Cellular Immuno-Therapy for COVID-19 ARDS Randomized Clinical Trial (CIRCA-19 RCT)

This is a Phase 2 multicenter randomized (2:1), placebo-controlled trial to evaluate early signs of efficacy of allogeneic, umbilical cord-derived (UC) mesenchymal stromal cells (MSCs) in patients with COVID-19 and Acute Respiratory Distress Syndrome (ARDS).

Randomized participants (N=54) will receive 3 daily doses of up to 90-million cells/unit dose (cumulative dose of up to 270 million UC-MSCs) or blinded placebo. The MSC product will be provided as 2.5 million cells/ml suspended in PlasmaLyte A containing 5% Human Albumin. The appearance-matched placebo product contains the same excipients, PlasmaLyte A and 5% Human Albumin, as the UC-MSCs.

Study Overview

• Status: Recruiting
• Conditions: Covid19; Acute Respiratory Distress Syndrome
• Intervention / Treatment: Biological: UC-MSCs; Biological: Placebo

• Study Type: Interventional
• Enrollment (Anticipated): 54
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Duncan J Stewart, MD; Phone Number: 7917 613-798-5555; Email: djstewart@ohri.ca

Study Locations

• Canada
  • Ontario
    • Oshawa, Ontario, Canada, ON L1G 2B9
      • Recruiting
      • Lakeridge Health
      • Contact: Karim Soliman, MD; Email: ksoliman@lh.ca
    • Ottawa, Ontario, Canada, K1H 8L6
      • Recruiting
      • The Ottawa Hospital
      • Contact: Duncan J Stewart, MD; Phone Number: 75083 +1 613-737-8899; Email: djstewart@toh.ca
      • Sub-Investigator: Shane English, MD
      • Sub-Investigator: Manoj Lalu, MD
      • Sub-Investigator: Bernard Thebaud, MD
      • Sub-Investigator: David Courtman, PhD
    • Toronto, Ontario, Canada, M5B 1W8
      • Not yet recruiting
      • St. Michael's Hospital
      • Contact: Claudia Dos Santos, MD; Email: Claudia.DosSantos@unityhealth.to
  • Quebec
    • Montréal, Quebec, Canada, H2X 3E4
      • Not yet recruiting
      • Centre Hospitalier de l'Universite de Montreal
      • Contact: Michaël Chassé, MD; Email: michael.chasse@umontreal.ca

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 with PEEP ≥5cm H20 or on HFNC), not due primarily to cardiac causes.

Exclusion Criteria:

• No consent/inability to obtain consent
• Rockwood Clinical Frailty Score > 4
• 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
• Documented deep venous thrombosis or pulmonary embolism within the preceding 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 change from baseline 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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: MSCs Arm; 3 daily doses of up to 90-million cells/unit dose (cumulative dose of up to 270 million UC-MSCs)	Biological: UC-MSCs; 3 daily doses of up to 90-million cells/unit dose (cumulative dose of up to 270 million UC-MSCs)
PLACEBO_COMPARATOR: Placebo Arm; 3 daily doses of up to 90-million cells/unit dose (cumulative dose of up to 270 million UC-MSCs)	Biological: Placebo; PlasmaLyte A and 5% Human Albumin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of days free of oxygen by NIV/HFNC or mechanical ventilation at Day 28	Day 28

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Biomarkers of systemic inflammatory response	Interleukin levels change from Baseline to 24 hours after each MSC infusion	Change from Baseline to 24 hours after each MSC infusion
Biomarkers of endothelial function	Angiopoietin levels change from Baseline to 24 hours after each MSC infusion	Change from Baseline to 24 hours after each MSC infusion
ICU mortality	Number of deaths at day 28	Day 28

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety events (SAEs, AEs)	allergic reactions, infusion related reactions, and venous and arterial thrombotic events	At time of infusion until one year post-infusion

Collaborators and Investigators

• Sponsor: Ottawa Hospital Research Institute
• Collaborators: Canadian Institutes of Health Research (CIHR)
• Investigators: Principal Investigator: Duncan J Stewart, MD, The Ottawa Hospital

Study record dates

Study Major Dates

• Study Start (ACTUAL): April 27, 2021
• Primary Completion (ANTICIPATED): April 1, 2022
• Study Completion (ANTICIPATED): April 1, 2022

Study Registration Dates

• First Submitted: April 27, 2021
• First Submitted That Met QC Criteria: April 27, 2021
• First Posted (ACTUAL): April 29, 2021

Study Record Updates

• Last Update Posted (ACTUAL): May 5, 2021
• Last Update Submitted That Met QC Criteria: May 4, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Respiration Disorders; Pneumonia, Viral; Pneumonia; Lung Diseases; Infant, Newborn, Diseases; Lung Injury; Infant, Premature, Diseases; COVID-19; Respiratory Distress Syndrome; Respiratory Distress Syndrome, Newborn; Acute Lung Injury
• Other Study ID Numbers: CIRCA-19 RCT

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No