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hCT-MSCs for COVID19 ARDS

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ClinicalTrials.gov Identifier: NCT04399889
Recruitment Status : Recruiting
First Posted : May 22, 2020
Last Update Posted : May 24, 2021
Sponsor:
Collaborator:
The Marcus Foundation
Information provided by (Responsible Party):
Joanne Kurtzberg, MD, Duke University

Brief Summary:

This is a 30 patient, Phase 1/2a multi-center pilot study to test the safety and to describe the preliminary efficacy of intravenous administration of allogenic human cord tissue mesenchymal stromal cells (hCT-MSC) as an investigational agent, under U.S. IND 19968 to patients with acute respiratory distress syndrome (ARDS) due to COVID-19 infection (COVID-ARDS). The key secondary endpoints are 28 day survival, an increase in PaO2/FiO2 ratio by 50% at 96 hours, days to hospital discharge to home or rehab, and number of days requiring mechanical ventilation.

Patients will be eligible for treatment with 3 daily consecutive doses of hCT-MSC at 1 million cells/kg (max dose 100 million cells), 18-30 hours apart, if they have a confirmed diagnosis of COVID-19 and meet clinical and radiographic criteria for ARDS.

Results from the first 10 patients will be compared with concurrent outcomes utilizing standard of care treatments in participating hospitals and in published reports in the medical literature. Results from the additional 20 patients will be combined with the first 10 and analyzed. The trial is relying on focused eligibility of the participants (patients with ARDS), single cohort with short trial time (4 weeks), and simple assessment of clinical outcome (survival, improvement of ARDS). This is a sequential design in the sense that after the first 10 patients are evaluated a decision will be made by the PIs and the Data Safety Monitoring Board whether to proceed with the exploratory randomized portion of the study.


Condition or disease Intervention/treatment Phase
COVID Corona Virus Infection COVID19 Biological: human cord tissue mesenchymal stromal cells Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Pilot Study of Safety and Efficacy of Cord Tissue Derived Mesenchymal Stromal Cells (hCT-MSC) in COVID-19 Related Acute Respiratory Distress Syndrome (ARDS)
Actual Study Start Date : June 18, 2020
Estimated Primary Completion Date : April 1, 2022
Estimated Study Completion Date : July 31, 2022


Arm Intervention/treatment
Experimental: Open Label infusion of hCT-MSC
The first 10 consecutive patients will all receive investigational product.
Biological: human cord tissue mesenchymal stromal cells
Infusion of human cord tissue mesenchymal stromal cells (hCT-MSC)
Other Name: hCT-MSC

Randomized infusion of hCT-MSC
An interim analysis, for safety will be conducted and reviewed by the Data Safety and Monitoring Board (DSMB) after the first 10 patients have completed treatment and reached the 28 day endpoint. If there are no safety concerns, the trial will proceed with enrollment on the phase 2 portion of the study where the subsequent 20 patients will be randomized in a 1:1 fashion between treatment with MSCs and standard of care.
Biological: human cord tissue mesenchymal stromal cells
Infusion of human cord tissue mesenchymal stromal cells (hCT-MSC)
Other Name: hCT-MSC

No Intervention: Standard of care
Subjects on this arm will not receive any hCT-MSCs (study product). They will receive standard of care treatment for COVID19, as clinically indicated by their care provider.



Primary Outcome Measures :
  1. Safety of the Investigational Product [ Time Frame: 24 hours ]
    Incidence of infusion reactions measured by any one of the following: fever, anaphlyaxis, rash, hypertension, hypotension, tachycardia, nausea, vomiting, or any other new or worsening symptoms associated with the infusion.

  2. Safety of the Investigational Product [ Time Frame: 28 days ]
    Incidence of later reactions attributed to the investigational product as measured by any one of the following: rash, infection, allergic reaction, or any other symptoms associated with infusion of the investigational product.

  3. Safety of the Investigational Product [ Time Frame: 28 days ]
    Formation of new anti-PRA antibodies as measured by an antibody screen test at 28 days post first infusion of the investigational product.


Secondary Outcome Measures :
  1. Describe the potential for MSC therapy to favorably alter the course of COVID-ARDs [ Time Frame: 28 days ]
    Survival after 28 days after the first dose of MSCs

  2. Describe the potential for MSC therapy to favorably alter the course of COVID-ARDs [ Time Frame: 3 days after MSCs ]
    Increase in PaO2/FiO2 ratio by 50%

  3. Describe the potential for MSC therapy to favorably alter the course of COVID-ARDs [ Time Frame: 90 days ]
    The number of days from hospitalization to discharge to home

  4. Describe the potential for MSC therapy to favorably alter the course of COVID-ARDs [ Time Frame: 90 days ]
    The number of ventilator free days

  5. Describe the potential for MSC therapy to favorably alter the course of COVID-ARDs [ Time Frame: 7 days ]
    A 50% decrease in opacities by CT chest one week post initiation of MSC therapy

  6. Describe the potential for MSC therapy to favorably alter the course of COVID-ARDs [ Time Frame: 90 days ]
    The number of days requiring oxygen support

  7. Describe the potential for MSC therapy to favorably alter the course of COVID-ARDs [ Time Frame: baseline, day 4, day 7, and day 28 ]
    Changes in viral load after MSCs measured by routine PCR testing from baseline to 4 days, 7 days and 28 days after MSCs

  8. Describe the potential for MSC therapy to favorably alter the course of COVID-ARDs [ Time Frame: 90 days ]
    Number of patients able to be on the randomized portion of this study



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. The patient or legally authorized representative (LAR) must have the ability to understand and the willingness to provide a signed and dated informed consent form.
  2. Age 18 years and over
  3. The patient agrees to use adequate contraception for the duration of the treatment protocol and for 6 months post treatment.
  4. Positive RT- PCR testing for COVID-19 nucleic acid using nasopharyngeal swabbing or any other site
  5. Patient meets ARDS criteria as defined by Berlin criteria, and is on mechanical ventilation a. Berlin criteria for ARDS are: i. bilateral opacities on chest imaging consistent with pulmonary edema ii. A need for positive pressure ventilation via endotracheal or tracheostomy tube iii. PaO2/FiO2 ratio ≤ 300mmHg with a minimum of 5 cmH20 PEEP iv. Infiltrates not fully explained by cardiac failure or fluid overload in the physician's best clinical judgement ARDS onset is considered the time that the last of criteria 1-4 is met. Infiltrates considered "consistent with pulmonary edema" include any infiltrate not due to mass, atelectasis, or effusion, or opacities known to be chronic (greater than 1 week old). Vascular redistribution or indistinct vessels or heart border alone do not qualify as opacities.

Exclusion Criteria:

  1. Evidence of multiorgan failure involving one or more organs, excluding the lungs as defined below:

    1. Presence of shock, defined as MAP < 65 mmHg with signs of peripheral hypoperfusion, or continuous infusion of 2 or more vasopressor or inotrope agents to maintain MAP ≥ 65 mmHg.
    2. Serum bilirubin > 10 mg/dl
    3. Platelet count < 50,000/ml
  2. Evidence of acquired or congenital immunodeficiency (due to immunosuppressive therapy, HIV, previous treatment for cancer, etc.)
  3. History of metastatic cancer in the past 3 years
  4. History of previous treatments with MSCs or other cell therapies
  5. Patient is co-enrolled in any other IND-sponsored clinical trials for COVID-19
  6. Evidence of pregnancy or lactation
  7. Moribund patient not expected to survive > 24 hours
  8. Unable/unwilling to deliver lung protective ventilation
  9. Patient is receiving Extracorporeal Membrane Oxygenation (ECMO)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04399889


Contacts
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Contact: Erin Arbuckle 9196681102 cordbloodtherapyinfo@dm.duke.edu
Contact: Linda Brown, RN cordbloodtherapyinfo@dm.duke.edu

Locations
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United States, North Carolina
Duke Hospital Recruiting
Durham, North Carolina, United States, 27705
Contact: Allie Frear       allie.frear@duke.edu   
Contact: Linda Brown, MD       linda.brown@duke.edu   
Sponsors and Collaborators
Joanne Kurtzberg, MD
The Marcus Foundation
Investigators
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Principal Investigator: Joanne Kurtzberg, MD Duke Health
Principal Investigator: Bryan Kraft, MD Duke Health
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Responsible Party: Joanne Kurtzberg, MD, Jerome S. Harris Distinguished Professor of Pediatrics, Duke University
ClinicalTrials.gov Identifier: NCT04399889    
Other Study ID Numbers: Pro00105410
First Posted: May 22, 2020    Key Record Dates
Last Update Posted: May 24, 2021
Last Verified: May 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Joanne Kurtzberg, MD, Duke University:
COVID
Coronavirus infection
COVID19
Covid ARDS
Acute Respiratory Distress Syndrome
ARDS
Additional relevant MeSH terms:
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Coronavirus Infections
Virus Diseases
Coronaviridae Infections
Nidovirales Infections
RNA Virus Infections