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Cellular Immuno-Therapy for COVID-19 Acute Respiratory Distress Syndrome - Vanguard (CIRCA-19)

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ClinicalTrials.gov Identifier: NCT04400032
Recruitment Status : Not yet recruiting
First Posted : May 22, 2020
Last Update Posted : May 22, 2020
Sponsor:
Collaborator:
Stem Cell Network
Information provided by (Responsible Party):
Ottawa Hospital Research Institute

Brief Summary:

The clinical picture of the novel corona virus 2 (SARS-CoV-2) disease (COVID-19) is rapidly evolving. Although infections may be mild, up to 25% of all patients admitted to hospital require admission to the intensive care unit, and as many as 40% will progress to develop severe problems breathing due to the acute respiratory distress syndrome (ARDS). ARDS often requires mechanical ventilation, with a 50% risk of mortality. Researchers at the Ottawa Hospital Research Institute (OHRI) have been studying the potential therapeutic role of mesenchymal stromal/stem cells, or MSCs, for the treatment of ARDS for over a decade. This has led to the world's first clinical trial using MSC therapy for patients with severe infections (sepsis) which is often associated with ARDS (NCT02421484). This trial demonstrated tolerability, and potential signs of efficacy. In addition, the investigators have established expertise in producing clinical-grade MSCs and have received approval from Health Canada for the use of MSCs in three different clinical studies.

The investigators propose a Phase 1, open label, dose-escalating and safety trial using a 3+3+3 design to determine the safety, and maximum feasible tolerated dose of repeated delivery of Bone Marrow (BM)-MSCs intravenously. This will take advantage of a limited supply of screened BM-MSCs lines which are available now in the GMP facility and will allow to have product ready to deliver to the first patient within weeks. The investigators will enroll up to 9 patients; each receiving repeated unit doses of BM-MSCs delivered by IV infusion on each of 3 consecutive days (24±4 hours apart) according to the following dose-escalation schedule (3 patients per dose panel): (i) Panel 1: 25 million cells/unit dose (cumulative dose: 75 million MSCs), (ii) Panel 2: 50 million cells/unit dose (cumulative dose: 150 million MSCs), (iii) Panel 3: up to 90 million cells/unit dose (cumulative dose: up to 270 million MSCs).


Condition or disease Intervention/treatment Phase
Acute Respiratory Distress Syndrome Covid19 Biological: Mesenchymal Stromal Cells Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 9 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Intervention Model Description:

This is a dose-escalating and safety trial using a 3+3+3 design to determine the safety, and maximum feasible tolerated dose (MFTD) of intravenously (IV) delivered bone marrow derived MSCs (BM-MSCs).

We will enroll up to 9 patients; each receiving repeated unit doses of BM-MSCs delivered by IV infusion on each of 3 consecutive days (24±4 hours apart) according to the following dose-escalation schedule (3 patients per dose panel): (i) Panel 1: 25 million cells/unit dose (cumulative dose: 75 million MSCs), (ii) Panel 2: 50 million cells/unit dose (cumulative dose: 150 million MSCs), (iii) Panel 3: up to 90 million cells/unit dose (cumulative dose: up to 270 million MSCs).

Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Cellular Immuno-Therapy for COVID-19 ARDS (CIRCA-19) the Vanguard Study
Estimated Study Start Date : May 2020
Estimated Primary Completion Date : January 2021
Estimated Study Completion Date : June 2021


Arm Intervention/treatment
Experimental: Panel 1
25 million cells/unit dose (cumulative dose: 75 million MSCs)
Biological: Mesenchymal Stromal Cells
The Mesenchymal Stromal Cells will be administered intravenously

Experimental: Panel 2
50 million cells/unit dose (cumulative dose: 150 million MSCs)
Biological: Mesenchymal Stromal Cells
The Mesenchymal Stromal Cells will be administered intravenously

Experimental: Panel 3
up to 90 million cells/unit dose (cumulative dose: up to 270 million MSCs)
Biological: Mesenchymal Stromal Cells
The Mesenchymal Stromal Cells will be administered intravenously




Primary Outcome Measures :
  1. Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE v4.0 [ Time Frame: At time of infusion until one year post-infusion ]
    Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE v4.0 to determine the maximum feasible tolerated dose (MFTD) of BM-MSCs given to patients with COVID-19


Secondary Outcome Measures :
  1. Number of Participants alive by Day 28 [ Time Frame: Day 28 ]
    Number of Participants alive by Day 28

  2. Number of Participants with ventilator-free Days by Day 28 [ Time Frame: Day 28 ]
    Number of Participants with ventilator-free Days by Day 28



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:

  • Age of 18 years and older
  • Laboratory-confirmed SARS-CoV-2 infection
  • On invasive mechanical ventilation ≤48h
  • ARDS as per the international consensus definition35 (P/F ratio < 300 on FiO2≥0.5, with PEEP ≥5cm H2O), not due primarily to cardiac causes.

Exclusion Criteria:

  • No consent/inability to obtain consent
  • Moribund patient not expected to survive 24 hours
  • Any other irreversible disease or condition for which 6-month mortality is estimated to be greater than 50%
  • Currently receiving extracorporeal life support
  • Anticipated extubation within 24 hours of enrollment
  • Pregnant or lactating
  • Presence of any active malignancy (other than non-melanoma skin cancer) that required treatment within the last year
  • Moderate to severe chronic liver disease (Childs-Pugh Score > 12)
  • Severe chronic respiratory disease with a baseline PaCO2 > 50 mm Hg or the use of home oxygen
  • Lung transplant patient
  • Documented deep venous thrombosis or pulmonary embolism within the past 3 months
  • Chronic immunosuppression (any chronic immunotherapy including daily oral steroid use >6months)
  • Known HIV, Hep B/C positive, or active TB
  • Multisystem shock (SOFA score of >2 in >2 systems)
  • Patient, surrogate, or physician not committed to full support (exception: a patient will not be excluded if he/she would receive all supportive care except for attempts at resuscitation from cardiac arrest)

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): NCT04400032


Contacts
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Contact: Duncan J Stewart, MD +1 613 737 8899 ext 75083 djstewart@toh.ca

Locations
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Canada, Ontario
The Ottawa Hospital
Ottawa, Ontario, Canada, K1H 8L6
Contact: Duncan J Stewart, MD    +1 613-737-8899 ext 75083    djstewart@toh.ca   
Sub-Investigator: Shane English, MD         
Sub-Investigator: Dean Fergusson, PhD         
Sub-Investigator: Manoj Lalu, MD         
Sub-Investigator: Bernard Thebaud, MD         
Sub-Investigator: David Courtman, PhD         
Sponsors and Collaborators
Ottawa Hospital Research Institute
Stem Cell Network
Investigators
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Principal Investigator: Duncan J Stewart, MD Ottawa Hospital Research Institute
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Responsible Party: Ottawa Hospital Research Institute
ClinicalTrials.gov Identifier: NCT04400032    
Other Study ID Numbers: 20200243-01H
First Posted: May 22, 2020    Key Record Dates
Last Update Posted: May 22, 2020
Last Verified: May 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Ottawa Hospital Research Institute:
ARDS
COVID-19
Mesenchymal Stromal Cells
Additional relevant MeSH terms:
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Respiratory Distress Syndrome, Newborn
Respiratory Distress Syndrome, Adult
Acute Lung Injury
Syndrome
Disease
Pathologic Processes
Lung Diseases
Respiratory Tract Diseases
Respiration Disorders
Infant, Premature, Diseases
Infant, Newborn, Diseases
Lung Injury