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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
Direct Biologics, LLC
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Covid19

Eligibility Criteria

18 Years - 85 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

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

    First Posted
    November 9, 2021
    Last Updated
    October 23, 2023
    Sponsor
    Direct Biologics, LLC
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    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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