Infusion for Post-Acute COVID-19 and Chronic Post-COVID-19 Syndrome
Primary Purpose
Covid19, Postviral Syndrome, Dyspnea
Status
Not yet recruiting
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
Bone Marrow Mesenchymal Stem Cell Derived Extracellular Vesicles
Saline
Sponsored by
About this trial
This is an interventional treatment trial for Covid19
Eligibility Criteria
Inclusion Criteria:
- Provision of signed and dated informed consent form (either by the individual or by the individual's healthcare proxy).
- Stated willingness to comply with all study procedures and availability for the duration of the study
- Male or female aged 18-85.
- Discharged from recent hospitalization for severe COVID-19 disease requiring supplemental oxygen but not requiring mechanical ventilation or ECMO or dialysis.
- Must be between 4 to 20 weeks since onset of acute COVID-19 symptoms onset.
- No return to baseline health or hiatus between acute COVID-19 and onset of post-acute COVID-19 or chronic post-COVID-19 syndrome.
- Current SARS-CoV-2 RT PCR must be negative prior to enrollment.
- 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).
- Medical Resource Council Dyspnea Score of < 3 out of 5.
- 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.)
- Baseline 6-Minute Walk Test (6-MWT) is 500 meters or less.
- Supplemental oxygen should be ≤5 L O2/min.
- 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:
- Vulnerable populations such as pregnant patients, children, individuals with severe physical or mental disabilities who cannot provide meaningful consent.
- Active malignancy requiring treatment within the last five years.
- 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.
- 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.
- 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.
- 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.
- Lab abnormalities: WBC ≥ 12,000 /μL, Creatinine ≥ 1.5 mg/dL, AST ≥ 100 IU/l, and/or ALT ≥ 100 IU/I
- Patients who require rolling walker or wheelchair or higher level of assistance for ambulation.
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Placebo Comparator
Experimental
Arm Label
Treatment Arm 1
Treatment Arm 2
Arm Description
Normal Saline 100 mL
Normal saline 85 mL and ExoFlo 15 mL, which is 10.5 x 10^8 EV
Outcomes
Primary Outcome Measures
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.
Incidence of Serious Adverse Events (SAEs)
Rate of SAEs observed over the duration of the study.
Secondary Outcome Measures
EuroQol-5D (EQ-5D)
Five dimensions include mobility, self-care, usual activities, pain/discomfort, and anxiety/depression
Medical Research Council (MRC) Dyspnea Scale
Degree of breathlessness related to activity, graded 1-5.
Full Information
NCT ID
NCT05116761
First Posted
November 9, 2021
Last Updated
October 23, 2023
Sponsor
Direct Biologics, LLC
1. Study Identification
Unique Protocol Identification Number
NCT05116761
Brief Title
ExoFlo™ Infusion for Post-Acute COVID-19 and Chronic Post-COVID-19 Syndrome
Official Title
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
Study Type
Interventional
2. Study Status
Record Verification Date
October 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
November 2023 (Anticipated)
Primary Completion Date
November 2023 (Anticipated)
Study Completion Date
December 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Direct Biologics, LLC
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Covid19, Postviral Syndrome, Dyspnea
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
Double-blinded
Allocation
Randomized
Enrollment
60 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Treatment Arm 1
Arm Type
Placebo Comparator
Arm Description
Normal Saline 100 mL
Arm Title
Treatment Arm 2
Arm Type
Experimental
Arm Description
Normal saline 85 mL and ExoFlo 15 mL, which is 10.5 x 10^8 EV
Intervention Type
Biological
Intervention Name(s)
Bone Marrow Mesenchymal Stem Cell Derived Extracellular Vesicles
Intervention Description
Intravenous administration of Bone Marrow Mesenchymal Stem Cell Derived Extracellular Vesicles
Intervention Type
Other
Intervention Name(s)
Saline
Intervention Description
Placebo Saline
Primary Outcome Measure Information:
Title
Increased distance on Six Minute Walk Test (6MWT)
Description
Meters walked in a self-paced test in which the subject is instructed to walk as fast as possible during 6 minutes.
Time Frame
61 Days
Title
Incidence of Serious Adverse Events (SAEs)
Description
Rate of SAEs observed over the duration of the study.
Time Frame
61 Days
Secondary Outcome Measure Information:
Title
EuroQol-5D (EQ-5D)
Description
Five dimensions include mobility, self-care, usual activities, pain/discomfort, and anxiety/depression
Time Frame
61 days
Title
Medical Research Council (MRC) Dyspnea Scale
Description
Degree of breathlessness related to activity, graded 1-5.
Time Frame
61 Days
Other Pre-specified Outcome Measures:
Title
C-Reactive Protein (CRP), D-dimer, Atrial Natriuretic Peptides (ANP)
Description
Acute phase reactants
Time Frame
61 Days
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
85 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Provision of signed and dated informed consent form (either by the individual or by the individual's healthcare proxy).
Stated willingness to comply with all study procedures and availability for the duration of the study
Male or female aged 18-85.
Discharged from recent hospitalization for severe COVID-19 disease requiring supplemental oxygen but not requiring mechanical ventilation or ECMO or dialysis.
Must be between 4 to 20 weeks since onset of acute COVID-19 symptoms onset.
No return to baseline health or hiatus between acute COVID-19 and onset of post-acute COVID-19 or chronic post-COVID-19 syndrome.
Current SARS-CoV-2 RT PCR must be negative prior to enrollment.
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).
Medical Resource Council Dyspnea Score of < 3 out of 5.
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.)
Baseline 6-Minute Walk Test (6-MWT) is 500 meters or less.
Supplemental oxygen should be ≤5 L O2/min.
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:
Vulnerable populations such as pregnant patients, children, individuals with severe physical or mental disabilities who cannot provide meaningful consent.
Active malignancy requiring treatment within the last five years.
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.
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.
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.
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.
Lab abnormalities: WBC ≥ 12,000 /μL, Creatinine ≥ 1.5 mg/dL, AST ≥ 100 IU/l, and/or ALT ≥ 100 IU/I
Patients who require rolling walker or wheelchair or higher level of assistance for ambulation.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Amy Lightner, MD
Phone
512-354-7124
Email
alightner@directbiologics.com
First Name & Middle Initial & Last Name or Official Title & Degree
Stephanie Cahill
Phone
252-481-1581
Email
scahill@directbiologics.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Amy Lightner, MD
Organizational Affiliation
Direct Biologics, LLC
Official's Role
Study Director
12. IPD Sharing Statement
Learn more about this trial
ExoFlo™ Infusion for Post-Acute COVID-19 and Chronic Post-COVID-19 Syndrome
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