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

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ClinicalTrials.gov Identifier: NCT04400032
Recruitment Status : Completed
First Posted : May 22, 2020
Last Update Posted : April 26, 2021
Sponsor:
Collaborators:
Stem Cell Network
Ontario Research Fund
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 April 26, 2021
Actual Study Start Date  ICMJE May 15, 2020
Actual Primary Completion Date April 22, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 8, 2021)
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 UC-MSCs given to patients with COVID-19
Original 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
Change History
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
Official Title  ICMJE Cellular Immuno-Therapy for COVID-19 ARDS (CIRCA-19)
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.

This protocol consists of 2 sequential trials using the same trial infrastructure, noted as the Phase 1 trial 'CIRCA-1901' and the Phase 2a trial 'CIRCA-1902'. CIRCA-1901 is an 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 Umbilical Cord Mesenchymal Stromal Cells (UC-MSC) intravenously. The investigators will enroll up to 9 patients; each receiving repeated unit doses of UC-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). If no safety issues are identified, we will continue to the Phase 2a trial.

CIRCA-1902 is a single-arm, open-label extension of the CIRCA-1901 trial to assess early signs of efficacy (major morbidity and mortality). The Phase 2a trial (CIRCA-1902) will enroll 12 patients to assess early signals of benefit on mortality and major morbidity in a high risk, high mortality population.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Intervention Model Description:

CIRCA-1901 is 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 umbilical cord derived MSCs (UC-MSCs). If no safety issues are identified, we will continue to the Phase 2a trial.

CIRCA-1902 is a single-arm, open-label extension of the CIRCA-1901 trial to assess early signs of efficacy (major morbidity and mortality). The Phase 2a trial (CIRCA-1902) will enroll 12 patients to assess early signals of benefit on mortality and major morbidity in a high risk, high mortality population.

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 Completed
Actual Enrollment  ICMJE
 (submitted: April 23, 2021)
15
Original Estimated Enrollment  ICMJE
 (submitted: May 20, 2020)
9
Actual Study Completion Date  ICMJE April 22, 2021
Actual Primary Completion Date April 22, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Age of ≥18 years
  • Laboratory-confirmed SARS-CoV-2 infection during the current admission
  • On invasive, non-invasive mechanical ventilation (NIV) (PEEP≥5 cmH20) or high-flow nasal canula (HFNC) oxygen therapy (minimum total flow rate of 40 lpm)
  • ARDS (onset <96h) as per the international consensus definition (P/F) ratio < 300 on fraction of inspired oxygen (FiO2)≥0.5, with PEEP ≥5cm H2O or on HFNC), not due to cardiac causes.

Exclusion Criteria:

An individual who meets any of the following criteria will be excluded from participation in this trial:

  • 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
  • Pregnant or lactating
  • Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
  • 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
  • Inability/contra-indications to receiving local standard of care thromboprophylaxis
  • Chronic immunosuppression (any chronic immunotherapy including daily oral steroid use >6months)
  • Known HIV, Hep B/C positive, or active Tuberculosis
  • Multisystem shock (SOFA score of >2 in >2 systems)
  • Patient, surrogate, or physician not committed to full support including intubation (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 information is only displayed when the study is recruiting subjects
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
  • Ontario Research Fund
Investigators  ICMJE
Principal Investigator: Duncan J Stewart, MD Ottawa Hospital Research Institute
PRS Account Ottawa Hospital Research Institute
Verification Date April 2021

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