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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

Tracking Information
First Submitted Date  ICMJE April 27, 2020
First Posted Date  ICMJE May 22, 2020
Last Update Posted Date May 22, 2020
Estimated Study Start Date  ICMJE May 2020
Estimated Primary Completion Date January 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 20, 2020)
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
Original Primary Outcome Measures  ICMJE Same as current
Change History No Changes Posted
Current Secondary Outcome Measures  ICMJE
 (submitted: May 20, 2020)
  • Number of Participants alive by Day 28 [ Time Frame: Day 28 ]
    Number of Participants alive by Day 28
  • Number of Participants with ventilator-free Days by Day 28 [ Time Frame: Day 28 ]
    Number of Participants with ventilator-free Days by Day 28
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Cellular Immuno-Therapy for COVID-19 Acute Respiratory Distress Syndrome - Vanguard
Official Title  ICMJE Cellular Immuno-Therapy for COVID-19 ARDS (CIRCA-19) the Vanguard Study
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).

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE 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
Condition  ICMJE
  • Acute Respiratory Distress Syndrome
  • Covid19
Intervention  ICMJE Biological: Mesenchymal Stromal Cells
The Mesenchymal Stromal Cells will be administered intravenously
Study Arms  ICMJE
  • Experimental: Panel 1
    25 million cells/unit dose (cumulative dose: 75 million MSCs)
    Intervention: Biological: Mesenchymal Stromal Cells
  • Experimental: Panel 2
    50 million cells/unit dose (cumulative dose: 150 million MSCs)
    Intervention: Biological: Mesenchymal Stromal Cells
  • Experimental: Panel 3
    up to 90 million cells/unit dose (cumulative dose: up to 270 million MSCs)
    Intervention: Biological: Mesenchymal Stromal Cells
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Not yet recruiting
Estimated Enrollment  ICMJE
 (submitted: May 20, 2020)
9
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE June 2021
Estimated Primary Completion Date January 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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)
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Duncan J Stewart, MD +1 613 737 8899 ext 75083 djstewart@toh.ca
Listed Location Countries  ICMJE Canada
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04400032
Other Study ID Numbers  ICMJE 20200243-01H
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Ottawa Hospital Research Institute
Study Sponsor  ICMJE Ottawa Hospital Research Institute
Collaborators  ICMJE Stem Cell Network
Investigators  ICMJE
Principal Investigator: Duncan J Stewart, MD Ottawa Hospital Research Institute
PRS Account Ottawa Hospital Research Institute
Verification Date May 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP